Target Volume Delineation and Field Setup.pdf
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The document is a practical guide in radiation oncology focusing on target volume delineation and field setup for conformal and intensity-modulated radiation therapy (IMRT). It aims to assist residents and practicing radiation oncologists in effectively applying current radiation oncology techniques and managing treatment planning for various cancers. The second edition includes expert contributions on contouring and treatment recommendations, particularly in advanced treatment options like IMRT and stereotactic body radiation therapy (SBRT).
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Table 1.1 Suggested clinical target volumes at the gross disease region
Target volumes Definition and description
GTV70
a
Primary: All gross disease on physical examination and imaging. Pre-
treatment imaging should be carefully scrutinized for invasion of the skull
base and perineural spread
Neck: All nodes ≥1 cm in short axis, with necrotic center; any FDG PET
avid nodes; given high likelihood of nodal involvement, contour the lymph
node in doubt as GTV
CTV70
a
Primary: CTV70p = GTV70p + 3–5 mm [Please note that, at the discretion of
the treating radiation oncologist, when there is complete certainty of the
GTV70p, then GTV70p can be equivalent to CTV70p without any margin.
Therefore, in this situation, GTV70p is equivalent to CTV70p]
A 0 mm margin is also acceptable if tumor is in close proximity to critical
OARs (i.e. brainstem, spinal cord)
If tumor is near the ipsilateral optic nerve, informed discussion of risks and
benefits is required. The authors favor coverage of the tumor, sacrificing the
ipsilateral optic apparatus, but strictly constraining the contralateral optic
nerve and optic chiasm
Neck: CTV70n = GTV70n + 3–5 mm
For nodes that are small (i.e. ~1 cm), lower doses of 63–66 Gy may be
considered at the discretion of the treating physician
[Please note that, at the discretion of the treating radiation oncologist, when
there is complete certainty of the GTV70n, then GTV70n can be equivalent to
CTV70n without any margin. Therefore, in this situation, GTV70n is
equivalent to CTV70n]
PTV70
a
Primary: PTV70p = CTV70p + 3–5 mm, depending on daily patient
positioning and on treatment imaging. If PTV overlaps with critical OARs
(brainstem, spinal cord, brain), compromise of PTV must be accepted
Neck: PTV70n = CTV70n + 3 mm
Please note that when the radiation oncologist is certain of the GTV70p or
GTV70n, these can also be known as CTV70p or CTV70n. In other words,
GTV70p = CTV70p (without margin) and GTV70n = CTV70n without margin
A 5 mm margin can then be added to the CTV70p to name this PTV70p. But
as stated above, when the target is near critical structures such as brain stem,
chiasm, and spinal cord, the PTV margin can be 0 mm. A 3 mm margin can
be added to the CTV70n to name this PTV70n
a
Suggested gross dose disease is 2–2.12 Gy/fraction to 69.96–70 Gy in 33–35 fractions
1 Nasopharyngeal Carcinoma](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-11-320.jpg)
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2
Oropharyngeal Carcinoma
Zain A. Husain, Jung Julie Kang, Nancy Y. Lee,
and Ian Poon
Contents
2.1 Introduction 15
2.2
General Principles of Anatomy and Patterns of Spread 16
2.3
Diagnostic Workup Relevant for Target Delineation 16
2.4
Simulation and Daily Localization 17
2.5
Target Volume Delineation and Treatment Planning 17
2.5.1
Selected IMRT Dose and Fractionation Schemes 17
2.5.2 Suggested Target Volumes 18
References 25
2.1 Introduction
Oropharyngeal carcinoma comprises primary tumors involving the tonsils, base of
tongue, soft palate, or posterior pharyngeal wall. The vast majority of oropharyn-
geal cancers are squamous cell carcinomas, most of which are associated with the
human papillomavirus (HPV). HPV-unrelated cancers are commonly associated
with tobacco or alcohol use. HPV-associated head and neck cancers have superior
prognosis [1, 2]. Since the last edition of this book, the American Joint Committee
Z. A. Husain (*) · I. Poon
Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences
Centre, Toronto, ON, Canada
e-mail: zain.husain@sunnybrook.ca; Ian.Poon@sunnybrook.ca
J. J. Kang · N. Y. Lee
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center,
New York, NY, USA
e-mail: kangj1@mskcc.org; leen2@mskcc.org
© Springer Nature Switzerland AG 2022
N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical
Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_2](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-22-320.jpg)
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on Cancer revised staging for oropharyngeal cancer, dividing it into two different
systems for HPV-positive and HPV-negative oropharyngeal cancers. Given the
prognostic importance of HPV status, viral testing should be performed in all oro-
pharyngeal carcinoma patients. However, de-escalation of therapy based on HPV
status should not be performed outside of a clinical trial [3–5]. In this chapter, we
outline radiotherapy target delineations with careful consideration of microscopic
mucosal spread of the primary tumor as well as knowledge of cervical nodal drain-
age patterns.
2.2
General Principles of Anatomy and Patterns of Spread
• The oropharynx is a cuboidal space bordered by the oral cavity anteriorly, the
nasopharynx superiorly, and the larynx and hypopharynx inferiorly.
• It consists of four subsites: the tonsils, base of tongue, soft palate, and the pha-
ryngeal wall, with the majority of cases arising in the tonsils and tongue base.
• The oropharynx is equipped with a rich lymphatic drainage and lymph nodes are
commonly involved.
2.3
Diagnostic Workup Relevant for Target Delineation
• Gross tumor volume delineation of the primary site is best identified by a combi-
nation of imaging and physical examination.
• The mucosal and superficial extents of disease are best accessed by visual inspec-
tion, palpation, and fiberoptic endoscopic examination. Photographic documen-
tation of disease at the time of consult or simulation is helpful in order to
document mucosal extension of disease that may be poorly seen on imaging
(Fig. 2.1).
Fig. 2.1 Direct
visualization helps
demonstrate involvement
of the soft palate and
evidence of the tumor
crossing midline
Z. A. Husain et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-23-320.jpg)
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HPV related tumors, the subclinical regions receive 30 Gy in 2 Gy per fraction
followed by a cone down to the gross disease receiving 40 Gy in 2 Gy per frac-
tion. The subclinical region is scrutinized heavily to ensure no gross disease with
MRI, CT with contrast, and PET/CT scans. Please refer to our publication, Tsai
et al. [6]. For HPV unrelated disease, the initial phase is 60 Gy in 2 Gy per frac-
tion to the gross disease while simultaneously treat 54 Gy in 1.8 Gy per fraction
to all subclinical regions. This is followed by a cone down of 10 Gy in 2 Gy per
fraction to the gross disease. If a low anterior neck AP field is matched to the
IMRT fields, HPV related tumors receive 30 Gy in 2 Gy per fraction to the low
neck while the HPV unrelated tumors receive 50 Gy in 2 Gy per fraction to the
low neck. Reduced elective doses should only be considered when treating with
concurrent cisplatin-based chemotherapy
• Another commonly used radiation technique is the simultaneous integrated boost.
Gross disease dose: 70 Gy (2 Gy/fx), high-risk subclinical dose: 56 Gy (1.6 Gy/
fx), and low-risk subclinical dose: 50–52.5 Gy (1.43–1.5 Gy/fx).
This technique should only be considered when using concurrent chemotherapy.
• Another fractionation schemes such as but not limited to RTOG 0022 [7] or
RTOG 1016 [3].
2.5.2 Suggested Target Volumes
• Suggested target volumes for gross disease (Table 2.1) and for subclinical dis-
ease (Table 2.2) are presented in the following.
Table 2.1 Suggested target volumes for gross disease
Target
volumes Definition and description
GTV70 Primary: All gross disease as defined by clinical exam and imaging
Nodes: all suspicious (1 cm, necrotic, enhancing, or FDG-avid) lymph nodes.
Borderline suspicious nodes can be given less than 70 Gy, i.e. 60–66 Gy for
example
CTV70 In areas of excellent visualization GTV70 can equal CTV70 (no added margin). In
situations where there is uncertainty of tumor extent CTV70 = GTV70 + 3–5 mm
PTV70 CTV70 + 3–5 mm depending on daily set up accuracy and the availability of image
guidance
Z. A. Husain et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-25-320.jpg)
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3
Stereotactic Body Radiotherapy
for Cancers of the Head and Neck Cancer
Dana Keilty, Irene Karam, Nancy Y. Lee, and Ian Poon
Contents
References 43
• Advanced Head and Neck Cancer (HNC) is commonly a disease of the elderly
and associated with a poor outcomes despite aggressive multi-modality treat-
ments. Select fit elderly patients, despite the expectation of a poor outcome, may
choose to undergo radical high-dose radiation to maximize cancer control but
with higher rates of toxicity and morbidity. In frail patients, the decision against
a prolonged RT course may be based on multiple factors: patient preference
(Fig. 3.1), tumor factors (expected morbidity of tumor progression versus the
morbidity/mortality risk of treatment and probability of a successful outcome
[Figs. 3.2, 3.3, 3.4, 3.5, and 3.6]), life expectancy (influence of age and comorbid
conditions [Figs. 3.1, 3.3, 3.4, 3.6, 3.7, 3.8, and 3.9]), tolerance of aggressive
D. Keilty · I. Karam · I. Poon (*)
Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of
Toronto, Toronto, ON, Canada
e-mail: dana.keilty@mail.utoronto.ca; irene.karam@sunnybrook.ca;
ian.poon@sunnybrook.ca
N. Y. Lee
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center,
New York, NY, USA
e-mail: leen2@mskcc.org
© Springer Nature Switzerland AG 2022
N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical
Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_3](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-33-320.jpg)
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treatment based on host (performance status [Fig. 3.8]), and non-host factors
(distance from hospital, availability of social/financial/psychological supports).
At high volume centers, Head and Neck stereotactic body radiotherapy (SBRT)
can be considered as a palliative treatment that may provide more durable local
control than standard palliative approaches in patients who are not candidates for
standard radical curative treatment. Previously, HN SBRT was primarily consid-
ered in re-irradiation, but the greater value of SBRT may be in the un-irradiated
setting, where the extended treatment and recovery time of radical therapy may
be undesirable or unrealistic for certain patients. SBRT can achieve durable local
control [1] with a shortened treatment course and acceptable side effect profile.
• HN SBRT requires a highly experienced multidisciplinary team of medical phys-
icists, dosimetrists, and radiation therapists.
• Accurate GTV delineation is critical for safe HN SBRT. Intraoral photos to docu-
ment clinical exam details can be valuable. Neuroradiology review can clarify
tumor extent and localize radiosensitive organs at risk.
• Contrast-enhanced computed tomography (CT) simulation is required for pre-
cise volume definition, with MRI (simulation) fusion greatly improving gross
disease visualization. If MRI is not available, double-contrast CT simulation
(Fig. 3.7) can be used. Dental fillings that create artefact and impact visualization
should be removed for SBRT (Fig. 3.8).
• Five-point thermoplastic mask and daily cone beam CT (CBCT) matching allows
for reproducible immobilization and reduction of PTV margins to 3 mm. Toxicity
is additionally minimized by eliminating the traditional comprehensive micro-
scopic volumes.
• The standard dose range to the GTV is 40–50 Gy, two fractions per week, with
45 Gy most commonly prescribed. The HN SBRT literature reports radiation
prescriptions in the range of 35–50 Gy in 3–8 fractions [1–3, 4]. A high dose and
low dose CTV expansion of the GTV is NOT used. A microscopic CTVn25 can
be created for immediately adjacent at-risk lymph node sites. A microscopic
dose is not expanded from the GTV (Table 3.1). A dose-reduced PTV35-40 is cre-
ated with a 3-mm expansion of the GTV/high-dose CTV.
• The hot spots should lie within the GTV and away from organs at risk. A confor-
mity index of 1.1 of the GTV40–50 and PTV35–40 is desirable.
• Target coverage must be compromised when in proximity to critical neurological
structures (brachial plexus, optic pathways, brain, and brainstem). Dose to the
carotid artery, however, should not compromise target coverage, except in re-
irradiation [5].
• A strong quality assurance (QA) program is needed. Our center employs a modi-
fied Winston–Lutz isocenter alignment test to ensure tolerance within 2.5 mm
[6]. Daily CBCT to match to bone and soft tissue is imperative; because the
number of CBCTs is minimal, attempts to decrease the CBCT dose are of little
value and should not preclude high-quality CBCT images.
• The rate of regression post-SBRT is variable and maximal response is often
achieved beyond traditional timelines (3 months).
D. Keilty et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-48-320.jpg)
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–
– Glottic Larynx.
Carotid-sparing IMRT should be considered [1–3].
A CT-based opposed laterals technique is also acceptable. The superior
border should extend to the bottom of the hyoid bone or the top of the
thyroid notch. The inferior border is the bottom of the cricoid cartilage.
The posterior border is the anterior edge of the vertebral bodies. There
should be 1 cm flash anteriorly. It may be necessary to angle the beams
5–10° inferiorly to avoid the shoulders. Often 15–30° wedges are used to
ensure a homogeneous dos distribution throughout the larynx.
For T1N0 glottic larynx tumors, we use a dose of 63 Gy in 28 fractions as
randomized evidence supports a local control advantage with hypofrac-
tionation at 2.25 Gy/fraction [4].
For T2N0 glottic larynx tumors, there are local control benefits with doses
65 Gy and dose per fraction ≥2.25 Gy [5]. We treat to 65.25 Gy in 29
fractions at 2.25 Gy per fraction. In select cases, treatment with chemora-
diotherapy may be acceptable.
–
– Due to higher risks of occult nodal disease in supraglottic and subglottic can-
cers, bilateral levels II–IV and in many instances level VI nodal chains should
be electively radiated. The superior limit of level II may stop where the poste-
rior belly of the digastric muscle crosses the internal jugular vein (Fig. 4.3).
• Advanced stage disease (≥T3 or node-positive disease):
–
– Bilateral necks should be included.
We favor a sequential cone down approach. An initial plan (30 fractions)
with a dose-painting approach delivers 54 Gy (1.8 Gy/fx) and 60 Gy (2 Gy/
fx) to the low and high-risk subclinical regions, respectively. This is fol-
lowed by a cone down plan (five fractions) which delivers an additional
10 Gy to gross disease only for a total of 70 Gy over 35 fractions.
One dose painted IMRT plan is also acceptable. An example fractionation:
over 35 days to deliver 2 Gy/fx, 1.8 Gy/fx, and 1.54 Gy/fx to achieve doses
of 70 Gy to gross disease, 63 Gy to high-risk subclinical disease, and
54 Gy to low-risk subclinical disease.
–
– Extended IMRT plans are favored over the use of a low anterior neck (LAN)
field. This is due to the risk of missing gross tumor or high-risk subclinical
disease in the low dose region of the match-line.
–
– One subclinical or two subclinical (high-risk, low-risk) CTVs may be con-
toured for microscopic disease (Table 4.2).
The subclinical primary site CTV should encompass the entire larynx from
the bottom of the thyroid notch to the first tracheal ring or extend inferiorly
when necessary.
The subclinical nodal CTV should encompass at least levels II–IV, and in
many instances level VI (Fig. 4.4).
In the elective node-negative neck, the superior border of level II stops
where the posterior belly of the digastric muscle crosses the internal jugu-
lar vein (this is the superior most extent of an elective neck dissection and
corresponds to the caudal edge of the lateral process of C1) (Fig. 4.5).
D. Fan et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-63-320.jpg)
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5
Hypopharyngeal Carcinoma
Linda Chen, Yao Yu, and Nancy Y. Lee
Contents
5.1
Anatomy and Patterns of Spread 61
5.2
Diagnostic Workup Relevant for Target Volume Delineation 63
5.3
Simulation and Daily Localization 64
5.4
Target Volume Delineation and Treatment Planning 64
5.5 Suggested Reading 73
References 73
5.1
Anatomy and Patterns of Spread
• The hypopharynx lies between the oropharynx superiorly and cervical esopha-
gus inferiorly. This is a portion of the pharynx that is defined superiorly by the
top of the hyoid bone (approximately C4) and inferiorly by the bottom of cri-
coid cartilage (approximately C6), with the larynx lying anteromedially. As
such, hypopharynx tumors have a propensity to disrupt speech and swallow
function.
• There are three subsites of the hypopharynx: the paired pyriform sinuses, poste-
rior pharyngeal wall, and the post-cricoid region. Tumors have a tendency for
submucosal spread with involvement of multiple sites of hypopharynx, the lar-
ynx, and adjacent soft tissue due to minimal barriers between anatomic sites [1].
Patterns of spread for each subsite are outlined in Table 5.1.
L. Chen (*) · Y. Yu · N. Y. Lee
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center,
New York, NY, USA
e-mail: ChenL1@mskcc.org; yuy2@mskcc.org; leen2@mskcc.org
© Springer Nature Switzerland AG 2022
N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical
Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_5](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-66-320.jpg)
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Table 5.1 Hypopharyngeal subsite and respective patterns of spread
Hypopharynx
subsite Patterns of spread
Pyriform sinus •
Anteromedially: Arytenoids, aryepiglottic folds, intrinsic laryngeal
muscles (which can result in vocal cord fixation), para-glottic space
• Posterior: Constrictor muscles, prevertebral tissue
• Lateral: Para-glottic space, Thyroid cartilage, and lateral neck
•
Superiorly: Oropharynx, pre-epiglottic space, thyrohyoid membrane
(referred otalgia from the internal branch of superior laryngeal nerve)
• Inferiorly: Post-cricoid area
•
Lymph nodes: Most commonly—RP, II, III. Additional levels at risk:
level IV, and level VI (inferior tumors involving the apex)
Posterior
pharyngeal wall
• Superiorly: Extension to the oropharynx
• Inferiorly: Extension to the cervical esophagus
• Posteriorly: Pre-vertebral fascia, retropharyngeal space
• Lymph nodes: RP, II–IV
Post-cricoid
region
• Anteriorly: Laryngeal invasion (vocal cord fixation)
• Superiorly: Pyriform sinuses
• Inferiorly: Cricoid cartilage, cervical esophagus
• Lymph nodes: II–IV, paratracheal
• Hypopharynx cancers also have a high propensity for lymph node involvement
due to an extensive submucosal lymphatic plexus. Bilateral cervical lymph nodes
and lateral retropharyngeal lymph nodes are commonly involved [2–6]. Posterior
level V involvement, level VI, and superior mediastinal LNs can be involved for
post-cricoid region tumors and pyriform sinus tumors that are inferior and
involve the apex [2, 5–9]. In patients who are clinically node negative, 30–35%
of patients have pathologic lymph node involvement [7]. Level 1b is rarely
involved but ranges between 5% and 20% in the node positive neck [2, 6].
• The pyriform sinuses are the most common site of hypopharynx cancer (65–85%)
and are paired potential spaces which lie laterally and posteriorly to the larynx
[10, 11]. The superior and widest portion of the pyriform sinuses are visualized
endoscopically, on either side of the larynx with the medial wall formed by ary-
epiglottic fold. The space narrows inferiorly until it reaches the apex at the crico-
arytenoid joint, forming the shape of an inverted cone.
• The hypopharyngeal wall (10% of hypopharyngeal cancers) is a continuation of
the lateral and posterior pharyngeal wall that lies between the oropharynx supe-
riorly and the cervical esophagus inferiorly. It is composed of mucosa which
encloses lateral and posterior constrictor muscles.
• The post-cricoid region (5%) is the least common site for hypopharyngeal can-
cers. Mucosa is comprised of the posterior wall of the larynx, spanning from the
arytenoids to the cricoid cartilage. Skip metastasis to the cervical esophagus
can occur.
L. Chen et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-67-320.jpg)
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• Diagnostic, contrast-enhanced CT or MRI should also be utilized to evaluate
extent of disease. Special attention to pre-epiglottic or paraglottic space
involvement, laryngeal extension, gross cartilage invasion, soft tissue extension,
esophageal invasion, and extra-capsular spread [12–15].
• PET/CT can also help to delineate borders, as this is a sensitive modality that can
aid in defining extent of disease (i.e. inferior apical tumor boundaries which can
be subtle) as well as hypermetabolic malignant cells within lymph nodes [16–18].
5.3
Simulation and Daily Localization
• Positioning: Patient should be simulated supine with head rest. The neck should
be hyperextended or a shoulder pull board can be used to lower the shoulders out
of the beam angle path. Custom immobilization should be used with a thermo-
plastic mask. In post-operative cases, all surgical scars should be wired.
• Imaging: Thin-cut 3 mm CT slices with imaging from the top of the skull down
to T5. Intravenous contrast should be administered unless medically contra-
indicated. Isocenter placement typically at the arytenoids.
• Localization: Daily imaging ideally consists of daily cone beam CT aligned to
the larynx. Daily kilovoltage imaging aligned to bone and weekly cone beam
CTs are also adequate.
5.4
Target Volume Delineation and Treatment Planning
• Intensity modulated radiation therapy (IMRT) planning is recommended. An ini-
tial plan (30 fractions) with a dose-painting approach with 54 Gy/1.8 Gy frac-
tions and 60 Gy/2 Gy fractions are used for the low- and high-risk subclinical
regions. This is followed by a 10 Gy cone down to gross disease for a total of
70 Gy over 35 fractions. A single dose-painted plan such to 70 Gy over 33–35
fractions is also appropriate (Fig. 5.1).
• Extended IMRT plans are recommended rather than use of a low anterior neck
field. This is due to high risk regions or gross disease that are likely be located in
the low dose region of the match-line.
• Early stage disease consists of T1N0 or T2N0 (AJCC 8) hypopharynx carci-
noma. A minority of cases present with early stage disease. Definitive radiation
is often preferred for local control, laryngeal preservation, maintenance of speech
and swallowing. Due to the high incidence of occult nodal disease, and central
location of the hypopharynx, bilateral nodal chains should be included in the
target (Figs. 5.1 and 5.2).
• Advanced stage disease consists of ≥T3 or node-positive disease (Figs. 5.3, 5.4,
and 5.5). Treatment options include definitive chemoradiation, laryngectomy
followed by adjuvant therapy, and induction chemotherapy followed by local
L. Chen et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-69-320.jpg)
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5.5 Suggested Reading
• Biau, Gregoire et al. (2019): An updated consensus guidelines of lymph node
target volumes for head and neck cancers treated with IMRT/VMAT [19].
• Gupta et al. (2009): Outcome analysis of a large cohort of hypopharynx patients
(n = 501) treated with a non-surgical approach [20].
• EORTC 24891: 10-year results of EORTC 24891 comparing surgery followed
by radiation to induction chemotherapy followed by radiotherapy for hypopha-
ryngeal carcinoma. Laryngeal preservation with induction chemotherapy fol-
lowed by radiation, does not compromise disease control or survival, and allowed
over 50% of survivors to retain their larynx [21].
• Lee et al. (2007): Concurrent chemotherapy and IMRT experience at MSKCC
for locoregionally advanced laryngeal and hypopharyngeal cancers [22].
• Prades et al. (2010): A randomized phase III trial comparing induction chemo-
therapy followed by radiation to concomitant chemoradiation in pyriform sinus
carcinoma, demonstrating improved survival with concurrent chemoradiother-
apy [23].
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dictor of outcome in squamous cell carcinoma of the head and neck. Head Neck J Sci Spec.
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cal surgery for carcinoma of the hypopharynx and cervical esophagus. Laryngoscope.
2001;111(6):1099–103. https://doi.org/10.1097/00005537-200106000-00031.
5 Hypopharyngeal Carcinoma](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-78-320.jpg)
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imaging, perineural spread, bone invasion, or meningeal infiltration can be better
visualized.
• CT simulation with intravenous contrast can be performed where the primary
tumor is in situ to help guide gross target volume (GTV) delineation. Fusion with
diagnostic MRI when available is recommended.
• Suggested target volumes at the gross disease and high-risk regions are detailed
in Tables 8.1 and 8.2 (Figs. 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, and 8.9).
Table 8.1 Suggested target volumes at the gross disease region
Target volumes Definition and description
GTV70
a
(the subscript 70
denotes radiation dose
delivered)
Parotid or submandibular primary: all gross disease on
physical examination and imaging
Neck nodes: all nodes ≥1 cm in short axis diameter or
nodes with necrotic center
CTV70 Add 5 mm so that GTV70 + 5 mm = CTV70
Alternatively, GTV70 can also be equivalent to CTV70 when
the treating MD is certain of the target
For nodes that are small but suspicious for disease (i.e.,
1 cm), consider a lower dose of 63–66 Gy
PTV70 Margin specific to treatment center and less if image
guidance available
Typically CTV70 + 3–5 mm = PTV70
a
Suggested dose to gross disease is 2 Gy/fraction to 70 Gy
Table 8.2 Suggested target volumes at the high-risk subclinical region
Target volumes Definition and description
CTV60 Parotid or submandibular CTV60 should encompass the entire GTV or the
surgical bed for postoperative patients
Landmarks for the parotid surgical bed
Anterior: masseter muscle
Lateral: soft tissue of neck
Medial: styloid process at depth; may need to extend to parapharyngeal fat
depending on the extent of parotid gland
Posterior: mastoid bone
Landmarks for the submandibular surgical bed
Include the entire surgical bed, all postoperative changes, and use the
contralateral submandibular gland as a guide
Highly consider a boost of 6–10 Gy to residual disease or positive margins.
The surgeon should be encouraged to leave clips where possible for
localization
For cases with perineural involvement [1]
Parotid tumors: Include facial nerve, glossopharyngeal nerve and V3; may
need to extend to Meckel’s cave
Submandibular and sublingual tumors: Include hypoglossal and lingual
nerve; may need to extend to Meckel’s cave especially for adenoid cystic
carcinoma; may also need to include facial nerve
M. S. F. Tseng et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-105-320.jpg)
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Various treatment techniques can be considered including 3D CRT and intensity
modulated radiation therapy (IMRT).
• In addition to thorough physical examination, adequate pre-operative imaging
studies and pathological examination should be obtained for diagnosis, staging,
and radiation treatment planning.
• All patients should undergo mammogram at diagnosis. Additional imaging com-
monly includes ultrasound. Although indications for MRI are limited for early-
stage
disease, images may be available in some patients. Available pre-operative imaging
studies should be reviewed prior to radiation planning to ensure adequate margins for
whole breast radiation as well as accurate targeting of boost radiation and/or APBI.
• Image-guided biopsy generally confirms a diagnosis of cancer. Surgery consist-
ing of lumpectomy, or segmental excision, alone for ductal carcinoma in situ
(DCIS) and lumpectomy and sentinel lymph node biopsy (SLNB) is recom-
mended for early invasive disease. Pathology should be reviewed to ensure ade-
quate margins (no tumor on ink for invasive and 2 mm for pure DCIS, per
SSO-ASTRO Consensus Guideline 2016). It is preferred, but not required, for
the surgeon to place surgical clips at the time of surgery to assist in delineation
of the tumor bed and for radiographic localization prior to radiation delivery;
clips can be particularly useful for APBI.
• For whole breast radiation planning, a CT with ≤3 mm slice thickness should be
performed in the supine or prone position. For APBI, a CT slice thickness of
1.5–2 mm through the lumpectomy cavity may enable improved delineation of
the lumpectomy cavity.
• For supine positioning, the patient should be positioned on a breast board with
arms above the head. Deep inspiration breath hold (DIBH) should be considered
for patients with left-sided breast cancer to reduce radiation dose to the heart.
• Patients with pendulous breasts may benefit from prone positioning to reduce separa-
tion and improve tissue homogeneity in treatment planning, which may reduce acute
toxicity. Prone also reduces radiation to lung and may be used for heart-avoidance,
though the heart can paradoxically move closer to the treatment field if the tumor bed
abuts the chest wall. For prone positioning, patient should be placed prone on a dedi-
cated prone breast board, and care should be taken to ensure that the patient is com-
fortable as this is very important to facilitate reproducibility. Patients with orthopedic
injuries to the back or neck may not be ideal candidates for prone positioning.
• Organs at risk should include the heart and lungs in all cases in order to estimate dose
to these critical structures. The heart should be contoured superiorly to the bifurcation
of the pulmonary artery, and should include the pericardium and epicardial fat
(between the heart muscle and pericardium), but does not need to extend to include
pericardial fat outside the pericardium. While the best evidence for cardiac avoidance
involves reducing the mean heart dose, data is emerging for importance of radiation
dose to the left anterior descending (LAD) and left ventricle (LV) and those structures
can also be contoured per published atlases by Feng et al. [1] and Duane et al. [2].
• Target volumes include the breast tissue and lumpectomy cavity for whole breast
irradiation. For APBI, lumpectomy CTV and lumpectomy PTV should also be
delineated.
• Suggested target volumes are described in Table 11.1 (Figs. 11.1, 11.2, 11.3,
11.4, 11.5, 11.6, 11.7, and 11.8).
E. F. Gillespie et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-135-320.jpg)
![143
Table 12.1 Suggested target volumes at the gross disease region
Target volumes Definition and description
Clinical target
volume (CTV)
Breast tissue or chest wall as defined by RADCOMP Breast Atlas [1],
ipsilateral regional lymph nodes [2], interconnecting lymphatic drainage
routes, breast prosthesis (if present) and chest wall musculature/skin to be
determined at risk for microscopic disease
Planning target
volume (PTV)
A margin of 3–5 mm medially, 5–10 mm laterally, and 3–5 mm posteriorly
with the exception of the internal mammary nodes (which should be 0 mm
margin posteriorly), and 5–10 mm superiorly, inferiorly, and anteriorly (to
include the skin surface) will be added to the CTV. The amount of lung can
be trimmed per physician discretion
Table 12.2 Breast VMAT dosimetric planning guidelines
Structure Parameter Objective
Target criteria—50 Gy in 25 fractions
PTV D95% ≥95%
V95% ≥95%
D05% ≤110%
Internal mammary node (IMN) D95% ≥100%
Normal tissue criteria
Ipsilateral lung V20Gy ≤33%
V10Gy ≤68%
Mean Gy ≤20 Gy
Contralateral lung V20Gy ≤25%
Heart V25Gy ≤25%
Mean Gy ≤9 Gya
; ≤8 Gyb
Dmax ≤50 Gy
Left anterior descending artery (LAD) Dmax ≤50 Gy
Contralateral intact breast Mean Gy ≤5 Gy
Contralateral implant Mean Gy ≤8 Gy
Esophagus Dmax ≤50 Gy
Thyroid Mean Gy ≤20 Gy
Brachial plexus Dmax ≤55 Gy
12 Regional Lymph Node Irradiation for Breast Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-148-320.jpg)
![147
13
Lung Cancer
N. Ari Wijetunga, Zhongxing Liao, and Daniel R. Gomez
Contents
13.1
General Principles of Planning and Target Delineation 147
References 163
13.1
General Principles of Planning and Target Delineation
• Computed tomography (CT)-based planning utilizing conformal techniques and
respiratory motion management are the standard of care in the treatment of both
NSCLC and SCLC. Three-dimensional conformal radiation therapy (3D-CRT),
intensity-modulated radiation therapy (IMRT), and stereotactic body radiother-
apy (SBRT) each use multiple beam angles and can vary in dose conformality.
Thus, each approach requires accurate delineation of target volumes, normal
structures, and organs-at-risk (OARs) and evaluation of dose volume histograms
during planning. In addition, it is necessary to understand the at-risk nodal levels
of the mediastinum, as have been previously published in consensus atlases such
as that developed at the University of Michigan [1].
N. A. Wijetunga · D. R. Gomez (*)
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center,
New York, NY, USA
e-mail: wijetunn@mskcc.org; gomezd@mskcc.org
Z. Liao
Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA
e-mail: zliao@mdanderson.org
© Springer Nature Switzerland AG 2022
N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical
Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_13](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-151-320.jpg)
![148
• Simulation. Assessment of respiratory motion, correct patient positioning, and
appropriate immobilization during radiation simulation are vital to radiation
planning. Patients should ideally be simulated with their arms above their head
to maximize the number of beam arrangements that can be utilized. A four-
dimensional (4D) simulation should be performed to assess for internal motion.
• In addition to the target volume, the following normal structures should be con-
toured when in proximity to the treatment field: heart, lungs, spinal cord, esopha-
gus, chest wall, great vessels, proximal bronchial tree (PBT), and the brachial
plexus for superiorly located tumors or high paratracheal/supraclavicular lymph
node involvement using available atlases [2]. The liver should be contoured for
right lower lobe tumor located close to diaphragm. For low lying left lower lung
tumors or left pleural tumor, the spleen may receive significant radiation.
Consensus guidelines for contouring the brachial plexus are available [3] and
should be referenced for accurate contouring.
• For both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)
in the setting of gross disease, an involved field approach is widely accepted
based on prior publications demonstrating a low rate of failure in elective nodal
regions [4, 5] and a randomized trial showing improved outcomes with an
involved field vs. elective nodal approach [6]. Therefore, elective nodal regions
should not routinely be covered if the treating physician is confident in the under-
standing of the sites of active disease.
• Physicians should delineate targets utilizing a combination of the physical exam-
ination, a CT scan with contrast, a positron emission tomography, and evaluation
of the mediastinum with either a mediastinoscopy or endobronchial ultra-
sound (EBUS).
• The gross target volume is defined as macroscopic disease. There are two poten-
tial approaches for expanding the GTV to subsequent target volumes. The first
technique is performed by delineating the GTV and then assessing for internal
motion, a structure called the iGTV. The iGTV is then expanded to create the
iCTV and further expanded to yield the PTV. The second technique involves an
expansion of the GTV to the CTV, followed by a further expansion to the ITV to
account for internal motion, followed by a PTV expansion for daily variations in
patient position and movement. This approach is also used in the post-operative
setting, where there is no GTV or iGTV.
• For early stage NSCLC, standard treatment margins from the iGTV to iCTV are
0–0.2 cm. The PBT should be consistently contoured. This structure includes the
distal 2 cm of the trachea, the carina, the right and left mainstem bronchi, and the
lobar bronchi. We define an area 2 cm beyond the PBT radially as the no-fly zone
(NFZ). Doses for SBRT are variable depending on the location and extent of the
lesion, with the primary criteria being achievement of a biologically equivalent
dose (BED) of 100 Gy.
• For locally advanced NSCLC (stage II–III), a margin from the iGTV to the iCTV
of 0.5–0.8 cm is typically used, based on prior histologic analyses [7]. PTV mar-
gins are dependent on estimation of setup error, often 1.0–1.5 cm if no assess-
ment of management for internal motion or daily image-guided radiation therapy
(IGRT), such as kV imaging or cone-beam CT scan; 0.5–1.0 cm if either 4D CT
N. A. Wijetunga et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-152-320.jpg)
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planning or CBCT, but not both; 0.3–0.5 cm from CTV (or iGTV) to PTV for 4D
CT planning and with kV/CBCT guidance, which is preferred. The standard dose
in the chemoradiation setting is 60 Gy in 30 fractions.
• In the postoperative scenario for NSCLC, there is no clear consensus as to target
delineation. Historically, large fields were used including the tumor bed, involved
lymph node levels, the bilateral mediastinum, ipsilateral bronchial stump, and
supraclavicular lymph nodes for superiorly located tumors. This approach is now
rarely used since the adoption of CT planning and comprehensive mediastinal
lymph node dissection. Many institutions, including our own, now use a limited
approach to treating the mediastinum, encompassing the involved lymph node
regions and the ipsilateral bronchial stump, with consideration of inclusion of
one lymph node level above and one level below the involved region. This
approach is similar to that used in the Lung ART trial [8]. Generally, a CTV (no
GTV present), ITV, and a PTV with an ITV to PTV expansion of approximately
0.5 cm are defined, contingent on available IGRT techniques.
• For SCLC, a “standard” GTV to CTV margin has not been well defined. Margins
of 0.5–1.0 cm are acceptable, often to include the ipsilateral hilum. We recom-
mend that the CTV to PTV margin follows similar guidelines as that for NSCLC
as noted above. Standard doses for limited stage SCLC are 45 Gy in 1.5 Gy frac-
tions or 66–70 Gy in 2.0 Gy fractions.
• Recommended target delineation does not differ significantly between limited
and extensive stage SCLC, the latter being in the context of consolidative or pal-
liative treatment. An involved field technique is utilized in both scenarios, with
standard doses as depicted in Table 13.1. Standard doses for consolidation tho-
racic radiation typically range from 30 to 45 Gy in ten fractions.
• Standard treatment doses for NSCLC and SCLC are depicted in Table 13.1. Dose
constraints are dependent on the total dose and the number of fractions delivered
and guidance is provided in the Quantitative Analyses of Normal Tissue Effects
Table 13.1 Appropriate radiation treatment regimens for lung cancer
Lung malignancy scenario Accepted treatment doses
NSCLC, stage I stereotactic body
radiation
therapy (SBRT)—peripheral
Variable—include 54 Gy in 18 Gy fractions, 48 Gy in
12 Gy fractions, 50 Gy in four fractions, and 50 Gy in
five fractions
NSCLC, stage I SBRT—central Variable—include 50 Gy in five fractions, 70 Gy in ten
fractions, 60 Gy in eight fractions
NSCLC, stage II–III standard
fractionation
60 Gy in 2 Gy fractions daily
Postoperative 50–54 Gy in 1.8–2.0 Gy fractions—R0 resection
54–60 Gy in 1.8–2.0 Gy fractions—R1 resection
60 Gy in 2.0 Gy fractions (consider concurrent
chemotherapy)—R2 resection
SCLC, limited stage 45 Gy in 1.5-Gy fractions BID with chemotherapy
OR
66–70 Gy in 2.0-Gy fractions daily
SCLC, extensive stage 30–45 Gy in 3.0 Gy fractions for consolidative chest
radiation
13 Lung Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-153-320.jpg)
![150
in the Clinic publication [9]. The stages cited in are as per the eighth Edition
Staging by the American Joint Committee on Cancer [10] (Table 13.1 and
Figs. 13.1, 13.2, 13.3, 13.4, 13.5, 13.6, 13.7).
Fig. 13.1 (a) Lymph node stations. (Reproduced with permission from [11].) (b) Risk of lymph
node involvement by tumor location. (Adapted from [12])
Supraclavicular zone
Upper zone
AP zone
Subcarinal zone
Lower zone
Hilar/Interlobal zone
Peripheral zone
1 Low cervical, supraclavicular, and
sternal notch nodes
2R Upper Paratracheal (right)
2L Upper Paratracheal (left)
3a Prevascular
3p Retrotracheal
4R Lower Paratracheal (right)
5 Subaortic
6 Para-aortic (ascending aorta or
phrenic)
4L Lower Paratracheal (left)
SUPERIOR MEDIASTINAL NODES
AORTIC NODES
INFERIOR MEDIASTINAL NODES
N1 NODES
7 Subcarinal
8 Paraesophageal (below carina)
9 Pulmonary ligament
10 Hilar
11 Interlobar
12 Lobar
13 Segmental
14 Subsegmental
a
N. A. Wijetunga et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-154-320.jpg)
![151
Involved Node Station
Lobe Involved by Primary Tumor
Right Upper
(n=45)
Right Middle/
Lower
(n=36)
Left Upper
(n=35)
Left Lower
(n=8)
Upper Mediastinum (1) 9% 3% 0 %
Paratracheal (2) 40% 31% 3 %
Prevascular,
retrotracheal,
pretracheal (3)
73% 47% 29 %
Lower paratracheal (4) 36% 28% 17% 13%
Subaortic (5) – – 71% 13%
Para-aortic (6) – – 43% 25%
Subcarinal (7) 36% 69% 20% 38%
Paraesophageal (8) 9% 11% 3% 50%
Pulmonary ligament (9) 2% 6% 6 3%
b
% 0
% 0
% 0
% 1
Fig. 13.1 (continued)
0-2 mm expansion
from iGTV to iCTV
a
Fig. 13.2 Early stage NSCLC [cT1N0] treated with SBRT. (a) A peripheral tumor treated with
54 Gy in three fractions. (b) A lesion in a medically inoperable patient approaching the pulmonary
tree, receiving 48 Gy in four fractions. (c) A central lesion encroaching on the bronchi receiving
50 Gy in five fractions. Generally, we constrain the maximum point dose to the PBT at 55 Gy. GTV
(yellow); iGTV (red); iCTV (green); PTV (sky blue); proximal bronchial tree, PBT (pink); no fly
zone, NFZ (purple)
13 Lung Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-155-320.jpg)
![153
Fig. 13.3 Locally advanced NSCLC [cT1cN3M0] (IIIB). The patient had a 2.3-cm right upper
lobe tumor with right hilar, subcarinal, precarinal, paratracheal and right supraclavicular lymph-
adenopathy. Lung windows on CT scan are utilized to delineate the primary tumor and hilar region.
Nodal stations delineated through assessment of PET/CT scan, CT scan with contrast, and endo-
bronchial ultrasound. The patient received 60 Gy in 30 fractions. GTV primary tumor (red); GTV
lymph nodes (light green); iGTV primary and lymph nodes (pink); iCTV (orange); PTV (aqua);
brachial plexus (purple). Locally advanced NSCLC [cT1cN3M0] (IIIB). GTV tumor (red); GTV
nodes (light green); iGTV (pink); iCTV (orange); PTV (aqua); brachial plexus (purple); esopha-
gus (dark green)
Right SCV LN Level 4R paratracheal LN
Level 7 subcarinal LN
Level 10 hilar LN
13 Lung Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-157-320.jpg)
![155
Fig. 13.4 Locally advanced lung adenocarcinoma [cT4N3M0] (IIIC). The patient presented with
SVC syndrome and was found to have a large right hilar/suprahilar mass compatible with a pri-
mary lung tumor vs. adenopathy and extensive mediastinal adenopathy including bilateral supra-
clavicular metastasis. The patient was treated to 60 Gy in 30 fractions. GTV (red); iGTV (pink);
iCTV (orange); PTV (aqua). Locally advanced lung adenocarcinoma [cT4N3M0] (IIIC). GTV
(red); iGTV (pink); iCTV (orange); PTV (aqua); brachial plexus (purple); esophagus (dark green);
larynx (yellow)
13 Lung Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-159-320.jpg)
![157
Fig. 13.5 Postoperative radiation for NSCLC. The patient had a 5.8-cm LUL tumor with EBUS
showing involved level 4L nodes [cT3N2]. The patient received neoadjuvant chemotherapy.
Pathologic findings from surgery showed negative margins, with levels 5 and 10L positive for
malignancy. A limited field including the tumor bed, levels 4L, 5, 7, the ipsilateral bronchial stump
is covered per the Lung ART guidelines. The prescription dose was 1.8 Gy × 30 fractions = 54 Gy.
CTV (orange); PTV (aqua); involved LNs (light green); heart (yellow). Postoperative radiation for
NSCLC. CTV (orange); PTV (aqua); esophagus (dark green). Postoperative radiation for
NSCLC. CTV (orange); PTV (aqua); esophagus (dark green)
LUL mass
preoperatively is
the only PET avid
disease
LN levels above
and below
involved nodes
are included
13 Lung Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-161-320.jpg)
![165
14
Esophageal Cancer
N. Ari Wijetunga, Daniel R. Gomez, and Abraham J. Wu
Contents
14.1
General Principles of Planning and Target Delineation 165
References 176
14.1
General Principles of Planning and Target Delineation
• The standard of care in radiotherapy for esophageal cancer involves computed
tomography (CT)-based planning with conformal techniques. Both intensity-
modulated radiation therapy (IMRT) and three-dimensional conformal radia-
tion therapy (3D-CRT) use multiple beam angles and allow for variation in
dose conformality. Thus, both approaches require accurate delineation of tar-
get volumes, normal structures, and organs-at-risk (OARs) as well as evalua-
tion of dose volume histograms during treatment planning. Because the
esophagus begins in the neck at the lower border of the cricoid cartilage and
anterior to the sixth cervical vertebra and descends through the mediastinum
passing through the diaphragm into the abdomen, it is necessary to understand
the anatomy of the neck, brachial plexus, mediastinum, lungs, heart, spinal
cord, normal esophagus, and heart. A contouring atlas has delineated these
structures and can be referenced [1].
N. A. Wijetunga · D. R. Gomez · A. J. Wu (*)
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center,
New York, NY, USA
e-mail: wijetunn@mskcc.org; gomezd@mskcc.org; wua@mskcc.org
© Springer Nature Switzerland AG 2022
N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical
Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_14](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-168-320.jpg)
![166
• Simulation. Ideally, patients are simulated with their arms above their head to
maximize the number of beam arrangements that can be used without having
beams pass through the arms. For distal or GE junction tumors, measures should
be taken to account for respiratory motion such as four-dimensional (4D) CT
scanning, respiratory gating, or breath-hold techniques. In addition, when tumors
involve the distal esophagus or GE junction, patients should be nil per os (NPO)
for at least 2–3 h prior to simulation and each treatment to limit daily variation in
anatomy from gastric and bowel gas. For IMRT, intravenous contrast at the time
of simulation can better delineate nodal fields.
• Using a 40 cm standard distance from the incisors to the GE junction, the cervi-
cal esophagus extends from the incisors to approximately 15–20 cm, the upper
or proximal thoracic esophagus extends from 18–20 to 25 cm, the mid or distal
thoracic esophagus extends from 25 to 30–32 cm, and the abdominal esophagus
extends from 30–32 to 40 cm.
• When contouring esophageal cancer, it is helpful to address esophageal malig-
nancies by their anatomic subdivision: upper-mid esophagus tumors (including
malignancies of the cervical esophagus), thoracic esophagus tumors, and gastro-
esophageal (GE) junction tumors. Tumors that span multiple esophageal subdivi-
sions can follow the contouring guidelines of all involved subsets. Regardless of
location of the tumor within the esophagus, the entire lungs should be contoured
for proper DVH analysis. In malignancies of the upper esophagus, the brachial
plexus and larynx should be contoured. In malignancies of the lower esophagus,
the heart, the liver, the kidneys, the stomach, and adjacent bowel should be delin-
eated [2].
• The following target structures should be delineated: gross tumor volume (GTV),
clinical target volume (CTV), and planning target volume (PTV). At our institu-
tion, we routinely define an ITV, the volume encompassing the internal motion
of the GTV as observed on the 4DCT. The ITV is then expanded to a CTV, fol-
lowed by a PTV.
• Physicians should delineate the GTV with reference to CT and positron emission
tomography (PET) imaging, as well as findings on upper endoscopy and endo-
scopic ultrasound. The endoscopic ultrasound can be used to better stage the
depth of invasion of the esophageal tumor and to classify small peri-esophageal
lymph nodes that are difficult to classify with CT or PET scan. A bronchoscopy
is recommended if a tumor is superior to the carina to rule out the presence of a
tracheoesophageal fistula, which may delay radiotherapy.
• Standard ITV to CTV expansions are 1 cm radially to encompass the peri-
esophageal lymph nodes and 3–4 cm in the superior-inferior direction (oriented
along the esophageal mucosa) to account for submucosal spread and the possi-
bility of skip lesions. The expansion to CTV can be limited to 0.5 cm in areas
overlapping the heart and uninvolved liver, assuming appropriate motion man-
agement techniques. Because a 4 cm caudad margin for distal esophagus and GE
N. A. Wijetunga et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-169-320.jpg)
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junction cases would include large volumes of stomach or abdominal viscera,
only 2 cm margin to CTV along clinically uninvolved gastric mucosa is recom-
mended, unless treating with preoperative-intent doses (≤4500 cGy) in which
case a 4 cm or greater gastric margin may be appropriate, particularly for tumors
with significant gastric extension. The uninvolved vertebral bodies and kidneys
are excluded from CTV. For involved lymph nodes, a GTV to CTV margin of
0.5–1.0 cm can be utilized. If there are grossly involved periesophageal nodes,
then the CTV should cover at least 1 cm cephalad to the involved nodes. An
expansion of 0.5 cm from CTV to PTV is recommended. These recommended
margins can be adjusted depending on the motion assessment technique and
one’s confidence in having accurately covered the extent of disease.
• Regional lymph nodes should be included in the CTV according to the location
of the primary tumor within the esophagus. For proximal thoracic and cervical
esophagus tumors, bilateral supraclavicular nodal basins are included. They are
bounded cranially at the lower edge of the cricoid cartilage, and they are bounded
anteriorly, posteriorly, and laterally by the sternocleidomastoid muscle. For
proximal thoracic tumors, mediastinal lymph nodes are included in addition to
the peri-esophageal nodes encompassing the entire trachea, levels 2 and 4, with
extension towards the sternum and clavicular heads to encompass level 3. For
distal tumors, the CTV should include the celiac nodes, which are bounded on
the right by the lateral aspect of T12, on the left 0.5–1 cm beyond the lateral
aspect of the aorta, posteriorly by vertebral bodies, and anteriorly by the pan-
creas. For distal tumors, it is not necessary to include the superior mediastinal
nodal stations electively, other than overlap with the aforementioned cranial
expansions. For GE junction tumors, CTV should include para-aortic and the
gastrohepatic ligament nodes in a volume bounded by the liver on the right, the
stomach on the left.
• When GE junction tumors significantly overlap the gastric cardia, it is unclear
whether they have a gastric origin rather than a esophageal origin. To overcome
this ambiguity, the Siewert–Stein classification defines GE junction tumors
according to their epicenter relative to the GE junction: type I lesions have an
epicenter 1–5 cm above the junction, type II lesions have an epicenter from 1 cm
proximal to 2 cm distal to the junction, and a type III lesions have an epicenter
2–5 cm below GE junction. A reasonable cutoff for esophageal cancer is Siewert
type II, and, in fact, the eighth edition AJCC staging system now defines esopha-
geal tumors as those whose epicenter extends no more than 2 cm into the gastric
cardia [3]. For Siewert Type II tumors, some or all of the splenic hilum and
greater curvature nodal region may be included. Based on prevailing guidelines
for gastric cancers, a diagnostic laparoscopy, J-tube placement, preoperative
chemoradiation [4] or postoperative chemoradiation [5] can be considered.
(Table 14.1 and Figs. 14.1, 14.2, 14.3, 14.4).
14 Esophageal Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-170-320.jpg)
![171
Fig. 14.2 Eighty-one-year-old with a lower thoracic esophageal adenocarcinoma [uT3N1]. (a)
PET imaging showing the primary and level 4R paratracheal lymph node. (b) Endoscopy showing
partially obstructing and circumferential esophageal adenocarcinoma 31–35 cm from the incisors.
(c) EUS showing T3 primary disease and suspicious level 4R lymph node. Eighty-one-year-old
with a lower thoracic esophageal adenocarcinoma [uT3N1]. Brachial plexus (purple); stomach
(dark green); GTV esophagus (red); ITV (pink); GTV nodes (light green); CTV (orange); PTV
50.4 Gy (dark blue)
b
c
Level 4R lymph node
PET-avid level
4R lymph node
PET-avid
primary
a
14 Esophageal Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-174-320.jpg)
![173
Coverage of CTV
to celiac axis
CTV extends into
proximal stomach
Fig. 14.3 Seventy-five-year-old with gastroesophageal junction adenocarcinoma [uT3N0].
Stomach (dark green); large bowel (brown); GTV esophagus (red); CTV (orange); PTV
50.4 Gy (aqua)
14 Esophageal Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-176-320.jpg)
![174
Fig. 14.4 Fifty-nine-year-old with adenocarcinoma of gastroesophageal junction [uT3N2]. (a)
PET imaging showing FDG-avid paraesophageal nodes and primary located at 36–40 cm from the
incisors. (b) Sagittal planning CT with contours. Stomach/duodenum (dark green); GTV nodes
(light green); GTV esophagus (red); ITV (pink); CTV (orange); PTV 50.4Gy (aqua). Fifty-nine-
year-old with adenocarcinoma of gastroesophageal junction [uT3N2]. Stomach/duodenum (dark
green); GTV nodes (light green); GTV esophagus (red); CTV (orange); PTV 50.4 Gy (aqua)
a
b
PET-avid paraesophageal lymph
node
PET-avid primary
ITV showing
movement of GTV
CTV covering
3-4 cm above ITV
N. A. Wijetunga et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-177-320.jpg)
![194
Table
15.10
Treatment
approaches
Trials
Year
N
Arms
OS
(%)
OS
median
HR
Notes
Adjuvant
chemoradiotherapy
(CRT)
INT0116
[8]
2001,
2012
556
1:
Surgery
41
(3-year)
27
months
1.32
P
=
0.005
10%
D2
surgery
2:
Surgery
→
Adjuvant
CRT
(5FU)
50
36
months
ARTIST
[9]
2012,
2015
458
1:
D2
surgery
→
Adjuvant
Chemo
(XP)
×
6
cycles
73
(5-year)
NR
NS
All
R0
resection;
No
SS
OS
difference;
Improved
DFS
for
node-
positive
disease
and
intestinal
histology
2:
D2
Surgery
→
XP
x
2
cycles
→
CRT
→
XP
×
2
cycles
75
NR
ARTIST
II
[10]
2021
546
1:
D2
surgery
→
S1
for
1
year
3-Year
DFS
65
NR
S1
vs.
SOX:
0.692
P
=
0.042
All
node-positive
Adjuvant
SOX
or
SOXRT
effective
in
prolonging
DFS
compared
to
adjuvant
SOX
alone
2:
D2
surgery
→
SOX
×
6
months
74
NR
3:
D2
surgery
→
SOX
×
2
months
→
S1/
RT
→
SOX
×
4
months
73
NR
SOX
vs.
SOXRT:
0.724
P
=
0.074
(continued)
J. Tey et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-197-320.jpg)
![195
Trials
Year
N
Arms
OS
(%)
OS
median
HR
Notes
Perioperative
MAGIC
[11]
2006
503
1:
Surgery
23
(5-year)
18
months
0.75
P
=
0.009
Chemo:
ECF
2.
Chemo
→
Surgery
→
Chemo
36
30
months
CRITICS
[12]
2018
788
1:
Chemo
→
Surgery
→
Chemo
41
(5-year)
43
months
NS
Chemo:
ECF
or
ECX
NS
difference
in
OS
or
toxicity
2:
Chemo
→
Surgery
→
Adjuvant
CRT
41
37
months
Adjuvant
chemotherapy
ACTS-GC
[13]
2007
1059
1:
Surgery
70
(3-year)
0.68
P
=
0.003
East
asian
population
2:
Surgery
→
Chemo
(S1)
80
CLASSIC
[14]
2012
1035
1:
Surgery
70
(5-year)
NR
0.66
P
=
0.0015
China,
South
korean,
Taiwan
2:
Surgery
→
Chemo
(CapeOx)
78
NR
Neoadjuvant
TOPGEAR
1:
Chemo
→
Surgery
Recruiting
2:
ChemoRT
→
Surgery
CRITICS
II
1:
Chemo
→
Surgery
Recruiting
2:
Chemo
→
ChemoRT
→
Surgery
3:
CRT
→
Surgery
N
number
of
recruited
patients,
OS
overall
survival,
DFS
disease-free
survival,
HR
hazard
ratio,
SS
statistically
significant,
NS
not
statistically
significant,
NR
not
reported,
S1
tegafur/gimeracil/steracil,
ECF
epirubicin/cisplatin/5-FU,
ECX
epirubicin/cisplatin/xeloda
Table
15.10
(continued)
15 Gastric Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-198-320.jpg)
![196
References
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online-analysis-map
2. UpToDate [Internet]. Uptodate.com. 2022 [cited 10 March 2022]. https://www.uptodate.
com/contents/adjuvant-and-neoadjuvant-treatment-of-gastric-cancer?search=stomach%20
cancersource=search_resultselectedTitle=3~150usage_type=defaultdisplay_rank=3
3. UpToDate [Internet]. Uptodate.com. 2022 [cited 10 March 2022]. https://www.uptodate.com/
contents/clinical-features-diagnosis-and-staging-of-gastric-cancer?search=stomach%20cance
rtopicRef=2523source=related_link
4. Matzinger O, Gerber E, Bernstein Z, Maingon P, Haustermans K, Bosset J, et al. EORTC-
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tion of adenocarcinomas of the gastroesophageal junction and the stomach. Radiother Oncol.
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5. National Comprehensive Cancer Network. Gastric Cancer (version 2.2022) [Internet].
NCCN. 2022 [cited 10 March 2022]. https://www.nccn.org/professionals/physician_gls/pdf/
gastric.pdf
6. Hartgrink H, van de Velde C. Status of extended lymph node dissection: Locoregional control
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8. Smalley S, Benedetti J, Haller D, Hundahl S, Estes N, Ajani J, et al. Updated analysis of
SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus
observation after curative gastric cancer resection. J Clin Oncol. 2012;30(19):2327–33.
9. Lee J, Lim D, Kim S, Park S, Park J, Park Y, et al. Phase III trial comparing capecitabine plus
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pletely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol.
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10. Park S, Lim D, Sohn T, Lee J, Zang D, Kim S, et al. A randomized phase III trial comparing
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oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial.
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11. Cunningham D, Allum W, Stenning S, Thompson J, Van de Velde C, Nicolson M, et al.
Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N
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12. Cats A, Jansen E, van Grieken N, Sikorska K, Lind P, Nordsmark M, et al. Chemotherapy
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13. Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, et al. Adjuvant
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14. Bang Y, Kim Y, Yang H, Chung H, Park Y, Lee K, et al. Adjuvant capecitabine and oxaliplatin
for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised con-
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J. Tey et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-199-320.jpg)
![198
• Motion management helps to lower doses to organs at risk (OARs) while maxi-
mizing target coverage and is required for any ablative approaches. Gating
(whether deep-
inspirational breath hold or expiratory gating) is preferred, but an
internal target volume (ITV) approach may be used as an alternative based patient
factors and available technology. Gating requires metal fiducials or metal stent.
• Patients are immobilized in a custom alpha-cradle with arms extended above the
head if tolerable.
• Suggested target volumes and relevant OARs are listed in the following tables,
organized by setting/dose.
• Ablative and non-ablative fractionation schemes may be appropriate in a particu-
lar setting based on the treatment intent, available technology, and patient anatomy.
• Treatment of high-risk resectable or borderline resectable disease with pre-
operative intent requires lower doses, and therefore, less complex technology,
but attention should be paid to adequate margins to fully encompass all micro-
scopic disease as well as radiographically occult extension of disease along the
vasculature (Table 16.1). Fractionation schemes including 25 Gy in 5 fractions,
30 Gy in 10 fractions, 36 Gy in 12 fractions, and 50.4 Gy in 28 fractions may be
appropriate.
• Unresectable tumors should be treated with ablative doses (BED10 ≥ 100 Gy)
if motion management techniques and image-guidance are available (Table 16.2).
The choice of the fractionation scheme is often driven by the available technol-
ogy. However, it is critical that the trend for fewer fractions, which is in part
driven by the resource-intensive nature of stereotactic planning and delivery, is
balanced by radiobiologic and dosimetric considerations and results in a dose
that is ablative (BED10 ≥ 100 Gy) [1]. Due to the proximity of the radiosensitive
luminal GI tract OARs to the target, the ability to achieve an ablative dose often
requires hypofractionated courses that exceed five fractions. We recommend
Table 16.1 Target volumes for treatment in the neoadjuvant setting for borderline resectable dis-
ease (see Fig. 16.1)
Target
volumes Definition and description
GTV all gross disease on imaging, including the primary tumor (typically hypointense),
paying particular attention to the extension along the vessels, and all suspicious
nodes
ITV-
optional
If using the ITV approach, use the guidelines for GTV delineation on all phases of
the 4D-CT
CTV Given the infiltrative nature of PDAC, adequate margin is critical, and should
include at least 1 cm uniform expansion on all gross disease
+ coverage of CA and SMA basins
+
additional margin along vessels if there is any uncertainty regarding tumor
extension
+ coverage of splenic hilum for body/tail lesions
+ optional coverage of porta hepatis basins for head of the pancreas lesions
PTV PTV margin is based on the motion management technique used (if any) and
should be at least 0.5 cm. For cases treated with free breathing (FB) and without an
ITV, expansions of 1–1.5 cm in the superior-inferior dimension is recommended
M. Reyngold and C. Crane](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-201-320.jpg)
![199
Table 16.2 Target volumes for neoadjuvant/definitive setting for unresectable disease (see
Fig. 16.2)
Target volumes Definition and description
GTV All gross disease on imaging, including the primary tumor (typically
hypointense), paying particular attention to the extension along the
vessels, and all suspicious nodes
ITV-optional If using the ITV approach, use the guidelines for GTV delineation on all
phases of the 4D-CT
CTVhigh dose Corresponds to GTV or ITV if used without additional margin
CTVmicroscopic dose Given the infiltrative nature of PDAC, adequate margin is critical, and
should include at least 1 cm uniform expansion on all gross disease (to
ensure coverage of peripancreatic nodes)
+ coverage of CA and SMA basins
+ splenic hilum basin (body/tail lesions only)
+
additional margin along vessels if there is any uncertainty regarding
tumor extension
Optional: Coverage of the porta hepatis basin (for head of the pancreas
tumors)
PTVhigh dose Uniform expansion 0–0.5 cm followed by subtraction of any overlapping
critical OAR with additional safety margin as below. Ablative doses are
preferred when possible
•
For 56 Gy in 28 fractions, or 33 Gy in 5 fractions
Subtract stomach and small bowel without additional margin
•
For 50 Gy in 10 fractions, 67.5 Gy in 15 fractions or 75 Gy in 25
fractions
Subtract stomach and small bowel with an additional uniform
expansion margin of 0.5 cm. Can use 0.7 cm for long interface
between the target and the given OAR (see Fig. 16.2)
PTVmicroscopic dose PTV margin is based on the motion management technique used (if any)
and should be at least 0.5 cm. For cases treated with FB and without an
ITV, expansions of 1–1.5 cm in the superior-inferior dimension is
recommended
Notable OAR
volumes
Applicable for doses ≥ 60 Gy in 25 fractions (or BED equivalent)
Stomach-
proximal
duodenum PRV
Stomach and duodenum segments 1 and 2 + 0.3 cm (0.5 cm for long
interface between target and OAR)
Small bowel PRV All other small bowel + 0.3 cm (0.5 cm for long interface between target
and OAR)
See [1] for more detailed information on contouring for ablative cases
75 Gy in 25 fractions for tumors within 1 cm of the OARs and 67.5 Gy in 15
fractions for tumors more than 1 cm. 50 Gy in five fractions may be selectively
used for tumors 2 cm away from the OARs. Extensive contact between tumor
and OARs may preclude effective target coverage with the treatment dose. In
those cases (either as determined after attempted ablative treatment planning or
empirically judged based on the experience of the treating radiation oncology),
non-ablative treatments of 50.4–56 Gy in 28 fractions or low dose SBRT
approach of 33Gy in 5 fractions may be used.
16 Pancreatic Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-202-320.jpg)
![202
Table 16.3 Target volumes for treatment in the adjuvant setting (see Fig. 16.3)
Target volumes Definition and description
GTV Not applicable
CTV Post-operative bed and pancreatojejunostomy (PJ)
Nodal basins including peripancreatic, CA, SMA, paraaortic, PV (head
tumors), and splenic (body/tail)
RTOG 0848 stepwise contouring approach to create CTV from ROIs
ROIs:
• CA (proximal 1–1.5 cm)
• SMA (proximal 2.5–3 cm)
• Portal vein (PV: starts at confluence of SMV and splenic vein)
• PJ
• Aorta (superiorly to most cephalad of CA, PV, or PJ contours;
inferiorly to bottom L2, or as low as L3 to cover pre-op GTV)
• Tumor bed (based on review of pre-op imaging, pathology report,
surgical clips if placed for that purpose only)
Expansions:
• Expand PV, PJ, CA, SMA by 1.0 cm
•
Expand aorta by 2.5–3.0 cm on the right, 1.0 cm on the left, 2–2.5 cm
anteriorly, 0.2 cm posteriorly
CTV = Expansions 1 + 2, confirm that tumor bed is encompassed
PTV PTV margin is based on the motion management technique used (if any) and
should be at least 0.5 cm. For cases treated with FB and without an ITV,
expansions of 1–1.5 cm in the superior-inferior dimension is recommended
• For adjuvant field design, the RTOG 0848 contouring atlas provides a stepwise
contouring approach based on identifiable regions of interest (ROI) that were
chosen on the basis of ease of identification and reproducibility on imaging
studies [2]. However, smaller fields targeting the post-operative bed, CA and
SMA may be appropriate in clinical scenarios with dose-limiting OARs
(Table 16.3).
• Suggested dose constraints are listed in Table 16.4.
M. Reyngold and C. Crane](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-205-320.jpg)
![210
17.1
General Principles of Planning and Target Delineation
• Step-and-shoot intensity-modulated radiation therapy (IMRT) and volumetric
modulated arc therapy, with limited number or range of gantry angles to reduce
low-dose spread of normal liver, have been the standard techniques for
HCC. SBRT with ≤5–6 fractions is preferable in cases with safe bowel sparing,
available facilities of high dose rate, adequate immobilization, and image guid-
ance. Hypofractionated treatment is sometimes used due to the proximity of tar-
geted tumor to luminal gastrointestinal tissues.
• In addition to a history and physical, laboratory examinations, a liver function
assessment and imaging studies should be obtained for diagnosis, staging, and
planning. Patients should undergo a contrast-enhanced (preferably tri-phasic
[arterial, portal-venous, and delayed phases]) computed tomography (CT) scan
of the liver, with 3–5 mm slice thickness. Multi-phase dynamic magnetic reso-
nance imaging (MRI) scans can be used if the required breath hold for image
acquisition is possible or CT contrast is contraindicated. With image fusion, MRI
scans may be complimentary to CT scans for target delineation. Positron emis-
sion tomography (PET) images with 18F-fluorodeoxyglucose (18F-FDG) or
other tracers, such as 11C-acetate and 11C-choline, may be helpful in localizing
the viable tumor(s) of individual cases such as patients with residual/recurrent
tumor(s) at previous lipiodol retention and/or radiofrequency ablation areas.
• Half-body or whole-body immobilization with respiratory control is needed for
better reproducibility. Devices such as a vacuum bag or chest board may be used
to immobilize a patient, preferably with arms up, during simulation and used
throughout the course of treatment. This will enable reproducibility and allow
spatial freedom of beam directions. The systems for immobilization should be
made of materials not attenuating radiation doses and should not interfere with
the gantry positions that may be required for coplanar and non-coplanar beams.
• Respiratory motion management using a number of techniques is frequently
needed to minimize imaging artifacts from changes in liver positioin due to
breathing. Active breath hold helps reduce the treated volume and is preferable
to patients who can hold breath for more than 30 s. Abdominal compression is
used for patients who could not tolerate breath hold and might result in deforma-
tion of abdomen or organ shape. Delineation of target volumes is most often
done on multi-phasic, multi-modality images, obtained in breath hold (i.e., simi-
lar to diagnostic images for HCC). Image-guided radiation therapy (IGRT) is
required to account for changes in the intra-/inter-fractional liver position. In
patients who cannot tolerate breath control, the use of passive abdominal com-
pression devices combined with four-dimensional CT (4DCT) provides informa-
tion about internal organ motion and can compensate for liver position changes.
Gated treatment takes longer duration for the selected inspiratory or expiratory
window and may also be useful for patients that cannot tolerate breath control.
• CT simulation with IV contrast to obtain multi-phase imaging is required. This
should be obtained with the patient in the treatment position and respiratory
coordination. Fusion of the different phase images and/or diagnostic images will
aid in the delineation of gross tumor volume (GTV). Usually the viable HCC is
Y. Chiang et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-212-320.jpg)
![212
Fig. 17.1 Residual hepatocellular carcinoma after transcatheter arterial chemoembolization and
radiofrequency ablation. Tri-phasic contrast-enhanced CT simulation (from left to right: no con-
trast phase, T1-weighted contrast-enhanced MRI image, arterial phase and venous [delayed]
phases), obtained with breath-hold coordination for liver immobilization. The GTV (in red)
includes the contrast enhancing tumor and the invaded IVC thrombosis. The CTV (in green)
includes a 5-mm margin within liver boundary and 3-mm intravascular margin around the GTV
Y. Chiang et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-214-320.jpg)
![213
Fig. 17.2 Recurrent hepatocellular carcinoma with partial inferior vena cava (IVC) thrombosis
after repeated radiofrequency ablation (RFA). Tri-phasic contrast-enhanced CT simulation (from
left to right: no contrast phase, T1-weighted contrast-enhanced MRI image, arterial phase and
venous [delayed] phases), obtained with breath-hold coordination for liver immobilization. The
CTV (in green) includes the contrast enhancing tumor and the tumor thrombus (GTV in red) as
well as a 5-mm margin around the GTV within liver boundary and previous radiofrequency ablated
zone (if clinically needed)
17 Hepatocellular Carcinoma](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-215-320.jpg)
![214
Fig. 17.3 Recurrent hepatocellular carcinoma after surgery and radiofrequency ablation (RFA)
with high risk of bile duct injury by RFA. Tri-phasic contrast-enhanced CT simulation (from left
to right: no contrast, arterial, portal, and venous [delayed] phases), obtained with breath-hold coor-
dination for liver immobilization. The CTV (in green) includes the contrast enhancing tumor (GTV
in red) and a 5-mm margin of liver parenchyma and 3-mm margin of intra-vascular space
around the GTV
Y. Chiang et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-216-320.jpg)
![215
Fig. 17.4 Hepatocellular carcinoma refractory to sorafenib treatment with progression of portal
vein and middle hepatic vein thromboses. Tri-phasic contrast-enhanced CT simulation (from left
to right: no contrast, arterial, portal, and venous [delayed] phases), obtained on breath-hold coor-
dination for liver immobilization. The CTV (in green) includes the contrast enhancing tumor (GTV
in red) and a three-dimensional 5-mm margin around the GTV within liver boundary
17 Hepatocellular Carcinoma](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-217-320.jpg)
![238
19.3
Simulation and Daily Localization
• The patient should be simulated supine with arms on chest in a body mold. Prone
positioning with a belly board can be used to allow for anterior displacement of
the bowel, but this is not as reproducible and complicates bolus placement. A
radiopaque marker should be placed at the anal verge.
• CT simulation with intravenous contrast and ≤3 mm slice thickness should be
performed to delineate the pelvic blood vessels and gross tumor volume. If PET/
CT is available, a PET/CT fusion should be performed to aid in target volume
delineation. MRI may also be useful.
• Bladder filling/emptying should be considered. A full bladder may keep bowel
from migrating into the pelvis, while an empty bladder may be more reproducible.
• We recommend image guidance with daily orthogonal kilovoltage imaging and
weekly cone-beam CT scans (to assess soft tissue) to verify alignment during
treatment. Cone beam CTs may be done more frequently if there is significant
variation in bladder and/or rectal filling.
19.4
Target Volume Delineation and Treatment Planning
• Conventional 3D conformal radiotherapy for anal canal cancers is complex due
to the need to irradiate the pelvis and inguinal lymph nodes. The “thunderbird”
technique was historically the most common method used to treat anal cancer.
An example of the thunderbird technique compared to an IMRT plan is shown in
Fig. 19.2. A detailed description of thunderbird technique variations is described
by Gilroy et al. [1]
c d
a b
Fig. 19.2 Dose distributions for a photon/electron thunderbird technique (panel (a) and (b)) and
intensity-modulated radiotherapy plan (panel (c) and (d))
J. A. Miller et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-240-320.jpg)
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• RTOG 0529 has established the feasibility of IMRT in a multi-institution setting
and demonstrated lower rates of grade 2 or higher hematologic toxicity and
lower rates of grade 3 or higher gastrointestinal or dermatologic toxicity when
compared to historical controls in the RTOG 9811 trial, which utilized 3D con-
formal radiotherapy [2, 3]. However, accurate target volume delineation is criti-
cal, as delineation that is non-compliant with consensus guidelines is associated
with an increased risk of disease recurrence (Table 19.2) [4–6].
Table 19.2 Suggested target volumes for gross and microscopic disease
Target volumes Definition and description
Gross tumor
volumes (GTV-P,
GTV-N)
Primary (GTV-P): all gross disease on physical examination and imaging
Regional nodes (GTV-N): all nodes ≥1.5 cm, PET-positive, and/or
biopsy-proven. Include any lymph nodes in doubt as GTV-N in the
absence of biopsy. Lymph nodes that are ≤3 cm (GTV-Na) may be
distinguished from those that are 3 cm (GTV-Nb)
Clinical target
volumes for gross
disease (CTV-P,
CTV-N)
CTV-P is the GTV-P with a 1.5–2.5 cm margin expansion excluding
uninvolved bone, muscle, or air. The CTV-N is the GTV-N with a
1.0–1.5 cm margin expansion excluding uninvolved bone, muscle, or air
High risk clinical
target volume
(CTV-HR)
Should cover CTV-P, CTV-N, the entire mesorectum, perirectal lymph
nodes, and bilateral internal iliac lymph nodes inferior to the inferior
border of the sacroiliac joint. If the inguinal or external iliac nodes are
involved, these regions should be included in CTV-HR. Similarly, the
upper internal iliac nodes should be included if involved
To cover the internal iliac nodes, a 0.7-cm margin around the internal iliac
vessels should be drawn (excluding muscle and bone) [4, 7]
To cover the external iliac nodes (for either inguinal or external iliac
node-positive disease), an additional 1 cm margin anterolaterally around the
vessels should be drawn. Any adjacent small nodes should be included [4, 7]
To cover the inguinal nodes (for inguinal or external iliac node-positive
disease), the entire inguinal compartment should be contoured, including
small vessels and adjacent lymph nodes bounded by muscle and bone
(Table 19.4).
A 1.8-cm wide volume between the external and internal iliac vessels
should be drawn to cover the obturator nodes [7]
Anteriorly, a margin of 1–1.5 cm should be added into bladder to account
for changes in bladder and rectal filling [4, 8]
Low risk clinical
target volume
(CTV-LR)
Should cover the uninvolved internal iliac lymph nodes superior to the
inferior border of the sacroiliac joint, as well as the uninvolved external
iliac and inguinal lymph nodes
To cover the internal iliac nodes, a 0.7-cm margin around the internal iliac
vessels should be drawn (excluding muscle and bone) [4, 7]
To cover the external iliac nodes, an additional 1 cm margin anterolaterally
around the vessels should be drawn. Any adjacent small nodes should be
included [4, 7]
To cover the inguinal nodes, the entire inguinal compartment should be
contoured, including small vessels and adjacent lymph nodes bounded by
muscle and bone (Table 19.4)
Planning target
volumes (PTV)
Each CTV should be expanded by 0.5–1 cm, depending on the physician’s
comfort level with setup accuracy, frequency of imaging, and the use of
IGRT
19 Anal Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-241-320.jpg)
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Table 19.3 Elective nodal regions described in RTOG anorectal contouring atlas [4]
Clinical target
volume Key highlights
CTV-A
(perirectal,
presacral,
internal iliac
regions)
Lower pelvis: The inferior border should be 2 cm below gross disease,
including the entire mesorectum. The volume does not need to extend more
than a few millimeters beyond the levator muscles unless there is extension
into the ischiorectal fossa
Mid pelvis: Includes the rectum, mesorectum, internal iliac nodes, and 1 cm
margin into the bladder for daily variation in bladder filling. Posterolaterally,
the volume extends to the pelvic sidewall muscles or bone (when muscles are
absent). At minimum, the posterior portion of the internal obturator vessels
should be included. A 7–8 mm margin in soft tissue around the internal iliac
vessels should be drawn. The volume should be trimmed off uninvolved
muscle and bone
Upper pelvis: The most superior extent should be at the bifurcation of the
common iliac vessels into the external/internal iliacs, approximately at the
sacral promontory
Recommend 7–8 mm margin in soft tissue around the internal iliac vessels,
but at least 1 cm anteriorly, especially if vessels or small nodes are seen in
this area. CTV should be trimmed off uninvolved muscle and bone
CTV-B
(external iliac
region)
The border between the inguinal and external iliac region is somewhat
arbitrary. The consensus was that the border should be set at the level of the
inferior extent of the internal obturator vessels (bony landmark: the upper
edge of the superior pubic rami)
Recommend 7–8 mm margin in soft tissue around the iliac vessels, but at
least 1 cm anteriorly, especially if vessels or small nodes are seen in this area.
CTV should be trimmed off uninvolved muscle and bone
CTV-C
(inguinal
region)
The most inferior extent should be 2 cm below the saphenous/femoral
junction. The border between CTV-B and CTV-C is approximately the upper
border of the superior pubic rami
The entire inguinal compartment should be contoured, including small
vessels and lymph nodes. CTV should be trimmed off uninvolved muscle and
bone
• Detailed contouring atlases available include the RTOG anorectal contouring
atlas and the Australasian GI Trials Group Atlas [4, 5].
• The RTOG anorectal contouring atlas describes three CTV regions that should
be included for all patients with anal canal cancer [4]. CTV-A includes the peri-
rectal, presacral, and internal iliac regions. CTV-B includes the external iliac
nodes. CTV-C includes the inguinal region. Table 19.3 provides a more detailed
description of these regions.
• The Australasian GI Trials Group Atlas describes seven elective regions to be
considered when treating anal cancer: mesorectum, presacral space, internal iliac
nodes, ischiorectal fossa, obturator nodes, external iliac nodes, and inguinal
nodes [5]. Table 19.4 is a summary of the definitions of these regions.
• Disagreement exists among anal cancer contouring guidelines (RTOG, AGITG,
BNG) with respect to contouring the inguinal lymph nodes. Recent data indicate
that 10–29% of involved inguinal lymph nodes appear to be situated outside of
recommended nodal borders [9]. To adequately cover this nodal chain, a 2 cm
J. A. Miller et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-242-320.jpg)
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Table
19.4
Description
of
the
borders
used
in
defining
the
elective
nodal
regions
from
the
Australasian
GI
Trials
Group
Contouring
Atlas
[5]
Mesorectum
Presacral
space
Internal
iliac
nodes
Ischiorectal
fossa
Obturator
nodes
External
iliac
nodes
Inguinal
nodes
Cranial
Recto-
s
igmoid
junction
Sacral
promontory
(L5/S1
interspace)
Bifurcation
of
common
iliac
arteries
(L5/S1
interspace)
Apex
formed
by
levator
ani,
gluteus
maximus,
and
obturator
internus
3–5
mm
cranial
to
obturator
canal
Bifurcation
of
common
iliac
artery
Level
where
external
iliac
artery
leaves
bony
pelvis
to
become
femoral
artery
Caudal
Ano-rectal
junction
(levators
fuse
with
external
sphincter)
Inferior
border
of
coccyx
Level
of
obturator
canal
or
level
where
there
is
no
space
between
obturator
internus
and
midline
organs
Anal
verge
Obturator
canal,
where
obturator
artery
exits
the
pelvis
Between
roof
of
acetabulum
and
superior
pubic
rami
Lower
edge
of
ischial
tuberosities
Posterior
Presacral
space
Position
at
anterior
border
of
sacral
bone;
should
include
sacral
hollow
N/A
Transverse
plane
joining
anterior
edge
of
medial
walls
of
the
gluteus
maximus
muscle
Internal
iliac
nodes
Internal
iliac
nodes
Muscle
boundaries
(continued)
19 Anal Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-243-320.jpg)
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Table 19.5 Suggested dose and fractionation schemes for anal canal cancer
Target
volume RTOG 9811 [3] RTOG 0529 [2]/Transaustralian [5]
PTV-P T1N0: 45–50.4 Gy at 1.8 Gy/fraction
T2N0: 50.4 Gy at 1.8 Gy/fraction
N+ or T3-T4: 54–59.4 Gy at 1.8 Gy/
fraction
T1N0: Not included on RTOG 0529
T2N0: 50.4 Gy at 1.8 Gy/fraction
N+ or T3-T4: 54 Gy at 1.8 Gy/
fraction
PTV-N 54–59.4 Gy at 1.8 Gy/fraction 50.4 Gy at 1.68 Gy/fraction if node
≤3 cm
54 Gy at 1.8 Gy/fraction if node
3 cm
PTV-HR 45 Gy at 1.8 Gy/fraction T2N0: 42 Gy at 1.5 Gy/fraction
N+ or T3-T4: 45 Gy at 1.5 Gy/
fraction
PTV-LR 30.6–36 Gy at 1.8 Gy/fraction
Alternatively, 40 Gy at 1.6 Gy/fraction
SIB may be used
A low-risk PTV was not used on
RTOG 0529
radial margin around the femoral vessels, 1 cm radial margin around the saphe-
nous/femoral junction, and 3 cm medial/lateral margin along the lower inguinal
ligament is necessary. The caudal border of the inguinal CTV should be the level
of the anal margin.
• There are multiple techniques and methods of dose prescription for anal cancer,
and the exact dose and fractionation will vary based on which technique is used.
The current recommendations are based on the treatment plan used in RTOG
9811 [3] (Table 19.5).
• Figure 19.3 shows a case example of a clinical T2N0 anal canal cancer treated
with definitive chemoradiotherapy with an IMRT plan. The PTV-LR and PTV-HR
were treated simultaneously to 40 Gy (1.6 Gy/fx) and 45 Gy (1.8 Gy/fx) in 25
fractions, respectively. Then, the PTV-P was boosted sequentially to 50.4 Gy (1.8
Gy/fx) in 28 total fractions.
• Figure 19.4 shows a case example of a clinical T3N1a anal canal cancer with
bilateral inguinal nodal involvement treated with definitive chemoradiotherapy
with an IMRT plan. The PTV-LR and PTV-HR were treated simultaneously to
40 Gy (1.6 Gy/fx) and 45 Gy (1.8 Gy/fx) in 25 fractions, respectively. Then, the
PTV-P and PTV-N were boosted sequentially to 54 Gy (1.8 Gy/fx) in 30 total
fractions.
• Figure 19.5 shows a case of a pathologic T1 (1.0 cm) clinical N0M0 squamous
cell carcinoma of the perianal skin (anal margin), which was resected with a
0.1cm close margin. The patient was treated with postoperative radiotherapy to
the postoperative bed and inguinal lymph nodes alone with an IMRT plan. The
PTV-HR and PTV-P were treated simultaneously to 45 Gy (1.8 Gy/fx) in 25
fractions. Then, the PTV-HR was boosted sequentially to 55.8 Gy (1.8 Gy/fx) in
31 total fractions.
19 Anal Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-245-320.jpg)
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19.5 Plan Assessment
• Ideally, at least 95% of each PTV should receive 100% of the prescription dose.
In addition, the maximum dose in the PTV should not exceed 10%.
• When evaluating plans with a sequential boost to gross disease, each individual
plan should be scrutinized before the “plan sum” to assess for hot spots or under-
coverage of each individual PTV.
• The organs-at-risk include the small bowel, large bowel, bladder, femoral heads,
iliac crest, and external genitalia. Uniform consensus guidelines for contouring
the small and large bowel, bladder, and femoral heads are available from an
RTOG consensus panel [10]. Suggested dose constraints from QUANTEC and
RTOG 0529 are listed in Table 19.6 [2, 11].
• Pelvic bone marrow is emerging as an important organ-at-risk with respect to
minimizing acute hematologic toxicity in patients receiving concurrent chemo-
Table 19.6 Dose constraints for organs-at-risk
Organ-at-risk Constraints
Small bowel QUANTEC
V15Gy 120 cc (individual loops)
V45Gy 195 cc (entire potential space within peritoneal cavity)
RTOG 0529
V30Gy 200 cc
V35Gy 150 cc
V45Gy 20 cc
Dmax 50 Gy
Large bowel RTOG 0529
V30Gy 200 cc
V35Gy 150 cc
V45Gy 20 cc
Bladder QUANTEC
Dmax 65 Gy
V65Gy 50%
RTOG 0529
V35Gy 50%
V40Gy 35%
V50Gy 5%
Femoral heads RTOG 0529
V30Gy 50%
V40Gy 35%
V44Gy 5%
Iliac crest RTOG 0529
V30Gy 50%
V40Gy 35%
V50Gy 5%
External genitalia RTOG 0529
V20Gy 50%
V30Gy 35%
V40Gy 5%
19 Anal Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-249-320.jpg)
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radiotherapy for anal cancer [12–14]. Currently, the pelvic bones serve as a sur-
rogate for the pelvic bone marrow. Delineation of the pelvic bone marrow
structure is described by Mell et al. [15]. The pelvic bone marrow structure con-
sists of 3 sub-sites: the lumbosacral spine, the ilium, and the low pelvis.
• We suggest that potential dose constraints for the pelvic bone marrow should
include mean dose 28 Gy, V10 90% and V20 75%. However, these con-
straints have not been validated prospectively and should not supercede other
planning objectives. The lumbosacral spine may be the most active sub-site of
the pelvic bone marrow [12, 13, 16], and limiting dose to this site may be suffi-
cient to reduce hematologic toxicity.
References
1. Gilroy JS, Amdur RJ, Louis DA, Li JG, Mendenhall WM. Irradiating the groin nodes with-
out breaking a leg: a comparison of techniques for groin node irradiation. Med Dosim.
2004;29(4):258–64.
2. Kachnic LA, Winter K, Myerson RJ, et al. RTOG 0529: a phase 2 evaluation of dose-painted
intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for
the reduction of acute morbidity in carcinoma of the anal canal. Int J Radiat Oncol Biol Phys.
2013;86(1):27–33.
3. Ajani JA, Winter KA, Gunderson LL, et al. Fluorouracil, mitomycin, and radiotherapy vs fluo-
rouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled
trial. JAMA. 2008;299(16):1914–21.
4. Myerson RJ, Garofalo MC, El Naqa I, et al. Elective clinical target volumes for conformal
therapy in anorectal cancer: a radiation therapy oncology group consensus panel contouring
atlas. Int J Radiat Oncol Biol Phys. 2009;74(3):824–30.
5. Ng M, Leong T, Chander S, et al. Australasian Gastrointestinal Trials Group (AGITG) con-
touring atlas and planning guidelines for intensity-modulated radiotherapy in anal cancer. Int J
Radiat Oncol Biol Phys. 2012;83(5):1455–62.
6. Rouard N, Peiffert D, Rio E, et al. Intensity-modulated radiation therapy of anal squamous
cell carcinoma: relationship between delineation quality and regional recurrence. Radiother
Oncol. 2019;131:93–100.
7. Taylor A, Rockall AG, Reznek RH, Powell ME. Mapping pelvic lymph nodes: guide-
lines for delineation in intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys.
2005;63(5):1604–12.
8. Daly ME, Murphy JD, Mok E, Christman-Skieller C, Koong AC, Chang DT. Rectal and blad-
der deformation and displacement during preoperative radiotherapy for rectal cancer: are cur-
rent margin guidelines adequate for conformal therapy? Pract Radiat Oncol. 2011;1(2):85–94.
9. Dapper H, Schiller K, Münch S, et al. Have we achieved adequate recommendations for target
volume definitions in anal cancer? A PET imaging based patterns of failure analysis in the
context of established contouring guidelines. BMC Cancer. 2019;19(1):742.
10. Gay HA, Barthold HJ, O'Meara E, et al. Pelvic normal tissue contouring guidelines for radia-
tion therapy: a Radiation Therapy Oncology Group consensus panel atlas. Int J Radiat Oncol
Biol Phys. 2012;83(3):353–62.
11. Marks LB, Yorke ED, Jackson A, et al. Use of normal tissue complication probability models
in the clinic. Int J Radiat Oncol Biol Phys. 2010;76(3):10–9.
12. Bazan JG, Luxton G, Kozak MM, et al. Impact of chemotherapy on normal tissue complication
probability models of acute hematologic toxicity in patients receiving pelvic intensity modu-
lated radiation therapy. Int J Radiat Oncol Biol Phys. 2013;87(5):983–91.
J. A. Miller et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-250-320.jpg)
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20
Postoperative Therapy for Cervical,
Vaginal, and Endometrial Cancer
Karen Tye, Loren K. Mell, and Dominique Rash
Contents
20.1 Introduction 251
20.2
Diagnostic Workup Relevant for Target Volume Delineation 252
20.3
Simulation and Daily Localization 253
20.4
Target Volume Delineation and Treatment Planning 254
20.5
External Beam Plan Assessment 260
References 261
20.1 Introduction
Intensity-modulated radiation therapy (IMRT) has become the treatment of choice
for adjuvant radiotherapy for patients with gynecological cancers, particularly cer-
vical and endometrial malignancies [1–3]. A Phase III randomized trial comparing
patient reported outcomes and quality of life (QOL) scores in patients who received
pelvic radiation with IMRT versus 3D conformal radiation therapy demonstrated
significant reduction in acute GI and GU toxicity as well as better QOL with
IMRT. Additionally, IMRT has been demonstrated to reduce the volume of irradi-
ated bone marrow in cervical and endometrial cancer patients who undergo postop-
erative pelvic radiotherapy (RT), producing a clinically significant reduction in
acute and chronic toxicity [4, 5].
K. Tye · L. K. Mell (*) · D. Rash
Department of Radiation Medicine and Applied Sciences, University of California San Diego,
La Jolla, CA, USA
e-mail: ktye@health.ucsd.edu; lmell@ucsd.edu; drash@health.ucsd.edu
© Springer Nature Switzerland AG 2022
N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical
Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_20](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-252-320.jpg)
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Target delineation is an essential component of IMRT treatment in cervical and
endometrial cancer patients. Multiple consensus guidelines for clinical target vol-
ume (CTV) delineation have been published in recent years [6–9]. The treatment
paradigm varies by disease site:
• For cervical cancer, surgery is preferred over radiation therapy for early stage
disease. Radiation therapy is delivered following surgery in patients with high-
risk features such as size ≥4 cm, lymphovascular space invasion (LVSI), deep
cervical stromal involvement, positive margins, or locally advanced disease
including parametria or lymph node involvement [10, 11].
• For endometrial cancer, treatment consists of upfront surgery, consisting of a
total abdominal or laparoscopic hysterectomy and bilateral salpingo-
oophorectomy (TAH or TLH-BSO) when possible. Radiation therapy is deliv-
ered following surgery in women with adverse pathologic features including
high-grade disease deep myometrial invasion, cervical stromal extension, and
regional lymph node involvement [12].
Postoperative RT is recommended for endometrial cancer patients at high risk
for recurrence in the lymph nodes, including stage I-II non-endometrioid histology
or grade 3 endometrioid adenocarcinoma with deep myometrial invasion [13–15].
Whole pelvis RT is strongly considered for patients with stage III–IV disease to
reduce the risk of pelvic and para-aortic recurrences [16–19].
A phase III randomized trial comparing vaginal cuff brachytherapy (VCB) and
chemotherapy to pelvic RT alone for high-intermediate and high-risk early stage
endometrial cancer patients did not demonstrate superiority with the addition of
chemotherapy to VCB compared to pelvic RT [20]. Acute toxicity was greater with
chemotherapy. As such, whole pelvis RT remains an effective, well-tolerated and
appropriate adjuvant treatment in high-risk early stage endometrial carcinomas of
all histologies.
Traditionally, most endometrial cancer patients undergoing adjuvant RT received
pelvic irradiation. However, low risk, early stage patients undergoing surgical stag-
ing who are found to have negative nodes may undergo vaginal brachytherapy alone
[21].Foradditionaldetails,pleaserefertothechapteronimageguidedbrachytherapy.
20.2
Diagnostic Workup Relevant for Target
Volume Delineation
• All gynecologic cancer patients should undergo a complete history and physical
examination including a pelvic exam and evaluation of the inguinal and supracla-
vicular lymph nodes as part of initial diagnosis and staging. Standard radio-
graphic workup in these patients includes a computed tomography (CT) scan to
assess the extent of local disease involvement and sites of extrauterine spread.
K. Tye et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-253-320.jpg)
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• During the pelvic exam, special attention should be given to evaluation of the
vaginal vault, rectovaginal septum, and bilateral parametria and sidewalls. Exam
under anesthesia is indicated if patient discomfort prohibits a thorough
examination.
• Patients suspected to have urinary bladder or rectal involvement should undergo
cystoscopy or rectosigmoidoscopy.
• Positron emission tomography/computed tomography (PET/CT) and magnetic
resonance imaging (MRI) of the pelvis are useful in selected patients to delineate
any residual gross tumor volume or involved lymph nodes. PET/CT is of particu-
lar use in diagnostic workup of cervical cancer, to assess for para-aortic nodal
spread and distant metastasis [22].
20.3
Simulation and Daily Localization
• Gynecologic cancer patients undergoing postoperative pelvic IMRT are simu-
lated in the supine position. Immobilization of the lower body (and upper body
in the setting of extended field radiation), such as with a cradle or Vac-Lok
device, is recommended.
• CT simulation with ≤3 mm slice thickness is the recommended simulation
approach and is performed with (comfortably) full and empty bladder scans
which can be fused to generate an integrated target volume (ITV).
• Intravenous contrast is recommended to identify the patient’s vasculature as a
surrogate for the lymph nodes, unless medically contraindicated.
• Consider use of oral contrast to opacify the small bowel as a critical organ
at risk.
• Patients are encouraged to empty their rectum the morning of simulation and for
daily treatment. Use of rectal enema may be considered.
• An internal vaginal marker to identify the apex of the vagina and an introitus
marker are standard.
• Whenever possible, it is desirable to simulate patients in both the empty and full
bladder state, to account for changes in target position due to bladder filling and
emptying, such as with an internal target volume (ITV) (Fig. 20.1). Patients
should be treated consistently in either a full bladder or empty bladder state to
minimize the impact of bladder filling on target motion.
• Daily orthogonal planar imaging (MV or kV) is recommended for setup.
• Weekly imaging with cone beam CT (CBCT) should be done at minimum to
verify treatment setup; daily CBCT to monitor variations in bladder and bowel
filling can also be done.
20 Postoperative Therapy for Cervical, Vaginal, and Endometrial Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-254-320.jpg)
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Fig. 20.1 An example of internal target volume (ITV) to planning target volume (PTV) expan-
sion. Target volumes are drawn both on a scan with a full bladder (cyan) and empty bladder (yel-
low) then combined to make an ITV (red), which is then expanded and included in the PTV
(dark blue)
20.4
Target Volume Delineation and Treatment Planning
• Delineated target volumes in cervical and uterine cancer patients undergoing
adjuvant pelvic IMRT include multiple CTVs (CTV1, CTV2, and CTV3), to allow
for anisotropic CTV to PTV expansions (Fig. 20.2). See Table 20.1 for a detailed
description of these components, which were used on TIME-C randomized clini-
cal trial.
• Regarding CTV1, the anterior portion of the uterosacral ligament is removed dur-
ing a radical hysterectomy. Consequently, the mesorectal fascia is used as a sur-
rogate structure for the posterior border of the vaginal cuff and parametrium
CTV [10].
• Vaginal boost can be considered if at higher risk for recurrence due to factors
such as cervical stromal invasion, supracervical hysterectomy, extensive LVSI,
or extensive vaginal involvement.
K. Tye et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-255-320.jpg)
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20.5
External Beam Plan Assessment
• Ideally at least 95% of the PTV should receive 100% of the prescription dose and
≥99% of the PTV will receive ≥90% of the prescription dose.
• The dose maximum should occur within the PTV and dose areas 100% of the
prescription dose outside of the PTV should be minimized.
• Organs at risk (OAR) used in treatment planning include the bowel, bladder,
and rectum and femoral heads. In patients undergoing adjuvant chemotherapy,
the pelvic bone marrow (BM) should be included as this technique has been
shown to help reduce the risk of hematologic toxicity [2] (Fig. 20.7). See
Table 20.2 for detailed descriptions for delineation of the OARs as well as dose
constraints used in gynecological cancer patients undergoing pelvic IMRT
treatment planning.
• The bowel contour should include the entire peritoneal space encompassing the
bowel such that the superoinferior boundaries extend 1.5 cm superior to the cau-
dal aspect of the PTV and inferiorly to the rectosigmoid junction. In the anterior-
posterior direction, the bowel should be delineated from the anterior abdominal
wall to the most posterior extent of bowel. The bilateral bowel edges serve as the
left-right boundaries.
c
a b
Fig. 20.7 Contours for organs at risk including bowel ((a), orange), rectum ((b), brown), bladder
((b), yellow), and bone marrow ((c), green) on representative computed tomography slices
K. Tye et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-261-320.jpg)
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have begun to incorporate IMRT as a standard treatment approach for definitive
therapy, indicating its widespread acceptance. However, 3D conformal techniques
remain in common use for this population, and delineation of targets and organs at
risk (OARs) are also important for defining fixed beam arrangements and evaluating
the dosimetry with conventional treatment plans. In contrast to the postoperative
setting, application of IMRT in patients with an intact uterus is complicated by even
greater mobility of targets and OARs. Moreover, treatment intensity is generally
higher, with radiation often given with concurrent chemotherapy and followed by
brachytherapy and/or nodal boosts, with higher overall doses delivered. Thus, nor-
mal tissue dose is a particularly critical factor in determining both treatment toler-
ance and risk for high grade late complications. Advanced technologies play a
prominent role in defining targets and OARs in this context, which remains an active
area of investigation.
21.2
General Principles of Workup, Imaging, and Staging
• All patients should undergo a complete history and physical examination with
attention on pelvic exam to size and location of tumor, extent of vaginal exten-
sion, and presence of urethral, parametrial, and/or sidewall involvement. Exam
under anesthesia may be necessary if patient is unable to otherwise tolerate a
thorough examination.
• If there is clinical suspicion for bowel or bladder involvement, pelvic MRI and
proctosigmoidoscopy and/or cystoscopy are indicated.
• Dynamic contrast-enhanced MRI is the optimal method for detecting cervix
invasion and myometrial invasion, with an accuracy of 85–93% [1], and has been
shown to be superior to CT and physical examination for determining tumor size
and extent of invasion [2].
• The sensitivity of MRI for detecting lymph node metastases is 27–66% with
specificity 73–94% in surgically staged patients [3]. However, PET/CT is prefer-
able if available, with sensitivity and specificity for assessing regional lymph
node metastases ranging from 50–100% and 87–100%, respectively [3].
• Radiologic workup with whole-body PET/CT is preferred for patients with at
least International Federation of Gynecology and Obstetrics (FIGO) stage IB
disease, given its greater sensitivity than CT [4], and is now admissible for FIGO
staging purposes [5].
• FIGO has published staging systems for cervical, endometrial, and ovarian can-
cers [5, 6]. There are also TNM staging systems produced by the American Joint
Committee on Cancer [7].
21.3
CT Simulation for Treatment Planning
• CT simulation should be obtained with the patient in a supine position with a
customized immobilization cradle to minimize treatment setup error. Scans
should be obtained with slice thickness ≤3 mm.
C. W. Williamson and L. K. Mell](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-265-320.jpg)
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• The degree of bladder and rectal fullness at simulation should ideally replicate
that which will be observed during daily treatment. Empty and full bladder scans
may be fused to generate an integrated target volume (ITV).
• Treatment can be delivered with either a (comfortably) full or empty bladder and
it is recommended to use a consistent bladder filling state (i.e., always full or
always empty) for both the simulation scan used for treatment planning, and for
daily treatment. Treatment with an empty bladder may be more reproducible and
reduces the absolute variation in bladder volume, whereas treatment with a full
bladder can displace bowel from the treatment field and improve bowel dosim-
etry [8].
• Bowel preparation with an enema can be used to achieve simulation with an
empty rectum.
• Given that the patient’s pelvic vasculature serves as a surrogate for lymph node
location, simulation with intravenous contrast is recommended, unless medically
contraindicated.
• Tools for improving target volume delineation include placement of fiducial
markers prior to CT simulation or placing radiopaque markers in the vaginal
apex and introitus at the time of simulation.
• Patients with disease involving the distal one-half of the vagina (or vaginal pri-
mary) should also receive bilateral inguinal RT, in which case CT simulation can
be performed in the “frog-leg” position to minimize skin fold toxicity.
21.4
General Principles of Target Delineation
• IMRT is increasingly used as a standard modality for gynecologic malignancies
in the definitive setting. Evidence demonstrates excellent outcomes and an
improved toxicity profile, with improvements in gastrointestinal (GI) and hema-
tologic toxicities, as well as reduced risk of pelvic fractures, compared to 3D
conformal techniques [9–15].
• Multiple ongoing clinical trials utilize IMRT, with their respective protocols
delineating specific treatment planning requirements [16–20].
• Fusion of pre-treatment PET/CT with CT simulation is recommended to assist in
delineation of gross tumor volume (GTV).
• See dedicated sections below for target delineation for cervical, vaginal, and
endometrial cancers, respectively, with definitions described in Table 21.1. These
recommendations are derived from the protocol for the multi-institutional coop-
erative group phase III NRG-GY006 clinical trial [16]. Note there are varying
standards across trials and institutions.
• Accurate target delineation is of critical importance for IMRT planning.
International consensus guidelines for contouring definitive cervix cases have
been published [21].
• Interactive online sample cases are available on educational websites, such as
eContour [22], to assist with contouring.
• An MRI study using injected iron oxide particles suggested that 95% of pelvic
(common iliac, internal iliac, medial and anterior external iliac, and obturator)
21 Definitive Therapy for Cervical, Vaginal, and Endometrial Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-266-320.jpg)
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Table 21.1 Target delineation for cervical cancer (per NRG-GY006 protocol) [16]
Name Details
GTV All visible gross disease as assessed by clinical information, physical
examination, radiographic studies, endoscopic examination, and biopsy results
CTV1 GTV + cervix + uterus
CTV2 Parametria and upper third of the vagina (or upper half if the vagina is clinically
involved)
CTV3 Common, external iliac, internal iliac, and presacral lymph nodes. The upper
border should start the aortic bifurcation (approximately L4–L5 interspace).
Presacral nodes should be included to the S2–S3 interspace; below this point
this nodal volume can be separated into two structures. External iliac nodes
should be included to the top of the femoral heads. If there is distal vaginal
involvement, the inguinal nodes should be included (from the external iliac
nodes to 2cm caudal to the saphenous/femoral junction). If para-aortic nodes
are involved, an extended field should be used, extending the superior border to
the L1/L2 interspace or 3cm cranial to gross disease. CTV3 should be obtained
by placing a 7mm margin around the vessels with inclusion of any adjacent
visible lymph nodes, lymphoceles, or surgical clips. This volume should be
modified to exclude bone, muscle, and bowel, and should not extend inferior to
the ischial tuberosities
CTV_boost Gross pelvic lymph nodes. If the patient will receive a parametrial boost, this
area should be included
ITV If an ITV approach is to be used, CTV1 should be delineated on both the full
and empty bladder scans and combined to generate the ITV
CTV_4500
or
CTV_4760
CTV1 + CTV2 + CTV3 + ITV
PTV1 CTV1 + 15 mm uniform expansion
PTV2 CTV2 + 10 mm uniform expansion
PTV3 CTV3 + 5 mm uniform expansion
PTV4 ITV + 7 mm uniform expansion
PTV_boost CTV_boost + 5 mm uniform expansion
PTV_4500
or
PTV_4760
PTV1 + PTV2 + PTV3 + PTV4 + PTV_boost. This should be trimmed up to
3 mm from the skin surface, if necessary, to spare skin. The CTV should be
fully encompassed by the PTV
lymph nodes are located within 7 mm of the pelvic vasculature [23]. However,
inguinal nodal basins should be delineated using an anatomic compartment
approach given greater range of potential lymph node location with respect to the
vessels [24].
• Common problems with target delineation observed in multi-center trials include:
–
– Inadequate margin around the vasculature/clinical target volume (CTV) that
is too close to the vessels
–
– Insufficient coverage around the internal iliac vasculature inferior and poste-
rior in the pelvis
–
– Insufficient coverage around the obturator vasculature inferior and anterolat-
erally in the pelvis
–
– Insufficient coverage of the presacral region
–
– Unnecessary extension of the CTV into the sacral hollows
C. W. Williamson and L. K. Mell](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-267-320.jpg)
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21.5
Organs at Risk
• Standard organs at risk (OARs) include the bowel, rectum, bone marrow, blad-
der, and femoral heads. Recommended dose constraints for these structures are
outlined in Table 21.2.
Table 21.2 Organ at risk definition (per NRG-GY006 protocol) [16]
OAR Description Dose constraints
All patients
Dosimetric
parameter
Per
protocol
Variation
acceptable
Bowel
space
Bowel space should be contoured
beginning from the axial slice 1cm above
the superior-most slice containing PTV (if
not present at this level, then beginning
from its most superior extent) and
extending to its most inferior extent in the
pelvis. The distal descending colon and
sigmoid colon should not be included. The
volume should include the outermost
extent of bowel loops plus any space
within the abdominal cavity the bowel may
occupy. Individual loops of bowel should
not be separately contoured. Rectum
should be contoured separately (next row)
V45 (cc)
DMax (Gy)
D30% (Gy)
≤200
≤59.4
≤40
≤250
≤62.1
≤50
Rectum The outer rectal wall should be contoured
and filled in and treated as a solid
continuous structure, spanning the level
of the sigmoid flexure to the anus
D50% (Gy)
D60% (Gy)
DMax (Gy)
≤45
≤30
≤50
≤54
≤50
≤55
Bone
marrow
The outer bone contour should be
delineated and filled in, treated as a solid
continuous structure. The os coxae, L4 and
L5 vertebral bodies, entire sacrum,
acetabulae, and proximal femora should be
included. The inferior-most extent should
be the level of the ischial tuberosities
Dmean (Gy)
V10 (%)
V20 (%)
≤27
≤85.5
≤66
≤29
≤90
≤75
Bladder The outer wall of the entire bladder
should be contoured and filled in, treating
the organ as a solid continuous structure
D50% (Gy)
DMax (Gy)
≤45
≤50
≤55
≤57.5
Femoral
heads
The outer contours of bilateral femoral
heads should be delineated and filled in,
treated as solid continuous structures, not
including the femoral necks
D15% (Gy)
DMax (Gy)
≤30
≤50
≤50
≤55
Extended field patients [17]
Bilateral
kidney
The outer organ contour of each kidney
should be delineated and filled in, treated
as a solid continuous structure
D50% (Gy) ≤18 ≤20
Spinal cord Should be contoured from T10/T11 to the
L1/L2 interspace
D0.03cc (Gy) ≤45 ≤47.5
Duodenum Should be contoured from the outer
border and filled in from the distal
stomach to the jejunum
D0.03cc
D50% (Gy)
≤56
≤40
≤60
≤50
Liver Should be contoured from the outer
border and filled in
D50% (Gy) ≤25 ≤30
21 Definitive Therapy for Cervical, Vaginal, and Endometrial Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-268-320.jpg)
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Fig. 21.1 Organs at risk for pelvic IMRT: Representative slices from a patient with FIGO IIIC2
cervical cancer (starting superiorly from the L2/L3 interspace). Contoured are the bladder (yellow),
rectum (light green), sigmoid (light brown), bone marrow (pink), bowel space (orange), left kidney
(blue), right kidney (green), left formal head (blue), right femoral head (green), spinal canal (orange)
• Figure 21.1 shows representative axial CT slices with OARs contoured for a
patient with FIGO IIIC2 cervical cancer treated with extended field RT.
• Normal tissue complication probability (NTCP) modeling studies have estab-
lished validated dose constraints for bowel [25] and bone marrow [26] in cervical
cancer patients undergoing chemoradiotherapy.
• IMRT has been shown to reduce GI toxicity [10, 11] and hematologic toxicity
[11], and may improve patient-reported GI and urinary toxicity.
C. W. Williamson and L. K. Mell](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-269-320.jpg)
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• PET/CT can be used to segment active subregions of bone marrow, where dose
accumulation has been correlated with higher rates of hematologic toxicity [27].
Moreover, this approach can reduce the overall bone and bone marrow dose [28].
Sparing metabolically active marrow with IMRT has been found to reduce neu-
tropenia and improve chemotherapy tolerance in prospective clinical trials
[11, 29].
21.6 Plan Assessment
• Ideally, at least 95% of the PTV should receive 100% of the prescription
dose, and ≥99% of the PTV should receive at least 90% of the prescrip-
tion dose.
• The dose maximum should occur within the PTV and dose areas 100% of the
prescription dose outside of the PTV should be minimized.
• Knowledge-based planning workflows are useful to help achieve optimal
dosimetry for more complicated IMRT plans in patients with cervical can-
cer [30].
21.7 Image-Guided Treatment Delivery
• Patients treated with conventional beam arrangements should undergo at least
weekly imaging with MV ports.
• Daily bony imaging with kV or cone beam CT (CBCT) can facilitate reduction
of planning margins to 5 mm around the nodal CTV [31, 32].
• Patients treated with IMRT should undergo image guidance with at least weekly
CBCT. CBCT with each fraction is recommended, whenever feasible, to check
for large variation in target position due to changes in rectal or bladder filling or
uterine motion.
21.8 Cervical Cancer
• Regional lymphatic spread typically follows a stepwise pattern by spreading to
pelvic nodes before para-aortic nodes. The cervix drains the paracervical lymph
nodes which in turn drain into the obturator, internal iliac, and external iliac
basins, followed by common iliac and para-aortic nodes.
• Patients with lesions involving the distal vagina are at risk for inguinal nodal
metastases.
• Delineated target volumes include a GTV and multiple clinical target volumes
(CTVs). See Table 21.1 for detailed descriptions of these volumes.
21 Definitive Therapy for Cervical, Vaginal, and Endometrial Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-270-320.jpg)
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• If para-aortic nodes are involved, an extended field technique should be employed
by extending the cranial border of CTV superiorly to the L1/L2 interspace or
3 cm cranial to the superior-most involved node.
• PTVs are created for each CTV and the final PTV used for treatment planning is
the combination of all PTVs. Different CTV-PTV expansions are used for each
CTV component based on its degree of internal organ motion and setup uncer-
tainty (29), which have been validated in a separate cohort [30]. Figure 21.1
shows representative axial CT slices for a patient with FIGO IIIC2 disease.
• A typical dose prescription is 45 Gy in 25 fractions to the node-negative pelvis,
or 47.6 Gy in 28 fractions if there is nodal disease, with a simultaneous inte-
grated boost (SIB) to involved nodes to 59.4 Gy.
• The nodal boost dose and/or dose per fraction may need to be reduced to respect
bowel tolerance; note there are acceptable variations in dose prescription in
practice.
• A parametrial boost may be added at the discretion of the treating physician for
parametrial involvement as long as that side is not to receive a SIB within the
parametrial boost field. Conventional AP/PA fields for a parametrial boost
include the sacroiliac joints (upper border), bottom of the obturator foramen
(lower border), and obturator internus muscle (lateral borders) with a 4–5 cm
midline block. A typical dose prescription is 6–10 Gy in 3–5 fractions.
• Brachytherapy boost is standard towards the end of or following the completion
of EBRT. See the following chapter for further discussion.
• Figure 21.2 shows sample slices from the CT simulation scan for a patient with
IB1 cervical cancer treated with pelvic IMRT.
• Figure 21.3 shows sample slices from the CT simulation scan for a patient with
IIIC2 cervical cancer treated with extended field IMRT.
C. W. Williamson and L. K. Mell](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-271-320.jpg)
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patients with non-bulky, distal, non-urethral disease. Definitive chemoradiation
therapy is a standard for stages II-IVA [33–35].
• The standard EBRT approach is pelvic RT with coverage of the entire vagina.
• Patients with disease involving the distal one-half of the vagina should receive
bilateral inguinal RT.
• Temporary fiducial markers can be used to delineate the vaginal apex and introi-
tus at the time of CT simulation.
• A typical EBRT dose prescription is 45 Gy in 25 fractions to the pelvis and entire
vagina, typically followed by a brachytherapy boost (e.g., 6 Gy × 4 fractions).
• Figure 21.4 shows sample slices from a CT simulation for a patient with stage
IVA (T4N0M0) squamous cell carcinoma of the distal posterior vagina with rec-
tal involvement, treated with pelvic IMRT.
Fig. 21.4 Representative slices from CT simulation scan for a patient with a stage IVA (T4N0M0)
squamous cell carcinoma of the distal posterior vagina with concern for rectal involvement.
Contours shown are CTV1 (light green), CTV2 (orange), and CTV3 (purple). The pelvis received
45 Gy in 25 fractions, followed by an HDR brachytherapy boost of 21.5 Gy in 3 fractions
21 Definitive Therapy for Cervical, Vaginal, and Endometrial Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-274-320.jpg)
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21.10 Endometrial Cancer
• The uterus is bordered anteriorly by the bladder and posteriorly by the rectum. It
is covered by peritoneal reflections and is divided into the fundus, isthmus,
and cervix.
• The uterine wall consists of an outer smooth muscle layer (the myometrium) and
an inner layer of glandular epithelium (endometrium).
• The uterus is supported by five ligaments: broad, round, cardinal, uterosacral,
and vesicouterine.
• Nodal areas at risk for uterine cancer patients include the obturator, external
iliac, internal iliac, common iliac, and para-aortic lymph nodes.
• Lesions involving the uterine fundus can spread directly to the para-aortic nodes.
• The incidence of pelvic and para-aortic lymph node involvement varies accord-
ing to risk categories (low, medium, and high), as well as tumor size and depth of
invasion, as defined in the Gynecologic Oncology Group (GOG) 33 trial [36]
• Hysterectomy is standard treatment for patients who are surgical candidates,
with consideration for adjuvant RT based on pathologic risk features.
• For medically inoperable patients, standard treatment is definitive RT with
brachytherapy, with or without EBRT. EBRT alone can be considered for patients
who are ineligible for or refuse brachytherapy [37–39]. Patients with recurrent
disease may also be candidates for EBRT.
• For patients to be treated with EBRT + brachytherapy, a standard EBRT dose is
45 Gy in 25 fractions.
• For patients treated with EBRT alone, pelvic RT can be followed by a cone-down
boost to the uterus and cervix. SBRT can be considered if the patient is unable to
receive brachytherapy.
• Target delineation is similar to pelvic RT for cervical cancer (Table 21.1).
–
– GTV includes all gross disease based on all available clinical and radio-
logic data.
–
– The CTV is divided into three subregions: CTV1, CTV2, and CTV3
a. CTV1: GTV + entire uterus
b. CTV2: paravaginal/parametrial tissues plus 3cm of the proximal vagina
c. CTV3: same as in the postoperative setting (see postoperative chapter)
–
– In patients with distal one-third vaginal involvement, the inguinal nodes
should be contoured continuously from the external iliac nodes to 2 cm cau-
dad to the saphenous/femoral function.
–
– If para-aortic nodes are involved, an extended field technique should be
employed by extending the cranial border of CTV3 in a similar fashion to that
described in Table 21.1.
–
– Each CTV should be expanded differentially to form PTV1, PTV2, and PTV3
(15 mm, 7–10 mm, and 5–7 mm margins, respectively).
• An additional boost of 5–15 Gy may be added for gross nodal disease or parame-
trial involvement, which may be done with an SIB or a sequential approach.
• Figure 21.5 shows a pre-treatment MRI from a patient with medically inoperable
FIGO stage IB endometrial cancer demonstrating deep myometrial invasion.
• Figure 21.6 shows sample slices from the CT simulation scan for the same
patient who was treated with definitive radiation therapy.
C. W. Williamson and L. K. Mell](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-275-320.jpg)
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22.1 General Principles
• All patients should undergo a complete history and physical examination includ-
ing a pelvic examination during initial diagnosis and staging. Standard radio-
graphic workup in these patients includes a contrast-enhanced computed
tomography (CT) scan, PET/CT and/or pelvic MRI to assess the extent of local
disease involvement and sites of metastatic spread.
• Brachytherapy treatment planning and delivery guidance is given by the
American Brachytherapy Society (ABS) [1] and GEC-ESTRO [2–4].
• Applicator choice should consider histopathologic diagnosis, tumor size, topog-
raphy, extension to nearby organs, and response to radiotherapy or chemoradio-
therapy when applicable.
• Brachytherapy is the standard central boost technique for cervical and uterine
cancer patients and other techniques including stereotactic body radiotherapy
(SBRT) are options only in the context of a clinical trial or in patients who refuse
brachytherapy.
• All patients should be counseled on long-term toxicities of brachytherapy and
use of a vaginal dilator if not having regular vaginal intercourse.
• Follow-up should be coordinated within a multidisciplinary team.
22.2 Cervical Cancer
• The use of brachytherapy in definitive treatment improves local control, disease-
free survival (DFS), and overall survival (OS) [5–7].
• Brachytherapy should be initiated Week 3–5 of external beam radiation (EBRT).
• Total treatment time should be 56 days or less.
• In the postoperative setting, patients with a positive vaginal margin should
receive brachytherapy following EBRT.
22.2.1
Initial Evaluation and Applicator Choice
• Full history and physical exam
• Labs: CBC, CMP (chemistry, LFTs, BUN, Cr)
• Radiographic studies:
–
– Contrast-enhanced CT chest/abdomen/pelvis at diagnosis
–
– Whole body PET/CT recommended at diagnosis
–
– Pelvic MRI (along with cystoscopy and/or sigmoidoscopy) at diagnosis if
concerns regarding bladder and/or rectal invasion
–
– Pelvic MRI recommended for brachytherapy planning in patients with larger
(4 cm) tumors
C. H. Feng and J. Mayadev](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-280-320.jpg)
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HR CTV
HR CTV
IR CTV
IR CTV
GTV GTV
Fig. 22.1 Suggested image-guided brachytherapy target volumes from the Groupe Européen de
Curiethérapie and the European Society for Radiotherapy Oncology (Haie-Meder et al. [2]).
HRCTV high-risk clinical target volume, IRCTV intermediate-risk clinical target volume, GTV
gross tumor volume. (Used with permission)
• If using CT for planning, target volumes often overestimate extent of disease.
• If using MRI for planning, definition of the GTV is possible.
For postoperative cervical cancer with a positive vaginal margin, the upper 1/3 of
the vagina should be treated.
22.2.4 Treatment Planning
• Common dose and fractionation schedules for intact cervical cancer are in
Table 22.2.
• Postoperative cervical cancer with positive vaginal margin is typically treated
with EBRT to 45 Gy in 25 fractions followed by vaginal cuff brachytherapy to
15 Gy in 3 fractions dosed to the surface of the upper vagina.
• Planning dosimetry goals are in Table 22.3.
C. H. Feng and J. Mayadev](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-282-320.jpg)
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Table 22.3 Cervical cancer brachytherapy target volume and OAR goals
Structure
Dosimetric
parameter
Ideal Goal EQD23
(Gy)
Maximum constraint EQD23
(Gy)
HRCTV
(EQD210)
D90% (Gy) ≥80 –
Bladder D2cc (Gy) ≤80 ≤90
Rectum D2cc (Gy) ≤65 ≤75
Sigmoid D2cc (Gy) ≤70 ≤75
22.3 Endometrial Cancer
• Brachytherapy can be used in the postoperative adjuvant, recurrent, and medi-
cally inoperable settings for uterine cancer.
• Upfront surgery is standard for patients who have operable endometrial cancer.
• Lymph node assessment should be considered in patients with FIGO grade 2–3
disease, 2 cm gross disease intraoperative, and/or 50% myometrial invasion.
22.3.1 Postoperative Adjuvant Treatment
• Adjuvant radiation therapy reduces risk of local recurrence in patients with
adverse pathologic features including high-grade disease, deep myometrial inva-
sion, cervical stromal extension, LVSI, and regional lymph node involve-
ment [8–12].
• Treatment recommendations for adjuvant therapy are in Table 22.4.
• Vaginal brachytherapy should commence within 12 weeks of surgery, only after
pelvic exam to assess for cuff healing.
• Vaginal brachytherapy boost following EBRT should commence within 2 weeks
of finishing EBRT.
22.3.1.1
Initial Evaluation and Applicator Choice
• Full history and physical exam
• Labs: CBC, CMP (chemistry, LFTs, BUN, Cr)
• Radiographic studies:
–
– Clinical stage I patients do not require routine imaging workup
–
– Contrast-enhanced CT chest/abdomen/pelvis for patients with locally
advanced disease
22.3.1.2 Implant Evaluation
• Thin-slice CT with applicator for 3D treatment planning.
• Vaginal cylinder should be largest diameter tolerated by patient.
• Verify applicator is flush with apex of the vaginal cuff and achieves mucosal
contact.
• Verify vaginal length.
C. H. Feng and J. Mayadev](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-284-320.jpg)
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–
– Reduced-dose EBRT: 30.6–36 Gy in 17–20 fractions.
–
– Consider boosting gross disease with EBRT or SBRT depending on normal
tissue tolerance and prior dose.
22.4 Vaginal Cancer
• Brachytherapy as a part of definitive organ-preserving treatment improves over-
all survival [13].
• Definitive radiation is the preferred approach for patients with Stage I disease,
with surgery as an option in select non-bulky stage I patients with distal non-
urethral disease.
• Definitive chemoradiation is the preferred approach for stage II-IVA.
22.4.1
Initial Evaluation and Applicator Choice
• Full history and physical exam.
• Labs: CBC, CMP (chemistry, LFTs, BUN, Cr).
• Radiographic studies:
–
– Contrast-enhanced CT chest/abdomen/pelvis for initial staging
–
– Pelvic MRI (along with cystoscopy and/or sigmoidoscopy) at diagnosis if
concerns regarding bladder and/or rectal invasion
• Interstitial brachytherapy is the standard approach, with exception of very small
tumors with thickness ≤5 mm where intracavitary applicators may be considered.
• Transrectal US can help guide interstitial needle placement and avoid placing
needles into bowel.
• Perform digital rectal exam at conclusion of interstitial procedure to ensure no
catheters are perforating rectum.
22.4.2 Implant Evaluation
• Thin-slice CT or MRI with applicator for 3D treatment planning.
–
– Diluted contrast can be placed into bladder and rectosigmoid region to assist
with organ visualization.
• If using interstitial needles, review for tumor coverage and proximity to critical
structures, especially rectum and bowel.
22.4.3 Volume Delineation
• Pelvic MRI can help determine superior and paravaginal extent to disease.
• Target structures and OAR delineation for vaginal cancer are in Table 22.8.
• Vaginal target volumes depend on the extent of initial involvement, treatment
response, and presence of multifocal disease or discontinuous spread.
22 Image-Guided Brachytherapy](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-289-320.jpg)
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contemporary clinical trial protocols, due to reduced rates of morbidity and high
treatment efficacy in most published series compared to historical techniques.
Publication of consensus contouring guidelines has advanced the quality of treat-
ment delivery, and evolving treatment planning recommendations have helped stan-
dardize approaches across institutions.
23.2 General Principles
• The treatment of vulvar cancer consists of upfront surgery, typically radical vul-
vectomy or wide local excision in select patients with small well-lateralized
tumors. Most patients undergo lymph node evaluation with either inguinofemo-
ral dissection or sentinel lymph node biopsy, particularly those found to have
tumor invasion 3 mm, lymphovascular space invasion (LVSI) and/or high-grade
disease.
• Radiation therapy (RT) is typically delivered following surgery in patients with
high-risk features including LVSI, tumor invasion 5 mm, surgical margins
8 mm, microscopically positive margins, grade 3 disease, and/or positive lymph
nodes [1–3]. Data suggests smaller margins (e.g., 5 mm) may be used as indica-
tion for adjuvant therapy [4–6].
• Patients presenting with unresectable disease are candidates for preoperative RT
[7, 8]. At many centers, these patients also receive concomitant chemotherapy
[9–11]. Patients with unresectable locally advanced disease have high rates of
clinical and pathologic response to chemoradiation [12], which is an area of
active investigation in a recently completed prospective Phase II clinical trial [13].
• The standard RT approach in vulvar cancer patients consists of pelvic-inguinal
irradiation. Brachytherapy has a limited role in vulvar cancer patients, apart from
women with a positive vaginal margin or those with medically inoperable
disease.
23.3
IMRT for Vulvar Cancer
• Given the large volumes irradiated and the growing experience using intensity-
modulated RT (IMRT) in patients with gynecologic cancer, IMRT is receiving
increasing attention in the treatment of vulvar cancer. The recently completed
Gynecology Oncology Group (GOG) 0279 trial of definitive chemoradiation
in locally advanced disease mandates IMRT [13].
• Dosimetric and preliminary clinical studies have reported superior normal tissue
sparing and lower rates of acute and chronic toxicities in patients with vulvar
cancer receiving IMRT compared to those undergoing conventional approaches
[14–17]. Long-term outcome in these patients, however, remains limited.
• Consensus recommendations for contouring and treatment planning, including a
pictorial contouring atlas, have been published [18].
A. E. Garda et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-294-320.jpg)
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23.4 Simulation
• Patients with vulvar cancer undergoing IMRT should be simulated in the supine
position using a modest frog-leg position with customized immobilization of the
upper and lower body, with the goal of reducing skin folds.
• Since the patient’s vasculature serves as a surrogate for the lymph nodes, it is
helpful to perform an IV contrast-enhanced computed tomography (CT)
simulation.
• The anus should be marked with a fiducial marker at the time of simulation.
• To assist in delineation of the tumor, radiopaque wire is used to identify gross
disease or surgical scars.
• It is advisable to simulate all patients with 0.5–1 cm bolus placed over the vulva,
particularly in patients treated preoperatively or with gross disease. Bolus over
the groins should be considered in cases of clinically evident skin involvement.
• Simulation scans should be obtained with full and empty bladder and an internal
target volume (ITV) should be generated [19] for locally advanced cases, espe-
cially in those with vaginal, urethral, and/or anal involvement. If rectum is dis-
tended 3.5 cm at the time of simulation, simulation should be repeated after
bowel preparation.
23.5 Image Registration
• In patients undergoing preoperative or definitive radiotherapy, positron-emission
tomography (PET)-CT is helpful for delineation of the gross tumor vol-
ume (GTV).
• Gadolinium-enhanced pelvic MRI with and without vaginal gel is useful to help
delineate the full extent of primary tumor and evaluate relationship between
tumor and adjacent normal tissues.
23.6 Target Delineation
• Delineated target volumes in vulvar cancer patients include a gross tumor vol-
ume (GTV) (in preoperative or definitive setting) and two clinical target volumes
(CTV). CTV1 encompasses the GTV (if applicable), uninvolved vulvar tissue,
and adjacent soft tissues. CTV2 includes the pelvic and inguinofemoral lymph
nodes bilaterally. CTV3 includes boost volumes to either primary and/or nodal
disease. Each CTV is then expanded to create planning target volumes (PTVs).
• See Table 23.1 for a detailed description of target volumes.
• See Table 23.2 for a description of boost target volumes.
• See Figs. 23.1 and 23.2 for pictorial atlas of contours in the definitive and post-
operative setting, respectively.
23 Vulvar Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-295-320.jpg)
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Fig. 23.2 Postoperative radiotherapy. The patient had FIGO Stage IIIA vulvar cancer (preopera-
tive primary outlined in blue). She underwent wide local excision, dissection of grossly enlarged
left inguinal lymph node (preoperative node outlined in yellow), and bilateral sentinel lymph node
dissection at an outside institution. Final pathology showed a 4 cm moderately differentiated squa-
mous cell carcinoma with 0.4 cm depth of invasion without lymphovascular space invasion.
Pathologic margins were 7 mm. A 3 cm left non-sentinel inguinal lymph node was involved with-
out extranodal extension. Two right and one left sentinel lymph nodes were negative for malig-
nancy. She was treated with adjuvant IMRT and concurrent chemotherapy. Pelvic and right
inguinal-femoral lymph nodes (magenta) were treated to 45 Gy, vulva (cyan) was treated to 50 Gy,
and left inguinal-femoral lymph nodes (orange) were treated to 55 Gy, all in 25 fractions. PTV
expansions were all 5 mm due to the use of daily CBCT
• Figure 23.3 depicts contours from consensus guidelines [18] and indicates the
extent of variation in target delineation amongst clinicians with expertise in
IMRT. Note that a contouring atlas is available on the NRG Oncology web-
site [20].
A. E. Garda et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-298-320.jpg)
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a
b
Fig. 23.3 Consensus contour (yellow), modified consensus contour (red), and individual contours
from 14 different physicians for a locally advanced vulvar case (case 1) (a) and postoperative case
(case 2) (b). The modified consensus contour was retracted from the space between the vulva and
groin (white arrow) and skin surface (blue arrow) when it was believed to be at low risk. (From
Gaffney et al. [18], reproduced with permission)
23 Vulvar Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-299-320.jpg)
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23.7 Prescription Recommendations
• Table 23.3 provides suggested dose and fractionation schemes.
• A primary site boost is typically given sequentially with IMRT, direct electron
field, or interstitial brachytherapy, depending on response and location of disease.
• When using a sequential boost for definitive treatment, consider rescanning and
adjusting the target volume prior to starting the boost phase of treatment.
• Using IMRT, grossly involved lymph nodes can be boosted using a simultaneous
integrated boost (SIB). A common SIB scheme involves delivery of 45 Gy in 25
fractions to the pelvis, with 2.25 Gy per fraction to positive pelvic lymph nodes
(plus PTV margin) and 2.5 Gy per fraction to positive inguinal lymph nodes
(plus PTV margin).
Table 23.3 Suggested dose fractionation schemes
Radiotherapy
timing PTV1 PTV2 PTV3
Preoperative 45–50.4 Gy/25–28
fractions
45–50.4 Gy/25–28
fractions
57.6 Gy/32 fractions
[12]
Definitive 45–50.4 Gy/25–28
fractions
45–50.4 Gy/25–28
fractions
Primary:
59.4–70.2 Gy/33–39
fractions
Lymph nodesa
:
59.4–70.2 Gy/33–39
fractions
Adjuvant 45–50.4 Gy/25–28
fractionsb
45–50.4 Gy/25–28
fractions
Gross residual disease:
For ENE: 64–66 Gy/32–33
fractions
54–64 Gy/30–32
fractions
PTV planning target volume, ENE extranodal extension
a
If using simultaneous integrated boost to lymph nodes, use EQD2 dose equivalent in 25 fractions
b
Consider higher dose for close/positive margins or lymphovascular space invasion
A. E. Garda et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-300-320.jpg)
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Table 23.5 Normal tissue dose constraints for vulvar cancer radiotherapy
Critical structure Recommendationa
Small bowel Max ≤52 Gyb
≤30% to receive ≥40 Gy
195 cm3
to receive ≥45 Gy
Rectum ≤80% to receive ≥40 Gy
Anus ≤80% to receive ≥40 Gy, Max ≤65 Gyc
Bladder ≤35% to receive ≥45 Gy
Femoral heads ≤50% to receive ≥30 Gy
≤35% to receive ≥45 Gy
≤5% to receive ≥44 Gy
Bone marrow ≤37% to receive ≥40 Gy
≤90% to receive ≥10 Gy
≤80% to receive ≥20 Gy
PTV planning target volume
a
Based on constraints from RTOG 1203 [21] and RTOG 0529 [22], as recommended in consensus
guidelines [18], and currently in use at Mayo Clinic in Rochester, MN
b
Small bowel is given priority over coverage of the PTV (pelvic lymph node boost) volume
c
May not be met in case of tumors immediately adjacent to or involving the anus
23.9 Image-Guided Radiation Therapy
• Daily image guidance typically includes a combination of kV and/or CBCT
imaging. CBCT is preferred for daily localization and matching with soft tissue.
References
1. Gaffney DK, Du Bois A, Narayan K, et al. Patterns of care for radiotherapy in vulvar cancer: a
Gynecologic Cancer Intergroup study. Int J Gynecol Cancer. 2009;19(1):163–7.
2. Heaps JM, FuYS, Montz FJ, Hacker NF, Berek JS. Surgical-pathologic variables predictive of
local recurrence in squamous cell carcinoma of the vulva. Gynecol Oncol. 1990;38(3):309–14.
3. Homesley HD, Bundy BN, Sedlis A, Adcock L. Radiation therapy versus pelvic node resection
for carcinoma of the vulva with positive groin nodes. Obstet Gynecol. 1986;68(6):733–40.
4. Baiocchi G, Mantoan H, de Brot L, et al. How important is the pathological margin distance in
vulvar cancer? Eur J Surg Oncol. 2015;41(12):1653–8.
5. Nooij LS, van der Slot MA, Dekkers OM, et al. Tumour-free margins in vulvar squamous cell
carcinoma: does distance really matter? Eur J Cancer. 2016;65:139–49.
6. Chan JK, Sugiyama V, Pham H, et al. Margin distance and other clinico-pathologic prognostic
factors in vulvar carcinoma: a multivariate analysis. Gynecol Oncol. 2007;104(3):636–41.
7. Acosta AA, Given FT, Frazier AB, Cordoba RB, Luminari A. Preoperative radiation therapy
in the management of squamous cell carcinoma of the vulva: preliminary report. Am J Obstet
Gynecol. 1978;132(2):198–206.
8. Boronow RC. Combined therapy as an alternative to exenteration for locally advanced vulvo-
vaginal cancer: rationale and results. Cancer. 1982;49(6):1085–91.
A. E. Garda et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-302-320.jpg)
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• Daily image-guided IMRT (IG-IMRT) improves localization of the targets and
the organs at risk (OARs) and can enable more conformal treatment plans while
maintaining tumoricidal doses.
• Adaptive re-planning can account for changes in tumor and patient anatomy
throughout the treatment course to potentially further improve target coverage
and reduce dose to OARs.
• Bone marrow-sparing IMRT can reduce hematologic toxicity.
• SBRT can be used as a boost for definitive therapy for patients who are ineligible
for brachytherapy or who refuse brachytherapy. SBRT can also enable delivery
of high dose RT to previously irradiated areas or to localized areas of recurrence
or limited sites of metastasis.
• Proton therapy may reduce toxicity due primarily to rapid dose fall-off distal to
the target although high quality directly comparative data with conventional RT
and/or IMRT are limited.
24.2 Image Guidance
• IMRT allows for sophisticated and conformal treatment planning which can
reduce the volume of irradiated area. However, this requires accurate delineation
of target structures and OARs as well as appropriate management of organ
motion and setup uncertainty. Pelvic organs are in motion both during and
between treatment fractions.
• IG-IMRT has been associated with improvement in both hematologic and gastro-
intestinal toxicity compared to IMRT alone [1, 2]
–
– Daily on-board orthogonal kV images can be used to align bony anatomy at
the time of treatment to the initial positioning at computed tomography (CT)
simulation.
–
– Cone-beam CT (CBCT) can be acquired daily and allows for improved iden-
tification of rectal and bladder filling status in comparison to the time of simu-
lation. With application of a shape model-based planning target volume (PTV)
expansion strategy and image guidance with daily CBCT, target coverage
within the 95% isodose cloud is excellent [3].
–
– Figure 24.1 shows an example of pre-treatment daily CBCT identifying
changes in bladder and rectal filling resulting in movement of the uterine fun-
dus outside the PTV.
C. W. Williamson et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-305-320.jpg)
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Fig. 24.1 Comparison between patient anatomy and coverage of the planning target volume
(PTV, pink line) at the time of CT simulation (left column) and on cone-beam CT before one of the
patient’s daily treatments (right column). The patient received treatment for a FIGO 2009 IIB
cervical cancer with pelvic and para-aortic involvement. Changes in filling status of the bladder
and rectum resulted in a portion of the uterine fundus falling outside the PTV (white arrow)
24.3
Bone Marrow-Sparing IMRT
• IMRT can be used to spare bone marrow for patients undergoing pelvic RT and
has been shown to reduce hematologic toxicity [2, 4].
• A variety of approaches have been implemented
–
– PET/CT-based IG-IMRT can be used by contouring pelvic bones and defining
active bone marrow as regions within bones with standardized uptake volume
(SUV) greater than the mean SUV within bones, then applying dose con-
straints to the bone marrow [2, 5].
24 Advanced Technologies and Treatment Techniques for Gynecologic Malignancies](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-306-320.jpg)
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Pelvic bone marrow constraints, with hard constraints based on NTCP
modeling: [6]
• Soft constraint: mean ≤27 Gy, V10(%) ≤85.5%, V20(%) ≤66%
• Hard constraint: mean ≤29 Gy, V10(%) ≤90%, V20(%) ≤75%
Active bone marrow constraints:
• Soft constraint: mean ≤28.5 Gy, V10(%) ≤90%, V20(%) ≤70%
• Hard constraint: mean ≤30 Gy, V10(%) ≤90%, V20(%) ≤75%
–
– An atlas-based approach is also feasible and offers an advantage if PET/CT is
unavailable [5].
–
– Another option in the absence of PET/CT is to demarcate bone marrow as the
low-density regions within bones on the simulation CT and to then apply dose
constraints [4].
24.4 Adaptive Re-planning
• Adaptive re-planning can be subdivided into three major categories: offline
between treatment fractions, online immediately prior to a treatment fraction, or
in real-time during treatment delivery.
• Several adaptive strategies have been proposed and can be considered
–
– A “plan-of-the-day” technique which generates a patient-specific library of
treatment plans corresponding to different target volumes and organ motion,
with pre-treatment CBCT used to select the library plan most similar to the
target and OAR configuration each day.
–
– Scheduled re-planning can be done with weekly magnetic resonance imag-
ing (MRI).
–
– Deformable image registration can be used to model accumulated dose to
targets and OARs.
• Offline adaptive RT (ART)
–
– Offline ART, e.g., generating a new treatment plan between treatment frac-
tions, should be considered for patients who experience significant weight
loss or substantial change in target size.
–
– Repeat simulation may be required if re-planning cannot be performed on
imaging acquired in the treatment room.
–
– Deformable image registration can be utilized to create new plans based on
pre-treatment imaging and/or interim diagnostic imaging (e.g., MRI, positron
emission tomography (PET)/CT).
–
– Advanced treatment planning systems can allow for automated dose monitor-
ing and dose-volume metrics that can be reviewed offline to guide decision-
making regarding the need for re-planning.
• Online ART
–
– Variation in rectum and bladder filling can lead to both target and OAR dis-
placement that may not be captured on CT simulation.
–
– Emerging technologies allow for integration of iterative CBCT for dose cal-
culation and daily re-planning based on pre-treatment imaging [7] or for
MRI-based online re-planning [8].
C. W. Williamson et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-307-320.jpg)
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24.5 Proton Therapy
• Proton therapy takes advantage of a relatively gradual dose build-up and a sharp
dose fall-off distal to the target compared to photons.
• Protons may therefore allow for decreased dose to OARs, particularly distal to
incident treatment fields as well as decreased integral dose while preserving ade-
quate dose to the targets.
• Treatment of para-aortic nodes and re-irradiation are additional scenarios in
which proton therapy may present advantages over IMRT.
• Dosimetric and early clinical studies suggest improvement in dose to nearby
normal structures including bowel, bladder, and bone marrow with protons com-
pared to IMRT [9].
• Protons may also allow for improved ovarian sparing in pre-menopausal women,
e.g., sparing one ovary to a mean dose of 15 Gy [10].
• For definitive management, target dosing should be the same as with photon
therapy (accounting for an assumed relative biological effectiveness (RBE) of
1.1 for protons).
• See the definitive EBRT chapter for gross tumor volume (GTV) and clinical
target volume (CTV) delineation. PTVs are beam-specific based on range uncer-
tainty. Avoid beam arrangements that result in critical structures in the field distal
to the target. Figure 24.2 shows sample images from a patient treated with
intensity-
modulated proton therapy (IMPT).
• Proton therapy can be considered as a boost alternative for patients who are
unable to receive brachytherapy, as protons can have dosimetric advantages in
the bladder, bowel, femoral heads, and the rectum compared to VMAT. For
example, the boost CTV can be determined using MRI obtained after 3 weeks of
chemoradiation and a dose of 30 Gy/Gy equivalent in 5 fractions then adminis-
tered in lieu of brachytherapy [11].
• However, it should be noted that high quality prospective evidence is lacking at
present and the link between improved dosimetry and clinically meaningful reduc-
tion in toxicity and/or the ability to deliver intensified therapy remains unproven.
Fig. 24.2 Representative cross-sectional images of an intensity-modulated proton therapy (IMPT)
plan for a 39-year-old woman with FIGO 2009 IIB cervical cancer with involvement of pelvic
nodes. The patient had a history of active lupus nephritis leading to hemodialysis and she was
referred for proton therapy given concern for increased risk of radiation-induced bowel injury. The
pelvis received 39.6 Gy in 22 fractions and the gross nodal disease was boosted to a total of
51.6 Gy. She then received a brachytherapy boost of 30 Gy in 4 fractions. Dose is shown in color
wash with legend in absolute dose (bottom right)
24 Advanced Technologies and Treatment Techniques for Gynecologic Malignancies](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-308-320.jpg)
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24.6
Stereotactic Body Radiation Therapy (SBRT)
24.6.1 Cervical Cancer
• For patients with locoregionally advanced cervical cancer, standard of care is
daily fractionated EBRT with concurrent cisplatin-based chemotherapy followed
by a brachytherapy boost with a final 2 Gy equivalent dose (EQD2) dose to the
target of 80–95 Gy.
• SBRT is a specialized EBRT modality which allows for high doses to be deliv-
ered in 1–5 fractions. Target visualization, accurate tumor and OAR delineation,
and high-fidelity setup with image guidance are crucial.
• Lymph nodes can be boosted with SBRT [12].
• SBRT can also be considered in the setting of re-irradiation for recurrent disease
or for treating limited sites of metastasis [12–15].
• Some patients are not candidates for brachytherapy due to severe medical comor-
bidities and some patients refuse brachytherapy, especially patients at risk for
posttraumatic stress disorder [16].
• SBRT can allow for conformal delivery of a high dose boost
–
– However, a recent phase II trial investigating the use of SBRT (28 Gy in 4
fractions) as a replacement for brachytherapy closed prematurely due to con-
cern for higher than expected toxicity and lower than expected 2-year local
control, progression-free survival, and overall survival [17]. Brachytherapy
remains the standard of care for eligible patients.
–
– A five-fraction regimen (e.g., 27.5 Gy in 5 fractions) following 45 Gy to the
pelvis could also be considered for patients who will not receive brachyther-
apy, which results in an EQD2 of 80 Gy (α/β = 10). Figure 24.3 shows images
from a patient treated with an SBRT boost following EBRT.
Fig. 24.3 Representative images from a stereotactic body radiation therapy (SBRT) boost given
in lieu of brachytherapy for a 52-year-old woman with FIGO 2009 IB1 cervical cancer who was
not a surgical candidate and not a candidate for brachytherapy due to comorbidities. She received
external beam radiation to the pelvis to 45 Gy in 25 fractions followed by an SBRT boost of 30 Gy
in 5 fractions. Dose is shown in color wash with legend in absolute dose (bottom right). Fiducial
markers were placed prior to simulation (white arrow)
C. W. Williamson et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-309-320.jpg)
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• Determination of dose and fractionation should take into account target size,
prior RT to the area, and tolerance of nearby OARs. For a 5 fraction regimen,
dose per fraction is typically in the 4–8 Gy range [18, 19]. Fractions of 8–15 Gy
per fraction have also been reported [20, 21].
• Total EQD2 should be calculated for the treated area.
24.6.2 Endometrial Cancer
• SBRT has also been considered as an alternative modality for boost delivery in
the setting of postoperative endometrial cancer [22–24].
• Lymph nodes can also be boosted with SBRT as above.
• Re-irradiation or metastasis-directed SBRT can also be considered.
• A retrospective series of patients with recurrent, persistent, or oligometastatic
foci treated with a median 24 Gy (range 10–50) in a median of 4 (range 1–6)
fractions showed 1 year and 3 year local control rates of 80% and 68%, with
more favorable control in smaller tumors [25]. The rate of grade ≥2 toxicity was
4.3% with only one grade 3 event and no grade 4 or 5 toxicities.
References
1. LiangY, et al. Prospective study of functional bone marrow-sparing intensity modulated radia-
tion therapy with concurrent chemotherapy for pelvic malignancies. Int J Radiat Oncol Biol
Phys. 2013;85:406. https://doi.org/10.1016/j.ijrobp.2012.04.044.
2. Mell LK, et al. Bone marrow-sparing intensity modulated radiation therapy with concur-
rent cisplatin for stage IB-IVA cervical cancer: an international multicenter phase II clinical
trial (INTERTECC-2). Int J Radiat Oncol Biol Phys. 2017;97:536. https://doi.org/10.1016/j.
ijrobp.2016.11.027.
3. Williamson CW, et al. Prospective validation of a high dimensional shape model for organ
motion in intact cervical cancer. Int J Radiat Oncol. 2016;96:801–7.
4. Huang J, Gu F, Ji T, Zhao J, Li G. Pelvic bone marrow sparing intensity modulated radiother-
apy reduces the incidence of the hematologic toxicity of patients with cervical cancer receiving
concurrent chemoradiotherapy: a single-center prospective randomized controlled trial. Radiat
Oncol. 2020;15:180. https://doi.org/10.1186/s13014-020-01606-3.
5. Yusufaly T, et al. A multi-atlas approach for active bone marrow sparing radiation therapy:
implementation in the NRG-GY006 trial. Int J Radiat Oncol Biol Phys. 2020;108:1240–7.
6. Rose BS, et al. Normal tissue complication probability modeling of acute hematologic toxic-
ity in cervical cancer patients treated with chemoradiotherapy. Int J Radiat Oncol Biol Phys.
2011;79:800. https://doi.org/10.1016/j.ijrobp.2009.11.010.
7. Ahunbay EE, et al. Online adaptive replanning method for prostate radiotherapy. Int J Radiat
Oncol Biol Phys. 2010;77:1561. https://doi.org/10.1016/j.ijrobp.2009.10.013.
8. Visser J, et al. Dosimetric comparison of library of plans and online MRI-guided radiother-
apy of cervical cancer in the presence of intrafraction anatomical changes. Radiat Oncol.
2019;14:126.
24 Advanced Technologies and Treatment Techniques for Gynecologic Malignancies](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-310-320.jpg)
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26
Bladder Cancer
Ariel E. Marciscano and Marisa A. Kollmeier
Contents
26.1
General Principles of Planning and Target Delineation 325
26.2
Three-Dimensional Conformal Radiation Therapy (3D-CRT) 326
26.3
Intensity-Modulated Radiation Therapy (IMRT) 328
26.4
Simulation and Planning 331
26.5 MSKCC Guidelines 332
References 334
26.1
General Principles of Planning and Target Delineation
• Organ-preservation with bladder-sparing trimodality therapy (TMT) is a standard
definitive treatment option for node-negative, muscle-invasive bladder cancer
(MIBC). TMT involves maximal, and ideally complete, TURBT followed by con-
current chemoradiotherapy [1–3]. For node positive bladder cancer, systemic che-
motherapy is the mainstay of therapy; however, for patients with disease confined
to the pelvis/para-aortic nodes, chemoradiation is a reasonable therapeutic option.
• RTOG/NRG protocols have classically used three-dimensional conformal radia-
tion therapy (3D-CRT). Future NRG studies, including the phase III SWOG/
NRG 1806 study (NCT03775265), permit intensity-modulated radiation therapy
(IMRT) for concurrent chemoradiotherapy.
A. E. Marciscano
Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA
e-mail: arm7007@med.cornell.edu
M. A. Kollmeier (*)
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center,
New York, NY, USA
e-mail: kollmeim@mskcc.org
© Springer Nature Switzerland AG 2022
N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical
Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_26](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-323-320.jpg)
![326
• The use of IMRT is increasingly utilized to minimize dose to adjacent normal
tissue, especially bowel—particularly, when dose constraints cannot be achieved
with 3D-CRT-based planning. When using IMRT, it is essential to account for
organ motion which may be accomplished by image-guidance.
• There is no consensus on optimal field design [4, 5] (whole bladder +/− prostate,
partial bladder, elective nodal coverage) or dose/fractionation regimen (daily
fractionation [6], BID hyperfractionation [6, 7], hypofractionation [8]).
• Definitive treatment should include the use of radiosensitizing therapy for all
eligible patients.Various chemotherapy regimens [1, 6, 7] and hypoxia-modifying
agents [9] have been studied. In general, the most commonly used radiosensitiz-
ers are cisplatin, fluorouracil (5 FU)/mitomycin C, or gemcitabine.
• The use of adjuvant radiotherapy for high-risk bladder cancer following radical
cystectomy is under investigation [10, 11]. In general, this approach is most
appropriate for pT3, pN+, and/or positive surgical margins. Additionally, the use
of intraoperative radiation therapy may be appropriate for some cystectomy-
eligible patients with locally advanced disease who are anticipated to have a need
for adjuvant local therapy due to positive surgical margins.
• Organs at risk (OARs) include: small bowel, large bowel, rectum, and femo-
ral heads.
26.2
Three-Dimensional Conformal Radiation Therapy
(3D-CRT)
• Recent RTOG studies (0712, 0926) have included a small pelvic field (defined as
CTV4140) which includes the entire bladder, prostate and prostatic urethra (in men),
proximal urethra (in women), and regional lymphatics followed by a cone down to
a whole bladder field (defined as CTV6120) which includes the entire bladder and any
gross tumor volume. Protocol OAR constraints are displayed in Table 26.1.
• The small pelvic field is generally planned as a four-field box arrangement
(Table 26.2, Fig. 26.1).
• The whole bladder field is generally planned as a four-field box or parallel
opposed laterals (Table 26.2).
• A randomized study comparing standard whole-bladder radiation therapy versus
reduced high-dose volume radiation therapy (RHDVRT) reported no significant
reduction in late toxicity and non-inferiority of locoregional control with RHDVRT as
compared with whole-bladder radiation therapy [12].A two-phase sequential boost or
single-phase concomitant boost approach can be used for RHDVRT (Fig. 26.2).
Table 26.1 Doses constraints for 3D-CRT selective bladder preservation
RTOG 0712/0926 OAR constraints for 3D-CRT-based selective bladder preservation
Rectum V30Gy 50% (0712) or V55Gy 50% (0926)
V55Gy 10% (0712)
Femoral heads V50Gy 20% (0712)
Dmax 45 Gy (0712, 0926)
Small bowel D45Gy 300 cm3
A. E. Marciscano and M. A. Kollmeier](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-324-320.jpg)
![328
26.3
Intensity-Modulated Radiation Therapy (IMRT)
• Target volumes with IMRT are similar to 3D-CRTand include the whole bladder,
prostate, and prostatic urethra in men/proximal urethra in women with or without
nodal coverage.
• Daily bladder target motion variability introduces significant uncertainty that
must be accounted for with PTV margin, daily setup, and image-guidance.
• In addition to accounting for consistency in bladder filling volume, it is also criti-
cal to assess variability in adjacent organs at risk (OARs). The daily variation in
the positioning of the small/large bowel in the superior, anterior, and lateral
directions as well as the position of the large bowel/sigmoid and rectum in the
posterior and lateral orientations.
• IMRT offers a reduction in dose to OARs directly adjacent to the high-dose PTV,
including the small and large bowel.
• IMRT offers an opportunity to optimize sparing of normal bladder for partial
bladder/reduced volume irradiation and potentially permit dose-escalation to the
TURBT bed [13–15].
• Please see Table 26.3 for summary of target volumes for IMRT for bladder cancer.
• Please see clinical vignettes and IMRT-based treatment fields for patients with
localized MIBC including (1) initial pelvic field (Fig. 26.3) and sequential blad-
der boost (Fig. 26.4); or (2) bladder-only field (Fig. 26.5).
• Common conventional dose-fractionation prescriptions are: 64–66.6 Gy deliv-
ered in 32–37. Elective treatment of the regional nodes (including CTV bladder)
is generally 39.6–45 Gy delivered in 1.8 Gy fractions prior to sequential bladder
boost of 19.8–21.6 Gy in 1.8 Gy fractions.
Table 26.3 Field design for selective bladder preservation using intensity-modulated radiation
therapy (IMRT) planning
Initial pelvic
field
•
Designed to cover entire bladder and regional pelvic nodes as well as
prostate/prostatic urethra in men using four-field box arrangement
•
GTV = any gross disease and/or tumor bed as defined by fiducials or
post-TURBT imaging
•
CTV bladder = whole bladder (including GTV) + prostate/prostatic
urethra (men) or proximal urethra (women)
•
PTV bladder = CTV bladder + 1.5 cm
•
CTV pelvis = includes bilateral pelvic nodal regions (perivesical, internal
iliac, external iliac, presacral, distal common iliac)
•
PTV pelvis = CTV pelvis + 8–10 mm on vessels (corresponding to nodal
regions)
•
If electing to treat pelvic nodes combine PTV bladder + PTV pelvis to
create composite PTV for initial pelvic field
Bladder-boost
field
•
GTV/CTV bladder boost = any gross disease and/or tumor bed as
defined by fiducials or post-TURBT imaging
•
PTV bladder boost = CTV + 1 cm isotropic expansion
A. E. Marciscano and M. A. Kollmeier](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-326-320.jpg)
![331
26.4 Simulation and Planning
• CT-based simulation in supine position with appropriate pelvic immobilization
device is recommended.
• Reproducible bladder filling and verification with image-guidance is critical to
effective and safe delivery of IGRT for MIBC [16].
• Image-guidance may vary by institution. For the initial phase, daily KV imaging
matched to bone and at least weekly CBCTs to verify bladder position are per-
formed. For the boost phase, daily KV imaging matched to fiducials and/or
CBCT daily is appropriate. When fiducials are not present, daily CBCT is rec-
ommended for the boost phase.
e
c d
Fig. 26.5 (continued)
26 Bladder Cancer](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-329-320.jpg)
![332
26.5 MSKCC Guidelines
• At our institution, definitive trimodality therapy generally involves maximal
TURBT with bladder mapping and placement of gold fiducial markers placed at
the periphery of the TUR bed.
• Following TUR with fiducial placement, a CT-based simulation is performed
with empty bladder. The choice of an empty bladder is for both consistency and
reduction of the initial bladder target volume. Oral contrast is used to delineate
bowel. IV contrast for simulation purposes should be used with caution in patient
with compromised renal function or those planned for nephrotoxic
chemotherapy.
• During Week 3–4 of concurrent chemoradiation, a CT-based re-simulation is
performed with full bladder in order to plan the cone down phase. The choice of
a full bladder is to displace bowel and uninvolved bladder walls from bladder
boost target.
• The prescription for the initial phase of treatment is 4500 cGy delivered in 25
daily fractions (180 cGy/fraction) and the targets for the initial phase of treat-
ment are: bladder (whole), prostate/prostatic urethra, regional pelvic nodes
(obturators/perivesical, external iliac, internal iliac, presacral, common iliac [to
aortic bifurcation]).
• The prescription for the cone down phase of treatment is 2160 cGy delivered 12
daily fractions (cumulative dose to PTV boost is 6660 cGy over 37 fractions).
The target for the cone down phase of treatment includes the TURBT bed as
defined by the fiducial markers with a 1 cm margin.
• In selected patients, hypofractionated regimens (55 Gy over 20 fractions) may be
used. Target volumes include the bladder/prostatic urethra and any gross tumor
with a 1.5 cm circumferential margin with daily CBCT for image-guidance.
Radiosensitizing chemotherapy is utilized when clinically appropriate. Selected
patients may include those with poor performance status or very elderly patients,
cystectomy-ineligible patients with multifocal disease, or palliation for locally
advanced disease.
• For node-positive patients, the initial phase may include a simultaneous inte-
grated boost (SIB) to dose-escalate gross adenopathy. Generally, a SIB dose of
5625 cGy delivered in 25 daily fractions (225 cGy/fraction) to gross nodal dis-
ease (PTV = GTV + 5 mm margin) respecting normal tissue tolerance is appro-
priate. See Figs. 26.6 and 26.7 for case example of locally advanced node positive
bladder cancer.
A. E. Marciscano and M. A. Kollmeier](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-330-320.jpg)
![337
27
Testicular Seminoma
Brandon S. Imber, Daniel Gorovets, Sean M. McBride,
and Michael J. Zelefsky
Contents
27.1
General Principles of Planning and Target Delineation 337
References 343
27.1
General Principles of Planning and Target Delineation
• In almost all cases, initial management of testicular cancer involves a radical
inguinal orchiectomy. Post-operative management depends on histological sub-
type and extent of disease.
• Post-operative radiation is generally only considered for pure seminomas (most
common type of testicular germ cell tumor, highly radiosensitive) and rarely
considered for non-seminomatous germ cell tumors (less common, less
radiosensitive).
• Prior to any treatment, adequate workup should be performed to ensure pure
seminoma, including detailed history and physical exam, serum tumor markers
(AFP, β-hCG, and LDH), chemistry panel, testicular ultrasound, and CXR [1].
Following radical inguinal orchiectomy for a pure seminoma, serum tumor
markers should be repeated, and additional staging studies should be performed
B. S. Imber · D. Gorovets (*) · S. M. McBride · M. J. Zelefsky
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center,
New York, NY, USA
e-mail: imberb@mskcc.org; gorovetd@mskcc.org; mcbrides@mskcc.org;
zelefskm@mskcc.org
© Springer Nature Switzerland AG 2022
N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical
Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_27](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-334-320.jpg)
![338
including CT chest/abdomen/pelvis +/− brain MRI (if indicated). All patients
planned for testicular cancer treatment should be offered fertility evaluation and
sperm banking.
• Laterality of testicular seminoma and prior surgery influences pattern of
spread [2].
–
– Right sided seminoma tends to drain to the paracaval, precaval, and aortoca-
val nodes.
–
– Left sided seminoma tends to drain to the lateroaortic and preaortic nodes.
–
– Pelvic, external iliac or inguinal nodes may be at risk in patients with prior
scrotal or inguinal surgery [3].
• Patients with stage I pure seminoma have several options. Generally, post-
orchiectomy surveillance is strongly preferred. However, based on results from
MRC TE 10 [4] and TE18 [5], those patients with stage I seminoma who refuse
surveillance can receive adjuvant radiotherapy to para-aortic lymph nodes alone
(i.e., PA strip, see Table 27.1 and Fig. 27.1) to a dose of 20–25.5 Gy unless there
is prior inguinal or scrotal violation. Another non-inferior adjuvant option is 1–2
cycles of carboplatin [1, 8].
• Patients with stage II pure seminoma can be treated using a dogleg field (see
Table 27.2 and Figs. 27.2 and 27.3) to either 30 Gy (stage IIA) or 36 Gy (stage
IIB) [1]. Alternatively, primary chemotherapy can be used, typically consisting
of etoposide/cisplatin +/− bleomycin for 3–4 cycles.
• At our institution, standard radiation simulation parameters for testicular semi-
noma include a 2 mm slice thickness CT with the patient positioned supine with
arms up. An alpha cradle is used for immobilization. IV contrast is often used for
stage II patients to help delineate gross nodal disease. If the patient has a staging
Table 27.1 Suggested target volumes for stage I testicular seminoma
Target volume
Definition based on CT imaging
and vascular anatomy (see
Fig. 27.1)
Definition based on anatomic
landmarks
CTV •
Contour inferior vena cava and
aorta from 2 cm below top of
kidney superiorly down to the
bifurcation of iliac vessels
inferiorly
•
Superior border: top of T11
(Note: some sources recommend
top of T12) [6]
•
Expand IVC contour by 1.2 cm
and aorta contour by 1.9 cm
•
Inferior border: bottom of L5
•
Combine the two volumes and
then subtract off of bone,
muscle, and bowel
•
Lateral borders: edge of
transverse processes (typically
10 cm width); For left sided
seminoma: nodal mapping studies
suggest that it is optional to cover
the left renal hilum [7].
PTV [20–25.5 Gy
in 1.5–2.0 Gy per
fraction]
•
Expand the final CTV by
0.5 cm + 0.7 cm to block edge
See [6] for more detailed information
B. S. Imber et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-335-320.jpg)
![340
PET scan, this can also be fused with the simulation CT scan. The contralateral
intact testicle should be shielded with a clamshell.
• 3D-CRT is the standard treatment approach for seminoma with AP/PA fields
based on bony anatomic landmarks or vascular anatomy.A general description of
target volumes and margins is indicated in Tables 27.1 and 27.2. See [6] for more
detailed information.
• In the case of prior inguinal or scrotal surgery, the ipsilateral inguinal and iliac
regions should be included in the field. If there was penetration of the scrotum,
consider electron boost to the scrotum and scar.
Fig. 27.1 (continued)
B. S. Imber et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-337-320.jpg)
![341
Table 27.2 Suggested target volumes for stage II testicular seminoma
Target volume and
dosing
Definition based on CT imaging and
vascular anatomy (see Fig. 27.2)
Definition based on anatomic
landmarks
CTVinitial • Create CTVvessels: Same IVC/aorta
contours and expansions as per
Table 27.1. Next, contour
common iliac vessels, proximal
internal iliac vessels (until takeoff
of superior gluteal), and external
iliac vessels down to the upper
border of the acetabulum and
expand by 1.2 cm respecting
anatomic boundaries
•
Superior border: top of T11
(Note: some sources
recommend top of T12) [6]
• Create CTVnodes: Contour gross
nodal disease (GTV) and expand
by 0.8 cm respecting anatomic
boundaries
•
Inferior border: top of the
acetabulum (Note: some
sources recommend middle or
bottom of the obturator
foramen) [6]
• Combine CTVvessels and CTVnodes
to form CTVinitial
•
Lateral border: tips of
transverse processes of
lumbar vertebra (typically L3
with consideration of kidney
location) and extending to
cover lateral acetabular edge
at inferior extent of the field
PTVinitial [20–25.5 Gy
in 1.5–2.0 Gy per
fraction]
• Expand CTVinitial by
0.5 cm + 0.7 cm to block edge
•
For left sided seminoma:
nodal mapping studies suggest
that it is optional to cover the
left renal hilum [7]
PTVconedown [Boost
volume to receive
total of 30–36 Gy in
2 Gy per fraction]
(see Fig. 27.3)
• Expand CTVnodes by
0.5 cm + 0.7 cm to block edge
•
Ensure 2 cm margin on all
visible gross adenopathy
See [6] for more detailed information
27 Testicular Seminoma](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-338-320.jpg)
![348
• 3D-CRT with opposed lateral photon beams of energy 6 MV is used typically
with a multileaf collimator (MLC) block (Figs. 28.1 and 28.2).
• For hippocampal avoidance, inverse-planned IMRT relies on a planning CT scan
fused to a gadolinium contrast-enhanced MRI scan (using the three-dimensional
spoiled gradient sequence with axial slice thickness 1.25–1.5 mm to define the
hippocampal avoidance region) (Fig. 28.3) [1].
• Orthogonal films for setup verification are done weekly with MV imaging. Daily
kV is usually reserved for IMRT-based WBRT.
c d
a b
Fig. 28.1 Standard WBRT fields as described in Table 28.1 with lateral opposed beams rotated
slightly off-axis (RAO/LAO) to avoid divergence into the lenses. (a) Beam’s eye view showing
coverage of the cribriform plate (blue) with MLCs blocking the lenses (green), (b) mid-cranium
axial view illustrating coplanar anterior field edges, (c) axial view showing adequate coverage of
the cribriform plate and avoidance of the lenses, (d) axial view illustrating adequate coverage of
the temporal lobes. Note: the isocenter can also be placed midline at the level of the canthus, allow-
ing no beam divergence to the eyes or lenses
C. Marques et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-345-320.jpg)
![351
28.3
SRS: General Principles of Planning
and Target Delineation
• Clinical scenarios employing SRS include single-fraction and fractionated SRS
(2–5 fractions) for intact brain metastases and post-resection cavity (Table 28.3,
Figs. 28.4 and 28.5). Dose fractionation depends on target size or volume and
distance from critical structures (Table 28.4).
• Instruments include the frame-based or frameless cobalt-based Leksell Gamma
Knife®
or LINAC-based systems.
• Target volume delineation and treatment planning using a volumetric contrast-
enhanced T1-weighted MRI scan (1–2 mm slices) is preferred (or contrast-
enhanced CT scan if unable to tolerate MRI or patient has an incompatible
implanted device). A thin-slice CT is acquired and co-registered for LINAC-
based SRS.
• For LINAC-based SRS, daily imaging is required.
Table 28.3 Suggested SRS target volume delineation using two different methods [2, 3]
Target GTV CTV
Unresected brain
metastases
Contrast enhancing
lesion on T1-weighted
sequence MRI
GTV + 0 mm
Postoperative gross
total resection cavity
(method 1) [2]
n/a •
2 mm expansion margin around the
resection cavity borders visualized on
postcontrast MRI
Postoperative gross
total resection cavity
(method 2) [3]
n/a •
Entire contrast enhancing region, surgical
cavity, and surgical tract seen on
postoperative MRI
•
5–10 mm margin along the bone flap
beyond the initial region of preoperative
tumor contact (if initial tumor was in
contact with the dura)
•
1–5 mm margin along the bone flap (if
initial tumor was NOT in contact with
the dura)
•
1–5 mm margin along the venous sinus
(if initial tumor was in contact with a
venous sinus)
28 Brain Metastases](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-348-320.jpg)
![352
Fig. 28.4 Single-fraction SRS to a 24 mm left temporal lobe surgical cavity, after gross total
resection of a 33 mm metastasis from primary rectal cancer with preoperative dural contact but no
venous sinus contact. Method 1 shows the contours as described by Soltys et al. [2], CTV delinea-
tion (red) = MRI T1 post-gadolinium enhancement and surgical cavity (blue) + 2 mm uniform
expansion margin. Method 2 shows the contours as described by Soliman et al. [3], CTV delinea-
tion (red) = MRI T1 post-gadolinium enhancement, surgical cavity, and surgical tract
(blue) + 10 mm margin along the bone flap. Single-fraction SRS was chosen due to the small cavity
size (3 cm) and sufficient distance from delicate brain structures. Patient was treated using
Leksell Gamma Knife®
by Elekta, hence PTV = CTV + 0 mm expansion margin. Contoured struc-
tures shown include the right optic nerve (yellow), left optic nerve (orange), and the brain-
stem (cyan)
C. Marques et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-349-320.jpg)
![353
Fig. 28.5 Multiple isocenter single-fraction SRS to new brain metastases from primary breast
cancer, ranging from 6 to 20 mm (volume ranging from 0.07 to 1.92 cm3
) in a patient who received
prior WBRT 30 Gy in 10 fractions. Lesion 1 is located in the right parietal lobe, lesion 2 in the left
parietal lobe, lesion 3 in the right temporal lobe, and lesion 4 in the left cerebellum. Single-fraction
treatment was chosen due to the smaller tumor sizes (less than 3 cm) and sufficient distance from
delicate brain structures. For all lesions, GTV delineation (red) = MRI T1 post-gadolinium
enhancement. Patient was treated using Leksell Gamma Knife®
by Elekta, hence PTV and CTV
used 0 mm expansion from GTV
Table 28.4 SRS dose and organ at risk constraints for different fractionation schemes (based on
Alliance A071801 trial) [4]
1 Fraction 3 Fractions 5 Fractions
PTV dose
(postop cavity)
20 Gy (4.2 cm3
) 27 Gy (30 cm3
) 30 Gy (≥30 cm3
to
5 cm)
18 Gy (≥4.2 to 8.0 cm3
)
17 Gy (≥8.0 to 14.4 cm3
)
15 Gy (≥14.4 to 20 cm3
)
14 Gy (≥20 to 30 cm3
)
12 Gy (≥30 cm3
to 5 cm)
PTV dose
(unresected
metastases)
24 Gy (1 cm) 27 Gy 30 Gy
22 Gy (≥1.0 to 2.0 cm)
18 Gy (≥2.0 to 3.0 cm)
15 Gy (≥3.0 to 4.0 cm)
Brainstem
constraint
V12 Gy 1 cm3
23.1 Gy max 28 Gy max
V18 Gy 0.5 cm3
V23 Gy 0.5 cm3
Optic apparatus
constraint
9 Gy max 17.4 Gy max 23 Gy max
V13.8 Gy 0.2 cm3
V20 Gy 0.2 cm3
28 Brain Metastases](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-350-320.jpg)
![392
31.1
General Principles of Tumor Volume Delineation
and Field Setup
• Delineation and field setup for radiation therapy (RT) for both Hodgkin (HL) and
non-Hodgkin lymphoma (NHL) depend on the origin of the disease, the quality
and patient positioning of pre-chemotherapy imaging, the use and response to
systemic chemotherapy, as well as the extent of disease.
• Extended-field radiation therapy (EFRT) was historically used as definitive man-
agement without chemotherapy. With combined modality therapy allowing for
reduction of treatment field size, involved-field radiation therapy (IFRT) then
became standard therapy to treat smaller fields resulting in lower doses delivered
to normal tissues compared to EFRT.
• With the most recent effective curative regimens despite shrinking radiation
fields, involved-site radiation therapy (ISRT) which further reduced volumes
based on 3-dimensional (3D) anatomy, focusing on the original extent of disease
with a margin to account for imaging limitations, has become the recommended
standard [1–3].
• ISRT has emerged over the past decade due to ongoing efforts to minimize late
effects of treatment and improve the quality of life of survivors [4].
• In practices where patients are seen by the radiation oncologist prior to diagnos-
tic imaging, involved-node radiation therapy (INRT) technique may be employed.
The principles of target volume delineation for INRT and ISRT are similar, with
differences in the quality and accuracy of pre-chemotherapy imaging suggesting
that the margins for ISRT should be larger to allow for uncertainties in contour-
ing the clinical target volume (CTV). INRT is the common approach in Europe
where optimal imaging is available, including a pre-chemotherapy PET-CT scan
acquired in the same position as the radiotherapy treatment positioning [5–8]. As
it is not yet a routine practice that optimal pre-treatment imaging is available,
ISRT is the standard practice in most healthcare systems in North America.
• Treatment doses to various subtypes of Hodgkin and non-Hodgkin lymphoma
differ based on their histology, stage, and response to chemotherapy and are
therefore out of the scope of this chapter on target volume selection/delineation
and field setup.
31.2
Principles of Involved-Site and Involved-Node
Radiation Therapy
• Below is a summary of published guidelines for defining INRT and ISRT treat-
ment volumes [1–3, 5].
A. D. Rao et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-388-320.jpg)
![393
• ISRT simulation must be based on a 3-dimensional simulation (CT simulator,
PET/CT simulator, or a magnetic resonance imaging simulator). If the patient’s
medical conditions permit, IV contrast should be used for accurate identification
of the vessels.
• When radiation therapy is performed as consolidation after chemotherapy, the
pre- and post-chemotherapy FDG-PET and CT should be ideally fused with the
simulation CT in the RT planning system.
• ISRT planning incorporates the standard definitions and nomenclature as out-
lined in the International Commission on Radiation Units and Measurements
(ICRU) Report 83, with consideration of whether radiation therapy is used as a
primary modality or as consolidation therapy [9].
• The gross tumor volume (GTV), CTV, internal target volume (ITV) when rele-
vant, and planning target volume (PTV) should be delineated as follows using all
the available imaging information including pre-chemotherapy imaging
(contrast-
enhanced CT and PET-CT as shown in the clinical examples discussed
throughout this chapter).
• Pre-chemotherapy GTV.
• Post-chemotherapy GTV.
• CTV: A volume encompassing the superior and inferior extent of the pre-
chemotherapy GTV with the radial extent respecting and avoiding overtly unin-
volved, normal structures (i.e. lungs, kidneys, muscles) based on clinical
judgment. The CTV should also take into account the differences in pre-
chemotherapy and post-chemotherapy imaging positioning and fusion accuracy,
pattern of spread of disease, changes in the volume of disease since imaging, risk
of subclinical involvement, and nearby structures. Typically, the superior and
inferior extent of the CTV often extends 1–2 cm beyond the pre-chemotherapy
GTV extent to account for these uncertainties. Nodal volumes that are more than
5 cm apart can be treated as separate fields.
• ITV: Target motion should be accounted for using an ITV as defined in the ICRU
Report 83 as the CTV with a margin to consider organ motion for an individual
patient [9]. A 4D CT simulation can be useful to obtain the ITV margins. If
unavailable, 1.5 to 2 cm margins may be necessary in the chest or upper abdomen
where respiratory movement can be significant.
• PTV: This margin should account for uncertainty in setup based on patient fac-
tors or immobilization that varies across institutions.
• The CTV for ISRT will generally be larger than that for INRT due to the lack of
optimal imaging information.
31 Hodgkin and Non-Hodgkin Lymphoma](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-389-320.jpg)
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• Radiotherapy may be used as a single modality for definitive treatment of certain
indolent, early-stage NHLs, and early-stage nodular lymphocyte-predominant
HL. In these scenarios, the CTV should be more generous given the concern of a
larger extent of subclinical disease without pre-treatment with chemother-
apy [1–3].
• For a reference of historical IFRT field borders, please refer to the chapter on HL
and NHL in the previous edition of this handbook [10].
31.3
Case-Based Examples for Target Delineation
• Early-stage Hodgkin lymphoma (Fig. 31.1).
• Advanced-stage Hodgkin lymphoma (Fig. 31.2).
• Nodular lymphocyte-predominant Hodgkin lymphoma (Fig. 31.3).
• Early-stage Diffuse Large B-cell Lymphoma of the Head and Neck (Fig. 31.4).
• Follicular lymphoma of the groin (Fig. 31.5).
Fig. 31.1 A 27-year-old male with Stage IIA, non-bulky, favorable-risk, nodular sclerosing
Hodgkin lymphoma involving the left supraclavicular and mediastinal lymph node regions was
treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A post-
chemotherapy PET demonstrated a complete metabolic response (Deauville 2). Since he met cri-
teria for the German Hodgkin Study Group H10, he was treated with 20 Gy of radiation therapy
following completion of 2 cycles of ABVD. For target delineation, the pre-chemotherapy PET/CT
was registered to the simulation CT. For target delineation, the pre-chemotherapy PET/CT was
registered to the simulation CT. (a) Axial slices from cranial to caudal extent of his disease on
pre-
chemotherapy PET/CT with gross disease (pre-chemo GTV) contoured in red. (b)
Corresponding axial slices in his post-chemotherapy simulation CT demonstrate the slight change
in anatomy between scans due to the different arm positioning, hyperextended neck, and five-point
mask retracting his shoulders at the time of simulation, differences that are accounted for by an
ISRT contouring approach. The small volume post-
chemotherapy residual disease (post-chemo
GTV) is shown in pink and the ISRT CTV in green. This patient was treated with a breath-hold
technique, so there is no expansion on the CTV to account for respiratory motion. Radiation ther-
apy was prescribed to the CTV plus an institutionally specified PTV margin
A. D. Rao et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-390-320.jpg)
![418
• In the treatment of both EWS and RMS, the conventional treatment algorithm
includes a combination of systemic chemotherapy and local therapy. Local ther-
apy can include surgical resection and/or radiotherapy.
• For unresectable EWS and RMS, radiotherapy alone is generally used for defini-
tive local management, while radiotherapy can be delivered postoperatively in
certain high-risk settings for both EWS and RMS.
• EWS and RMS, like many sarcomas, can occur in virtually any anatomic loca-
tion in the body. This precludes in-depth discussion for the purposes of this chap-
ter regarding nuances of each specific anatomic location where these sarcomas
may arise.
• However, it is noteworthy that EWS most commonly occurs in the pelvis (25%
of cases) followed by the femur (16% of cases). Patients with pelvic tumors are
typically not amenable to resection and often dispositioned to definitive radio-
therapy for local management of these tumors.
• RMS has a wide distribution across anatomic primary sites in the body, most
commonly in the head-and-neck (35%), followed by genitourinary system
(20%), and then extremity (20%). Primary tumor location of RMS is dichoto-
mized into favorable and unfavorable sites, which directly impacts staging, risk
stratification, and treatment algorithms for RMS patients. Within the head-and-
neck lesions, tumors are classified as being parameningeal (15% of all RMS
cases), orbital (10%), or other head-and-neck locations (10%). Parameningeal
lesions, which occur in one of the eight specific sites (middle ear, mastoid, nasal
cavity, nasopharynx, infratemporal fossa, pterygopalatine fossa, paranasal
sinuses, and parapharyngeal space [commonly abbreviated with the mnemonic
“MMNNOOPP”]), have increased risk of direct extension into the central ner-
vous system and are classified as unfavorable primary site tumors.
• Generally, in considering local patterns of spread, uninvolved bone and intraos-
seous membranes provide anatomic boundaries for microscopic spread. That
said, tumor erosion and invasion of bone are not uncommon and should be evalu-
ated on imaging (primarily CT-based imaging for assessment of bone).
• As both EWS and RMS are often treated with chemotherapy before radiother-
apy, post-chemotherapy volume reduction should be considered where pre-
treatment imaging demonstrates tumor “pushing” on nearby structures and
displacing them (especially lung, bladder, and bowel); post-chemotherapy imag-
ing in these settings generally shows that these anatomic structures return to a
more normal position after response to induction chemotherapy. In contrast,
direct invasion into surrounding structures (identified on pre-chemotherapy
imaging) should warrant at least some coverage with post-induction radiother-
apy fields.
• Nodal spread, while not commonly observed among most pediatric sarcomas, can
be seen among select RMS cases, often by anatomic primary site. Extremity RMS
has higher rates of nodal metastases and is often evaluated by sentinel node biopsy;
certain genitourinary RMS (particularly paratesticular) patients may under surgical
ipsilateral nerve-sparing retroperitoneal nodal dissection (generally reserved for
patients 10 years old). While discussion regarding elective nodal coverage is
ongoing in select contexts for RMS patients, elective nodal coverage is generally
E. B. Ludmir et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-414-320.jpg)
![419
not recommended for most RMS and EWS patients. However, when nodal metas-
tases are observed, it is recommended to ensure at least some radiotherapy cover-
age of the entire nodal basin (not only the involved node/s).
33.2
Diagnostic Imaging for Target Volume Definition
• A combination of diagnostic imaging techniques is helpful for both target vol-
ume definition (gross tumor volume [GTV] and clinical tumor volume [CTV]) as
well as staging.
• CT imaging is particularly helpful for outlining bony involvement/erosion, and
MRI provides excellent soft tissue delineation to assess extent of disease includ-
ing intracranial invasion. Both modalities are commonly utilized for both EWS
and RMS.
• PET imaging has increasingly been utilized for both RMS and EWS at time of
initial staging, with supporting literature for its adoption over other imaging
techniques (such as bone scans). It may be helpful in identifying initially involved
sites of disease pre-induction-chemotherapy.
33.3
Target Volume Delineation and Treatment Planning
• In the treatment of EWS, target volumes are generally split into two categories:
a volume defined by extent of disease at initiation presentation (GTV1, CTV1)
and a generally smaller volume defined by post-chemotherapy (and sometimes
post-surgery) residual disease (GTV2, CTV2). Additional margins added to the
CTVs for set-up uncertainty leads to resultant planning target volumes (PTVs).
Table 33.1 outlines general target volume definitions for EWS, while Table 33.2
provides suggested doses based on the Children’s Oncology Group (COG)
AEWS1031 protocol.
• RMS radiotherapy can be delivered as a single volume (dose-level) or as two
dose-levels similar to EWS; generally volume reductions for boost doses beyond
36 Gy in the treatment of RMS are recommended for “pushing” tumors into the
thoracic or pelvis (see similar discussion regarding EWS above). Full details
regarding this are presented in the ongoing COG ARST1431 protocol (for
intermediate-
risk RMS), but invasive RMS lesions may still require complete
coverage of the pre-chemotherapy volume with the maximum dose (often
50.4 Gy for gross disease), irrespective of response to chemotherapy. This is
particularly relevant for parameningeal head-and-neck RMS lesions, where the
GTV2 volume should generally include pre-chemotherapy extent of disease
regardless of induction chemotherapy response. For lesions “pushing” into sur-
rounding structures, cone-down beyond 36 Gy can be performed. Table 33.3 pro-
vides general guidelines for target volume definitions for RMS; see the ongoing
COG ARST1431 protocol for full details, which are beyond the scope of this
chapter.
33 Pediatric Sarcoma](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-415-320.jpg)
![421
• While the staging, grouping, and risk stratification of RMS are beyond the scope
of this chapter, it is noteworthy that conventional definitions of RMS histology
are shifting. Whereas previously RMS was broadly divided by the two most
common histologic subtypes, embryonal (lower risk) and alveolar (higher risk),
this is now shifting to a molecular definition of histologic risk. For ongoing COG
RMS protocols, molecular fusion status is being used instead of embryonal/alve-
olar histology. Patients with translocations involving FOX01 (chromosome 13)
are associated with higher-risk alveolar-histology natural histories; these fusions
typically include PAX3-FOX01 and PAX7-FOX01 translocations, represented by
t(2;13) and t(1;13), respectively. Data support fusion-negative alveolar-histology
RMS to behave similarly to embryonal-histology RMS. Table 33.4 outlines gen-
eral guidelines for RMS RT dosing.
Table 33.4 Rhabdomyosarcoma doses (all in doses of 1.8 Gy per daily fraction)
Group
Fusion status
(histology) Dose (Gy)
I (R0 resection) Negative
(embryonal)
0
I (R0 resection) Positive (alveolar) 36.0
II, node-negative (R1 [microscopic
residual])
Either 36.0 (to pre-
chemotherapy
disease)
II, node-positive (involved node, resected) Either 41.4 (to pre-
chemotherapy
site and nodal region)
III, non-orbital and orbital if incomplete
response after induction chemotherapy
Either 50.4*
III, orbital if complete response after
induction chemotherapy
Either 45.0**
Special considerations
III, per ongoing ARST1431 for tumors
5 cm in size pre-chemotherapy who do
not achieve complete response to
induction chemotherapy (protocol only)
Either 59.4*
III, per ongoing ARST1431 if radiographic
or biopsy-proven complete response at
week 9 after induction chemotherapy
Either 36.0***
Extremity RMS, N0 (clinical and
pathological), s/p amputation
Either (including
alveolar/
fusion-positive)
0
RMS rhabdomyosarcoma; N0 node-negative.*Per ongoing ARST1431, volume reduction can be
performed after 36.0 Gy, such that PTV1 receives 36.0 Gy, and PTV2 receives the cone-down dose
(either an additional 14.4 Gy or 23.4 Gy, depending on primary tumor size as above [5 cm cut-
off]).**Per ongoing ARST1431, group III disease with complete response (either radiographic or
biopsy-proven) at week 9 restaging (following induction chemotherapy) can be treated to a single
dose-level to 36.0 Gy to the PTV1, without further boost or cone-down. Therefore, orbital prima-
ries with week 9 complete response on ARST1431 may be treated to 36.0 Gy; see ARST1431
protocol for full details.***Per ongoing ARST1431, radiographic complete response by CT/MRI
as well as complete metabolic response by FDG-PET or biopsy-proven absence of residual disease
at week 9 restaging after induction chemotherapy allows for single dose-level treatment to 36.0 Gy
to PTV1; see ARST1431 protocol for full details
33 Pediatric Sarcoma](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-417-320.jpg)
![432
• Comprehensive staging is critical in determining treatment dose and volume. All
patients must undergo a comprehensive history and physical exam, a thin-cut
(1–3 mm slice thickness) contrast-enhanced MRI of the brain both pre- and post-
operatively, MRI of the spine with contrast, and CSF sampling to rule of
dissemination. Patients with positive CSF cytology, gross metastasis, or ≥1.5 cm2
of residual disease in the tumor bed on postoperative MRI are classified as hav-
ing high risk disease while those with no tumor spread (M0 disease) and 1.5 cm2
tumor bed residual are considered standard risk.
• CT simulation, with or without anesthesia depending on patient cooperativity,
should be done in a reproducible manner. This often consists of a full body Vac-
Lok or alpha cradle immobilization system in addition to a standard brain mask
with multiple markings for both triangulation and longitudinal spinal alignment.
Many CT software packages allow for variable CT slice thickness by region and
this can be helpful to allow thinner slices through the brain to allow detailed
contouring and thicker slices throughout the spine to limit the amount of con-
touring throughout the remainder of the body. The scan range should include all
immobilization devices, include the top of the head cranially, and capture the
gonads caudally.
• Careful discussion should take place between the radiation oncologist and the
anesthesiologist regarding anesthesia needs when making the mask. For exam-
ple, if a patient is intubated to start treatment but is anticipated to be treated with
a laryngeal mask airway (LMA) or even nasal cannula later in the treatment an
oral airway can be added to ensure reproducible chin position and avoid the need
to resimulate due to a loose mask.
• Careful delineation of target and organ as risk (OAR) volumes should be done on
every slice of the planning CT as seen in Figs. 34.1 and 34.2. The recommended
target volumes for the craniospinal axis, tumor bed involved field boost, and
whole posterior fossa boost are included in Tables 34.1 and 34.2.
• When using proton therapy to treat a growing child, some have recommended
treating the entire vertebral body to a dose up to 30 Gy when 36 Gy CSI is given
[1]. Many radiation oncologists include the bone in the PTV with no further
expansion to avoid intentionally giving dose to the esophagus and lungs
(Fig. 34.3). However, there is limited [2] and early data [3] that intentionally
covering the whole vertebral body may not be necessary and is the subject of an
ongoing clinical trials (ClinicalTrials.gov Identifier: NCT03281889).
• Care should be taken to identify the bottom of the thecal sac that is often, but not
always, at the S2 vertebral level. Treating more inferiorly than necessary may
increase exit dose to the gonads when using a single posterior photon field. This
is not a concern with proton treatment.
• There were increased failures on the 18 Gy craniospinal dose arm of Children’s
Oncology Group (COG) ACNS0331 and 23.4 Gy craniospinal irradiation
remains the standard of care for standard risk disease. This trial demonstrated the
equivalence of an involved field boost to whole posterior fossa irradiation in
patients with standard risk disease. Thus our recommendation is 23.4 Gy to the
entire craniospinal axis followed by an involved field boost to 54 Gy for standard
risk disease.
B. T. Cooper et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-427-320.jpg)
![440
34.3 Pure Germinoma
34.3.1
General Principles of Target Delineation and Radiation
Treatment Planning
• CT-based volumetric target delineation and planning are required regardless of
radiation therapy technique (3DCRT, IMRT, or proton therapy).
• All patients should undergo high quality (1–3 mm slice thickness) pre- and post-
operative MRI of the brain and total spine in addition to a detailed history and
physical.
• Unless medically contraindicated MRI of the spine and CSF cytology should be
obtained to rule out tumor dissemination though germinoma is less likely to dis-
seminate to the spinal axis at diagnosis when compared to medulloblastoma.
• Additionally, serum and CSF beta-human chorionic gonadotropin (β-hCG) and
alpha-fetoprotein (AFP) levels are done to rule out a non-germinomatous germ
cell tumor (NGGCT) component such as choriocarcinoma or endodermal
sinus tumor.
• Off protocol in North America, NGGCT is currently treated with CSI though
investigation into a more limited treatment field is ongoing [4].
• Patients with any elevation of AFP are treated as NGGCT.
• On ACNS 1123, the most recent COG trial for localized germ cell tumors, only
patients with serum or CSF β-hCG ≤ 100 mIU/mL were treated as germinoma
with patients with β-hCG 100 treated as NGGCT.
• Construction of a face mask in the supine treatment position with standard brain
triangulation marks is critical for setup reproducibility. If CSI is required for dis-
seminated disease, the immobilization will be similar to patients with medullo-
blastoma above.
• Patients with involvement of only the suprasellar and pineal regions (bifocal ger-
minoma) are treated as localized disease with the standard treatment approach of
whole ventricular irradiation followed by an involved field boost to initial gross
disease.
• The target volume includes the prechemotherapy tumor volume, any residual
disease and the ventricles. It is critical to outline the prechemotherapy disease at
initial treatment planning because this boost volume will often extend outside of
the normal ventricular volume.
• The boost CTV is prechemotherapy GTV + 1–1.5 cm.
• Inclusion of the prepontine cistern is optional but should be considered for
patients that have undergone a third ventriculostomy and for patients with large
suprasellar tumors (Figs. 34.8 and 34.9).
• A whole ventricular contouring atlas was generated for ACNS 1123 and can be
found at https://www.qarc.org/cog/ACNS1123_Atlas.pdf.
• If radiation is being used as the sole treatment modality the whole ventricular
volume is treated to 21–24 Gy with a boost to bring the total dose to the preche-
motherapy volume to 45 Gy. Given the good prognosis of this disease and the
B. T. Cooper et al.](https://image.slidesharecdn.com/targetvolumedelineationandfieldsetup-250112133857-b1f53424/85/Target-Volume-Delineation-and-Field-Setup-pdf-435-320.jpg)
Target Volume Delineation and Field Setup.pdf
- 1. Practical Guides in Radiation Oncology Series Editors: NancyY. Lee · Jiade J. Lu NancyY. Lee Jiade J. Lu YaoYu Editors TargetVolume Delineation and Field Setup A Practical Guide for Conformal and Intensity-Modulated Radiation Therapy SecondEdition
- 2. Practical Guides in Radiation Oncology Series Editors Nancy Y. Lee, Department of Radiation Oncology Memorial Sloan-Kettering Cancer Center New York, NY, USA Jiade J. Lu, Department of Radiation Oncology Shanghai Proton and Heavy Ion Center Shanghai, China
- 3. The series Practical Guides in Radiation Oncology is designed to assist radiation oncology residents and practicing radiation oncologists in the application of current techniques in radiation oncology and day-to-day management in clinical practice, i.e., treatment planning. Individual volumes offer clear guidance on contouring in different cancers and present treatment recommendations, including with regard to advanced options such as intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT). Each volume addresses one particular area of practice and is edited by experts with an outstanding international reputation. Readers will find the series to be an ideal source of up-to-date information on when to apply the various available technologies and how to perform safe treatment planning.
- 4. Nancy Y. Lee • Jiade J. Lu • Yao Yu Editors Target Volume Delineation and Field Setup A Practical Guide for Conformal and Intensity-Modulated Radiation Therapy Second Edition
- 5. Editors Nancy Y. Lee Department of Radiation Oncology Memorial Sloan Kettering Cancer Center New York, NY, USA Yao Yu Department of Radiation Oncology Memorial Sloan Kettering Cancer Center New York, NY, USA Jiade J. Lu Department of Radiation Oncology Shanghai Proton and Heavy Ion Center Shanghai, China ISSN 2522-5715 ISSN 2522-5723 (electronic) Practical Guides in Radiation Oncology ISBN 978-3-030-99589-8 ISBN 978-3-030-99590-4 (eBook) https://doi.org/10.1007/978-3-030-99590-4 © Springer Nature Switzerland AG 2022 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
- 6. v 1 Nasopharyngeal Carcinoma���������������������������������������������������������������������� 1 Irene Karam, Nancy Y. Lee, Quynh-Thu Le, Brian O’Sullivan, Jiade J. Lu, and Ian Poon 2 Oropharyngeal Carcinoma ���������������������������������������������������������������������� 15 Zain A. Husain, Jung Julie Kang, Nancy Y. Lee, and Ian Poon 3 Stereotactic Body Radiotherapy for Cancers of the Head and Neck Cancer������������������������������������������������������������������������������ 27 Dana Keilty, Irene Karam, Nancy Y. Lee, and Ian Poon 4 Larynx Cancer ������������������������������������������������������������������������������������������ 45 Dan Fan, Jung Julie Kang, Yao Yu, Oren Cahlon, Nadeem Riaz, and Nancy Y. Lee 5 Hypopharyngeal Carcinoma�������������������������������������������������������������������� 61 Linda Chen, Yao Yu, and Nancy Y. Lee 6 Oral Cavity Cancers���������������������������������������������������������������������������������� 75 Keith Unger, Matthew Forsthoefel, Nadeem Riaz, Allen Chen, and Nancy Y. Lee 7 Nasal Cavity and Paranasal Sinus Tumors���������������������������������������������� 87 Ming Fan, Yao Yu, Jung Julie Kang, and Nancy Y. Lee 8 Major Salivary Glands������������������������������������������������������������������������������ 99 Michelle S. F. Tseng, Ivan W. K. Tham, and Nancy Y. Lee 9 Thyroid Cancer������������������������������������������������������������������������������������������ 109 Kaveh Zakeri, Shyam S. D. Rao, Nadeem Riaz, Nancy Y. Lee, and Robert L. Foote 10 Squamous Cell Carcinoma of Unknown Primary in the Head and Neck ������������������������������������������������������������������������������������������ 121 Daniel Ma, Nadeem Riaz, Allen Chen, and Nancy Y. Lee 11 Early Breast Cancer���������������������������������������������������������������������������������� 129 Erin F. Gillespie, Brian Napolitano, and Shannon M. MacDonald Contents
- 7. vi 12 Regional Lymph Node Irradiation for Breast Cancer���������������������������� 137 Alice Y. Ho, Samantha A. Dunn, and Simon Powell 13 Lung Cancer���������������������������������������������������������������������������������������������� 147 N. Ari Wijetunga, Zhongxing Liao, and Daniel R. Gomez 14 Esophageal Cancer������������������������������������������������������������������������������������ 165 N. Ari Wijetunga, Daniel R. Gomez, and Abraham J. Wu 15 Gastric Cancer ������������������������������������������������������������������������������������������ 177 Jeremy Tey, Jiade J. Lu, and Ivy Ng 16 Pancreatic Cancer�������������������������������������������������������������������������������������� 197 Marsha Reyngold and Christopher Crane 17 Hepatocellular Carcinoma������������������������������������������������������������������������ 209 Yun Chiang, Laura A. Dawson, Sameh A. Hashem, and Jason Chia-Hsien Cheng 18 Rectal Cancer �������������������������������������������������������������������������������������������� 217 Jacob A. Miller, Jose G. Bazan, Erqi L. Pollom, Albert C. Koong, and Daniel T. Chang 19 Anal Cancer������������������������������������������������������������������������������������������������ 235 Jacob A. Miller, Jose G. Bazan, Erqi L. Pollom, Albert C. Koong, and Daniel T. Chang 20 Postoperative Therapy for Cervical, Vaginal, and Endometrial Cancer�������������������������������������������������������������������������� 251 Karen Tye, Loren K. Mell, and Dominique Rash 21 Definitive Therapy for Cervical, Vaginal, and Endometrial Cancer�������������������������������������������������������������������������� 263 Casey W. Williamson and Loren K. Mell 22 Image-Guided Brachytherapy������������������������������������������������������������������ 279 Christine H. Feng and Jyoti Mayadev 23 Vulvar Cancer�������������������������������������������������������������������������������������������� 293 Allison E. Garda, Loren K. Mell, and Ivy A. Petersen 24 Advanced Technologies and Treatment Techniques for Gynecologic Malignancies������������������������������������������������������������������ 305 Casey W. Williamson, Whitney Sumner, and Loren K. Mell 25 Prostate Adenocarcinoma�������������������������������������������������������������������������� 313 Daniel Gorovets, Brandon S. Imber, Neil Desai, and Michael J. Zelefsky 26 Bladder Cancer������������������������������������������������������������������������������������������ 325 Ariel E. Marciscano and Marisa A. Kollmeier Contents
- 8. vii 27 Testicular Seminoma���������������������������������������������������������������������������������� 337 Brandon S. Imber, Daniel Gorovets, Sean M. McBride, and Michael J. Zelefsky 28 Brain Metastases���������������������������������������������������������������������������������������� 345 Christophe Marques, Julie Jang, Fahad Momin, Michael Reilly, and Eric L. Chang 29 Benign Tumors of the CNS������������������������������������������������������������������������ 355 Rupesh Kotecha, Samuel T. Chao, Erin S. Murphy, and John H. Suh 30 Malignant Tumors of the CNS������������������������������������������������������������������ 375 Rupesh Kotecha, Samuel T. Chao, Erin S. Murphy, and John H. Suh 31 Hodgkin and Non-Hodgkin Lymphoma�������������������������������������������������� 391 Avani D. Rao, Harold C. Agbahiwe, and Stephanie A. Terezakis 32 Soft Tissue Sarcoma���������������������������������������������������������������������������������� 405 Charles Catton, Amy Parent, Colleen Dickie, and Brian O’Sullivan 33 Pediatric Sarcoma�������������������������������������������������������������������������������������� 417 Ethan B. Ludmir, Benjamin T. Cooper, and Arnold C. Paulino 34 Pediatric Brain Tumors ���������������������������������������������������������������������������� 431 Benjamin T. Cooper, Ethan B. Ludmir, and Arnold C. Paulino Contents
- 9. 1 1 Nasopharyngeal Carcinoma Irene Karam, Nancy Y. Lee, Quynh-Thu Le, Brian O’Sullivan, Jiade J. Lu, and Ian Poon Contents 1.1 General Principles of Planning and Target Delineation 2 Further Reading 13 I. Karam (*) · I. Poon Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada e-mail: irene.karam@sunnybrook.ca; ian.poon@sunnybrook.ca N. Y. Lee Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA e-mail: leen2@mskcc.org Q.-T. Le Department of Radiation Oncology, Stanford University, Stanford, CA, USA e-mail: qle@stanford.edu B. O’Sullivan Department of Radiation Oncology, Princes Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada e-mail: brian.osullivan@rmp.uhn.ca J. J. Lu Department of Radiation Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_1
- 10. 2 1.1 General Principles of Planning and Target Delineation • Both physical examination and imaging data are required for accurate delinea- tion of the primary tumor. A detailed endoscopic examination should be per- formed focusing on the anterior nasal space, nasopharynx, and oropharynx to describe the tumor extension and infiltration. • Unless there is a contraindication (i.e. pacemaker), patients should undergo a diagnostic contrast-enhanced MRI of the nasopharynx and neck fused to the planning CT scan. Ideally, the MRI should be acquired in the treatment position with the radiation therapy immobilization device. Marrow infiltration of disease is best seen on T1-weighted non-contrast MRI sequence. MRI is critical for delineation of skull base and perineural disease. • PET/CT should only be used as a guide for delineation of the primary site as it may underestimate or overestimate the true extent of disease, particularly at the skull base. • PET/CT scan is extremely helpful, particularly for identifying small lymph node metastases. Simulation should be performed in the supine position with the head and neck in the neutral position with a 5-point thermoplastic mask covering from skull with or without the shoulder. The CT simulation (preferably 2–3 mm slice thickness) scan should be acquired with IV contrast typically from vertex to 2 cm below the sternoclavicular joints. In centers that prefer to treat with a beam split technique with a low anterior neck AP or AP/PA fields (N0 patients), thicker slices can be obtained in the low neck. • EBER status should be obtained from tissue biopsies to assist in the discussion of prognosis. When possible, one can obtain EBV DNA in a CLIA or equivalent certified laboratory. • Target volumes include gross tumor volumes (GTV) and clinical target volumes (CTV). Accurate selection and delineation of the primary tumor CTV (i.e. CTV70) and subclinical region (CTV54–59.4) are of great importance when consid- ering tumor progression and ease of tumor spread along neural pathways and foramina in the IMRT era for NPC. For more dosing options, can refer to NRG HN001 clinical trial. See Tables 1.1 and 1.2. • Figures 1.1, 1.2, 1.3, 1.4, 1.5, and 1.6 demonstrate several examples of target delineation for different nasopharyngeal carcinoma cases. • For additional dosing options, can refer to NRG HN001 clinical trial or the inter- national consensus guidelines. Sequential no SIB techniques can also be done. The subclinical regional volume can receive 50–54 Gy with a sequential boost to the gross disease of 16–20 Gy to a total dose of 70 Gy. I. Karam et al.
- 11. 3 Table 1.1 Suggested clinical target volumes at the gross disease region Target volumes Definition and description GTV70 a Primary: All gross disease on physical examination and imaging. Pre- treatment imaging should be carefully scrutinized for invasion of the skull base and perineural spread Neck: All nodes ≥1 cm in short axis, with necrotic center; any FDG PET avid nodes; given high likelihood of nodal involvement, contour the lymph node in doubt as GTV CTV70 a Primary: CTV70p = GTV70p + 3–5 mm [Please note that, at the discretion of the treating radiation oncologist, when there is complete certainty of the GTV70p, then GTV70p can be equivalent to CTV70p without any margin. Therefore, in this situation, GTV70p is equivalent to CTV70p] A 0 mm margin is also acceptable if tumor is in close proximity to critical OARs (i.e. brainstem, spinal cord) If tumor is near the ipsilateral optic nerve, informed discussion of risks and benefits is required. The authors favor coverage of the tumor, sacrificing the ipsilateral optic apparatus, but strictly constraining the contralateral optic nerve and optic chiasm Neck: CTV70n = GTV70n + 3–5 mm For nodes that are small (i.e. ~1 cm), lower doses of 63–66 Gy may be considered at the discretion of the treating physician [Please note that, at the discretion of the treating radiation oncologist, when there is complete certainty of the GTV70n, then GTV70n can be equivalent to CTV70n without any margin. Therefore, in this situation, GTV70n is equivalent to CTV70n] PTV70 a Primary: PTV70p = CTV70p + 3–5 mm, depending on daily patient positioning and on treatment imaging. If PTV overlaps with critical OARs (brainstem, spinal cord, brain), compromise of PTV must be accepted Neck: PTV70n = CTV70n + 3 mm Please note that when the radiation oncologist is certain of the GTV70p or GTV70n, these can also be known as CTV70p or CTV70n. In other words, GTV70p = CTV70p (without margin) and GTV70n = CTV70n without margin A 5 mm margin can then be added to the CTV70p to name this PTV70p. But as stated above, when the target is near critical structures such as brain stem, chiasm, and spinal cord, the PTV margin can be 0 mm. A 3 mm margin can be added to the CTV70n to name this PTV70n a Suggested gross dose disease is 2–2.12 Gy/fraction to 69.96–70 Gy in 33–35 fractions 1 Nasopharyngeal Carcinoma
- 12. 4 Table 1.2 Suggested clinical target volumes at the high-risk subclinical region Target volumes Definition and description CTV56– 59.4 a Primary: CTV56–59.4p = GTV70p + 10 mm (when possible) + whole nasopharynx. In addition, ensure adequate coverage of soft palate inferiorly, posterior nasal cavity (at least 5 mm from choana), posterior maxillary sinuses (ensuring coverage of pterygopalatine fossae where V2 resides), posterior ethmoid sinus when indicated, skull base (foramen ovale, rotundum, lacerum), cavernous sinus to Meckel’s cave (if T3–T4; involved side only), pterygoid fossa/parapharyngeal spaces, sphenoid sinus (inferior half if T1–T2; whole if T3–T4), clivus (1/3 if no invasion; whole if invasion; when in doubt, whole clivus should be targeted) Importance of reviewing bone window while contouring on CT scan to ensure coverage of skull base foramina Neck: CTV54.12-56n = bilateral retropharyngeal nodes, levels IB, II, III, IV, and V Level IB can be omitted in the N0 neck Level IB can also be omitted in N+ neck at the discretion of the treating radiation oncologist after ensuring there are no suspicious IB lymph nodes Can consider omitting low neck for N0 neck PTV56– 59.4 a Primary: PTV56–59.4p = CTV56–59.4p + 3–5 mm, depending on daily patient positioning and on treatment imaging. When the target is near critical structures like brain stem, chiasm, and spinal cord, the PTV margin can be 0 mm Neck: PTV54.12-56n = CTV54.12-56n + 3 mm a High-risksubclinicaldose:for35fractions:1.6–1.7Gyperday;for33fractions:1.64–1.8Gyperday I. Karam et al.
- 13. 5 Fig. 1.1 A patient with T1N1 EBV positive nasopharyngeal carcinoma with right-sided level II and III nodes in a cranial to caudal direction. This patient was simulated with a planning MRI scan and PET/CT in the treatment position. Please note that these are representative slices and not all slices are included. The treating radiation oncologist can use the dosing according to institution or protocol guidelines CTV56p: Coverage of parapharyngeal space GTV70 CTV56 1 Nasopharyngeal Carcinoma
- 14. 6 CTV56n: Notice omission of contralateral level IB nodal region: At discretion of the treating radiation oncologist, can omit ipsilateral IB despite N+ Fig. 1.1 (continued) I. Karam et al.
- 15. 7 CTV56p: Coverage of foramen ovale. Because it is T1, at the discretion of the treating radiation oncologist, half of the skull base is covered. Fig. 1.1 (continued) CTV56p: Coverage of the posterior third of the maxillary sinus CTV56p: Coverage of the pterygopalatine fossa CTV56p: Coverage of 1/3 of the clivus as no invasion Fig. 1.2 Example of GTV and CTVs displayed on bone windows. The treating radiation oncologist can use the dosing according to institution or protocol guidelines 1 Nasopharyngeal Carcinoma
- 16. 8 Fig. 1.3 A patient with T4N2 EBV positive nasopharyngeal carcinoma. The treating radiation oncologist can use the dosing according to institution or protocol guidelines GTV70 CTV56 I. Karam et al.
- 17. 9 CTV56n: Importance to have posterior neck coverage of level V (trapezius muscle) Can consider coverage of the fat posterior to the clavicle. Fig. 1.3 (continued) 1 Nasopharyngeal Carcinoma
- 18. 10 CTV56p: Coverage of whole sphenoid sinus CTV56p: Coverage of foramen ovale CTV56p: Coverage of whole clivus CTV56p: Coverage of parapharyngeal fat CTV56p: Coverage of retrostyloid space RP node seen on MRI a b c Fig. 1.4 Example of GTV and CTVs displayed on: (a) soft tissue window and MRI T1 + GAD, (b) bone window and MRI T1 + GAD, (c) soft tissue window and MRI + T1 + GAD. The treating radiation oncologist can use the dosing according to institution or protocol guidelines I. Karam et al.
- 19. 11 PTV56 PTV70 Must accept PTV dose compromise posteriorly in areas near brainstem in order to achieve organ at risk tolerance (or the PTV margin can be 0 mm) PTV56 PTV70 Fig. 1.5 Example of the final 3-mm PTV images. The treating radiation oncologist can use the dosing according to institution or protocol guidelines 1 Nasopharyngeal Carcinoma
- 20. 12 CTV56p: Drop of GTV superiorly but CTV56p remains unchanged to cover microscopic disease. a b c d Fig. 1.6 Example of an adaptive nasopharyngeal plan. Patient with cT3N2 NPC who underwent mid-treatment adaptive replanning with MRI simulation showing shrinkage of disease superiorly allowing for reduction of the GTV away from the optic chiasm, and improvement in coverage: (a) Phase 1 GTV in red and CTV56p in blue on original CT sim and (b) Phase 1 MRI sim T1 post GAD, (c) Phase 2 GTV in red and CTV56p in blue on original CT sim, and (d) Phase 2 MRI sim T1 post GAD. The treating radiation oncologist can use the dosing according to institution or protocol guidelines I. Karam et al.
- 21. 13 Further Reading Lee N, Harris J, Garden AS, et al. Intensity-modulated radiation therapy with or without chemo- therapy for nasopharyngeal carcinoma: radiation therapy oncology group phase II trial 0225. J Clin Oncol. 2009;27(22):3684–90. Lee AW, Ng WT, Pan JJ, et al. International guideline for the delineation of the clinical target vol- umes (CTV) for nasopharyngeal carcinoma. Radiother Oncol. 2018;126(1):25–36. https://doi. org/10.1016/j.radonc.2017.10.032. NRG HN001 Clinical Trial Protocol. 1 Nasopharyngeal Carcinoma
- 22. 15 2 Oropharyngeal Carcinoma Zain A. Husain, Jung Julie Kang, Nancy Y. Lee, and Ian Poon Contents 2.1 Introduction 15 2.2 General Principles of Anatomy and Patterns of Spread 16 2.3 Diagnostic Workup Relevant for Target Delineation 16 2.4 Simulation and Daily Localization 17 2.5 Target Volume Delineation and Treatment Planning 17 2.5.1 Selected IMRT Dose and Fractionation Schemes 17 2.5.2 Suggested Target Volumes 18 References 25 2.1 Introduction Oropharyngeal carcinoma comprises primary tumors involving the tonsils, base of tongue, soft palate, or posterior pharyngeal wall. The vast majority of oropharyn- geal cancers are squamous cell carcinomas, most of which are associated with the human papillomavirus (HPV). HPV-unrelated cancers are commonly associated with tobacco or alcohol use. HPV-associated head and neck cancers have superior prognosis [1, 2]. Since the last edition of this book, the American Joint Committee Z. A. Husain (*) · I. Poon Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada e-mail: zain.husain@sunnybrook.ca; Ian.Poon@sunnybrook.ca J. J. Kang · N. Y. Lee Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA e-mail: kangj1@mskcc.org; leen2@mskcc.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_2
- 23. 16 on Cancer revised staging for oropharyngeal cancer, dividing it into two different systems for HPV-positive and HPV-negative oropharyngeal cancers. Given the prognostic importance of HPV status, viral testing should be performed in all oro- pharyngeal carcinoma patients. However, de-escalation of therapy based on HPV status should not be performed outside of a clinical trial [3–5]. In this chapter, we outline radiotherapy target delineations with careful consideration of microscopic mucosal spread of the primary tumor as well as knowledge of cervical nodal drain- age patterns. 2.2 General Principles of Anatomy and Patterns of Spread • The oropharynx is a cuboidal space bordered by the oral cavity anteriorly, the nasopharynx superiorly, and the larynx and hypopharynx inferiorly. • It consists of four subsites: the tonsils, base of tongue, soft palate, and the pha- ryngeal wall, with the majority of cases arising in the tonsils and tongue base. • The oropharynx is equipped with a rich lymphatic drainage and lymph nodes are commonly involved. 2.3 Diagnostic Workup Relevant for Target Delineation • Gross tumor volume delineation of the primary site is best identified by a combi- nation of imaging and physical examination. • The mucosal and superficial extents of disease are best accessed by visual inspec- tion, palpation, and fiberoptic endoscopic examination. Photographic documen- tation of disease at the time of consult or simulation is helpful in order to document mucosal extension of disease that may be poorly seen on imaging (Fig. 2.1). Fig. 2.1 Direct visualization helps demonstrate involvement of the soft palate and evidence of the tumor crossing midline Z. A. Husain et al.
- 24. 17 • While contrast-enhanced CT scans remain the mainstay of diagnostic imaging for this disease, both MRI and PET/CT have well-defined roles. – – T1-weighted pre-contrast MRI sequences are ideal for the evaluation of fat planes and bone marrow signals. – – T1-weighted contrast-enhanced MRI sequences may be critical for delinea- tion of the anterior extension of base of tongue tumors and for the assessment of perineural invasion. – – T2-weighted fat-saturated sequences offer utility for the evaluation of RP nodes and soft tissue extent in the parapharyngeal and pre-epiglottic spaces. – – FDG-PET provides metabolic information that complements both CT and MRI, and may identify tumor extent missed by CT or MRI. – – Limitations of FDG-PET include poor spatial resolution and low sensitivity for small-volume lymph node metastases. Thus, the absence of FDG uptake in an otherwise suspicious lymph node should not necessarily be considered reassuring. 2.4 Simulation and Daily Localization • The patient should be set up in the supine position with head rest with the neck extended. The customized immobilization device (5-point Aquaplast mask) should provide adequate head, neck, and shoulder immobilization. A bite-block and/or mouth guard may be inserted. Patients are instructed not to swallow dur- ing scans or during treatment. • CT simulation with IV contrast using ≤3 mm slice thickness encompassing the entire vertex of the skull down through the carina. • The isocenter is typically placed at the arytenoid cartilages. A low anterior con- ventional AP neck field can be matched to the IMRT fields. • MRI and PET images may be registered or fused to the CT simulation scan. The use of immobilization mask during PET scan improves the fusion accuracy, but the use of immobilization mask during the MRI may preclude the use of a dedi- cated head and neck coil. • At MSKCC, image guidance is achieved with daily linear accelerator-mounted 2D kV imaging and daily kV and conebeam CT. Conebeam CT can also be used weekly, with daily KV imaging as an alternative strategy. Alternative methods for image guidance may include orthogonal kV imaging (“ExacTrac”) or linear accelerator-mounted MV CT images (“TomoTherapy”). 2.5 Target Volume Delineation and Treatment Planning 2.5.1 Selected IMRT Dose and Fractionation Schemes • There are many different treatment approaches. At MSKCC, the preferred approach is a sequential technique. Total dose to the gross disease is 70 Gy. For 2 Oropharyngeal Carcinoma
- 25. 18 HPV related tumors, the subclinical regions receive 30 Gy in 2 Gy per fraction followed by a cone down to the gross disease receiving 40 Gy in 2 Gy per frac- tion. The subclinical region is scrutinized heavily to ensure no gross disease with MRI, CT with contrast, and PET/CT scans. Please refer to our publication, Tsai et al. [6]. For HPV unrelated disease, the initial phase is 60 Gy in 2 Gy per frac- tion to the gross disease while simultaneously treat 54 Gy in 1.8 Gy per fraction to all subclinical regions. This is followed by a cone down of 10 Gy in 2 Gy per fraction to the gross disease. If a low anterior neck AP field is matched to the IMRT fields, HPV related tumors receive 30 Gy in 2 Gy per fraction to the low neck while the HPV unrelated tumors receive 50 Gy in 2 Gy per fraction to the low neck. Reduced elective doses should only be considered when treating with concurrent cisplatin-based chemotherapy • Another commonly used radiation technique is the simultaneous integrated boost. Gross disease dose: 70 Gy (2 Gy/fx), high-risk subclinical dose: 56 Gy (1.6 Gy/ fx), and low-risk subclinical dose: 50–52.5 Gy (1.43–1.5 Gy/fx). This technique should only be considered when using concurrent chemotherapy. • Another fractionation schemes such as but not limited to RTOG 0022 [7] or RTOG 1016 [3]. 2.5.2 Suggested Target Volumes • Suggested target volumes for gross disease (Table 2.1) and for subclinical dis- ease (Table 2.2) are presented in the following. Table 2.1 Suggested target volumes for gross disease Target volumes Definition and description GTV70 Primary: All gross disease as defined by clinical exam and imaging Nodes: all suspicious (1 cm, necrotic, enhancing, or FDG-avid) lymph nodes. Borderline suspicious nodes can be given less than 70 Gy, i.e. 60–66 Gy for example CTV70 In areas of excellent visualization GTV70 can equal CTV70 (no added margin). In situations where there is uncertainty of tumor extent CTV70 = GTV70 + 3–5 mm PTV70 CTV70 + 3–5 mm depending on daily set up accuracy and the availability of image guidance Z. A. Husain et al.
- 26. 19 Table 2.2 Suggested target volumes for subclinical disease Target volumes Definition and description General guidelines As a useful guideline, the primary site CTV subclinical should encompass the GTV70 + 1 cm (shaved off of anatomic barriers to spread such as air, bone, and skin) Tonsil primary, CTVsubclinical Ensure adequate margin to the primary tumor ~1 cm. Highly recommend inclusion of pterygoid plates with advanced primary disease (Fig. 2.2). Consider inclusion of the ipsilateral retromolar trigone if tumor spread anterolaterally along the pharyngeal constrictor is suspected Base of tongue primary, CTVsubclinical Glossotonsillar sulcus, vallecula, and the pre-epiglottic space (Fig. 2.3). Ensure a mucosal margin of at least 1.0 cm around the base of tongue primary tumor; anteriorly, this may extend into the oral tongue. MRI is very helpful to ensure accurate delineation of anterior extension of the tumor (Figs. 2.4 and 2.5) Soft palate primary, CTVsubclinical Entire soft palate, superior aspect of tonsillar pillars + fossa, adjacent nasopharynx superiorly to the pterygoid plate. For advanced primaries, consider inclusion of the pterygopalatine fossa. If the pterygopalatine fossa is involved, assessment of the base of skull with MRI is required. Ensure adequate coverage anteriorly, which may require coverage of a portion of the hard palate Pharyngeal wall primary, CTVsubclinical Generous superior and inferior margins given the possibility of skip lesions. In patients with advanced primary tumors, consider extending CTV cranially to include the nasopharynx and caudally to include the hypopharynx Elective neck nodes, CTVsubclinical The nodal regions can be treated to microscopic doses of 54 Gy in 1.8 Gy fractions, 54.12 Gy in 1.64 Gy fractions, 56 Gy in 1.6 Gy fractions, or 59.4 Gy in 1.8 Gy fractions depending on whether these regions are high risk or low risk In node-negative cases, at risk areas include bilateral levels II-IV and lateral retropharyngeal nodes. At MSKCC, we do not routinely treat levels IB or V, unless grossly involved (Figs. 2.5 and 2.6). The exception would be with gross oral cavity extension of disease, in which case IB nodes may be considered at risk (Figs. 2.2 and 2.4) In node-positive cases, the retropharyngeal nodes and retrostyloid nodes should be covered superiorly to the skull base (Fig. 2.4). If there is gross involvement of low-lying nodes, consider coverage of the supraclavicular space (Fig. 2.5) For T1–2, N0–N1 well-lateralized tonsil cancers (at least 1 cm lateral from midline) with no extension to the base of tongue or soft palate, ipsilateral neck treatment is acceptable (Fig. 2.6). The superior extent of coverage for the node-negative neck may begin at the transverse process of C1 or when the posterior belly of the digastric just starts to cross over the internal jugular vein (Fig. 2.6) 2 Oropharyngeal Carcinoma
- 27. 20 Coverage to pterygoid plates Ipsilateral 1b coverage given oral tongue invasion = GTV Legend: = CTV Fig. 2.2 Representative axial slices from a contrast-enhanced CT simulation for a patient with HPV-negative cT4N2 squamous cell carcinoma of the left tonsil Z. A. Husain et al.
- 28. 21 Fig. 2.3 Coverage of the pre-epiglottic space in base of tongue tumors (GTV: blue, CTV: red) 2 Oropharyngeal Carcinoma
- 29. 22 Tumor crosses midline in oral tongue, can consider 1b coverage Coverage to skull base on node positive side = GTV Legend: = CTV Fig. 2.4 Representative axial slices from a contrast-enhanced CT simulation for a patient with P16-positive, HPV-associated cT4N1 squamous cell carcinoma of the left base of tongue Z. A. Husain et al.
- 30. 23 = GTV Legend: = CTV No coverage of Level 1b Generous margin anteriorly Coverage of pre-epiglottic space Note coverage of subclavicular space given low nodes Fig. 2.5 Representative axial slices from a contrast-enhanced CT simulation for a patient with P16-positive, HPV-associated cT1N1 squamous cell carcinoma of the left base of tongue 2 Oropharyngeal Carcinoma
- 31. 24 = GTV Legend: = CTV Nodal coverage starting at transverse process of C1 Coverage of ipsilateral tongue base and soft palate No coverage of Level 1b Fig. 2.6 Representative axial slices from a contrast-enhanced CT simulation for a patient with P16-positive, HPV-associated cT2N0 squamous cell carcinoma of the right tonsil (with no evi- dence of base of tongue or soft palate invasion) to be treated with unilateral radiation. At MSKCC, for tonsil cancers regardless of stage, the ipsilateral subclinical region almost always extend supe- riorly to include coverage of the ipsilateral pterygoid plate Z. A. Husain et al.
- 32. 25 References 1. Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oro- pharyngeal cancer. N Engl J Med. 2010;363:24–35. 2. O’Sullivan B, Huang SH, Su J, et al. Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study. Lancet Oncol. 2016;17:440–51. 3. Gillison ML, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019;393(10166):40–50. 4. Mehanna H, Robinson M, HartleyA, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet. 2019;393(10166):51–60. 5. Yom SS, Torres-Saavedra P, Caudell JJ, et al. NRG-HN002: a randomized phase II trial for patients with p16-positive, non-smoking-associated, locoregionally advanced oropharyngeal cancer. Int J Radiat Oncol Biol Phys. 2019;105(3):684–5. 6. Tsai CJ, McBride SM, Riaz N, Lee NY. Reducing the radiation therapy dose prescription for elective treatment areas in human papillomavrius-associated oropharyngeal carcinoma being treated with primary chemoradiotherapy at Memorial Sloan-Kettering Cancer Center. Pract Radiat Oncol. 2019;9:98–101. 7. Eisbruch A, Harris J, Garden AS, et al. Multi-institutional trial of accelerated hypofractionated intensity-modulated radiation therapy for early-stage oropharyngeal cancer (RTOG 00-22). Int J Radiat Oncol Biol Phys. 2010;76(5):1333–8. 2 Oropharyngeal Carcinoma
- 33. 27 3 Stereotactic Body Radiotherapy for Cancers of the Head and Neck Cancer Dana Keilty, Irene Karam, Nancy Y. Lee, and Ian Poon Contents References 43 • Advanced Head and Neck Cancer (HNC) is commonly a disease of the elderly and associated with a poor outcomes despite aggressive multi-modality treat- ments. Select fit elderly patients, despite the expectation of a poor outcome, may choose to undergo radical high-dose radiation to maximize cancer control but with higher rates of toxicity and morbidity. In frail patients, the decision against a prolonged RT course may be based on multiple factors: patient preference (Fig. 3.1), tumor factors (expected morbidity of tumor progression versus the morbidity/mortality risk of treatment and probability of a successful outcome [Figs. 3.2, 3.3, 3.4, 3.5, and 3.6]), life expectancy (influence of age and comorbid conditions [Figs. 3.1, 3.3, 3.4, 3.6, 3.7, 3.8, and 3.9]), tolerance of aggressive D. Keilty · I. Karam · I. Poon (*) Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada e-mail: dana.keilty@mail.utoronto.ca; irene.karam@sunnybrook.ca; ian.poon@sunnybrook.ca N. Y. Lee Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA e-mail: leen2@mskcc.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_3
- 34. 28 a Fig. 3.1 Unresectable piriform sinus tumor. A 73-year-old lady was diagnosed with a T1 N3 squamous cell carcinoma of the left piriform sinus compressing the internal jugular vein. She elected against a protracted radiation course. (a) 50 Gy in five fractions, two fractions per week, was prescribed to the GTVn (orange) and 40 Gy in five fractions, two fractions per week, was pre- scribed to the GTVp (red). Target coverage was not compromised in an attempt to spare the carotid artery (arrow). (b) No evidence of disease at 2 years D. Keilty et al.
- 35. 29 b Fig. 3.1 (continued) 3 Stereotactic Body Radiotherapy for Cancers of the Head and Neck Cancer
- 36. 30 a Fig. 3.2 Extensive HNC. A 65-year-old female presented with a painful squamous cell carcinoma of the oral cavity, measuring 6.9 by 4.0 cm, extending from the base of the skull along the infra- temporal fossa into the masticator space and the right mandible, causing pathologic fracture and trismus with a mouth opening of 1.5 cm. She received 45 Gy in five fractions, two fractions per week. (a) GTVp45 is delineated in red. (b) Four years later, she can open her mouth 4 cm and remains disease-free D. Keilty et al.
- 37. 31 Fig. 3.2 (continued) b 3 Stereotactic Body Radiotherapy for Cancers of the Head and Neck Cancer
- 38. 32 a Fig. 3.3 HNC with concurrent life-threatening cancer. A 66-year-old gentleman presented with superior vena cava obstruction from a 10-cm non-small cell lung mass. Palliative radiation and chemotherapy rendered his disease stable for 18 months. Imaging to investigate painful dysphagia showed a 3-cm mass at the left base of tongue crossing the midline and a 3.3-cm left level II lymph node. Flexible nasopharyngoscopy showed the mass extended into the vallecula, displacing the epiglottis. This T2N1 base of tongue cancer was treated with 45 Gy in five fractions, two fractions per week, after which he started second-line lung systemic therapy. (a) GTVp45 is delineated in red; GTVn45 is delineated in orange; GTVn40 is delineated in green. (b) There is no evidence of disease at 18 months, and he is tolerating all food textures without pain D. Keilty et al.
- 39. 33 Fig. 3.3 (continued) b 3 Stereotactic Body Radiotherapy for Cancers of the Head and Neck Cancer
- 40. 34 Fig. 3.4 HNC recurrence in centenarian. A 100-year-old female with squamous cell carcinoma of the skin recurred at the parotid and neck nodes. CTVn25 (blue) encompasses the nodal basin at high risk of relapse. GTV45 is delineated in red. She remained well for 6 months and then recurred regionally, both inside and outside the low-dose field D. Keilty et al.
- 41. 35 Fig. 3.4 (continued) 3 Stereotactic Body Radiotherapy for Cancers of the Head and Neck Cancer
- 42. 36 Fig. 3.5 Oligometastatic disease adjacent to brachial plexus. A 55-year-old female presented with an unresectable solitary oligometastatic colorectal cancer at the supraclavicular fossa. This 6-cm node was treated with 45 Gy in five fractions, two fractions per week. The radiation plan was cre- ated with MRI simulation to differentiate the GTV (red) from the brachial plexus (blue). The mass recurred 3 years later in the left neck D. Keilty et al.
- 43. 37 Fig. 3.6 Primary parotid tumor. A 91-year-old gentleman presented with facial nerve palsy sec- ondary to a poorly-differentiated carcinoma in the left parotid (red) with two retropharyngeal nodes (orange). He received 50 Gy in five fractions, two fractions per week. He achieved a com- plete clinical response and facial nerve function returned. A minor paralytic ectropion of the eye will be treated with canthotomy and canthopexy. There is no evidence of disease at 6 months 3 Stereotactic Body Radiotherapy for Cancers of the Head and Neck Cancer
- 44. 38 Fig. 3.6 (continued) Fig. 3.7 Double-contrast simulation CT when MRI is not available. A 79-year-old lady with a T1N1 squamous cell carcinoma of the base of tongue had single-contrast (80 mL) CT simulation (a) that did not adequately visualize the GTV (arrow). (b) Double-contrast (160 mL) CT simula- tion allowed for excellent GTV (arrow) definition a b D. Keilty et al.
- 45. 39 a b Fig. 3.8 CT artefact removal. An 87-year-old frail gentleman, with an MRI-incompatible pace- maker, was diagnosed with a (a) squamous cell carcinoma of the left mandibular gingivobuccal sulcus. (a, b) Artefact caused by a dental filling (arrow) severely impacted target visualization. (c) GTV delineation (red) was made possible by tooth extraction. Alternatively, these can be replaced with non-metal fillings 3 Stereotactic Body Radiotherapy for Cancers of the Head and Neck Cancer
- 46. 40 Fig. 3.8 (continued) c a Fig. 3.9 HNC recurrence with discordant post-treatment imaging. An 83-year-old lady treated surgically 3 years previous for a squamous cell carcinoma of the right tongue presented with a painful, right level II nodal mass deep to the parotid and extending into the parotid, parapharyngeal space, and carotid sheath. She was not a candidate for radical chemoradiation. She received 45 Gy in five fractions, two fractions per week. (a) GTV (red) delineation was aided by MRI fusion; (CT on the left, MRI on the right). (b) While her pain had improved, MRI at 4 months after treatment showed possible progression at T1 (left) but response on T2 (right). (c) At 9 months, MRI shows disease stability and the patient is pain-free D. Keilty et al.
- 47. 41 c b Fig. 3.9 (continued) 3 Stereotactic Body Radiotherapy for Cancers of the Head and Neck Cancer
- 48. 42 treatment based on host (performance status [Fig. 3.8]), and non-host factors (distance from hospital, availability of social/financial/psychological supports). At high volume centers, Head and Neck stereotactic body radiotherapy (SBRT) can be considered as a palliative treatment that may provide more durable local control than standard palliative approaches in patients who are not candidates for standard radical curative treatment. Previously, HN SBRT was primarily consid- ered in re-irradiation, but the greater value of SBRT may be in the un-irradiated setting, where the extended treatment and recovery time of radical therapy may be undesirable or unrealistic for certain patients. SBRT can achieve durable local control [1] with a shortened treatment course and acceptable side effect profile. • HN SBRT requires a highly experienced multidisciplinary team of medical phys- icists, dosimetrists, and radiation therapists. • Accurate GTV delineation is critical for safe HN SBRT. Intraoral photos to docu- ment clinical exam details can be valuable. Neuroradiology review can clarify tumor extent and localize radiosensitive organs at risk. • Contrast-enhanced computed tomography (CT) simulation is required for pre- cise volume definition, with MRI (simulation) fusion greatly improving gross disease visualization. If MRI is not available, double-contrast CT simulation (Fig. 3.7) can be used. Dental fillings that create artefact and impact visualization should be removed for SBRT (Fig. 3.8). • Five-point thermoplastic mask and daily cone beam CT (CBCT) matching allows for reproducible immobilization and reduction of PTV margins to 3 mm. Toxicity is additionally minimized by eliminating the traditional comprehensive micro- scopic volumes. • The standard dose range to the GTV is 40–50 Gy, two fractions per week, with 45 Gy most commonly prescribed. The HN SBRT literature reports radiation prescriptions in the range of 35–50 Gy in 3–8 fractions [1–3, 4]. A high dose and low dose CTV expansion of the GTV is NOT used. A microscopic CTVn25 can be created for immediately adjacent at-risk lymph node sites. A microscopic dose is not expanded from the GTV (Table 3.1). A dose-reduced PTV35-40 is cre- ated with a 3-mm expansion of the GTV/high-dose CTV. • The hot spots should lie within the GTV and away from organs at risk. A confor- mity index of 1.1 of the GTV40–50 and PTV35–40 is desirable. • Target coverage must be compromised when in proximity to critical neurological structures (brachial plexus, optic pathways, brain, and brainstem). Dose to the carotid artery, however, should not compromise target coverage, except in re- irradiation [5]. • A strong quality assurance (QA) program is needed. Our center employs a modi- fied Winston–Lutz isocenter alignment test to ensure tolerance within 2.5 mm [6]. Daily CBCT to match to bone and soft tissue is imperative; because the number of CBCTs is minimal, attempts to decrease the CBCT dose are of little value and should not preclude high-quality CBCT images. • The rate of regression post-SBRT is variable and maximal response is often achieved beyond traditional timelines (3 months). D. Keilty et al.
- 49. 43 Table 3.1 Target volumes Target volumes Definition and description GTV40–50 Primary: All gross disease on physical exam and imaging, including T1-gadolinium, T1 with fat saturation, and T2 MRI sequences Fusion of contrast-enhanced simulation CT with MRI If patient factors preclude MRI, GTV visualization on simulation CT can be enhanced using double contrast (Fig. 3.8) Neck lymph nodes: With necrotic center, or that are PET-avid CTV40–50 With precise GTV delineation, this volume is equal to GTV40–50 PTV35–40 CTV40–50 (equivalent to GTV40–50 ) + 3 mm, with daily CBCT CTV35–40 Suspicious nodes (round, enhancing) PTV30–35 CTV35–40 + 3 mm if this volume is near other high-dose volumes and good cone beam match is expected If the above cannot be achieved, CTV35–40 + 5 mm equals PTV30–35 CTV25 Includes high-risk lymph node basins immediately adjacent to treatment volumes, where repeat radiation to regional recurrence would be difficult PTV25 CTV25 + 3–5 mm References 1. Baliga S, Kabarriti R, Ohri N, et al. Stereotactic body radiotherapy for recurrent head and neck cancer: a critical review. Head Neck. 2017;39(3):595–601. 2. Grewal AS, Jones J, Lin A. Palliative radiation therapy for head and neck cancers. Int J Radiat Oncol Biol Phys. 2019;105(2):254–66. 3. Al-Assaf H, Poon I, Lee JW, Karam I, Higgins K, Enepekides D. Stereotactic body radio- therapy (SBRT) for medically unfit head and neck cancer. Int J Radiat Oncol Biol Phys. 2017;99(2):E319. 4. Voruganti IS, Poon I, Husain ZA, et al. Stereotactic body radiotherapy for head and neck skin cancer. Radiother Oncol. 2021;165:1–7. 5. Karam I, Poon I, Lee J, et al. Stereotactic body radiotherapy for head and neck cancer: an addi- tion to the armamentarium against head and neck cancer. Future Oncol. 2015;11(21):2937–47. 6. Denton TR, Shields LB, Howe JN, Spalding AC. Quantifying isocenter measurements to estab- lish clinically meaningful thresholds. J Appl Clin Med Phys. 2015;16(2):5183. 3 Stereotactic Body Radiotherapy for Cancers of the Head and Neck Cancer
- 50. 45 4 Larynx Cancer Dan Fan, Jung Julie Kang, Yao Yu, Oren Cahlon, Nadeem Riaz, and Nancy Y. Lee Contents 4.1 General Principles of Anatomy and Patterns of Spread 45 4.2 Diagnostic Workup Relevant for Target Delineation 46 4.3 Simulation and Daily Localization 47 4.4 Target Volume Delineation and Treatment Planning 47 References 59 4.1 General Principles of Anatomy and Patterns of Spread • The larynx is divided into three subsites: the supraglottis, glottis, and subglottis. • The supraglottic larynx includes the ventricles, false vocal cords (FVC), aryte- noids, aryepiglottic (AE) folds, and epiglottis (suprahyoid, infrahyoid, and laryn- geal surface). – – Bilateral elective nodal irradiation is warranted for all supraglottic larynx. D. Fan Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Department of Radiation Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China e-mail: fandan0211@csu.edu.cn J. J. Kang · Y. Yu · O. Cahlon · N. Riaz · N. Y. Lee (*) Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA e-mail: kangj1@mskcc.org; yuy2@mskcc.org; cahlono@mskcc.org; riazn@mskcc.org; leen2@mskcc.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_4
- 51. 46 • The glottic larynx includes the true vocal cords (TVC), anterior commissure, posterior commissure, and the infraglottic space (0.5 cm inferiorly from the free margin of the true vocal cords). – – Early-stage (T1–T2 N0) does not require elective nodal irradiation. – – Advanced (≥T3 or node-positive) glottic cancers require bilateral elective nodal irradiation and small larynx-only fields are inappropriate. • The subglottic larynx extends from the inferior border of the glottis to the supe- rior border of the trachea. – – Bilateral elective nodal irradiation including level VI should always be treated due to a propensity for nodal spread. • TVC mobility must be assessed on laryngoscopy (normal, hypomobile, fixed). – – A medialized fixed cord indicates recurrent laryngeal nerve injury. – – A lateralized fixed or hypomobile cord indicates injury to the intrinsic laryn- geal muscles and is often seen with laryngeal cancer. • The paraglottic and pre-epiglottic spaces are connected fat planes with no barri- ers to spread between then. The paraglottic space is bounded by the thyroid car- tilage laterally and the TVCs and FVCs medially. The pre-epiglottic fat space is bounded by the mucosal surface of the vallecula superiorly, hyoid/thyroid strap muscles anteriorly, root of the epiglottis posteriorly, and inferiorly communi- cates with the paraglottic space. • A dedicated CT and/or MRI is highly recommended for clinically staged T1–2 glottic larynx to rule out paraglottic extension which changes staging to T3. • The thyroid cartilage has an inner and outer cortex. Invasion of the inner cortex only signifies T3 disease, while invasion through the outer cortex signifies T4 disease. The degree of invasion can only be assessed through imaging (i.e. CT and/or MRI) with appropriate windowing and must be carefully assessed. • For true T4 disease, total laryngectomy is the preferred approach, although an organ preservation approach can be considered in select cases. 4.2 Diagnostic Workup Relevant for Target Delineation • In addition to physical examination with laryngoscopy. – – Imaging should include a dedicated, thin slice (1–2 mm cuts) high-resolution CT and/or MRI of the larynx with IV contrast. Careful attention should be directed towards evaluation of pre-epiglottic or paraglottic space extension and invasion of the thyroid cartilage. – – A contrast-enhanced MRI is also helpful for visualizing the locoregional extent of disease. Note that more than 1 cm of base of tongue invasion, was an exclusion criterion for larynx preservation trials (RTOG 91–11). – – PET/CT is helpful for identifying lymph nodes and metastatic disease. D. Fan et al.
- 52. 47 4.3 Simulation and Daily Localization • The patient should be simulated supine with head rest with the neck extended in a five-point customized Aquaplast mask that immobilizes the head, neck, and shoulders. A shoulder pull board can be used to lower the shoulders out of the beam angle path. • For patients with many metal fillings, a custom mouthguard can be helpful to absorb electron scatter and mitigate treatment-related mucositis. • The CT simulation should use ≤3 mm slices with IV contrast. • The CT should include the entire vertex of the head through the carina. • The isocenter is typically placed at the arytenoids if there is no subglottic or hypopharyngeal extension. If either is present, then the isocenter is placed 1 cm inferiorly. • For postoperative cases, it is helpful to place a radiopaque marker on the scar. • There are various appropriate IGRT approaches. Daily imaging ideally consists of daily cone beam CT aligned to the larynx. Daily kilovoltage imaging aligned to bone and weekly cone beam CTs are also adequate. • Patients should be instructed not to swallow during simulation scan, IGRT or during treatment. • Placement of bolus is needed to ensure adequate anterior coverage of the tumor, especially for those tumors that involve the anterior commissure. 4.4 Target Volume Delineation and Treatment Planning • The GTV should be delineated using all relevant clinical information derived from laryngoscopy, CT, MRI, and PET (Table 4.1). • Positive lymph nodes in the neck should be defined as those with central necro- sis, extracapsular extension, and/or a short axis diameter 1 cm. For borderline Table 4.1 Suggested target volumes for gross disease in locally advanced glottic, supraglottic, or subglottic laryngeal cancers Target volumes Definition and description GTV 70 Primary: All gross disease on physical examination and imaging Neck nodes: All nodes ≥1 cm or PET positive should be included as nodal GTV. Include borderline lymph nodes in doubt as GTV to avoid undertreatment CTV 70 Usually same as GTV70 (typically no need to add margin unless there is uncertainty about the extent of gross disease). An additional 0–0.5-cm margin may be to GTV70 to create CTV70 PTV 70 CTV70 + 3–5 mm, depending on reproducibility of daily patient positioning and available IGRT 4 Larynx Cancer
- 53. 48 nodes, those with FDG avidity should be considered disease (Table 4.1). Small nodes that are bean-shaped or exhibit a fatty hilum are more likely benign. Enlarged RP nodes, although unusual in laryngeal cancer, should be considered positive even if small. • Suggested target volumes are detailed in Tables 4.1, 4.2, and 4.3 (Figs. 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, and 4.7). Table 4.2 Suggested target volumes for subclinical disease in supraglottic, subglottic, or locally advanced glottic laryngeal cancers Target volumes Definition and description CTV 54–60a CTV 54–60 should encompass the entire GTV Includes the entire larynx, from the bottom of the hyoid or the top of the thyroid notch to the bottom of the cricoid cartilage and extend inferiorly when necessary High-risk nodal regions include levels II–IV and the retrostyloid space on the involved node-positive neck In the node-positive neck, level II should be treated to the base of skull Level VI should be included if there is subglottic extension or a trach PTV 54–60a CTV 54–60 + 3–5 mm, depending on immobilization, IGRT, etc. CTV 54b Levels II–IV of the uninvolved neck In the node-negative neck, the superior border of level II stops where the posterior belly of the digastric muscle crosses the internal jugular vein (or the caudal edge of the lateral process of C1) Level IB and V nodes are not included unless there is gross involvement of nodes at those levels RP nodes may be covered at physician discretion on the side of bulky adenopathy because of retrograde flow Level VII coverage is recommended for subglottic extension or hypopharyngeal involvement PTV 54b CTV 54 + 3–5 mm, depending on immobilization, localization, etc. Subclinical disease may be drawn as one CTV or two CTVs (high risk and low risk) a High-risk subclinical dose: 1.8–2 Gy per fraction to 54–60 Gy b Low-risk subclinical dose: 1.54–1.8 Gy per fraction to 54 Gy Table 4.3 Suggested target volumes for postoperative laryngeal cases Target volumes Definition and description CTV 60a CTV 60 should encompass the entire operative bed, the scar, the stoma, and the node-positive neck (levels II–IV, the retrostyloid space and involved nodal stations) CTV 54a The node-negative neck Levels VI and VII should be included if there is subglottic extension or a stoma CTV 66b Areas of positive margins, extracapsular extension, or stoma boost if indicated PTV CTV + 3–5 mm, depending on immobilization, IGRT, etc. Subclinical disease may be drawn as one CTV or two CTVs (high risk and low risk) a Subclinical dose: 1.8–2 Gy per fraction to 54–60 Gy b CTV 66 may be delivered with a sequential cone down or dose painting D. Fan et al.
- 54. 49 Fig. 4.1 A patient with T1aN0 squamous cell carcinoma of the left vocal cord. Please note that these are representative slices and not all slices are included. Blue GTV, Green CTV, Red PTV. GTV is delineated by laryngoscopy findings only. For T1 larynx tumors, there are typically no CT abnor- malities. The entire larynx is delineated as CTV to include both false and true vocal cords, anterior and posterior commissures, arytenoids and aryepiglottic folds, as well as the subglottic region. The PTV extends from thyroid notch to the bottom of the cricoid cartilage. A 5-mm margin added in all directions except posterolaterally was limited to 3 mm to respect the ICA. The orange circle is the carotid artery • Early stage disease (T1N0 or T2N0): – – The CTV should encompass the entire larynx including the anterior and pos- terior commissures and the arytenoids. We suggest coverage of the entire glot- tis superiorly from the bottom of the thyroid notch inferiorly to the cricoid cartilage for T1 tumors (Figs. 4.1 and 4.2), and inferiorly to the first tracheal ring for T2 tumors. It is critical to ensure coverage inferiorly as most recur- rences tend to be inferior. Ipsilateral cord can be considered. 4 Larynx Cancer
- 55. 50 Fig. 4.2 A patient with T1bN0M0 squamous cell carcinoma involving both vocal cords. Blue = GTV, Orange = CTV, Red = PTV D. Fan et al.
- 56. 51 Fig. 4.3 A patient with T2N0M0 left supraglottic squamous cell carcinoma with involvement of left ventricle and true vocal cord, anterior commissure, and anterior aspect of right supraglottic larynx. Red = GTV, Green = CTV54, Orange = CTV60, Blue = CTV70. Please note that these are representative slices and not all slices are included 4 Larynx Cancer
- 57. 52 Fig. 4.4 A patient with T3N0M0 squamous cell carcinoma of the left vocal cord with extension to anterior commissure and right cord, with subglottic extension and extension into inner thyroid cartilage. Red = GTV, Orange = CTV54, Blue = CTV60, Green = CTV70 D. Fan et al.
- 58. 53 Fig. 4.5 A patient with T2 N2c M0 squamous cell carcinoma of the epiglottis involving right AE fold and bilateral cervical lymph nodes. Please note that these are representative slices and not all slices are included. Magenta GTV LN, Purple GTV primary, Blue CTV 60, Orange CTV 54. The treating MD in this case chose to include level IB which can be omitted. In addition, the treating MD did not treat the upper trachea which if indicated should be included 4 Larynx Cancer
- 59. 54 Fig. 4.5 (continued) D. Fan et al.
- 60. 55 Fig. 4.5 (continued) 4 Larynx Cancer
- 61. 56 Fig. 4.6 A patient with T3N1M0 supraglottic squamous cell carcinoma with subglottic extension. GTV is in red. CTV60 is in orange. CTV54 is in green D. Fan et al.
- 62. 57 Fig. 4.7 A patient with pT4 N0 M0 squamous cell carcinoma of the left glottis status total laryn- gectomy and left neck dissection. In the postoperative setting, the high-risk CTV (the entire opera- tive bed) receives 60 Gy in 2 Gy/fraction and the low-risk CTV receives 54 Gy in 1.8 Gy/fraction. Blue CTV 54, Green CTV 60 4 Larynx Cancer
- 63. 58 – – Glottic Larynx. Carotid-sparing IMRT should be considered [1–3]. A CT-based opposed laterals technique is also acceptable. The superior border should extend to the bottom of the hyoid bone or the top of the thyroid notch. The inferior border is the bottom of the cricoid cartilage. The posterior border is the anterior edge of the vertebral bodies. There should be 1 cm flash anteriorly. It may be necessary to angle the beams 5–10° inferiorly to avoid the shoulders. Often 15–30° wedges are used to ensure a homogeneous dos distribution throughout the larynx. For T1N0 glottic larynx tumors, we use a dose of 63 Gy in 28 fractions as randomized evidence supports a local control advantage with hypofrac- tionation at 2.25 Gy/fraction [4]. For T2N0 glottic larynx tumors, there are local control benefits with doses 65 Gy and dose per fraction ≥2.25 Gy [5]. We treat to 65.25 Gy in 29 fractions at 2.25 Gy per fraction. In select cases, treatment with chemora- diotherapy may be acceptable. – – Due to higher risks of occult nodal disease in supraglottic and subglottic can- cers, bilateral levels II–IV and in many instances level VI nodal chains should be electively radiated. The superior limit of level II may stop where the poste- rior belly of the digastric muscle crosses the internal jugular vein (Fig. 4.3). • Advanced stage disease (≥T3 or node-positive disease): – – Bilateral necks should be included. We favor a sequential cone down approach. An initial plan (30 fractions) with a dose-painting approach delivers 54 Gy (1.8 Gy/fx) and 60 Gy (2 Gy/ fx) to the low and high-risk subclinical regions, respectively. This is fol- lowed by a cone down plan (five fractions) which delivers an additional 10 Gy to gross disease only for a total of 70 Gy over 35 fractions. One dose painted IMRT plan is also acceptable. An example fractionation: over 35 days to deliver 2 Gy/fx, 1.8 Gy/fx, and 1.54 Gy/fx to achieve doses of 70 Gy to gross disease, 63 Gy to high-risk subclinical disease, and 54 Gy to low-risk subclinical disease. – – Extended IMRT plans are favored over the use of a low anterior neck (LAN) field. This is due to the risk of missing gross tumor or high-risk subclinical disease in the low dose region of the match-line. – – One subclinical or two subclinical (high-risk, low-risk) CTVs may be con- toured for microscopic disease (Table 4.2). The subclinical primary site CTV should encompass the entire larynx from the bottom of the thyroid notch to the first tracheal ring or extend inferiorly when necessary. The subclinical nodal CTV should encompass at least levels II–IV, and in many instances level VI (Fig. 4.4). In the elective node-negative neck, the superior border of level II stops where the posterior belly of the digastric muscle crosses the internal jugu- lar vein (this is the superior most extent of an elective neck dissection and corresponds to the caudal edge of the lateral process of C1) (Fig. 4.5). D. Fan et al.
- 64. 59 In the node-positive neck, level II should be treated to the base of skull and the ipsilateral retrostyloid nodes should be included. Cover level VI if there is subglottic involvement or a trach (Fig. 4.6). See Table 4.2 for recommendations on coverage of levels IB, VII, and RP nodes. • Post-operative radiation: Adverse pathologic features that warrant post- operative radiation as per NCCN v.2020 include positive margins, close margins, extra-nodal extension, pT4 primary, pN2–pN3 nodal disease, perineural inva- sion, vascular invasion, lymphatic invasion. Concurrent chemotherapy should be added for extracapsular extension or positive margin. – – The entire surgical bed, stoma, scar, and dissected node-positive neck should be included in a high-risk CTV to a dose of 60 Gy. Areas of positive margin or extracapsular extension may be boosted to 66 Gy (Fig. 4.7). – – The undissected node-negative neck can be included in the low-risk CTV to a dose of 54 (Fig. 4.7). – – The stoma may be boosted to 66 Gy for subglottic extension or if an emergent tracheostomy was performed. Anatomically, a stomal recurrence is a tracheo- esophageal node. • Radiationfollowinginductionchemotherapy:Inadditiontopost-chemotherapy targeting, pre-chemotherapy imaging should be fused for target delineation. The high-risk subclinical volume should include the pre-chemotherapy extent of dis- ease and take into consideration the adjacent anatomical sites at risk for microscopic spread. This pre-chemotherapy CTV should be modified for ana- tomical differences after chemotherapy and exclude natural barriers to spread such as air and bone. • Planning: – – A PTV margin of 0.3–0.5 cm may be used, depending immobilization and laryngeal motion. – – For patients with involvement of the anterior commissure, flash and bolus should be used to ensure adequate coverage of the superficial extent of gross or subclinical disease. – – Care should be taken to limit the heterogeneity to 105% of prescription when treating over the larynx. References 1. Chera BS, Amdur RJ, Morris CG, Mendenhall WM. Carotid-sparing intensity-modulated radiotherapy for early-stage squamous cell carcinoma of the true vocal cord. Int J Radiat Oncol Biol Phys. 2010;77(5):1380–5. 2. Gomez D, Cahlon O, Mechalakos J, Lee N. An investigation of intensity-modulated radiation therapy versus conventional two-dimensional and 3D-conformal radiation therapy for early stage larynx cancer. Radiat Oncol. 2010;5:74. 3. Rosenthal DI, Fuller CD, Barker JL Jr, et al. Simple carotid-sparing intensity-modulated radio- therapy technique and preliminary experience for T1–2 glottic cancer. Int J Radiat Oncol Biol Phys. 2010;77(2):455–61. 4 Larynx Cancer
- 65. 60 4. Yamazaki H, Nishiyama K, Tanaka E, et al. Radiotherapy for early glottic carcinoma (T1N0M0): results of prospective randomized study of radiation fraction size and overall treat- ment time. Int J Radiat Oncol Biol Phys. 2006;64:77–82. 5. Le QT, Fu KK, Kroll S, et al. Influence of fraction size, total dose, and overall time on local control of T1–T2 glottic carcinoma. Int J Radiat Oncol Biol Phys. 1997;39(1):115–26. D. Fan et al.
- 66. 61 5 Hypopharyngeal Carcinoma Linda Chen, Yao Yu, and Nancy Y. Lee Contents 5.1 Anatomy and Patterns of Spread 61 5.2 Diagnostic Workup Relevant for Target Volume Delineation 63 5.3 Simulation and Daily Localization 64 5.4 Target Volume Delineation and Treatment Planning 64 5.5 Suggested Reading 73 References 73 5.1 Anatomy and Patterns of Spread • The hypopharynx lies between the oropharynx superiorly and cervical esopha- gus inferiorly. This is a portion of the pharynx that is defined superiorly by the top of the hyoid bone (approximately C4) and inferiorly by the bottom of cri- coid cartilage (approximately C6), with the larynx lying anteromedially. As such, hypopharynx tumors have a propensity to disrupt speech and swallow function. • There are three subsites of the hypopharynx: the paired pyriform sinuses, poste- rior pharyngeal wall, and the post-cricoid region. Tumors have a tendency for submucosal spread with involvement of multiple sites of hypopharynx, the lar- ynx, and adjacent soft tissue due to minimal barriers between anatomic sites [1]. Patterns of spread for each subsite are outlined in Table 5.1. L. Chen (*) · Y. Yu · N. Y. Lee Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA e-mail: ChenL1@mskcc.org; yuy2@mskcc.org; leen2@mskcc.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_5
- 67. 62 Table 5.1 Hypopharyngeal subsite and respective patterns of spread Hypopharynx subsite Patterns of spread Pyriform sinus • Anteromedially: Arytenoids, aryepiglottic folds, intrinsic laryngeal muscles (which can result in vocal cord fixation), para-glottic space • Posterior: Constrictor muscles, prevertebral tissue • Lateral: Para-glottic space, Thyroid cartilage, and lateral neck • Superiorly: Oropharynx, pre-epiglottic space, thyrohyoid membrane (referred otalgia from the internal branch of superior laryngeal nerve) • Inferiorly: Post-cricoid area • Lymph nodes: Most commonly—RP, II, III. Additional levels at risk: level IV, and level VI (inferior tumors involving the apex) Posterior pharyngeal wall • Superiorly: Extension to the oropharynx • Inferiorly: Extension to the cervical esophagus • Posteriorly: Pre-vertebral fascia, retropharyngeal space • Lymph nodes: RP, II–IV Post-cricoid region • Anteriorly: Laryngeal invasion (vocal cord fixation) • Superiorly: Pyriform sinuses • Inferiorly: Cricoid cartilage, cervical esophagus • Lymph nodes: II–IV, paratracheal • Hypopharynx cancers also have a high propensity for lymph node involvement due to an extensive submucosal lymphatic plexus. Bilateral cervical lymph nodes and lateral retropharyngeal lymph nodes are commonly involved [2–6]. Posterior level V involvement, level VI, and superior mediastinal LNs can be involved for post-cricoid region tumors and pyriform sinus tumors that are inferior and involve the apex [2, 5–9]. In patients who are clinically node negative, 30–35% of patients have pathologic lymph node involvement [7]. Level 1b is rarely involved but ranges between 5% and 20% in the node positive neck [2, 6]. • The pyriform sinuses are the most common site of hypopharynx cancer (65–85%) and are paired potential spaces which lie laterally and posteriorly to the larynx [10, 11]. The superior and widest portion of the pyriform sinuses are visualized endoscopically, on either side of the larynx with the medial wall formed by ary- epiglottic fold. The space narrows inferiorly until it reaches the apex at the crico- arytenoid joint, forming the shape of an inverted cone. • The hypopharyngeal wall (10% of hypopharyngeal cancers) is a continuation of the lateral and posterior pharyngeal wall that lies between the oropharynx supe- riorly and the cervical esophagus inferiorly. It is composed of mucosa which encloses lateral and posterior constrictor muscles. • The post-cricoid region (5%) is the least common site for hypopharyngeal can- cers. Mucosa is comprised of the posterior wall of the larynx, spanning from the arytenoids to the cricoid cartilage. Skip metastasis to the cervical esophagus can occur. L. Chen et al.
- 68. 63 5.2 Diagnostic Workup Relevant for Target Volume Delineation • Pathologically, the vast majority of hypopharyngeal cancers are squamous cell carcinomas. Variants such as verrucous carcinoma, basaloid squamous carcino- mas, spindle cell carcinoma as well as minor salivary gland carcinomas comprise a minority of cases. • Clinical history should focus on tobacco/alcohol use, otalgia (CN X involve- ment) respiratory function, voice quality as well as baseline swallow function, especially when considering organ preservation for locally advanced tumors. • Clinical exam should include palpation of the base of tongue (evaluation of pre- epiglottic involvement), evaluation of laryngeal mobility (laryngeal invasion), presence of a thyroid click (absent in posterior lesions which anteriorly displace the larynx), and presence of cervical adenopathy should be evaluated. • Endoscopic fiber-optic examination should be undertaken to identify whether adjacent mucosal subsites are involved as well as fixation of vocal cords, and is critical for AJCC 8 staging and treatment decision making (Table 5.2). Phonation and valsalva maneuvers during the exam can aid in visualizing the hypopharynx. Table 5.2 AJCC 8 staging hypopharynx cancer T1 – Tumor limited to one subsite of hypopharynx – Tumor ≤2 cm or smaller in greatest dimension T2 – Tumor invades more than one subsite of hypopharynx or an adjacent site – Tumor 2–4 cm – Without fixation of hemilarynx T3 – Tumor larger than 4 cm in greatest dimension – Or with fixation of hemilarynx – Or extension to esophageal mucosa T4a – Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, esophageal muscle or central compartment soft tissue (pre-laryngeal strap muscles and subcutaneous fat) T4b – Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures N0 No regional lymph node metastasis N1 – Metastasis in a single ipsilateral lymph node – ≤3 cm and ENE(−) N2a – Metastasis in a single ipsilateral node 3–6 cm and ENE(−) N2b – Metastases in multiple ipsilateral nodes, none larger than 6 cm in greatest dimension and ENE(−) N2c Metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(−) N3a Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(−) N3b Metastasis in any node(s) and clinically overt ENE(+) 5 Hypopharyngeal Carcinoma
- 69. 64 • Diagnostic, contrast-enhanced CT or MRI should also be utilized to evaluate extent of disease. Special attention to pre-epiglottic or paraglottic space involvement, laryngeal extension, gross cartilage invasion, soft tissue extension, esophageal invasion, and extra-capsular spread [12–15]. • PET/CT can also help to delineate borders, as this is a sensitive modality that can aid in defining extent of disease (i.e. inferior apical tumor boundaries which can be subtle) as well as hypermetabolic malignant cells within lymph nodes [16–18]. 5.3 Simulation and Daily Localization • Positioning: Patient should be simulated supine with head rest. The neck should be hyperextended or a shoulder pull board can be used to lower the shoulders out of the beam angle path. Custom immobilization should be used with a thermo- plastic mask. In post-operative cases, all surgical scars should be wired. • Imaging: Thin-cut 3 mm CT slices with imaging from the top of the skull down to T5. Intravenous contrast should be administered unless medically contra- indicated. Isocenter placement typically at the arytenoids. • Localization: Daily imaging ideally consists of daily cone beam CT aligned to the larynx. Daily kilovoltage imaging aligned to bone and weekly cone beam CTs are also adequate. 5.4 Target Volume Delineation and Treatment Planning • Intensity modulated radiation therapy (IMRT) planning is recommended. An ini- tial plan (30 fractions) with a dose-painting approach with 54 Gy/1.8 Gy frac- tions and 60 Gy/2 Gy fractions are used for the low- and high-risk subclinical regions. This is followed by a 10 Gy cone down to gross disease for a total of 70 Gy over 35 fractions. A single dose-painted plan such to 70 Gy over 33–35 fractions is also appropriate (Fig. 5.1). • Extended IMRT plans are recommended rather than use of a low anterior neck field. This is due to high risk regions or gross disease that are likely be located in the low dose region of the match-line. • Early stage disease consists of T1N0 or T2N0 (AJCC 8) hypopharynx carci- noma. A minority of cases present with early stage disease. Definitive radiation is often preferred for local control, laryngeal preservation, maintenance of speech and swallowing. Due to the high incidence of occult nodal disease, and central location of the hypopharynx, bilateral nodal chains should be included in the target (Figs. 5.1 and 5.2). • Advanced stage disease consists of ≥T3 or node-positive disease (Figs. 5.3, 5.4, and 5.5). Treatment options include definitive chemoradiation, laryngectomy followed by adjuvant therapy, and induction chemotherapy followed by local L. Chen et al.
- 70. 65 a b c d e f g h i j k Fig. 5.1 T2N0 left pyriform sinus squamous cell carcinoma treated with definitive radiation in 35 fractions. Patient was treated with simultaneous integrated planning PTV_6996 (magenta), PTV_5940 (aqua), and PTV_5610 (almond) in 33 fractions. (a) FDG avid lesion in the left pyri- form sinus visualized on PET/CT, extends to midline with inferior margin approaching the post- cricoid region. (b) T1-post gadolinium contrast enhance MRI. Mass displaces the left aryepiglottic fold without definitive spread into the supraglottis. (c, d) bilateral coverage of retrostyloid and retropharyngeal lymph node regions with PTV_5610. (e) Continuation of bilateral lymph node coverage of bilateral level 2. (f–i) Inclusion of larynx from top of the hyoid to bottom of the cri- coid, posterior pharyngeal wall, lateral pharyngeal wall in the high-risk subclinical dose in PTV_5940. Bilateral level III covered by PTV_5610. (j, k) Inclusion of airway 2 cm below the bottom of cricoid, as well as coverage of level IV and VI due to the inferior extent of pyriform sinus tumor in the PTV_5610 low-risk volume. Alternative fractionations are 70 Gy/63 Gy/56 Gy over 35 fractions or a sequential technique therapy (surgery + adjuvant therapy as indicated, radiation, or chemoradiation). Larynx-preservation strategies are not ideal for patients with advanced T4 dis- ease, poor baseline function, and/or those unlikely to recover baseline function, although can be done in select cases. In the definitive setting, radiation treatment volumes should include gross disease, high-risk subclinical regions, and bilateral neck lymph node regions as outlined in Tables 5.3, 5.4, and 5.5. 5 Hypopharyngeal Carcinoma
- 71. 66 b d e f g h i j k i a c Fig. 5.2 T1N0 squamous cell carcinoma of posterior pharyngeal wall, with submucosal extension inferiorly into the post cricoid region treated with definitive radiation in 33 fractions: PTV_6996 (magenta), PTV_5940 (aqua), PTV_5610 (almond). (a) Superior extent of exophytic posterior pharyngeal wall mass as seen on flexible fiberoptic naso-pharyngo-laryngoscopy. On direct exam in the operating room, there is no involvement of the pyriform sinus or post-cricoid mucosa of the larynx. (b) FDG-avid mass on PET/CT extending along the posterior pharyngeal wall posterior to cricoid cartilage. (c, d) Bilateral coverage of lateral retropharyngeal and level II lymph nodes by PTV_5610. (e–h) PET-avid posterior pharyngeal wall disease with a 5 mm margin covered in PTV_6996. The high-risk subclinical region covered by PTV_5940 includes the gross tumor with 1 cm margin laterally and 2 cm superior/inferior margin. PTV_5940 also includes the entire poste- rior pharyngeal wall, lateral pharyngeal wall, and pre-vertebral fascia between the hyoid and cri- coid. The entire larynx and bilateral level III included in PTV_5610. (i–k) Coverage of bilateral level IV with PTV_5610. Alternative fractionations are 70 Gy/63 Gy/56 Gy over 35 fractions or a sequential technique L. Chen et al.
- 72. 67 a b c d e f c b f g h i Fig. 5.3 T3N0 squamous cell carcinoma of the pyriform sinus treated with definitive chemoradia- tion—35 fractions using sequential and serial cone down technique where first phase is 54 Gy in 1.8 Gy per fraction simultaneously 60 Gy in 2 Gy per fraction over 30 fractions with a 10 Gy boost in 2 Gy per fraction: PTV_70 (magenta), PTV_60 (aqua), PTV_54 (almond). (a) Pyriform sinus mass extending to the paraglottic space on CT. (b, c) Bilateral coverage of lateral retropharyngeal lymph nodes and level II. (d–g) Gross FDG avid disease with a 1 cm lateral margin, as well as the larynx from top of the hyoid to bottom of the cricoid, posterior pharyngeal wall, lateral pharyngeal wall in the high-risk subclinical dose in PTV_60. Bilateral level III treated to 54 Gy. (h, i) Bilateral Level IV and level VI treated to 54 Gy 5 Hypopharyngeal Carcinoma
- 73. 68 a b c d e f g h i j Fig. 5.4 T2N2b squamous cell carcinoma of the pyriform sinus treated with definitive chemora- diation in 35 fractions using sequential and serial cone down technique where first phase is 54 Gy in 1.8 Gy per fraction simultaneously 60 Gy in 2 Gy per fraction over 30 fractions with a 10 Gy boost in 2 Gy per fraction:: PTV_70 (magenta), PTV_60 (aqua), PTV_54 (almond). (a) Image obtained from flexible fiberoptic naso-pharyngo-laryngoscopy demonstrates a mass effacing the pyriform sinus as well as the left aryepiglottic fold. (b) FDG-avid left pyriform sinus lesion on PET/CT with additional FDG avid left level III and left level IV lymph nodes. (c, d) Retropharyngeal and retrostyloid lymph node coverage beginning at the skull base. The ipsilateral node-positive neck is treated to 60 Gy, the node-negative neck is treated to 54 Gy for this well lateralized tumor. (e) Bilateral coverage of level II. (f, g) Inclusion of the gross primary tumor with a 1 cm margin, the arytenoids, paraglottic space, larynx from hyoid to cricoid, as well as ipsilateral node positive neck in PTV_60. (h–j). Inclusion of FDG avid lymph nodes and a 5 mm margin in PTV_70. Bilateral coverage of level III, IV, inclusion of trachea 2 cm below the cricoid, with continuation of PTV_60 to the inferior extent of level IV. Alternatively a simultaneous integrated boost in one plan can be done L. Chen et al.
- 74. 69 a b c d e f g h i a g h i Fig. 5.5 T3N2c squamous cell carcinoma of the posterior pharyngeal wall—treated with defini- tive chemoradiation in 35 fractions using sequential and serial cone down technique where first phase is 54 Gy in 1.8 Gy per fraction simultaneously 60 Gy in 2 Gy per fraction over 30 fractions with a 10 Gy boost in 2 Gy per fraction:: PTV_70 (magenta, PTV_60 (aqua), PTV_54 (almond). (a) PET/CT demonstrates a 4.3 cm posterior pharyngeal wall mass extending inferiorly to the cervical esophagus as well as bilateral FDG avid lymph nodes. (b–d) Coverage of bilateral lateral retropharyngeal and level II lymph nodes starting at the skull base. (e–i) Primary tumor and FDG avid lymph nodes treated to 70 Gy. High-risk primary subclinical region (including 2 cm past inferior extent of tumor) as well as bilateral cervical lymph nodes, and left level V covered by PTV_60 given that there is gross nodal disease. The larynx, level VI, and superior mediastinal nodal regions treated to 54 Gy.Alternatively a simultaneous integrated boost in one plan can be done 5 Hypopharyngeal Carcinoma
- 75. 70 Table 5.3 Suggested target volumes for the gross disease regiona Target volumes Definition and description GTV_70 – Primary: All gross disease delineated on CT, MRI, or PET – Lymph nodes: Lymph nodes ≥1 cm, or suspicious FDG avid lymph nodes CTV_70 At MSKCC an additional margin for CTV_70 is not utilized routinely. However, if there is uncertainty with regard to extent of disease, a margin can be utilized – Primary: GTV_70 + 5 mm margin – Lymph nodes: GTV_70 + 3 mm margin (Note: In general GTV_70 = CTV_70 where no additional CTV margin is needed) PTV_70 – Primary: CTV_70 + 3–5 mm margin (based on comfort with daily imaging and set-up error) – Lymph nodes: CTV_70 + 3-5 mm margin a Dose suggested for 70 Gy prescribed in 2 Gy fractions. If using a 70/60/54 for gross disease, high- risk and low-risk subclinical regions, respectively, can plan with a simultaneous integrated plan for 60 Gy/2 Gy fractions and 54 Gy/1.8 Gy fractions with a single 10 Gy cone down to PTV70 • Post-operative radiation. Adverse pathologic features that warrant post- operative radiation as per NCCN v.2019 include positive margins, close margins, extra-nodal extension, pT3–T4 primary, pN2–pN3 nodal disease, perineural invasion, vascular invasion, lymphatic invasion. Adjuvant radiation should start ideally within 6 weeks of surgery. The entire surgical bed and dissected node- positive neck should be included in high-risk sub-clinical region (Table 5.4 and Fig. 5.6). The dissected node-negative neck can be included in low-risk sub- clinical region (Table 5.5). • Radiationfollowinginductionchemotherapy.Inadditiontopost-chemotherapy targeting, pre-chemotherapy imaging should be fused for target delineation. The high-risk subclinical volume should include extent of pre-chemotherapy gross disease, as well as taking adjacent anatomical sites at risk for microscopic spread into consideration for coverage. This pre-chemotherapy CTV should be modified for anatomical differences after chemotherapy and exclude air and bone. L. Chen et al.
- 76. 71 Table 5.4 Suggested target volumes for the high-risk subclinical regiona Target volumes Definition and description CTV_60 • Primary: GTV_70 with a 1 cm margin + the entire subsite + the larynx (from hyoid to cricoid). Additional adjacent mucosal sits at risk for mucosal or submucosal infiltration should also be taken into consideration for coverage: – Pyriform sinus: Arytenoids, paraglottic space, and thyroid cartilage for laterally involved lesions, constrictor muscles or prevertebral muscle if there is posterior involvement, pre-epiglottic space or structures in the oropharynx if there is superior extension, and post-cricoid area for inferior lesions – Posterior pharyngeal wall: Pre-vertebral fascia and retropharyngeal space, consider coverage of adjacent oropharynx if there is superior extension, consider coverage of the proximal cervical esophagus if there is inferior extension – Post cricoid region: Consider coverage of pyriform sinuses for superior extending lesions, cover the cricoid cartilage if involved, and the proximal cervical esophagus if there is an inferiorly extending lesion • Lymph nodes: – Any lymph nodes in CTV_70 should be included – Ipsilateral or node positive neck: Lymph node regions that should be covered include the: lateral retropharyngeal lymph nodes (start at skull base at the entrance of carotid canal), II–IV (with inclusion of the retrostyloid space for superior level II) – For inferior hypopharyngeal tumors, pyriform sinus tumors involving the apex, and advanced T-stage—cover level VI – For midline post-cricoid and posterior pharyngeal wall tumors with an involved lymph node consider bilateral lateral retropharyngeal, II–IV, and VI coverage. For inferior tumors consider paratracheal coverage in the superior mediastinum – Retropharyngeal lymph node coverage in the node positive neck – Consider covering ipsilateral 1B if level II is involved. If posterior level II–IV lymph nodes consider covering level V Post-operative cases: Include the entire surgical bed and the bilateral dissected neck inclusive of clips and wired scars. Areas at risk for positive margin or extra capsular spread should be delineated in conjunction with the surgeon and this area can be treated to 66 Gy PTV_60 CTV_60 + 3–5 mm margin, depending on comfort with daily target localization a Dose suggested for 60 Gy prescribed in 2 Gy fractions. If using a 70/60/54 for gross disease, high- risk and low-risk subclinical regions respectively can plan with a simultaneous integrated plan for 60 Gy/2 Gy fractions and 54 Gy/1.8 Gy fractions with a single 10 Gy cone down to PTV70 5 Hypopharyngeal Carcinoma
- 77. 72 Table 5.5 Suggested target volumes for the low-risk subclinical regiona Target volumes Definition and description CTV_54 – Contralateral or N0 Neck: Lymph node regions that should be covered include the: lateral retropharyngeal lymph nodes (can start at C1 vertebral body), II–IV (level II can start where the posterior belly of the digastric crosses the internal jugular vein). Exception—in a midline hypopharyngeal tumor where bilateral retropharyngeal nodal region should be included – Exception: In midline hypopharyngeal tumors that are node-positive, the contralateral neck is also considered high risk PTV_54 CTV_54 + 3–5 mm margin, depending on comfort with daily target localization a Dose suggested for 60 Gy prescribed in 2 Gy fractions. If using a 70/60/54 for gross disease, high- risk, and low-risk subclinical regions respectively can plan with a simultaneous integrated plan for 60 Gy/2 Gy fractions and 54 Gy/1.8 Gy fractions with a single 10 Gy cone down to PTV70 a b c d e f g h i Fig.5.6 cT3N2c squamous cell carcinoma of the hypopharynx status post-pharyno-laryngectomy, cervical esophagectomy with jejunal reconstruction with positive margins and extranodal exten- sion with 9/52 lymph nodes positive bilaterally. (a, b) Bilateral retropharyngeal and retrostyloid space covered starting at the skull base. (c–i) Bilateral level II–IV, level IV covered given extensive nodal disease treated to 60 Gy. The entire surgical bed is included in PTV_60, with area of positive margin and extranodal extension delineated in conjunction with the surgeon and treated to 66 Gy L. Chen et al.
- 78. 73 5.5 Suggested Reading • Biau, Gregoire et al. (2019): An updated consensus guidelines of lymph node target volumes for head and neck cancers treated with IMRT/VMAT [19]. • Gupta et al. (2009): Outcome analysis of a large cohort of hypopharynx patients (n = 501) treated with a non-surgical approach [20]. • EORTC 24891: 10-year results of EORTC 24891 comparing surgery followed by radiation to induction chemotherapy followed by radiotherapy for hypopha- ryngeal carcinoma. Laryngeal preservation with induction chemotherapy fol- lowed by radiation, does not compromise disease control or survival, and allowed over 50% of survivors to retain their larynx [21]. • Lee et al. (2007): Concurrent chemotherapy and IMRT experience at MSKCC for locoregionally advanced laryngeal and hypopharyngeal cancers [22]. • Prades et al. (2010): A randomized phase III trial comparing induction chemo- therapy followed by radiation to concomitant chemoradiation in pyriform sinus carcinoma, demonstrating improved survival with concurrent chemoradiother- apy [23]. References 1. Ho CM, Lam KH, Wei WI, Yuen PW, Lam LK. Squamous cell carcinoma of the hypophar- ynx—analysis of treatment results. Head Neck J Sci Spec. 1993;15(5):405–12. https://doi. org/10.1002/hed.2880150507. 2. Candela FC, Shah J, Jaques DP, Shah JP. Patterns of cervical node metastases from squamous carcinoma of the larynx. Arch Otolaryngol Head Neck Surg. 1990;116(4):432–5. https://doi. org/10.1001/archotol.1990.01870040054013. 3. Lindberg R. Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer. 1972;29(6):1446–9. https://doi.org/10.100 2/1097-0142(197206)29:61446::aid-cncr28202906043.0.co;2-c. 4. Allen AM, Haddad RI, Tishler RB. Retropharyngeal nodes in hypopharynx cancer on posi- tron emission tomography. J Clin Oncol. 2007;25(5):599–601. https://doi.org/10.1200/ JCO.2006.09.1488. 5. Yoshimoto S, Kawabata K. Retropharyngeal node dissection during total pharyngolaryn- gectomy for hypopharyngeal cancer. Auris Nasus Larynx. 2005;32(2):163–7. https://doi. org/10.1016/j.anl.2004.11.003. 6. McLaughlin MP, Mendenhall WM, Mancuso AA, et al. Retropharyngeal adenopathy as a pre- dictor of outcome in squamous cell carcinoma of the head and neck. Head Neck J Sci Spec. 1995;17(3):190–8. https://doi.org/10.1002/hed.2880170304. 7. Byers RM, Wolf PF, Ballantyne AJ. Rationale for elective modified neck dissection. Head Neck Surg. 1988;10(3):160–7. https://doi.org/10.1002/hed.2890100304. 8. Shah JP. Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract. Am J Surg. 1990;160(4):405–9. https://doi.org/10.1016/ s0002-9610(05)80554-9. 9. Amatsu M, Mohri M, Kinishi M. Significance of retropharyngeal node dissection at radi- cal surgery for carcinoma of the hypopharynx and cervical esophagus. Laryngoscope. 2001;111(6):1099–103. https://doi.org/10.1097/00005537-200106000-00031. 5 Hypopharyngeal Carcinoma
- 79. 74 10. Curado MP, Hashibe M. Recent changes in the epidemiology of head and neck cancer. Curr Opin Oncol. 2009;21(3):194–200. https://doi.org/10.1097/CCO.0b013e32832a68ca. 11. Mourad M, Jetmore T, Jategaonkar AA, Moubayed S, Moshier E, Urken ML. Epidemiological trends of head and neck cancer in the United States: a SEER population study. J Oral Maxillofac Surg. 2017;75(12):2562–72. https://doi.org/10.1016/j.joms.2017.05.008. 12. Castelijns JA, Gerritsen GJ, Kaiser MC, et al. Invasion of laryngeal cartilage by cancer: com- parison of CT and MR imaging. Radiology. 1988;167(1):199–206. https://doi.org/10.1148/ radiology.167.1.3347723. 13. Roychowdhury S, Loevner LA,Yousem DM, ChalianA, Montone KT. MR imaging for predict- ing neoplastic invasion of the cervical esophagus.AJNRAm J Neuroradiol. 2000;21(9):1681–7. 14. Rumboldt Z, DayTA, Michel M. Imaging of oral cavity cancer. Oral Oncol. 2006;42(9):854–65. https://doi.org/10.1016/j.oraloncology.2006.01.010. 15. Wenig BL, Ziffra KL, Mafee MF, Schild JA. MR imaging of squamous cell carcinoma of the larynx and hypopharynx. Otolaryngol Clin North Am. 1995;28(3):609–19. 16. Di Martino E, Nowak B, Hassan HA, et al. Diagnosis and staging of head and neck can- cer: a comparison of modern imaging modalities (positron emission tomography, computed tomography, color-coded duplex sonography) with panendoscopic and histopathologic find- ings. Arch Otolaryngol Head Neck Surg. 2000;126(12):1457–61. https://doi.org/10.1001/ archotol.126.12.1457. 17. Adams S, Baum RP, Stuckensen T, Bitter K, Hör G. Prospective comparison of 18F-FDG PET with conventional imaging modalities (CT, MRI, US) in lymph node staging of head and neck cancer. Eur J Nucl Med. 1998;25(9):1255–60. https://doi.org/10.1007/s002590050293. 18. Schwartz DL, Ford E, Rajendran J, et al. FDG-PET/CT imaging for preradiotherapy staging of head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2005;61(1):129–36. https://doi.org/10.1016/j.ijrobp.2004.03.040. 19. Biau J, Lapeyre M, Troussier I, et al. Selection of lymph node target volumes for definitive head and neck radiation therapy: a 2019 update. Radiother Oncol. 2019;134:1–9. https://doi. org/10.1016/j.radonc.2019.01.018. 20. Gupta T, Chopra S, Agarwal JP, et al. Squamous cell carcinoma of the hypopharynx: single- institution outcome analysis of a large cohort of patients treated with primary non-surgical approaches. Acta Oncol. 2009;48(4):541–8. https://doi.org/10.1080/02841860802488839. 21. Lefebvre J-L, Andry G, Chevalier D, et al. Laryngeal preservation with induction chemo- therapy for hypopharyngeal squamous cell carcinoma: 10-year results of EORTC trial 24891. Ann Oncol. 2012;23(10):2708–14. https://doi.org/10.1093/annonc/mds065. 22. Lee NY, O'Meara W, Chan K, et al. Concurrent chemotherapy and intensity-modulated radio- therapy for locoregionally advanced laryngeal and hypopharyngeal cancers. Int J Radiat Oncol Biol Phys. 2007;69(2):459–68. https://doi.org/10.1016/j.ijrobp.2007.03.013. 23. Prades J-M, Lallemant B, Garrel R, et al. Randomized phase III trial comparing induction chemotherapy followed by radiotherapy to concomitant chemoradiotherapy for laryngeal pres- ervation in T3M0 pyriform sinus carcinoma. Acta Otolaryngol. 2010;130(1):150–5. https:// doi.org/10.3109/00016480902914080. L. Chen et al.
- 80. 75 6 Oral Cavity Cancers Keith Unger, Matthew Forsthoefel, Nadeem Riaz, Allen Chen, and Nancy Y. Lee Contents 6.1 General Principles of Planning and Target Delineation 75 6.1 General Principles of Planning and Target Delineation • Patients should undergo a comprehensive oral examination, biopsy, and imaging studies for staging and treatment planning. Computed tomography (CT) scan is commonly used to evaluate the local extent of the tumor and regional spread to cervical lymph nodes. CT is particularly valuable for detecting invasion into the mandible, maxilla, and pterygopalatine fossa. MRI is superior to CT in evaluat- ing soft tissue extension and perineural spread. Positron emission tomography (PET) scan is useful for detecting regional lymph nodes involvement and distant disease. K. Unger (*) · M. Forsthoefel Department of Radiation Medicine, Georgetown University Hospital, Washington, DC, USA e-mail: kxu2@gunet.georgetown.edu; Matthew.Forsthoefel@gunet.georgetown.edu N. Riaz · N. Y. Lee Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA e-mail: riazn@mskcc.org; leen2@mskcc.org A. Chen Department of Radiation Oncology, UC Davis Comprehensive Cancer Center, Sacramento, CA, USA e-mail: allen.chen@uci.edu © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_6
- 81. 76 • CT simulation with IV contrast should be performed. A bite block can be placed during simulation and throughout radiation to depress the tongue and protrude the lower lip, as well as to elevate the hard palate. In the case of extranodal extension or when the scar is at risk, tissue-equivalent skin bolus can be used. A wire should be placed on any surgical scars and drain sites. The patient should be immobilized in the supine position with the neck slightly hyperextended using a five-point thermoplastic mask. • In the definitive treatment setting, the clinical target volumes include the CTV70, which encompasses all known gross disease and is typically identical to the GTV70; the high-risk CTV (CTV59.4–66), which includes additional mar- gin around the primary gross disease and high risk nodal levels; and the low- risk CTV (CTV54), which includes nodal levels at lower risk as detailed in Table 6.1. • In the post-operative setting, the clinical target volumes include the high-risk CTV (CTV66), which includes regions of positive margins or extranodal exten- sion, when present; the intermediate risk CTV (CTV60), which includes the oper- ative bed and high-risk nodal regions; and the low-risk CTV (CTV54), which includes low-risk nodal levels as detailed in Table 6.2. • Suggested target volumes for specific subsites within the oral cavity are detailed in Table 6.3 (Figs. 6.1, 6.2, 6.3, 6.4, 6.5, and 6.6). Table 6.1 Suggested target volumes and dosing for definitive treatment of oral cavity cancers Target volumesa Definition and description GTV70 Primary: All gross disease on physical examination and imaging Neck nodes: All gross disease on physical examination and imaging CTV70 Same as GTV70, although a5 mm margin, excluding bone, can be added if there is uncertainty regarding the full extent of gross disease CTV59.4 Primary: Encompass the entire CTV70 and the entire anatomic subsite, e.g. if it is an oral tongue cancer, the entire oral tongue should be included in the subclinical target volume; if it is buccal mucosa tumor, the entire buccal mucosa should be included, etc. Neck nodes: nodal levels with pathologic involvement and adjacent ipsilateral or contralateral nodal regions at high risk for subclinical disease (site-specific recommendations given in Table 6.3) CTV54 Ipsilateral and/or contralateral uninvolved nodal levels at low risk for subclinical disease (site-specific recommendations given in Table 6.3) a Subscript numbers represent suggested prescribed doses. PTV70 is 69.96 Gy in 2.12 Gy/fraction, PTV59.4 is 59.4 Gy in 1.8 Gy/fraction, and PTV54 is 54 Gy in 1.64 Gy/fraction; alternative fraction- ations are 70 Gy in 2 Gy per fraction done in a sequential or simultaneous integrated boost techniques K. Unger et al.
- 82. 77 Table 6.2 Suggested target volumes and dosing for post-operative treatment of oral cavity cancers Target volumesa,b Definition and description CTV66 Primary: Regions of soft tissue/bone invasion or microscopically positive margins if present Neck nodes: Regions of extracapsular extension if present CTV60 Primary: Preoperative gross disease and the entire tumor bed and the entire relevant anatomic subsite Neck nodes: Preoperative gross disease; entire operative bed; and ipsilateral or contralateral nodal regions at high risk for subclinical disease (site-specific recommendations given in Table 6.3) CTV54 Ipsilateral and/or contralateral uninvolved nodal levels at low risk for subclinical disease (site-specific recommendations given in Table 6.3) a Subscript numbers represent suggested prescribed doses. PTV66 is 66 Gy in 2.2–2.0 Gy/fraction, PTV60 is 60 Gy in 2 Gy/fraction, and PTV54 is 54 Gy in 1.8 Gy/fraction b If gross residual disease is present, then a GTV should be delineated Table 6.3 Site-specific guidelines for clinical target delineation of oral cavity cancers Tumor site Stage High-risk clinical target volume (CTV59.4 or CTV60)a Low-risk clinical target volume (CTV54) Oral tongue, floor of mouth T1–T4N0 Tumor bed, entire oral tongue, base of the tongue, and bilateral levels I–IV at the physician’s discretion regarding whether some levels should be in the high-risk or low-risk target volumeb Bilateral levels I–IV at the physician’s discretion regarding whether some levels should be in the high-risk or low-risk target volume.b Prophylactic overage of level VI when indicated T1–T4N1–3 Same as above except to also include level VI nodal regions Same as above except to also include level VI nodal regions Buccal mucosa, retromolar trigone, hard palate, gingiva T1–T2N0 Tumor bed and ipsilateral levels I–IV at physician’s discretionb Ipsilateral lymph nodes levels I–IV at physician’s discretionb T3–T4N0 Tumor bed and ipsilateral levels I–IV Contralateral lymph nodes levels II–IVc T1–T4N1–3 Tumor bed and ipsilateral levels I–V or bilateral levels I–V if contralateral involved nodesc Contralateral lymph nodes levels II–IVc if uninvolved a 66 Gy for microscopically positive margins or extracapsular extension; 70 Gy if gross resid- ual disease b Decision to include in low- or high-risk region based on other tumor features, and at physician’s discretion. Level VI is a drainage site for oral tongue cancer, often in patients with node positive disease. Highly recommend including level VI in the target c For buccal mucosa, gingiva, retromolar trigone cancers that are well lateralized, treatment of the contralateral neck can be omitted at the discretion of the treating physician. Hard palate tumors are typically of salivary origin, i.e. adenoid cystic carcinoma where coverage of the track of trigeminal nerves should be included. Given the low nodal spread of these tumors, the neck can be omitted 6 Oral Cavity Cancers
- 83. 78 Fig. 6.1 A patient with squamous cell carcinoma of the oral tongue, pathologic stage T3N2b status post-partial glossectomy with microscopically positive surgical margins. (a) The high-risk CTV (CTV66) is shown in red and encompasses the positive margin. The intermediate-risk CTV (CTV60) is shown in green, and the low-risk CTV (CTV54) is shown in blue. Neck nodal levels I–V are included on the ipsilateral side and levels I–IV are included on the contralateral uninvolved side. Coverage of level V is recommended for oral tongue primaries, especially after surgical manipulation of the neck and ipsilateral nodal disease. (b) Level IA should be covered for oral tongue primaries. The use of bolus and flash is recommended when there are concerns of soft tis- sue involvement to provide adequate coverage. (c) The ipsilateral retrostyloid space is at risk for nodal metastasis, especially with level II nodal involvement. The retropharyngeal nodes are at low risk and are not included. Though not shown in this case, coverage of level VI is highly recom- mended especially for patients with node positive disease a K. Unger et al.
- 84. 79 c b Fig. 6.1 (continued) 6 Oral Cavity Cancers
- 85. 80 Fig. 6.2 A patient with squamous cell carcinoma of the buccal mucosa, pathologic stage T4aN0 with minimal cortical bone invasion status post-tumor resection, marginal mandibulectomy, and left neck dissection. The surgical margins were widely clear. The high-risk CTV (CTV60) is shown in green. Neck nodal levels I–IV are included on the ipsilateral side. The CTV extends cranially to the buccal-gingival sulcus and infratemporal fossa, caudally to the buccal-gingival sulcus and sub- mandibular gland, anteriorly at least to the lip commissure, and posteriorly to the retromolar tri- gone. Bolus is placed on the skin to provide adequate coverage of the high-risk CTV. Can include ipsilateral parotid if clinically concerned K. Unger et al.
- 86. 81 Fig. 6.3 A patient with squamous cell carcinoma of the retromolar trigone, pathologic stage T4aN2b with medial pterygoid involvement, status post-tumor resection with gross residual dis- ease in the tumor bed and right neck dissection. (a) The gross disease CTV (CTV70) is shown in shaded red and is delineated based on operative findings as well as pre- and post-operative imag- ing. The high-risk CTV (CTV59.4) is shown in red in the region of the tumor bed and in green in the ipsilateral neck. The low-risk CTV (CTV54) is shown in blue and includes the contralateral neck nodal levels IB–IV. (b) The pterygopalatine fossa is a gateway for tumor spread to the middle cranial fossa and should be adequately covered, especially with tumor invading the pterygoid mus- cle. (c) Post-operative tumor volumes should include coverage of the entire operative bed based on visualization of tissue inflammation and edema on the planning CT a 6 Oral Cavity Cancers
- 87. 82 c b Fig. 6.3 (continued) K. Unger et al.
- 88. 83 Fig. 6.4 A patient with squamous cell carcinoma of the gingiva, pathologic stage T4aN1 with bone invasion, status post-tumor resection, marginal mandibulectomy, and left neck dissection. (a) The high-risk CTV (CTV66) is shown in red, and encompasses the region of bone invasion by tumor. The intermediate-risk CTV (CTV60) is shown in green and includes the entire operative bed and ipsilateral neck nodal levels I–IV. (b) The low-risk CTV (CTV54) is shown in blue and includes the contralateral neck nodal levels I–IV. Given Node positive and T4 disease, the contralateral neck was included in the low risk subclinical region a 6 Oral Cavity Cancers
- 89. 84 b Fig. 6.4 (continued) K. Unger et al.
- 90. 85 Fig. 6.5 A patient with squamous cell carcinoma of the buccal mucosa, pathologic stage T2N3b status post-tumor resection and right neck dissection with extranodal extension in the nodal level IB. Surgical margins were negative but close along the deep margin. The high-risk CTV (CTV66) is shown in red and covers the nodal region with extranodal extension. The intermediate-risk CTV (CTV60) includes the operative bed and entire buccal mucosa. Neck nodal levels I–IV are included on the ipsilateral side. The CTV is extended cranially to the buccal-gingival sulcus and infratem- poral fossa at the inferior orbital rim, caudally to the buccal-gingival sulcus and submandibular gland, anteriorly at least to the lip commissure, and posteriorly to the retromolar trigone. Wide margins should be used, even for smaller primary tumors. Bolus is placed on the skin to provide adequate coverage of the high- and intermediate-risk CTVs. The low-risk CTV (CTV54) includes the contralateral neck nodal levels I–III due to the extent of nodal disease present in the ipsilat- eral neck 6 Oral Cavity Cancers
- 91. 86 Fig. 6.6 A patient with squamous cell carcinoma of the floor of mouth, pathologic stage T4aN2b with mandibular invasion status post-right hemi-mandibulectomy and bilateral neck. The high-risk CTV (CTV66) is shown in red includes the area of extensive bony invasion. The intermediate-risk CTV (CTV60) is shown in green and includes the entire operative bed and neck nodal levels I–V on the ipsilateral side. The ipsilateral retrostyloid space is also at high risk for nodal metastasis and should be included in the CTV60, especially with neck nodal level II involvement. The CTV60 is also extended to include the entire floor of mouth complex. The low-risk CTV (CTV54) is shown in blue and includes the contralateral nodal levels I–IV K. Unger et al.
- 92. 87 7 Nasal Cavity and Paranasal Sinus Tumors Ming Fan, Yao Yu, Jung Julie Kang, and Nancy Y. Lee Contents 7.1 General Principles of Anatomy and Patterns of Spread 87 7.2 Diagnostic Workup Relevant for Target Delineation 96 7.3 Simulation and Daily Localization 96 7.4 Target Volume Delineation and Treatment Planning 96 Further Reading 98 7.1 General Principles of Anatomy and Patterns of Spread • Tumors of the paranasal sinuses include diverse histologies with variable behav- iors, including squamous cell carcinoma, minor salivary gland adenocarcinoma, adenoid cystic carcinoma, esthesioneuroblastoma (ENB), sinonasal undifferenti- ated carcinoma (SNUC), small cell neuroendocrine carcinoma (SNEC), melano- mas, NUT midline carcinoma, among others. • Paranasal sinus and nasal cavity are interconnected via multiple ostia and sepa- rated only by thin septi, allowing for spread via local extension into adjacent cavities. M. Fan · Y. Yu · J. J. Kang · N. Y. Lee (*) Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA e-mail: fanm@mskcc.org; yuy2@mskcc.org; kangj1@mskcc.org; leen2@mskcc.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_7
- 93. 88 – – ENB, SNUCs, and SNECs arise in the superior nasal cavity easily invade the cribriform plate into the anterior cranial fossa. These regions should be encompassed in the target volume. – – Maxillary sinus cancers may invade the nasal cavity (via the porous medial wall), maxillary gingiva (through the lateral wall of the antrum), infratempo- ral or pterygopalatine fossa (via posterior spread), orbit (by direct extension superiorly or via the ethmoid sinuses). • Consider coverage of afferent and efferent cranial nerves for tumors with peri- neural extension. Generous margins should be given on cranial nerves as micro- scopic skip metastases are common and recurrences may be difficult to salvage. – – If cranial nerve involvement is present, it is important to cover the involved nerve(s) back to the skull base. – – Cranial nerve coverage is strongly recommended for adenoid cystic carcino- mas, even in cases without pathologic perineural invasion. • Elective nodal should be considered in selected cases. – – Elective neck radiation should be considered for ENB and advanced squa- mous cell carcinoma (especially if originating from the maxillary sinus or if there is involvement of areas with extensive lymphatic supply such as the nasopharynx, mucosa, skin, cheek, anterior nose, maxillary gingiva or alveo- lar ridge). • Suggested target volumes and prescription doses at the gross disease and high- and low-risk regions are detailed in Tables 7.1 and 7.2. • Figures 7.1, 7.2, 7.3, 7.4, and 7.5 show examples of target delineation based on different clinical cases. Table 7.1 Suggested target volumes and prescription doses for gross disease Target volumes Definition and description GTV70 a All gross disease on physical examination and imaging (CT and MRI). PET can help further define the tumor extent. MRI can help identify perineural invasion, which may be occult on PET CTV70 a Usually identical to GTV70. A 3–5 mm margin may be added if there is uncertainty in primary tumor delineation. Given the proximity to the nearby critical structures, this margin may be as small as 0 mm. In other words, GTV70 can equal CTV70 PTV70 a CTV70 + 3–5 mm depending on setup uncertainty. This can be reduced to 1 mm in areas near critical normal structures, such as the brainstem and optic chiasm a Prescription doses for the GTV are delivered in 1.8–2 Gy fractions to an total dose of 70 Gy M. Fan et al.
- 94. 89 Table 7.2 General principles for target volumes and prescription doses for high- and low-risk subclinical regions Target volumes Definition and description CTV60–66 a CTV60 encompasses regions at high risk for microscopic disease – In the post-operative setting, this should include the resection bed, areas of nodal extension, and all initial preoperative sites of disease. Consider coverage of the entire post-operative bed and flap – In the definitive setting, this should include a 5–10 mm expansion on the primary tumor and covering the relevant anatomic subsite, respecting anatomic boundaries CTV66 should be considered for positive margins or areas of extranodal extension. This may be delivered sequentially at 6 Gy in three fractions CTV50–54 CTV50–54 encompass the low-risk subclinical regions, including non-violated neck or prophylactic coverage of cranial nerves PTV60–66 CTV60–66 + 3–5 mm, depending on setup uncertainty and techniques used for image guidance. The PTV margins can be as small as 1 mm in areas adjacent to critical normal structures PTV50–54 CTV50–54 + 3–5 mm, depending on setup uncertainty and techniques used for image guidance a For postoperative cases, the clinical target volume contoured may be an expansion of the preop- erative and (when applicable) postoperative GTV, based on the extent and location of the tumor 7 Nasal Cavity and Paranasal Sinus Tumors
- 95. 90 Fig. 7.1 An example of a 61-year-old female patient with a T4aN0M0 SNUC of the nasal cavity. The patient received three cycles of induction chemotherapy followed by endoscopic resection of the tumor. Surgical margins were negative. She then received adjuvant chemoradiation with weekly cisplatin. The primary tumor bed was treated to 60 Gy (CTV60, orange), with the high-risk CTV covering the cribriform plate, ethmoid sinus, sphenoid sinus, and hard palate. Bilateral elec- tive nodal radiation was delivered to RP nodes and Levels 1B–4 (CTV54, pink) M. Fan et al.
- 96. 91 Fig. 7.2 Seventy-four-year-old male with an unresectable T4bN1M0 poorly differentiated SCC of the left maxillary sinus, with invasion of the anterior cranial fossa and cranial nerve involve- ment. The patient received definitive concurrent chemoradiotherapy. The gross primary tumor and involved lymph node were treated to 70 Gy (GTV70) in red. Subclinical CTV50 is noted in pink, encompassing the orbital floor, infraorbital fissure, foramen rotundum, pterygopalatine fossa, infratemporal fossa, and masticator space. CTV5050 covers the ipsilateral neck only, given the stage and grade. (Node positive side: retropharyngeal, IB–IV) 7 Nasal Cavity and Paranasal Sinus Tumors
- 97. 92 Fig. 7.2 (continued) M. Fan et al.
- 98. 93 Fig. 7.3 Sixty-six-year-old female with a moderately differentiated SCC of the anterior nasal cav- ity. The patient underwent endoscopic resection of the primary tumor and bilateral modified radi- cal neck dissection (Level I–IV). Pathology report noted a close surgical margin, and bilateral Level I lymph node metastases, along with extranodal extension. The patient then received adju- vant concurrent chemoradiotherapy. The low-risk CTV54 (green) encompasses the nasal cavity, RP nodes, and facial lymph nodes. The high-risk CTV60 (orange) encompasses the resection bed, all preoperative macroscopic disease extent, and levels 1B–4. CTV66 is noted in red, and covers the regions of extranodal extension 7 Nasal Cavity and Paranasal Sinus Tumors
- 99. 94 Fig. 7.4 An example of a 59-year-old female patient with a Kadish C esthesioneuroblastoma of the ethmoid sinus. The bulky tumor extended to the frontal lobe and she remained a non-surgical candidate even after three cycles of induction chemotherapy. She was referred to receive definitive chemoradiation. GTV70 is noted in red, and covered the primary tumor and involved lymph nodes. CTV60 is noted in orange, and encompassed all high-risk areas (cribriform plate, dura, medial maxillary sinus, ethmoid sinus, sphenoid sinus, nasal cavity, pterygopalatine fossa, foramen rotun- dum) as well as bilateral upper cervical neck (retropharyngeal and Level IB–II). CTV54 is noted in green for low-risk elective nodes in Levels III–IV bilaterally M. Fan et al.
- 100. 95 Fig. 7.4 (continued) Fig. 7.5 An example of a 77-year-old male patient with a T3N0M0 adenoid cystic carcinoma of maxillary sinus. Patient received maxillectomy and pathologic report noted positive margins. The post-op images revealed patchy residual tumor at the posterior maxillary wall. GTV70 is noted in red, which covers the gross residual tumor. CTV60 is noted in orange, and covered high-risk areas including nerve courses (superior orbital fissure, inferior orbital fissure, foramen rotundum, ptery- gopalatine fossa, Vidian canal). The elective neck was not treated in this case due to the patho- logical type 7 Nasal Cavity and Paranasal Sinus Tumors
- 101. 96 7.2 Diagnostic Workup Relevant for Target Delineation • Detailed review of the pre-operative history/symptoms, neurologic examination with emphasis on cranial nerve exam, pre and post-operative imaging, operative report, and pathology report are needed to define target volumes. • In addition to fiberoptic endoscopy, high-quality diagnostic imaging is critical for tumor localization: – – Early cortical bone erosion is best visualized on thin slice (1–2 mm cuts) high-resolution CT of the nasal cavity and paranasal sinuses with IV contrast. – – Soft tissue spread, intracranial extension, perineural invasion, and involve- ment of the cranial nerve foramina and canals are best visualized on a thin- sliced MRI with IV contrast and fat-suppressed sequences. – – PET/CT is helpful for identifying lymph nodes and metastatic disease. 7.3 Simulation and Daily Localization • The patient should be simulated supine with head rest with the neck extended in a five-point customized Aquaplast mask that immobilizes the head, neck, and shoulders. A shoulder pull board can be used to lower the shoulders out of the beam angle path. • A bite block may be used to push the tongue inferiorly away from the high-dose nasopharynx. For patients with many metal fillings, a custom mouthguard can be helpful to absorb electron scatter and mitigate treatment-related mucositis. • The CT simulation should use ≤3 mm slices with IV contrast. • The CT should include the entire vertex of the head through the carina. • The isocenter is typically placed at the arytenoids. • For postoperative cases, it is helpful to place a radiopaque marker on any scars. • There are various appropriate IGRT approaches. Daily imaging ideally consists of daily cone beam CT aligned to bone. Daily kilovoltage imaging aligned to bone and weekly cone beam CTs are also adequate. 7.4 Target Volume Delineation and Treatment Planning • The GTV should be delineated using all relevant clinical information derived from endoscopy, CT, MRI, and PET (Tables 7.1, 7.2 and 7.3). • The high-risk CTV should encompass all initial sites of disease and potential regions of subclinical tumor spread. – – All preoperative scans (CT and MRI) should be evaluated to ensure that the initial tumor volume is covered in the high-risk CTV. – – A detailed review of the operative report and pathology report are necessary to ensure appropriate CTV delineation. – – MRI should be used in all cases to assist target delineation of the tumor unless medically contraindicated. M. Fan et al.
- 102. 97 Table 7.3 Subsite-specific anatomical considerations for delineation of the primary CTV60– CTV66 and CTV70 Maxillary sinus SCC Superior: Orbital floor/skull base. Coronal MRI can be useful in delineating orbital floor involvement. In cases with intracranial extension, consider a 5 mm dural margin Inferior: Hard palate, including at least a 10 mm margin around the initial gross disease Medial: Nasal septum for lateralized cases. In cases with medial extension beyond the septum, consider coverage of the entire nasal cavity Lateral: Infratemporal fossa, including the masticator space. If there is lateral extension, consider extending coverage along the temporalis muscle Posterior: The pterygopalatine fossa and skull base, paying attention to include the infraorbital fissure. The posterior hard palate is innervated from a branch of CN V2. In cases with posterior involvement, cover the courses of CN V2/V3 to Meckel’s cave Nerves: Branches of the second division of the trigeminal nerve (CN V2), the infraorbital nerve, and the greater palatine nerves Nasal cavity SCC, ENB, SNUC, SNEC, melanoma Superior: Cribriform plate, if intact; otherwise include the dural graft. Consider a 5 mm margin along the dura in cases where the cribriform plate is involved or if there is gross intracranial extension Inferior: Hard palate Medial: Include the entire nasal cavity Lateral: Medial border of the ipsilateral maxillary sinus for localized cases Posterior: The pterygoid plates, pterygopalatine fossa, ethmoid sinus, and sphenoid sinus Nerves: Branches of the olfactory nerve (CN I), and the first and second divisions of the trigeminal nerve (CN V1 and CN V2) including the nasociliary and nasopalatine nerves SNEC: See nasal cavity volumes. There is a high risk for metastatic disease. Consider either standard fractionation or treatment to 45 Gy/30 fractions given BID. Elective nodal coverage may be omitted Nasal cavity mucosal melanoma: See nasal cavity volumes. There is a high risk for metastatic disease. Consider standard fractionation for larger tumors. For small tumors, treatment to 30–36 Gy in 6 Gy fractions given twice weekly to the primary site only Ethmoid sinus Superior: See nasal cavity Inferior: Include a 10 mm margin on the initial tumor extent. For early stage tumors, the inferior turbinate is acceptable. For more advanced tumors, include the hard palate Medial/Lateral: Nasal cavity, ethmoid sinuses, and the ipsilateral maxillary sinus. In cases where the lamina papyracea has been breached, include the medial rectus. More advanced orbital involvement may require additional coverage Posterior: Skull base. Include the sphenoid sinus. The retropharyngeal lymph nodes should be encompassed if the tumor involves the nasopharynx or for N1 disease Nodal metastases are uncommon. Consider elective nodal coverage for large tumors (T4) or high-grade disease (SCC or adenocarcinoma) Nerves: Branches of the first and second divisions of the trigeminal nerve (CN V1 and CN V2). Parasympathetic innervation is via the Vidian nerve – – Adenoid cystic carcinomas are highly neurotrophic, so target volumes should encompass the afferent and efferent local nerves to the skull base. – – ENB arise in the superior nasal cavity and tend to invade the cribriform plate and anterior cranial fossa in their early stages, so these regions should be encompassed in the high-risk CTV. 7 Nasal Cavity and Paranasal Sinus Tumors
- 103. 98 • The surgical approach (midface degloving, lateral rhinotomy, craniofacial resec- tion, or endoscopic resection) should be considered in the field design. – – If a craniofacial resection has been performed, the frontal graft should be included in the target volume. Surgical fiducial markers can help delineate the tumor bed. • Elective neck irradiation should be considered at the discretion of the treating physician, depending on primary tumor site and disease extension. – – Regional nodal drainage patterns include the retropharyngeal nodes, and IB–IV. – – Level V should be included in cases with nasopharyngeal involvement. – – Facial node coverage should be considered for nasal cavity tumors. – – Bilateral nodal irradiation is typically administered as most primaries are midline structures. – – Unilateral nodal radiation is administered for maxillary sinus cancers. • Suggested target volumes are detailed in Tables 7.1, 7.2 and 7.3 (Figs. 7.1, 7.2, 7.3, 7.4 and 7.5). • Planning. – – We favor a sequential cone down approach. An initial plan (30 fractions) with a dose-painting approach delivers 54 Gy (1.8 Gy/fx) and 60 Gy (2 Gy/fx) to the low and high-risk subclinical regions, respectively. This is followed by a cone down plan (5 fractions) which delivers an additional 10 Gy to gross dis- ease only for a total of 70 Gy over 35 fractions. Further Reading Bristol IJ, Ahamad A, Garden AS, et al. Postoperative radiotherapy for maxillary sinus cancer: long-term outcomes and toxicities of treatment. Int J Radiat Oncol Biol Phys. 2007;68:719–30. Chen AM, Daly ME, Bucci MK, et al. Carcinomas of the paranasal sinuses and nasal cavity treated with radiotherapy at a single institution over five decades: are we making improvement? Int J Radiat Oncol Biol Phys. 2007;69:141–7. Fan M, Kang JJ, Lee A, et al. Outcomes and toxicities of definitive radiotherapy and reirradia- tion using 3-dimensional conformal or intensity-modulated (pencil beam) proton therapy for patients with nasal cavity and paranasal sinus malignancies. Cancer. 2020;126(9):1905–16. Hoppe BS, Stegman LD, Zelefsky MJ, et al. Treatment of nasal cavity and paranasal sinus cancer with modern radiotherapy techniques in the postoperative setting—the MSKCC experience. Int J Radiat Oncol Biol Phys. 2007;67(3):691–702. Le QT, Fu KK, Kaplan MJ, et al. Lymph node metastasis in maxillary sinus carcinoma. Int J Radiat Oncol Biol Phys. 2000;46:541–9. M. Fan et al.
- 104. 99 8 Major Salivary Glands Michelle S. F. Tseng, Ivan W. K. Tham, and Nancy Y. Lee Contents 8.1 General Principles of Planning and Target Delineation 99 Reference 108 8.1 General Principles of Planning and Target Delineation • Contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the head and neck region, from the base of skull to the clavicles, should be performed for salivary gland cancer. • Neoplastic lesions are better visualized and delineated with MRI, given the supe- rior soft tissue contrast in the gland. The T1-weighted images can give an excel- lent assessment of the margin of the tumor, its deep extent, and its pattern of infiltration. With the addition of fat-saturated, contrast-enhanced T1-weighted M. S. F. Tseng (*) Department of Radiation Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore e-mail: michelle_tseng@nuhs.edu.sg I. W. K. Tham Radiation Oncology Centre, Mount Elizabeth Novena Hospital, Singapore, Singapore e-mail: ivan.tham@parkwaypantai.com N. Y. Lee Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA e-mail: leen2@mskcc.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_8
- 105. 100 imaging, perineural spread, bone invasion, or meningeal infiltration can be better visualized. • CT simulation with intravenous contrast can be performed where the primary tumor is in situ to help guide gross target volume (GTV) delineation. Fusion with diagnostic MRI when available is recommended. • Suggested target volumes at the gross disease and high-risk regions are detailed in Tables 8.1 and 8.2 (Figs. 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, and 8.9). Table 8.1 Suggested target volumes at the gross disease region Target volumes Definition and description GTV70 a (the subscript 70 denotes radiation dose delivered) Parotid or submandibular primary: all gross disease on physical examination and imaging Neck nodes: all nodes ≥1 cm in short axis diameter or nodes with necrotic center CTV70 Add 5 mm so that GTV70 + 5 mm = CTV70 Alternatively, GTV70 can also be equivalent to CTV70 when the treating MD is certain of the target For nodes that are small but suspicious for disease (i.e., 1 cm), consider a lower dose of 63–66 Gy PTV70 Margin specific to treatment center and less if image guidance available Typically CTV70 + 3–5 mm = PTV70 a Suggested dose to gross disease is 2 Gy/fraction to 70 Gy Table 8.2 Suggested target volumes at the high-risk subclinical region Target volumes Definition and description CTV60 Parotid or submandibular CTV60 should encompass the entire GTV or the surgical bed for postoperative patients Landmarks for the parotid surgical bed Anterior: masseter muscle Lateral: soft tissue of neck Medial: styloid process at depth; may need to extend to parapharyngeal fat depending on the extent of parotid gland Posterior: mastoid bone Landmarks for the submandibular surgical bed Include the entire surgical bed, all postoperative changes, and use the contralateral submandibular gland as a guide Highly consider a boost of 6–10 Gy to residual disease or positive margins. The surgeon should be encouraged to leave clips where possible for localization For cases with perineural involvement [1] Parotid tumors: Include facial nerve, glossopharyngeal nerve and V3; may need to extend to Meckel’s cave Submandibular and sublingual tumors: Include hypoglossal and lingual nerve; may need to extend to Meckel’s cave especially for adenoid cystic carcinoma; may also need to include facial nerve M. S. F. Tseng et al.
- 106. 101 Fig. 8.1 Axial contrast- enhanced CT image of a patient with a history of excision of a cutaneous squamous cell carcinoma (SCC) in the right temporal region, who now presents with an ipsilateral parotid mass, (arrowed) confirmed on biopsy to be metastatic SCC Target volumes Definition and description CTV50 Clinically node positive tumors Electively irradiate rest of the ipsilateral neck (levels Ib–V) to 50 Gy; can consider omitting level V Clinically node negative tumors Ipsilateral neck: Include at least levels Ib–III/IV for high-grade or large (T3–4) tumors. Adenoid cystic or acinic cell cancers typically do not require elective nodal irradiation because of the low risk of lymphatic spread Contralateral neck: Parotid tumors: Consider treating when clinically concerned Submandibular tumors: Consider treating when clinically concerned PTV60 Margin specific to treatment center and less if image guidance available Typically CTV60 + 3–5 mm = PTV60 Table 8.2 (continued) 8 Major Salivary Glands
- 107. 102 Fig. 8.2 CT simulation with 3-mm slices in a head shell was performed in the same patient fol- lowing superficial parotidectomy with clear margins. These are representative slices and not all slices are included. Of note, the temporal region where the skin cancer originated should also be included using either electrons matching to IMRT or 3D CRT, or an all-inclusive IMRT or 3D CRT plan, especially if the primary site treatment was less than a year prior. The structures at the base of skull in the first figure are labelled in Fig. 8.3. The orange contour denotes the CTV60 M. S. F. Tseng et al.
- 108. 103 Fig. 8.3 Base of skull Delineation of structures should be done using bone windows. Structures as follows: red foramen ovale, blue cochlea, orange vestibule, violet internal auditory canal, and green semicircular canals Fig. 8.4 The parapharyngeal space (red arrow) is a predominantly fat-filled space extending from the base of skull to the hyoid and should be included for large or deep parotid tumors. The retrostyloid space (green arrow) is posterolateral to the styloid process, may contain lymph nodes, and should be included in the CTV60 8 Major Salivary Glands
- 109. 104 Fig. 8.5 Stylomastoid foramen. Note pattern of perineural recurrence in these T1-weighted contrast- enhanced MRI images, which show recurrent mucoepidermoid carcinoma of the left parotid gland infiltrating the left facial nerve through the stylomastoid foramen (green arrow heads). For parotid tumors, include facial nerve when involved or if histology is adenoid cystic carcinoma. Include intra-temporal course of the nerve, via the facial canal, which extends from the internal auditory canal to the stylomastoid foramen M. S. F. Tseng et al.
- 110. 105 Fig. 8.6 Skin. Include involved skin as a target structure by utilizing a bolus if there is clinical or radiological (red arrow) evidence of dermal infiltration. Include the scar in cases with perioperative tumor spillage Fig. 8.7 BONE. Assess bone involvement with bone windows on CT scans and include in CTV if required. White arrow indicates periosteal reaction at posterior aspect of left ramus of mandible, suggesting involvement 8 Major Salivary Glands
- 111. 106 Fig.8.8 Submandibular gland. Selected CT simulation images of a patient who underwent complete excision of a cT1N1M0 high-grade mucoepidermoid carcinoma of the right submandibular gland with clear margins. Structures as follows: red CTV60–66 (surgical bed) and green CTV50–54 (ipsilateral nodal stations and parapharyngeal space to base of skull). Lingual or hypoglossal nerves should be treated to base of skull especially when these named nerves are involved. The lingual nerve originates from the mandibular (V3) branch of the trigeminal nerve at the foramen ovale and courses deep to the lateral pterygoid muscle, then between the medial pterygoid muscle and the ramus of the mandible towards the medial aspect of the submandibular gland before terminating in the tongue M. S. F. Tseng et al.
- 112. 107 Jugular foramen Styloid process Fig. 8.9 The glossopharyngeal nerve exits the base of skull through the jugular foramen and descends down the neck, anterolaterally to the internal carotid artery, which is medial to the styloid process. It terminates in branches to the pharynx. Red oval denotes the course of the glossopharyn- geal nerve through different CT images. The last picture uses soft tissue windowing to show the expected location of the glossopharyngeal nerve 8 Major Salivary Glands
- 113. 108 Reference 1. Armstrong K, Ward J, Hughes NM, Mihai A, Blayney A, Mascott C, et al. Guidelines for clini- cal target volume definition for perineural spread of major salivary gland cancers. Clin Oncol (R Coll Radiol). 2018;30(12):773–9. M. S. F. Tseng et al.
- 114. 109 9 Thyroid Cancer Kaveh Zakeri, Shyam S. D. Rao, Nadeem Riaz, Nancy Y. Lee, and Robert L. Foote Contents 9.1 General Principles of Planning and Target Delineation 109 9.1 General Principles of Planning and Target Delineation • In addition to thorough physical examination, adequate imaging studies should be obtained for diagnosis, staging, and planning. The use of iodinated contrast with CT imaging should be avoided if the patient will subsequently require radioactive iodine administration as it can interfere with uptake for up to 6 months. MRI and ultrasound may be valuable in detecting lymphadenopathy or extrathyroidal extension. Unlike most well-differentiated thyroid carcinomas, poorly differentiated or anaplastic thyroid cancer may be FDG-avid. • CT simulation should be performed to help guide the gross target volume (GTV) delineation, particularly for the lymph nodes. As above, the use of iodinated contrast should be clearly justified as necessary before administered. K. Zakeri (*) · N. Riaz · N. Y. Lee Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA e-mail: zakerik@mskcc.org; riazn@mskcc.org; leen2@mskcc.org S. S. D. Rao Department of Radiation Oncology, UC Davis Cancer Center, Sacramento, CA, USA e-mail: sdrao@ucdavis.edu R. L. Foote Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, MN, USA e-mail: foote.robert@mayo.edu © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_9
- 115. 110 • A thermoplastic mask to immobilize the head, neck, and shoulders is preferable to immobilizing only the head and neck region. The head should be slightly extended to lower the dose to the oral cavity. • Gross disease or tumor bed with positive margins should be treated to 66–70 Gy. At-risk regions should be treated to 54–63 Gy. Patients may be treated in 30–35 fractions with an all-in-one dose-painting IMRT plan or alternatively an initial IMRT course followed by a boost. We recommend clinical target volume (CTVs) be treated with daily fractions sizes between 1.8 and 2 Gy. • Target volumes include GTV and CTV which should be delineated on every slice of the planning CT. Accurate selection and delineation of CTV for gross disease (i.e., CTV66–70) and at-risk subclinical region (CTV54–63) is critical for the treat- ment of thyroid cancer using IMRT. Suggested target volumes for gross disease and at-risk regions are detailed in Tables 9.1 and 9.2 (Figs. 9.1, 9.2, 9.3, 9.4, and 9.5). Table 9.1 Suggested target volumes for gross disease Target volumes Definition and description GTV66–70 a (the subscript 66–70 denotes the radiation dose delivered) Primary: All gross disease on physical examination and imaging Neck nodes: All nodes ≥1 cm or with necrotic center CTV66–70 a Usually CTV66–70 is the same as GTV66–70. If a margin is needed due to uncertainty of the gross disease, add 3–5 mm so that GTV66–70 + 3–5 mm = CTV66–70 If the GTV is adjacent to the spinal cord, a 1-mm margin is acceptable, as protection of the spinal cord is required For suspicious nodes that are small (i.e., 1 cm), a lower dose of 66 Gy (CTV66) can be considered PTV66–70 a CTV66–70 + 3–5 mm, depending on variability in daily patient positioning. If the CTV is adjacent to the spinal cord, a 1-mm margin is acceptable a Suggested dose for gross disease is 70 Gy. In cases where there is concern for brachial plexus, laryngeal, spinal cord, lung, or esophageal toxicity, 66 Gy may be considered. In postoperative cases with gross resection but significant concern for residual disease based on positive margin(s), the tumor bed or region of concern can be treated to 66 Gy K. Zakeri et al.
- 116. 111 Table 9.2 Suggested target volumes for at-risk subclinical region Target volumes Definition and description CTV54–63 a Primary: Should include tracheoesophageal groove and 5-mm margin around any CTV66–70 In the postoperative setting, should encompass tumor bed and tracheoesophageal groove on the involved side(s). If tracheostomy performed, should also encompass tracheostomy stoma to the skin surface Optimally, the upper larynx (vocal cords/arytenoid cartilage and above) and posterior esophagus should be excluded, if not adjacent to tumor/tumor bed (See Table 9.1, regarding positive margins) Lateral Neck regions: Include bilateral nodal levels II–VII. However, coverage of the lateral necks can be omitted when treating the central compartment and the upper mediastinum down to the level of the carina as above. The level I and retropharyngeal nodes are generally omitted unless at risk PTV54–63 a CTV54–63 + 3–5 mm, depending on variability in daily patient positioning. If the CTV is adjacent to the spinal cord, a 1-mm margin is acceptable a Suggested at-risk subclinical dose: 60–63 Gy. Uninvolved nodal regions may be deemed as low- risk subclinical regions and treated to 54 Gy at the discretion of the treating physician Fig.9.1 A 58-year-old male with metastatic papillary thyroid carcinoma status post-multiple surgical resections who presented with an unresectable local recurrence and multiple mediastinal lymph nodes. He received definitive chemoradiotherapy to prevent local progression. CTV70Gy is in red and CTV60Gy is in green. Also, note that these are representative slices and not all slices are included a 9 Thyroid Cancer
- 117. 112 b Fig. 9.1 (continued) K. Zakeri et al.
- 118. 113 Fig. 9.2 A 73-year-old female with unresectable anaplastic thyroid carcinoma invading the lar- ynx, trachea, and esophagus. She received definitive chemoradiotherapy with concurrent doxoru- bicin to prevent local progression. CTV70Gy is in red and CTV60Gy is in green. Although the manubrium is not routinely encompassed in the at-risk volume, it was included for this patient with aggressive bulky anterior neck disease. These are representative slices and not all slices are included a 9 Thyroid Cancer
- 119. 114 b Fig. 9.2 (continued) K. Zakeri et al.
- 120. 115 Fig. 9.3 A 50-year-old woman with anaplastic thyroid carcinoma s/p resection with extra-thyroid extension and positive margins but no involved lymph nodes. She received post-operative chemo- radiation. CTV70Gy is in red and CTV60Gy is in green. CTV70Gy includes the tumor bed and surgical clips. These are representative slices and not all slices are included a 9 Thyroid Cancer
- 121. 116 b Fig. 9.3 (continued) K. Zakeri et al.
- 122. 117 Fig. 9.4 A 61-year-old woman with a multiply recurrent metastatic tall cell variant of papillary thyroid cancer s/p three prior surgeries who presented with a multi-focal recurrence. She was treated with definitive chemoradiation. GTV70Gy is in red and CTV60Gy is in green. These are repre- sentative slices and not all slices are included a 9 Thyroid Cancer
- 123. 118 b Fig. 9.4 (continued) K. Zakeri et al.
- 124. 119 Fig. 9.5 A 69-year-old woman with history of poorly differentiated thyroid cancer of follicular phenotype adherent to trachea and esophagus s/p resection and radioactive iodine who recurred with a right paratracheal mass that invaded the trachea followed by resection and neck dissection. She was treated with adjuvant chemoradiation. CTV60Gy is in green. Note that treatment of the lateral neck was omitted given the high risk for recurrence in the central compartment. These are representative slices and not all slices are included a 9 Thyroid Cancer
- 125. 120 b Fig. 9.5 (continued) K. Zakeri et al.
- 126. 121 10 Squamous Cell Carcinoma of Unknown Primary in the Head and Neck Daniel Ma, Nadeem Riaz, Allen Chen, and Nancy Y. Lee Contents 10.1 General Principles of Planning and Target Delineation 121 Further Reading 128 10.1 General Principles of Planning and Target Delineation • A thorough workup is necessary to rule out a site of origin before proceeding with a diagnosis of an unknown primary. At a minimum, this should consist of a careful physical examination including testing of the cranial nerves; fiberoptic examination visualizing the nasopharynx, oropharynx, larynx, and hypopharynx; and cross-sectional imaging with at least a high-resolution CT scan with con- trast. Detailed skin and scalp exam. D. Ma (*) Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA e-mail: ma.daniel@mayo.edu N. Riaz · N. Y. Lee Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA e-mail: RiazN@mskcc.org; leen2@mskcc.org A. Chen Department of Radiation Oncology, UC Davis Comprehensive Cancer Center, Sacramento, CA, USA e-mail: allenmc2@uci.edu © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_10
- 127. 122 • Obtaining a careful patient history is also critical to determine risk factors for cancer and to consider possible infraclavicular primary sources (e.g., thoracic, gynecologic, or gastrointestinal). PET/CT may identify some additional prima- ries not detected by other methods but should be performed before biopsy to decrease the incidence of false-positive findings. Panendoscopy may also be useful. • HPV and EBV testing should be performed to help determine possible primary locations. In AJCC eighth edition, HPV and EBV associated nodes are classified as T0 oropharynx or nasopharynx cancers, respectively. • Directed biopsies of all suspicious lesions in the pharyngeal axis are mandatory; blind biopsies of normal appearing mucosa have traditionally been recommended but are only occasionally helpful in identifying the primary tumor. • Transoral tongue base mucosectomy (i.e., lingual tonsillectomy) and at least ipsilateral palatine tonsillectomy may detect around 80% of unknown primary cases, particularly among HPV-related cases. Some centers will perform bilat- eral palatine tonsillectomies and may not perform lingual tonsillectomy. • For patients with a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and without extranodal extension, consider single modality therapy with either surgery or radiation therapy. • CT simulation with IV contrast should be performed to help guide delineation of involved lymph nodes. • If an extended field IMRT plan is used, a thermoplastic mask immobilizing the head, neck, and shoulders is preferable to only immobilize the head and neck region. • Treatment to the bilateral neck and areas of pharynx at risk for harboring a pri- mary is typically recommended. Some institutions have treated to the ipsilateral neck alone; however, the neck relapse rate and distant metastasis rate appear to be higher than with comprehensive radiotherapy. • Traditionally, the entire pharynx has been included in treatment. IMRT allows more specific targeting of the portions of the pharynx most likely to contain the original primary site and can better spare normal structures, thereby minimizing side effects. • The extent of the pharynx to irradiate must be determined on a case-by-case basis and remains an area of active investigation. For instance, irradiating the oropharynx alone may be sufficient for an HPV+ patient, whereas an EBV+ patient especially those with Asian ethnicity may only need treatment to the nasopharynx. The pattern of lymph node spread can further help guide decisions on how much of the pharynx to treat. Some authors have advocated sparing the larynx when there are no low lymph nodes involved. When in doubt, the entire pharynx should be treated. D. Ma et al.
- 128. 123 • For cases that have had full TORS evaluation, emerging data suggests that the pharyngeal axis may be safely spared, although this needs further prospective testing. • Cervical (levels Ib–V) and retropharyngeal lymph nodes should be included for the node positive neck. For the contralateral neck, nodal levels II–IV and the retropharyngeal nodes should be targeted to a prophylactic dose. • In the postoperative setting, concurrent chemotherapy should be considered when extracapsular extension is present (ECE). In the definitive setting, advanced nodal disease is a consideration for concurrent chemotherapy. • Suggested target volumes for gross disease and high-risk regions of the pharynx are detailed in Table 10.1 (Figs. 10.1, 10.2, and 10.3). Table 10.1 Suggested target volumes Target volumes Definition and description GTV70 a (the subscript 70 denotes the radiation dose delivered) All lymph nodes ≥1 cm in short axis, significantly FDG avid, or positive on biopsy. Contour any lymph nodes in doubt as GTV; GTV70 = CTV70 PTV70 a GTV70 + 3–5 mm depending on institutional accuracy of daily patient positioning CTVnasopharynx b Extends from the base of skull superiorly to the soft palate inferiorly. Anteriorly extends from the posterior choana to the posterior pharyngeal wall. Laterally ensures adequate coverage on the fossa of Rosenmüller CTVoropharynx b Extends superiorly from the surface of the soft palate to the floor of the vallecula inferiorly (or hyoid bone). Anteriorly, the base of tongue should be covered; however, an additional margin covering the oral tongue is not necessary. Laterally, the tonsils should be covered adequately. Posteriorly, the entire pharyngeal wall should be covered CTVlarynxhypopharynx b Extends superiorly from the hyoid bone to the bottom of cricoid cartilage PTVmucosa b A 3–5-mm expansion on the mucosal surface CTVs depending on institutional accuracy of daily patient positioning Note: If the patient underwent surgery, the postoperative dissected neck should be treated any- where from 60 to 66 Gy in 2 Gy per fraction a Suggested dose to gross disease is 70 Gy in 33–35 fractions b Suggested dose to mucosal surfaces at risk for harboring a primary is 54–60 Gy 10 Squamous Cell Carcinoma of Unknown Primary in the Head and Neck
- 129. 124 Fig. 10.1 A 62-year-old male with a TxN2a unknown primary referred for postoperative treat- ment. He underwent bilateral tonsillectomy and a right neck dissection which revealed a single 4.6-cm level II lymph node. Notice the difference in the target delineation in the involved neck versus the contralateral neck. The CTV66Gy is in red, the CTV54–60Gy is in green, and the CTV54Gy is in blue. Please note that these are representative slices and not all slices are included a D. Ma et al.
- 130. 125 b Fig. 10.1 (continued) Fig. 10.2 Sagittal image at midline demonstrating landmarks delineating nasopharynx, oropharynx, and larynx/hypopharynx. Viewing contours on the sagittal images can ensure adequate coverage of intended target. Red circle is radiographic iso-center 10 Squamous Cell Carcinoma of Unknown Primary in the Head and Neck
- 131. 126 Fig. 10.3 A 50-year-old gentleman with a TxN2c squamous cell carcinoma referred for definitive treatment. An open biopsy of a left-sided lymph node demonstrated extra-nodal extension. HPV ISH and p16 testing were negative. He received definitive chemoradiotherapy. The CTV70Gy is in red, the CTV60Gy is in green, and the CTV54Gy is in blue. Please note that these are representative slices and not all slices are included a D. Ma et al.
- 132. 127 b Fig. 10.3 (continued) 10 Squamous Cell Carcinoma of Unknown Primary in the Head and Neck
- 133. 128 Further Reading Amin MB, Edge S, Greene F, et al. AJCC cancer staging manual. 8th ed. New York: Springer International Publishing: American Joint Commission on Cancer; 2017. Barker CA, Morris CG, Mendenhall WM. Larynx-sparing radiotherapy for squamous cell carci- noma from an unknown head and neck primary site. Am J Clin Oncol. 2005;28:445–8. Farooqa F, Khandavillia S, Dretzke J, et al. Transoral tongue base mucosectomy for the identifica- tion of the primary site in the work-up of cancers of unknown origin: Systematic review and meta-analysis. Oral Oncol. 2019;91:97–106. Gillison ML, D’Souza G, Westra W, et al. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst. 2008;100:407–20. Grewal AS, Rajasekaran K, Cannady SB, et al. Pharyngeal-sparing radiation for head and neck carcinoma of unknown primary following TORS assisted work-up. Laryngoscope. 2020;130(3):691–7. Nieder C, Gregoire V, Ang KK. Cervical lymph node metastases from occult squamous cell carci- noma: cut down a tree to get an apple? Int J Radiat Oncol Biol Phys. 2001;50:727–33. Strojan P, Ferlito A, Langendijk JA, et al. Contemporary management of lymph node metasta- ses from an unknown primary to the neck: II. A review of therapeutic options. Head Neck. 2013a;35(2):286–93. Strojan P, Ferlito A, Medina JE, et al. Contemporary management of lymph node metastases from an unknown primary to the neck: I. A review of diagnostic approaches. Head Neck. 2013b;35(1):123–32. D. Ma et al.
- 134. 129 11 Early Breast Cancer Erin F. Gillespie, Brian Napolitano, and Shannon M. MacDonald Contents 11.1 General Principles of Planning and Target Delineation 129 References 136 11.1 General Principles of Planning and Target Delineation • Three-dimensional conformal radiation therapy (3D CRT) with appropriate compensation (i.e. field-in-field technique, mixed energy beams) providing homogeneous dose to the breast tissue is the standard technique for adjuvant radiation therapy for early stage breast cancer. The highest level of evidence sup- ports hypofractionated whole breast irradiation. • A subsequent boost to the tumor bed (lumpectomy cavity) further reduces the risk of local recurrence, but may be omitted in low-risk patients. Boost radiation planning is most often performed using an en face electron beam, with beam energy selection based on the depth to tumor bed plus a margin, not extending beyond the anterior surface of the pectoralis muscles. For a deep tumor bed, mini-tangents can be considered. • Accelerated partial breast irradiation (APBI), although not yet the standard of care, is an acceptable alternative for select low-risk patients with unifocal disease. E. F. Gillespie (*) Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA e-mail: efgillespie@ucsd.edu B. Napolitano · S. M. MacDonald Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA e-mail: bnapolitano@mgh.harvard.edu; smacdonald@mgh.harvard.edu © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_11
- 135. 130 Various treatment techniques can be considered including 3D CRT and intensity modulated radiation therapy (IMRT). • In addition to thorough physical examination, adequate pre-operative imaging studies and pathological examination should be obtained for diagnosis, staging, and radiation treatment planning. • All patients should undergo mammogram at diagnosis. Additional imaging com- monly includes ultrasound. Although indications for MRI are limited for early- stage disease, images may be available in some patients. Available pre-operative imaging studies should be reviewed prior to radiation planning to ensure adequate margins for whole breast radiation as well as accurate targeting of boost radiation and/or APBI. • Image-guided biopsy generally confirms a diagnosis of cancer. Surgery consist- ing of lumpectomy, or segmental excision, alone for ductal carcinoma in situ (DCIS) and lumpectomy and sentinel lymph node biopsy (SLNB) is recom- mended for early invasive disease. Pathology should be reviewed to ensure ade- quate margins (no tumor on ink for invasive and 2 mm for pure DCIS, per SSO-ASTRO Consensus Guideline 2016). It is preferred, but not required, for the surgeon to place surgical clips at the time of surgery to assist in delineation of the tumor bed and for radiographic localization prior to radiation delivery; clips can be particularly useful for APBI. • For whole breast radiation planning, a CT with ≤3 mm slice thickness should be performed in the supine or prone position. For APBI, a CT slice thickness of 1.5–2 mm through the lumpectomy cavity may enable improved delineation of the lumpectomy cavity. • For supine positioning, the patient should be positioned on a breast board with arms above the head. Deep inspiration breath hold (DIBH) should be considered for patients with left-sided breast cancer to reduce radiation dose to the heart. • Patients with pendulous breasts may benefit from prone positioning to reduce separa- tion and improve tissue homogeneity in treatment planning, which may reduce acute toxicity. Prone also reduces radiation to lung and may be used for heart-avoidance, though the heart can paradoxically move closer to the treatment field if the tumor bed abuts the chest wall. For prone positioning, patient should be placed prone on a dedi- cated prone breast board, and care should be taken to ensure that the patient is com- fortable as this is very important to facilitate reproducibility. Patients with orthopedic injuries to the back or neck may not be ideal candidates for prone positioning. • Organs at risk should include the heart and lungs in all cases in order to estimate dose to these critical structures. The heart should be contoured superiorly to the bifurcation of the pulmonary artery, and should include the pericardium and epicardial fat (between the heart muscle and pericardium), but does not need to extend to include pericardial fat outside the pericardium. While the best evidence for cardiac avoidance involves reducing the mean heart dose, data is emerging for importance of radiation dose to the left anterior descending (LAD) and left ventricle (LV) and those structures can also be contoured per published atlases by Feng et al. [1] and Duane et al. [2]. • Target volumes include the breast tissue and lumpectomy cavity for whole breast irradiation. For APBI, lumpectomy CTV and lumpectomy PTV should also be delineated. • Suggested target volumes are described in Table 11.1 (Figs. 11.1, 11.2, 11.3, 11.4, 11.5, 11.6, 11.7, and 11.8). E. F. Gillespie et al.
- 136. 131 Table 11.1 Suggested target volumes for 3-D treatment planning for early stage breast cancer Target volumes Definition and description Breast Clinical reference is required for breast tissue delineation. Breast tissue may be wired or borders may be placed clinically at the time of CT. Contour should include all glandular breast tissues. The cranial border should be below the head of the clavicle and at the insertion of the second rib. Caudal border is defined by the loss of breast tissue. Medial border is at the edge of the sternum and should not cross midline. Lateral border is defined by the midaxillary line but is dependent on ptosis of the breast tissue. Anterior border is the skin or a few millimeters from the surface of the skin (for dose reporting), and the posterior border is the pectoralis muscles and muscles of the chest wall. The volume should not include these muscles or the ribs. Borders may extend slightly beyond these definitions to ensure adequate margin on the lumpectomy cavity, particularly in extreme medial or lateral cases Lumpectomy cavity Seroma, surgical clips, and notable differences in the glandular breast tissue should be included. Comparison to the contralateral breast may be useful, particularly when fluid and/or surgical clips are not present. All imaging studies should be reviewed prior to planning to assist in delineating this volume. This volume should not extend outside of the breast tissue Lumpectomy CTVa Lumpectomy cavity with a 1.0–1.5-cm expansion. This volume should not extend outside of the body or into the pectoralis muscles and/or muscles of the chest wall Lumpectomy PTVa Lumpectomy CTV with a margin based on setup uncertainty and predicted patient motion (generally 0.5–1.0 cm). This volume may extend outside of the patient surface and into the pectoralis muscles and/or muscles of the chest wall. Adjustments to this volume may be necessary for dose-reporting purposes a For APBI only; for whole breast irradiation, the lumpectomy cavity alone is the target for boost Fig. 11.1 Axial images in the supine position for a woman with left-sided stage I breast cancer 11 Early Breast Cancer
- 137. 132 Fig. 11.2 Axial images in the prone position for a woman with left-sided DCIS Fig. 11.3 Axial images for APBI. Lumpectomy cavity is based on seroma, clips placed by sur- geon, and information from review of mammogram, US, and MRI, when available. CTV is typi- cally a 1.5-cm expansion around the lumpectomy cavity that excludes pectoralis muscle, rib, and chest wall and does not extend outside of the contoured breast tissue. Typically, the CTV does not extend to the skin (restricted to 5 mm from patient surface). PTV is formed by an expansion of approximately 5 mm (depending on institutional setup uncertainty) around the CTV E. F. Gillespie et al.
- 138. 133 Fig. 11.4 Supine breast plan using tangent fields with a field-in-field technique for homogeneity and a small MLC block for cardiac shielding. Prescribed dose is 42.4 Gy at 2.65 Gy per fraction followed by an electron boost to the lumpectomy cavity to 10 Gy at 2.5 Gy per fraction Fig. 11.5 Prone breast plan using tangent fields with a field-in-field technique. Prescribed dose is 42.4 Gy at 2.65 Gy per fraction followed by a mini-tangent photon boost to the lumpectomy cavity to 10 Gy at 2.5 Gy per fraction. The posterior edge of the field should include part of the pectora- lis muscle 11 Early Breast Cancer
- 139. 134 Fig. 11.6 APBI plan using a mini-tangent photon fields in combination with an en face elec- tron field Fig. 11.7 The tumor bed boost in the supine position. Electron energy (12 MEV) is selected to ensure coverage of the 90% isodose line to the anterior surface of the pectoralis muscle E. F. Gillespie et al.
- 140. 135 Fig. 11.8 The heart is contoured to include the pericardium but not the pericardial fat (red arrow) that extends outside the pericardium 11 Early Breast Cancer
- 141. 136 References 1. Feng, et al. https://pubmed.ncbi.nlm.nih.gov/20421148/. 2. Duane, et al. https://pubmed.ncbi.nlm.nih.gov/28233564/. E. F. Gillespie et al.
- 142. 137 12 Regional Lymph Node Irradiation for Breast Cancer Alice Y. Ho, Samantha A. Dunn, and Simon Powell Contents 12.1 General Principles of Target Delineation for Regional Nodal Irradiation in Breast Cancer 137 12.2 Target and Nodal Volumes for Unreconstructed Right Chest Wall 145 12.3 Target and Nodal Volumes for Reconstructed (Tissue Expander) Left Chest Wall 145 12.4 Conventional 3D Conformal Planning 145 References 145 12.1 General Principles of Target Delineation for Regional Nodal Irradiation in Breast Cancer • Patients undergo CT simulation in the treatment position with both arms extended above their head using breast board immobilization; IV contrast is optional. • In cases where the patient has an in-tact breast, the borders of the breast and the lumpectomy scar may be wired on the patient’s skin prior to scanning. • Patients are scanned from the cricoid through 5 cm below the clinically marked inferior port edge. The entirety of both lungs must be included. A. Y. Ho (*) · S. A. Dunn Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA e-mail: alice.ho@mgh.harvard.edu; SDUNN7@mgh.harvard.edu S. Powell Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA e-mail: powells@mskcc.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_12
- 143. 138 • The planning target volume (PTV) is defined as any breast tissue or chest wall, ipsilateral level I–III axillary lymph nodes, ipsilateral supraclavicular lymph nodes, ipsilateral interpectoral lymph nodes, and ipsilateral internal mammary lymph nodes (Figs. 12.1, 12.2, 12.3, 12.4, 12.5, 12.6, 12.7, 12.8 and Tables 12.1, 12.2, 12.3). • Bolus of 3 mm is used daily over the chest wall for all VMAT/IMRT plans. A thicker bolus (1 cm) may be applied in cases of inflammatory breast cancer in which the skin GTV dose is ≥100% of the prescription dose. Fig. 12.1 Coronal view. Red PTV, light orange CTV, blue level I lymph nodes, light purple level II lymph nodes, dark orange level III lymph nodes, green supraclavicular lymph nodes, yellow green internal mammary nodes (IMN) A. Y. Ho et al.
- 144. 139 Fig. 12.2 Sagittal view. Red PTV, light orange CTV, blue level I lymph nodes, light purple level II lymph nodes, dark orange level III lymph nodes, green supraclavicular lymph nodes, yellow green internal mammary nodes (IMN) 12 Regional Lymph Node Irradiation for Breast Cancer
- 145. 140 Fig. 12.3 Axial slices in the cranial to caudal direction Fig. 12.4 Sagittal view. Red PTV, light orange CTV, blue level I lymph nodes, light purple level II lymph nodes, dark orange level III lymph nodes, green supraclavicular lymph nodes, yellow green internal mammary nodes (IMN), yellow heart, dark purple contralateral breast A. Y. Ho et al.
- 146. 141 Fig. 12.5 Axial slices in the cranial to caudal direction Fig. 12.6 Axial view of three beams: a medial en face electron beam (red) matched to two lateral opposing tangent fields (blue and green) 12 Regional Lymph Node Irradiation for Breast Cancer
- 147. 142 Fig. 12.7 Coronal view of supraclavicular field and lymph node targets Fig. 12.8 3D view of a boost to the tumor bed: An en face electron field with a custom cutout (blue) encompasses the tumor bed (maroon), clips (light green) and lumpectomy scar (gray) A. Y. Ho et al.
- 148. 143 Table 12.1 Suggested target volumes at the gross disease region Target volumes Definition and description Clinical target volume (CTV) Breast tissue or chest wall as defined by RADCOMP Breast Atlas [1], ipsilateral regional lymph nodes [2], interconnecting lymphatic drainage routes, breast prosthesis (if present) and chest wall musculature/skin to be determined at risk for microscopic disease Planning target volume (PTV) A margin of 3–5 mm medially, 5–10 mm laterally, and 3–5 mm posteriorly with the exception of the internal mammary nodes (which should be 0 mm margin posteriorly), and 5–10 mm superiorly, inferiorly, and anteriorly (to include the skin surface) will be added to the CTV. The amount of lung can be trimmed per physician discretion Table 12.2 Breast VMAT dosimetric planning guidelines Structure Parameter Objective Target criteria—50 Gy in 25 fractions PTV D95% ≥95% V95% ≥95% D05% ≤110% Internal mammary node (IMN) D95% ≥100% Normal tissue criteria Ipsilateral lung V20Gy ≤33% V10Gy ≤68% Mean Gy ≤20 Gy Contralateral lung V20Gy ≤25% Heart V25Gy ≤25% Mean Gy ≤9 Gya ; ≤8 Gyb Dmax ≤50 Gy Left anterior descending artery (LAD) Dmax ≤50 Gy Contralateral intact breast Mean Gy ≤5 Gy Contralateral implant Mean Gy ≤8 Gy Esophagus Dmax ≤50 Gy Thyroid Mean Gy ≤20 Gy Brachial plexus Dmax ≤55 Gy 12 Regional Lymph Node Irradiation for Breast Cancer
- 149. 144 Table 12.3 Breast IMRT/VMAT dosimetric planning guidelines Structure Parameter Objective Target criteria—50 Gy in 25 fractions PTV D95% ≥95% V95% ≥95% D05% ≤110% Inside implant PVT D95% ≤120% Internal mammary node (IMN) D95% ≥90% Normal tissue criteria Non-DIBH DIBH Ipsilateral lung V20Gy 30% (33%) 27% (30%) V10Gy 65% (68%) 60% (63%) Mean Gy 18 Gy 18 Gy Contralateral lung V20Gy 5% Heart V25Gy—left breast 3% Right breast 0.5% Dmax 50 Gy Mean Gy—left breast and IMN D95% ≥ 90% 7 Gy (8 Gy) 6 Gy (7 Gy) Right breast and IMN D95% ≥ 90% 4 Gy Left breast and IMN D95% ≥ 100% 8 Gy (9 Gy) 7 Gy (8 Gy) Right breast and IMN D95% ≥ 100% 5 Gy If any of the constraints above cannot be achieved 10 Gy (12 Gy) 9 Gy (10 Gy) Left anterior descending artery (LAD) Dmax 25 Gy (35 Gy) Contralateral intact breast Mean Gy 6 Gy Contralateral implant Mean Gy 8 Gy Esophagus Dmax 35 Gy (40 Gy) Thyroid Mean Gy 20 Gy Brachial plexus Dmax 55 Gy Liver (for right side) Mean Gy 8 Gy (10 Gy) Stomach Mean Gy 5 Gy 3 Gy Cord Dmax 20 Gy DIBH deep inspiratory breath hold A. Y. Ho et al.
- 150. 145 12.2 Target and Nodal Volumes for Unreconstructed Right Chest Wall See Figs. 12.1, 12.2, and 12.3. 12.3 Target and Nodal Volumes for Reconstructed (Tissue Expander) Left Chest Wall See Figs. 12.4 and 12.5. 12.4 Conventional 3D Conformal Planning See Figs. 12.6, 12.7, and 12.8. References 1. MacDonald S et al. RADCOMP BreastAtlas. RTOG Foundation: Radiation Therapy Oncology Group, Feb 23. 2016. https://www.rtog.org/LinkClick.aspx?fileticket=eVB451KQ83M%3d tabid=429 2. DeSelm C,Yang TJ, Cahlon O, Tisnado J, KhanA, Gillespie E, Powell S, HoA. A 3-dimensional mapping analysis of regional nodal recurrences in breast cancer. Int J Radiat Oncol Biol Phys. 2019;103(3):583–91. Epub 2018 Oct 24. https://doi.org/10.1016/j.ijrobp.2018.10.021. 3. Dumaine VA, Saksornchai K, ZhouY, Hong L, Powell S, Ho AY. Reduction in low-dose to nor- mal tissue with the addition of deep inspiration breath hold (DIBH) to volumetric modulated arc therapy (VMAT) in breast cancer patients with implant reconstruction receiving regional nodal irradiation. Radiat Oncol. 2018;13(1):187. https://doi.org/10.1186/s13014-018-1132-9. 12 Regional Lymph Node Irradiation for Breast Cancer
- 151. 147 13 Lung Cancer N. Ari Wijetunga, Zhongxing Liao, and Daniel R. Gomez Contents 13.1 General Principles of Planning and Target Delineation 147 References 163 13.1 General Principles of Planning and Target Delineation • Computed tomography (CT)-based planning utilizing conformal techniques and respiratory motion management are the standard of care in the treatment of both NSCLC and SCLC. Three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and stereotactic body radiother- apy (SBRT) each use multiple beam angles and can vary in dose conformality. Thus, each approach requires accurate delineation of target volumes, normal structures, and organs-at-risk (OARs) and evaluation of dose volume histograms during planning. In addition, it is necessary to understand the at-risk nodal levels of the mediastinum, as have been previously published in consensus atlases such as that developed at the University of Michigan [1]. N. A. Wijetunga · D. R. Gomez (*) Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA e-mail: wijetunn@mskcc.org; gomezd@mskcc.org Z. Liao Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA e-mail: zliao@mdanderson.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_13
- 152. 148 • Simulation. Assessment of respiratory motion, correct patient positioning, and appropriate immobilization during radiation simulation are vital to radiation planning. Patients should ideally be simulated with their arms above their head to maximize the number of beam arrangements that can be utilized. A four- dimensional (4D) simulation should be performed to assess for internal motion. • In addition to the target volume, the following normal structures should be con- toured when in proximity to the treatment field: heart, lungs, spinal cord, esopha- gus, chest wall, great vessels, proximal bronchial tree (PBT), and the brachial plexus for superiorly located tumors or high paratracheal/supraclavicular lymph node involvement using available atlases [2]. The liver should be contoured for right lower lobe tumor located close to diaphragm. For low lying left lower lung tumors or left pleural tumor, the spleen may receive significant radiation. Consensus guidelines for contouring the brachial plexus are available [3] and should be referenced for accurate contouring. • For both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in the setting of gross disease, an involved field approach is widely accepted based on prior publications demonstrating a low rate of failure in elective nodal regions [4, 5] and a randomized trial showing improved outcomes with an involved field vs. elective nodal approach [6]. Therefore, elective nodal regions should not routinely be covered if the treating physician is confident in the under- standing of the sites of active disease. • Physicians should delineate targets utilizing a combination of the physical exam- ination, a CT scan with contrast, a positron emission tomography, and evaluation of the mediastinum with either a mediastinoscopy or endobronchial ultra- sound (EBUS). • The gross target volume is defined as macroscopic disease. There are two poten- tial approaches for expanding the GTV to subsequent target volumes. The first technique is performed by delineating the GTV and then assessing for internal motion, a structure called the iGTV. The iGTV is then expanded to create the iCTV and further expanded to yield the PTV. The second technique involves an expansion of the GTV to the CTV, followed by a further expansion to the ITV to account for internal motion, followed by a PTV expansion for daily variations in patient position and movement. This approach is also used in the post-operative setting, where there is no GTV or iGTV. • For early stage NSCLC, standard treatment margins from the iGTV to iCTV are 0–0.2 cm. The PBT should be consistently contoured. This structure includes the distal 2 cm of the trachea, the carina, the right and left mainstem bronchi, and the lobar bronchi. We define an area 2 cm beyond the PBT radially as the no-fly zone (NFZ). Doses for SBRT are variable depending on the location and extent of the lesion, with the primary criteria being achievement of a biologically equivalent dose (BED) of 100 Gy. • For locally advanced NSCLC (stage II–III), a margin from the iGTV to the iCTV of 0.5–0.8 cm is typically used, based on prior histologic analyses [7]. PTV mar- gins are dependent on estimation of setup error, often 1.0–1.5 cm if no assess- ment of management for internal motion or daily image-guided radiation therapy (IGRT), such as kV imaging or cone-beam CT scan; 0.5–1.0 cm if either 4D CT N. A. Wijetunga et al.
- 153. 149 planning or CBCT, but not both; 0.3–0.5 cm from CTV (or iGTV) to PTV for 4D CT planning and with kV/CBCT guidance, which is preferred. The standard dose in the chemoradiation setting is 60 Gy in 30 fractions. • In the postoperative scenario for NSCLC, there is no clear consensus as to target delineation. Historically, large fields were used including the tumor bed, involved lymph node levels, the bilateral mediastinum, ipsilateral bronchial stump, and supraclavicular lymph nodes for superiorly located tumors. This approach is now rarely used since the adoption of CT planning and comprehensive mediastinal lymph node dissection. Many institutions, including our own, now use a limited approach to treating the mediastinum, encompassing the involved lymph node regions and the ipsilateral bronchial stump, with consideration of inclusion of one lymph node level above and one level below the involved region. This approach is similar to that used in the Lung ART trial [8]. Generally, a CTV (no GTV present), ITV, and a PTV with an ITV to PTV expansion of approximately 0.5 cm are defined, contingent on available IGRT techniques. • For SCLC, a “standard” GTV to CTV margin has not been well defined. Margins of 0.5–1.0 cm are acceptable, often to include the ipsilateral hilum. We recom- mend that the CTV to PTV margin follows similar guidelines as that for NSCLC as noted above. Standard doses for limited stage SCLC are 45 Gy in 1.5 Gy frac- tions or 66–70 Gy in 2.0 Gy fractions. • Recommended target delineation does not differ significantly between limited and extensive stage SCLC, the latter being in the context of consolidative or pal- liative treatment. An involved field technique is utilized in both scenarios, with standard doses as depicted in Table 13.1. Standard doses for consolidation tho- racic radiation typically range from 30 to 45 Gy in ten fractions. • Standard treatment doses for NSCLC and SCLC are depicted in Table 13.1. Dose constraints are dependent on the total dose and the number of fractions delivered and guidance is provided in the Quantitative Analyses of Normal Tissue Effects Table 13.1 Appropriate radiation treatment regimens for lung cancer Lung malignancy scenario Accepted treatment doses NSCLC, stage I stereotactic body radiation therapy (SBRT)—peripheral Variable—include 54 Gy in 18 Gy fractions, 48 Gy in 12 Gy fractions, 50 Gy in four fractions, and 50 Gy in five fractions NSCLC, stage I SBRT—central Variable—include 50 Gy in five fractions, 70 Gy in ten fractions, 60 Gy in eight fractions NSCLC, stage II–III standard fractionation 60 Gy in 2 Gy fractions daily Postoperative 50–54 Gy in 1.8–2.0 Gy fractions—R0 resection 54–60 Gy in 1.8–2.0 Gy fractions—R1 resection 60 Gy in 2.0 Gy fractions (consider concurrent chemotherapy)—R2 resection SCLC, limited stage 45 Gy in 1.5-Gy fractions BID with chemotherapy OR 66–70 Gy in 2.0-Gy fractions daily SCLC, extensive stage 30–45 Gy in 3.0 Gy fractions for consolidative chest radiation 13 Lung Cancer
- 154. 150 in the Clinic publication [9]. The stages cited in are as per the eighth Edition Staging by the American Joint Committee on Cancer [10] (Table 13.1 and Figs. 13.1, 13.2, 13.3, 13.4, 13.5, 13.6, 13.7). Fig. 13.1 (a) Lymph node stations. (Reproduced with permission from [11].) (b) Risk of lymph node involvement by tumor location. (Adapted from [12]) Supraclavicular zone Upper zone AP zone Subcarinal zone Lower zone Hilar/Interlobal zone Peripheral zone 1 Low cervical, supraclavicular, and sternal notch nodes 2R Upper Paratracheal (right) 2L Upper Paratracheal (left) 3a Prevascular 3p Retrotracheal 4R Lower Paratracheal (right) 5 Subaortic 6 Para-aortic (ascending aorta or phrenic) 4L Lower Paratracheal (left) SUPERIOR MEDIASTINAL NODES AORTIC NODES INFERIOR MEDIASTINAL NODES N1 NODES 7 Subcarinal 8 Paraesophageal (below carina) 9 Pulmonary ligament 10 Hilar 11 Interlobar 12 Lobar 13 Segmental 14 Subsegmental a N. A. Wijetunga et al.
- 155. 151 Involved Node Station Lobe Involved by Primary Tumor Right Upper (n=45) Right Middle/ Lower (n=36) Left Upper (n=35) Left Lower (n=8) Upper Mediastinum (1) 9% 3% 0 % Paratracheal (2) 40% 31% 3 % Prevascular, retrotracheal, pretracheal (3) 73% 47% 29 % Lower paratracheal (4) 36% 28% 17% 13% Subaortic (5) – – 71% 13% Para-aortic (6) – – 43% 25% Subcarinal (7) 36% 69% 20% 38% Paraesophageal (8) 9% 11% 3% 50% Pulmonary ligament (9) 2% 6% 6 3% b % 0 % 0 % 0 % 1 Fig. 13.1 (continued) 0-2 mm expansion from iGTV to iCTV a Fig. 13.2 Early stage NSCLC [cT1N0] treated with SBRT. (a) A peripheral tumor treated with 54 Gy in three fractions. (b) A lesion in a medically inoperable patient approaching the pulmonary tree, receiving 48 Gy in four fractions. (c) A central lesion encroaching on the bronchi receiving 50 Gy in five fractions. Generally, we constrain the maximum point dose to the PBT at 55 Gy. GTV (yellow); iGTV (red); iCTV (green); PTV (sky blue); proximal bronchial tree, PBT (pink); no fly zone, NFZ (purple) 13 Lung Cancer
- 156. 152 2.0 cm expansion from PBT to NFZ 0.5 cm expansion from iCTV to PTV b c Fig. 13.2 (continued) N. A. Wijetunga et al.
- 157. 153 Fig. 13.3 Locally advanced NSCLC [cT1cN3M0] (IIIB). The patient had a 2.3-cm right upper lobe tumor with right hilar, subcarinal, precarinal, paratracheal and right supraclavicular lymph- adenopathy. Lung windows on CT scan are utilized to delineate the primary tumor and hilar region. Nodal stations delineated through assessment of PET/CT scan, CT scan with contrast, and endo- bronchial ultrasound. The patient received 60 Gy in 30 fractions. GTV primary tumor (red); GTV lymph nodes (light green); iGTV primary and lymph nodes (pink); iCTV (orange); PTV (aqua); brachial plexus (purple). Locally advanced NSCLC [cT1cN3M0] (IIIB). GTV tumor (red); GTV nodes (light green); iGTV (pink); iCTV (orange); PTV (aqua); brachial plexus (purple); esopha- gus (dark green) Right SCV LN Level 4R paratracheal LN Level 7 subcarinal LN Level 10 hilar LN 13 Lung Cancer
- 158. 154 iGTV accounting for LN motion iCTV edited to remove esophagus iGTV to iCTV 0.7 cm expansion iCTV to PTV 0.5 cm expansion iCTV edited to remove bone Dose coverage of PTV Fig. 13.3 (continued) N. A. Wijetunga et al.
- 159. 155 Fig. 13.4 Locally advanced lung adenocarcinoma [cT4N3M0] (IIIC). The patient presented with SVC syndrome and was found to have a large right hilar/suprahilar mass compatible with a pri- mary lung tumor vs. adenopathy and extensive mediastinal adenopathy including bilateral supra- clavicular metastasis. The patient was treated to 60 Gy in 30 fractions. GTV (red); iGTV (pink); iCTV (orange); PTV (aqua). Locally advanced lung adenocarcinoma [cT4N3M0] (IIIC). GTV (red); iGTV (pink); iCTV (orange); PTV (aqua); brachial plexus (purple); esophagus (dark green); larynx (yellow) 13 Lung Cancer
- 160. 156 L SCV LNs R SCV LNs Level 2L LNs Level 2R LNs Level 3a LNs Level 3p LNs Level 7 LNs Fig. 13.4 (continued) N. A. Wijetunga et al.
- 161. 157 Fig. 13.5 Postoperative radiation for NSCLC. The patient had a 5.8-cm LUL tumor with EBUS showing involved level 4L nodes [cT3N2]. The patient received neoadjuvant chemotherapy. Pathologic findings from surgery showed negative margins, with levels 5 and 10L positive for malignancy. A limited field including the tumor bed, levels 4L, 5, 7, the ipsilateral bronchial stump is covered per the Lung ART guidelines. The prescription dose was 1.8 Gy × 30 fractions = 54 Gy. CTV (orange); PTV (aqua); involved LNs (light green); heart (yellow). Postoperative radiation for NSCLC. CTV (orange); PTV (aqua); esophagus (dark green). Postoperative radiation for NSCLC. CTV (orange); PTV (aqua); esophagus (dark green) LUL mass preoperatively is the only PET avid disease LN levels above and below involved nodes are included 13 Lung Cancer
- 162. 158 Level 4L Level 5 Fig. 13.5 (continued) N. A. Wijetunga et al.
- 163. 159 Ipsilateral bronchial stump Level 7 Fig. 13.5 (continued) 13 Lung Cancer
- 164. 160 Fig. 13.6 Small cell lung cancer. The patient was found to have right paratrachael and right hilar masses showing cT2N2 limited-stage SCLC, with involvement of the anterior mediastinum and contiguous involvement of the right hilum and precarinal lymph nodes.An involved nodal approach was used, with coverage of the appropriate mediastinal and hilar regions. The prescription dose was 1.5 Gy × 30 fractions BID = 45 Gy. GTV (red); iGTV (pink); iCTV (orange); PTV (aqua); brachial plexus (purple); esophagus (dark green). Small cell lung cancer. GTV (red); iGTV (pink); iCTV (orange); PTV (aqua); brachial plexus (purple); esophagus (dark green) N. A. Wijetunga et al.
- 165. 161 iGTV iGTV to iCTV 0.6cm exansion iCTV to PTV 0.5cm exansion Fig. 13.6 (continued) 13 Lung Cancer
- 166. 162 Collapse of left lung Improved lung aeration Fig. 13.7 Metastatic pulmonary lesion. The patient presented with an obstructive lesion (left) and was treated with 45 Gy in 15 fractions. During treatment, the patient improved and through CBCT it was noted that they required adaptive re-planning to account for changes in the lung anatomy (right). GTV (red); CTV (orange); PTV (aqua); esophagus (green) N. A. Wijetunga et al.
- 167. 163 References 1. Chapet O, Kong FM, Quint LE, et al. CT-based definition of thoracic lymph node stations: an atlas from the University of Michigan. Int J Radiat Oncol Biol Phys. 2005;63:170–8. 2. Ritter T, Quint DJ, Senan S, Gaspar LE, Komaki RU, Hurkmans CW, Timmerman R, Bezjak A, Bradley JD, Movsas B, Marsh L. Consideration of dose limits for organs at risk of thoracic radiotherapy: atlas for lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. Int J Radiat Oncol Biol Phys. 2011;81(5):1442–57. 3. Kong FM, Ritter T, Quint DJ, et al. Consideration of dose limits for organs at risk of thoracic radiotherapy: atlas for lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. Int J Radiat Oncol Biol Phys. 2011;81(5):1442–57. 4. Rosenzweig KE, Sim SE, Mychalczak B, et al. Elective nodal irradiation in the treatment of non-small-cell lung cancer with three-dimensional conformal radiation therapy. Int J Radiat Oncol Biol Phys. 2001;50:681–5. 5. Rosenzweig KE, Sura S, Jackson A, et al. Involved-field radiation therapy for inoperable non small-cell lung cancer. J Clin Oncol. 2007;25:5557–61. 6. Yuan S, Sun X, Li M, et al. A randomized study of involved-field irradiation versus elec- tive nodal irradiation in combination with concurrent chemotherapy for inoperable stage III nons- mall cell lung cancer. Am J Clin Oncol. 2007;30:239–44. 7. Giraud P, Antoine M, Larrouy A, et al. Evaluation of microscopic tumor extension in non- small- cell lung cancer for three-dimensional conformal radiotherapy planning. Int J Radiat Oncol Biol Phys. 2000;48:1015–24. 8. Spoelstra FO, Senan S, Le Pechoux C, et al. Variations in target volume definition for post- operative radiotherapy in stage III non-small-cell lung cancer: analysis of an international contouring study. Int J Radiat Oncol Biol Phys. 2009;76:1106–13. 9. Marks LB, Yorke ED, Jackson A, et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys. 2010;76:S10–9. 10. American Joint Committee. Cancer staging manual. 8th ed. New York: Springer; 2010. 11. Rusch VW, Asamura H, Watanabe H, Giroux DJ, Rami-Porta R, Goldstraw P. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2009;4(5):568–77. 12. WatanabeY,ShimizuJ,TsubotaM,IwaT.Mediastinalspreadofmetastaticlymphnodesinbron- chogenic carcinoma: mediastinal nodal metastases in lung cancer. Chest. 1990;97(5):1059–65. 13 Lung Cancer
- 168. 165 14 Esophageal Cancer N. Ari Wijetunga, Daniel R. Gomez, and Abraham J. Wu Contents 14.1 General Principles of Planning and Target Delineation 165 References 176 14.1 General Principles of Planning and Target Delineation • The standard of care in radiotherapy for esophageal cancer involves computed tomography (CT)-based planning with conformal techniques. Both intensity- modulated radiation therapy (IMRT) and three-dimensional conformal radia- tion therapy (3D-CRT) use multiple beam angles and allow for variation in dose conformality. Thus, both approaches require accurate delineation of tar- get volumes, normal structures, and organs-at-risk (OARs) as well as evalua- tion of dose volume histograms during treatment planning. Because the esophagus begins in the neck at the lower border of the cricoid cartilage and anterior to the sixth cervical vertebra and descends through the mediastinum passing through the diaphragm into the abdomen, it is necessary to understand the anatomy of the neck, brachial plexus, mediastinum, lungs, heart, spinal cord, normal esophagus, and heart. A contouring atlas has delineated these structures and can be referenced [1]. N. A. Wijetunga · D. R. Gomez · A. J. Wu (*) Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA e-mail: wijetunn@mskcc.org; gomezd@mskcc.org; wua@mskcc.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_14
- 169. 166 • Simulation. Ideally, patients are simulated with their arms above their head to maximize the number of beam arrangements that can be used without having beams pass through the arms. For distal or GE junction tumors, measures should be taken to account for respiratory motion such as four-dimensional (4D) CT scanning, respiratory gating, or breath-hold techniques. In addition, when tumors involve the distal esophagus or GE junction, patients should be nil per os (NPO) for at least 2–3 h prior to simulation and each treatment to limit daily variation in anatomy from gastric and bowel gas. For IMRT, intravenous contrast at the time of simulation can better delineate nodal fields. • Using a 40 cm standard distance from the incisors to the GE junction, the cervi- cal esophagus extends from the incisors to approximately 15–20 cm, the upper or proximal thoracic esophagus extends from 18–20 to 25 cm, the mid or distal thoracic esophagus extends from 25 to 30–32 cm, and the abdominal esophagus extends from 30–32 to 40 cm. • When contouring esophageal cancer, it is helpful to address esophageal malig- nancies by their anatomic subdivision: upper-mid esophagus tumors (including malignancies of the cervical esophagus), thoracic esophagus tumors, and gastro- esophageal (GE) junction tumors. Tumors that span multiple esophageal subdivi- sions can follow the contouring guidelines of all involved subsets. Regardless of location of the tumor within the esophagus, the entire lungs should be contoured for proper DVH analysis. In malignancies of the upper esophagus, the brachial plexus and larynx should be contoured. In malignancies of the lower esophagus, the heart, the liver, the kidneys, the stomach, and adjacent bowel should be delin- eated [2]. • The following target structures should be delineated: gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV). At our institu- tion, we routinely define an ITV, the volume encompassing the internal motion of the GTV as observed on the 4DCT. The ITV is then expanded to a CTV, fol- lowed by a PTV. • Physicians should delineate the GTV with reference to CT and positron emission tomography (PET) imaging, as well as findings on upper endoscopy and endo- scopic ultrasound. The endoscopic ultrasound can be used to better stage the depth of invasion of the esophageal tumor and to classify small peri-esophageal lymph nodes that are difficult to classify with CT or PET scan. A bronchoscopy is recommended if a tumor is superior to the carina to rule out the presence of a tracheoesophageal fistula, which may delay radiotherapy. • Standard ITV to CTV expansions are 1 cm radially to encompass the peri- esophageal lymph nodes and 3–4 cm in the superior-inferior direction (oriented along the esophageal mucosa) to account for submucosal spread and the possi- bility of skip lesions. The expansion to CTV can be limited to 0.5 cm in areas overlapping the heart and uninvolved liver, assuming appropriate motion man- agement techniques. Because a 4 cm caudad margin for distal esophagus and GE N. A. Wijetunga et al.
- 170. 167 junction cases would include large volumes of stomach or abdominal viscera, only 2 cm margin to CTV along clinically uninvolved gastric mucosa is recom- mended, unless treating with preoperative-intent doses (≤4500 cGy) in which case a 4 cm or greater gastric margin may be appropriate, particularly for tumors with significant gastric extension. The uninvolved vertebral bodies and kidneys are excluded from CTV. For involved lymph nodes, a GTV to CTV margin of 0.5–1.0 cm can be utilized. If there are grossly involved periesophageal nodes, then the CTV should cover at least 1 cm cephalad to the involved nodes. An expansion of 0.5 cm from CTV to PTV is recommended. These recommended margins can be adjusted depending on the motion assessment technique and one’s confidence in having accurately covered the extent of disease. • Regional lymph nodes should be included in the CTV according to the location of the primary tumor within the esophagus. For proximal thoracic and cervical esophagus tumors, bilateral supraclavicular nodal basins are included. They are bounded cranially at the lower edge of the cricoid cartilage, and they are bounded anteriorly, posteriorly, and laterally by the sternocleidomastoid muscle. For proximal thoracic tumors, mediastinal lymph nodes are included in addition to the peri-esophageal nodes encompassing the entire trachea, levels 2 and 4, with extension towards the sternum and clavicular heads to encompass level 3. For distal tumors, the CTV should include the celiac nodes, which are bounded on the right by the lateral aspect of T12, on the left 0.5–1 cm beyond the lateral aspect of the aorta, posteriorly by vertebral bodies, and anteriorly by the pan- creas. For distal tumors, it is not necessary to include the superior mediastinal nodal stations electively, other than overlap with the aforementioned cranial expansions. For GE junction tumors, CTV should include para-aortic and the gastrohepatic ligament nodes in a volume bounded by the liver on the right, the stomach on the left. • When GE junction tumors significantly overlap the gastric cardia, it is unclear whether they have a gastric origin rather than a esophageal origin. To overcome this ambiguity, the Siewert–Stein classification defines GE junction tumors according to their epicenter relative to the GE junction: type I lesions have an epicenter 1–5 cm above the junction, type II lesions have an epicenter from 1 cm proximal to 2 cm distal to the junction, and a type III lesions have an epicenter 2–5 cm below GE junction. A reasonable cutoff for esophageal cancer is Siewert type II, and, in fact, the eighth edition AJCC staging system now defines esopha- geal tumors as those whose epicenter extends no more than 2 cm into the gastric cardia [3]. For Siewert Type II tumors, some or all of the splenic hilum and greater curvature nodal region may be included. Based on prevailing guidelines for gastric cancers, a diagnostic laparoscopy, J-tube placement, preoperative chemoradiation [4] or postoperative chemoradiation [5] can be considered. (Table 14.1 and Figs. 14.1, 14.2, 14.3, 14.4). 14 Esophageal Cancer
- 171. 168 Table 14.1 Summary of recommendations for contouring esophageal cancers Esophagus subdivision Definition ITV to CTV margin CTV to PTV margin Elective nodal coverage Dose Cervical Incisors to approximately 15–20 cm 3 cm superior and inferior (oriented along mucosa), 1 cm radially 0.5 cm Periesophageal, supraclavicular, ± anterior mediastinal 50.4 Gy in 1.8 Gy per fraction, with consideration of boost to 60–70 Gy for SCC Upper thoracic From 18–20 cm to approximately 25 cm 3 cm superior and inferior (oriented along mucosa), 1 cm radially 0.5 cm Periesophageal, supraclavicular, ± anterior mediastinal 50.4 Gy in 1.8 Gy per fraction Lower thoracic From 25 cm to approx. 37 cm 3 cm superior and inferior (oriented along mucosa), 1 cm radially 0.5 cm Periesophageal 50.4 Gy in 1.8 Gy per fraction (definitive) 41.4–50.4 Gy in 1.8 Gy per fraction (pre-operative) Abdominal (GE junction) From approx. 37 to 42 cm 3 cm superior (along esophageal mucosa) and 1–2 cm inferior (along gastric mucosa) for 50.4 Gy dose. For preoperative- intent doses (≤4500 cGy) ≥ 4 cm gastric margin may be appropriate 0.5 cm Periesophageal, gastrohepatic ligament (i.e. paracardiac and left gastric stations), celiac axis, ± splenic hilum 50.4 Gy in 1.8 Gy per fraction (definitive) 41.4–50.4 Gy in 1.8 Gy per fraction (pre-operative) N. A. Wijetunga et al.
- 172. 169 Fig. 14.1 Sixty-nine-year-old with SCC of the cervical/upper thoracic esophagus. PET scan images showing FDG avid primary and mildly avid paratracheal lymph nodes. EGD showed an ulcerating, submucosal mass 15–23 cm from the incisors. Sixty-nine-year-old with SCC of the cervical/upper thoracic. Brachial plexus (purple); larynx (yellow); GTV esophagus (red); GTV nodes (green); CTV (orange); PTV 54 Gy (aqua); PTV 60 Gy (dark blue) PET-avid paratracheal lower mediastinal node PET-avid primary 14 Esophageal Cancer
- 173. 170 Larynx CTV does not extend above cricoid Superior border of SCV LN field is at inferior border of cricoid cartilage Elective bilateral SCV node coverage Fig. 14.1 (continued) N. A. Wijetunga et al.
- 174. 171 Fig. 14.2 Eighty-one-year-old with a lower thoracic esophageal adenocarcinoma [uT3N1]. (a) PET imaging showing the primary and level 4R paratracheal lymph node. (b) Endoscopy showing partially obstructing and circumferential esophageal adenocarcinoma 31–35 cm from the incisors. (c) EUS showing T3 primary disease and suspicious level 4R lymph node. Eighty-one-year-old with a lower thoracic esophageal adenocarcinoma [uT3N1]. Brachial plexus (purple); stomach (dark green); GTV esophagus (red); ITV (pink); GTV nodes (light green); CTV (orange); PTV 50.4 Gy (dark blue) b c Level 4R lymph node PET-avid level 4R lymph node PET-avid primary a 14 Esophageal Cancer
- 175. 172 3-4 cm inferior coverage Level 4R lymph node with a 0.5 cm GTV to CTV margin Fig. 14.2 (continued) N. A. Wijetunga et al.
- 176. 173 Coverage of CTV to celiac axis CTV extends into proximal stomach Fig. 14.3 Seventy-five-year-old with gastroesophageal junction adenocarcinoma [uT3N0]. Stomach (dark green); large bowel (brown); GTV esophagus (red); CTV (orange); PTV 50.4 Gy (aqua) 14 Esophageal Cancer
- 177. 174 Fig. 14.4 Fifty-nine-year-old with adenocarcinoma of gastroesophageal junction [uT3N2]. (a) PET imaging showing FDG-avid paraesophageal nodes and primary located at 36–40 cm from the incisors. (b) Sagittal planning CT with contours. Stomach/duodenum (dark green); GTV nodes (light green); GTV esophagus (red); ITV (pink); CTV (orange); PTV 50.4Gy (aqua). Fifty-nine- year-old with adenocarcinoma of gastroesophageal junction [uT3N2]. Stomach/duodenum (dark green); GTV nodes (light green); GTV esophagus (red); CTV (orange); PTV 50.4 Gy (aqua) a b PET-avid paraesophageal lymph node PET-avid primary ITV showing movement of GTV CTV covering 3-4 cm above ITV N. A. Wijetunga et al.
- 178. 175 Inclusion of paraesophageal LN Fig. 14.4 (continued) 14 Esophageal Cancer
- 179. 176 References 1. Kong FM, Ritter T, Quint DJ, Senan S, Gaspar LE, Komaki RU, Hurkmans CW, Timmerman R, Bezjak A, Bradley JD, et al. Consideration of dose limits for organs at risk of thoracic radiotherapy: atlas for lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. Int J Radiat Oncol Biol Phys. 2011;81(5):1442–57. 2. Wu AJ, et al. Expert consensus contouring guidelines for intensity modulated radiation therapy in esophageal and gastroesophageal junction cancer. Int J Radiat Oncol Biol Phys. 2015;92:911–20. 3. Szántó I, VörösA, Gonda G, et al. Siewert–Stein classification of adenocarcinoma of the esoph- agogastric junction. Magy Seb. 2001;54(3):144–9. 4. Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, et al. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006;24(24):3953–8. 5. Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725–30. N. A. Wijetunga et al.
- 180. 177 15 Gastric Cancer Jeremy Tey, Jiade J. Lu, and Ivy Ng Contents 15.1 Anatomy and Patterns of Spread 177 15.2 Diagnostic Workup Relevant for Target Volume Delineation 180 15.3 General Principles of Planning and Target Delineation for Adjuvant Radiation for Adenocarcinomas of the Gastro-Esophageal Junction and the Stomach 181 15.4 Clinical Target Volumes for a Patient with T1N1M0 Adenocarcinoma of the Gastric Cardia Post Total Gastrectomy 187 15.5 Clinical Target Volumes for a Patient with T3N3M0 Adenocarcinoma of the Gastric Body Post Distal Gastrectomy 189 15.6 Clinical Target Volumes for a Patient with T2N1M0 Adenocarcinoma of the Antrum/Pylorus Post Distal Gastrectomy 191 15.7 Plan Assessment 192 References 196 15.1 Anatomy and Patterns of Spread • The stomach begins at the gastro-esophageal junction and ends at the pylorus. The greater curvature forms the left and convex border of the stomach, and the lesser curvature forms the right and concave border of the stomach. It is divided into four parts: the cardia, fundus, body, and antrum. Its wall is divided into five J. Tey (*) · I. Ng Department of Radiation Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore e-mail: jeremy_tey@nuhs.edu.sg; ivy_ng@nuhs.edu.sg J. J. Lu Shanghai Proton and Heavy Ion Centre, Shanghai, China © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_15
- 181. 178 layers: mucosa, submucosa, muscularis externa, subserosa, and serosa (Fig. 15.1a). • It is covered with peritoneum and is closely related to the left lobe of the liver, spleen, left adrenal gland, superior portion of the left kidney, pancreas, trans- verse colon, and major blood vessels including the celiac axis and superior mes- enteric artery (Fig. 15.1b). • Regions of stomach and the probability of gastric carcinoma, according to the primary location: tumours arising from gastro-esophageal junction, cardia, and fundus account for ~35%; from the body, ~25%; from antrum and distal stom- ach, ~40%. • Local extension: – – The tumour can invade locally with direct involvement of the liver, duode- num, pancreas, transverse colon, omentum, and diaphragm. – – Proximal tumours may spread upwards to involve the oesophagus. – – Perineural invasion can occur. • Regional lymph node metastases (Fig. 15.2 and Table 15.1): – – Lymph node involvement is seen in up to 80% of cases at diagnosis. – – Lymph node involvement depends on the origin of primary disease. – – Proximal/gastro-esophageal junction tumours may spread to lower parao- esophageal lymph nodes. – – Tumours of the body can involve all nodal sites. – – Tumours of the distal stomach/antrum may involve periduodenal and porta hepatic lymph nodes. Esophagus Cardia Longitudinal muscle layer Circular muscle layer Pyloric sphincter Duodenum Lesser curvature (medial surface) Pylorus Rugae Fundus Body Left gastroepiploic vessels Anterior surface Oblique muscle layer overlying mucosa Greater curvature (lateral surface) Aorta Head and uncinate process of pancreas Duodenum Right colic flexure Celiac trunk Portal vein Hepatic artery Bile duct Right suprarenal gland Inferior vena cava Right inferior phrenic Left inferior phrenic artery Left gastric artery Left suprarenal gland Splenic artery Hilum of spleen Left colic flexure Pancreatic duct Duodenojejunal junction Superior mesenteric vein and artery Ureter Stomach Spleen Right kideny Third part First part Second part Left kidney a b Fig. 15.1 Anatomy and relations of stomach J. Tey et al.
- 182. 179 a b Fig. 15.2 Lymph node groups surrounding the stomach Table 15.1 Lymph node stations commonly involved in gastric cancer (Japanese Research Society for the Study of Gastric Cancer—JRSGC) N1 1 Right cardial nodes 2 Left cardial nodes 3 Nodes along lesser curvature 4 Nodes along greater curvature 5 Suprapyloric nodes 6 Infrapyloric nodes N2 7 Nodes along left gastric artery 8 Nodes along common hepatic artery 9 Nodes along celiac axis 10 Nodes at the splenic hilus 11 Nodes along splenic artery N3 12 Nodes in the hepatoduodenal ligament 13 Nodes at the posterior aspect of pancreatic head 14 Nodes at the root of mesenterium N4 15 Nodes in the mesocolon of transverse colon 16 Para-aortic lymph nodes Source: Figure and table adapted from Hartgrink, Van De Velde (2005) Status of extended lymph node dissection: Journal of Surg Oncol 90:153–165. Used with permission from Wiley Inc. 15 Gastric Cancer
- 183. 180 15.2 Diagnostic Workup Relevant for Target Volume Delineation • Prior to radiotherapy planning, it is imperative to review surgical and pathology reports, and discuss with the surgeon to identify the areas considered to be the highest risk for recurrence; type of operation, i.e. total vs. partial gastrectomy, needs to be noted. • Preoperative CT scans should be reviewed to identify location of primary tumour and involved regional lymphatics. • 18-Fluodeoxyglucose (FDG) PET alone is not adequate diagnostic imaging modality for preoperative staging of gastric cancer as diffuse and mucinous tumour subtypes have low FDG uptake. • Consider pre-radiation quantitative renal perfusion study to evaluate relative bilateral renal function. • Post-operative diagnostic CT scan with oral and intravenous contrast is required with the identification of the following: – – Oesophagus and gastric remnant. – – Anastomosis (gastrojejunal, oesophagojejunal). – – Duodenal stump. – – Portal hepatis. – – Splenic hilum. – – Pancreas. – – Coeliac artery and superior mesenteric artery. • Type of surgery performed depends on location of tumour and histology pattern (Fig. 15.3). Esophagus Stomach Stomach Roux-en-Y esophago- jejunostomy Billroth II Gastro- jejunostomy Pancreas and ducts Pancreas and ducts Jejuno- jejunostomy Jejunostomy Jejunum Jejunum Duodenum Duodenum Tumor Tumor A A B B a’ a’ Alternative reconstruction c’ c’ d’ d’ a’ a’ a’ b’ b’ b’ b’ a b Esophagus Fig. 15.3 Types of gastric cancer surgery J. Tey et al.
- 184. 181 15.3 General Principles of Planning and Target Delineation for Adjuvant Radiation for Adenocarcinomas of the Gastro-Esophageal Junction and the Stomach • Patients should be fasted for 2–3 h before CT simulation and before treatments. • Radiotherapy planning CT scans of 3–5 mm thickness should be obtained with patient in the supine position with arms overhead, from top of diaphragm (for stomach) or carina (for tumour involving GE junction or cardia) to the bot- tom of L4. • Immobilisation with a vacuum bag such as VacLok® is recommend for treatment with intensity modulated radiotherapy (IMRT). • Intravenous contrast is preferred to demonstrate blood vessels and guide clinical target volume (CTV) delineation, particularly for lymph nodes; preoperative CT scans should be used to aid identification of preoperative tumour volume and nodal groups to be treated. • CTV for adjuvant radiation therapy for gastric cancer depends on the position of the primary disease as well as the status of lymph node metastasis. Suggested target volumes for CTV coverage depending on subsite are detailed in Tables 15.2, 15.3, 15.4, 15.5, 15.6, 15.7, 15.8 and Fig. 15.4. Table 15.2 Target volume definition and description Target volumes Definition and description GTV Gross residual disease defined by CT imaging and surgical findings PTV (residual disease) GTV/positive margins + 1.5 cm. Cone down boost after 45 Gy to a total dose of 50.4–54 Gy in 1.8 Gy/fraction CTV45 Coverage of nodal groups according to subsite (see Tables 15.5, 15.6, 15.7, and 15.8). Also includes remnant stomach, anastomosis (gastrojejunal, oesophagojejunal), duodenal stump PTV45 CTV45 + 1 cm margin. A larger margin may be required for organ motion and setup uncertainties Table 15.3 General considerations for clinical target volume Target volumes Definition and description Duodenal stump Should preferably be covered in patients who have had a partial gastrectomy for distal/antral tumours Should not be covered in patients with proximal/cardia tumours who have had a total gastrectomy Anastomosis Gastrojejunal anastomosis (partial gastrectomy for tumours of the distal stomach) Oesophagojejunal anastomosis (total gastrectomy for tumours of proximal stomach or GE junction) should be treated Para-aortic nodes Should be included for the entire length of the CTV Paraoesophageal nodes 4 cm margin of the oesophagus should be included in the clinical target volume for tumours of the gastro-esophageal junction 15 Gastric Cancer
- 185. 182 Table 15.4 General guidelines of impact of T and N category on inclusion of remaining stomach, tumour bed, and nodal sites within radiation fields AJCC eighth edition TN category Remaining stomach Tumour bed Nodes T1-2N0 (not into subserosa) No No No T2N0 (into subserosa) Variable Yes No T3N0 Variable Yes No T4N0 Variable Yes Variable T1-2N+ Yes No Yes T3-4N+ Yes Yes Yes This table was published in Clinical Radiation Oncology, fourth Edition, Leonard et al., Page 928, Copyright Elsevier Table 15.5 Recommended target volumes depending on stage and site of primary tumour in stomach: Gastro-esophageal (GE) Junction Site of primary and stage Remaining stomacha Tumour bed volumesa Nodal volume GE Junction If allows exclusion of 2/3 right kidney T stage dependent N stage dependent T2N0, invasion of subserosa Variable, dependent on surgical pathological findingsb Medial left hemidiaphragm; adjacent body of pancreas None or PG, PEN T3N0 Variable, dependent on surgical pathologic findingsb Medial left hemidiaphragm; adjacent body of pancreas None or PG, PEN, CN, MNc T4N0 Preferable but dependent on surgical pathologic findingsb As for T3N0 plus site(s) of adherence with 3–5 cm margin Nodes related to site(s) of adherence ± PG, PEN, CN, MN T1-2N+ Preferable Not indicated for T1, as above for T2 into subserosa Proximal PG, PEN, CN, MN T3-4N+ Preferable As for T3N0, T4N0 As for T1-2N+ and T4N0 PG perigastric, CN celiac, PEN perioesophageal, MN mediastinal This table was published in Clinical Radiation Oncology, fourth Edition, Leonard et al., Page 928, Copyright Elsevier a Use preoperative imaging (CT, barium swallow), surgical clips, and post-operative imaging (CT, barium swallow) b For tumours with 5 cm margins confirmed pathologically, treatment of residual stomach is optional, especially if this would result in substantial increase in normal tissue morbidity c Optional node inclusion for T2-3N0 lesions if adequate surgical node dissection (D2) and at least 10–15 nodes are examined pathologically J. Tey et al.
- 186. 183 Table 15.6 Recommended target volumes depending on stage and site of primary tumour in stomach: cardia/proximal third of stomach Site of primary and stage Remaining stomacha Tumour bed volumesa Nodal volume Cardia/ Proximal third of stomach Yes, but spare 2/3 of one kidney, usually right T category dependent N category dependent, spare 2/3 of one kidney T2N0, invasion of subserosa Variable, dependent on surgical pathological findingsb Medial left hemidiaphragm, adjacent body of pancreas ± tail None or PGc T3N0 Variable, dependent on surgical pathological findingsb Medial left hemidiaphragm, adjacent body of pancreas ± tail None or PG Optional: PEN, CN, MNc T4N0 Variable, dependent on surgical pathological findingsb As for T3N0 plus site(s) of adherence with 3–5 cm margin Nodes related to site(s) of adherence ± PG, CN, MN T1-2N+ Preferable Not indicated for T1 PG, CN, splenic, SP, ± MN, PD, PHd T3-4N+ Preferable As for T3N0, T4N0 As for T1-2N+ and T4N0 PG perigastric, CN celiac, SP suprapancreatic, PH porta hepatis, PD pancreaticoduodenal, PEN perioesophageal, MN mediastinal This table was published in Clinical Radiation Oncology, fourth Edition, Leonard et al., Page 928. e1, Copyright Elsevier a Use preoperative imaging (CT, barium swallow), surgical clips, and post-operative imaging (CT, barium swallow) b For tumours with 5 cm margins confirmed pathologically, treatment of residual stomach is optional, especially if this would result in substantial increase in normal tissue morbidity c Optional node inclusion for T2-3N0 lesions if adequate surgical node dissection (D2) and at least 10–15 nodes are examined pathologically d Pancreaticoduodenal and porta hepatis nodes are at low risk if nodal positivity is minimal (i.e. 1–2 positive nodes with 10–15 nodes examined), and this region does not need to be irradiated. Perioesophageal and mediastinal nodes are at risk if there is oesophageal extension 15 Gastric Cancer
- 187. 184 Table 15.7 Recommended target volumes depending on stage and site of primary tumour in stomach: body/middle third of stomach Site of primary and stage Remaining stomacha Tumour bed volumesa Nodal volume Body/mid third of stomach Yes, but spare 2/3 of one kidney T category dependent N category dependent, spare 2/3 of one kidney T2N0, invasion of subserosa Yes Body of pancreas ± tail None or PG Optional: CN, splenic, SP, PD, PHb T3N0 Yes Body of pancreas ± tail None or PG Optional: CN, splenic, SP, PD, PHb T4N0 Yes As for T3N0 plus site(s) of adherence with 3–5 cm margin Nodes related to site(s) of adherence ± PG, CN, splenic, SP, PD, PH T1-2N+ Yes Not indicated for T1EEEEE PG, CN, splenic, SP, PD, PH T3-4N+ Yes As for T3N0, T4N0 As for T1-2N+ and T4N0 PG perigastric, CN celiac, SP suprapancreatic, PH porta hepatis, PD pancreaticoduodenal, PEN perioesophageal, MN mediastinal This table was published in Clinical Radiation Oncology, fourth Edition, Leonard et al., Page 929, Copyright Elsevier a Use preoperative imaging (CT, barium swallow), surgical clips, and post-operative imaging (CT, barium swallow) b Optional node inclusion for T2-3N0 lesions if adequate surgical node dissection (D2) and at least 10–15 nodes are examined pathologically • Three areas must be identified as CTV for adjuvant radiotherapy: the gastric tumour bed, the anastomosis or stumps, and the regional lymphatics. • In addition, the hepatogastric ligament should preferably be treated in all cases as it is at high risk of recurrence. It represents the part of the lesser omentum that runs between the lesser curvature of the stomach and liver, and contains the left and right gastric nodes that are not always completely removed at surgery. • The benefits of IMRT have been suggested by many publications. If used, tumour bed and subclinical target volumes including lymphatic draining regions should be delineated. • Planning Target Volume (PTV): CTV + margin considering organ motion and setup uncertainties. A minimum expansion of 1 cm is suggested. • A total dose of 45 Gy in 25 fractions is recommended for adjuvant radiotherapy with concurrent chemotherapy, using high energy (≥6 MV) photons. Boosts to 50.4–54 Gy for positive margins or residual disease should be given, if doses to surrounding critical organs are within tolerance. J. Tey et al.
- 188. 185 Table 15.8 Recommended target volumes depending on stage and site of primary tumour in stomach: antrum/pylorus/distal third of stomach Site of primary and stage Remaining stomacha Tumour bed volumesa Nodal volume Pylorus/distal third of stomach Yes, but spare 2/3 of one kidney, usually left T category dependent N category dependent, spare 2/3 of one kidney T2N0, invasion of subserosa Variable, dependent on surgical pathological findingsb Head of pancreas ± body, first and second portion of duodenum None or PG Optional: CN, SP, PD, PHc T3N0 Variable, dependent on surgical pathological findingsb Head of pancreas ± body, first and second portion of duodenum None or PG Optional: CN, SP, PD, PHc T4N0 Variable, dependent on surgical pathological findingsb As for T3N0 plus site(s) of adherence with 3–5 cm margin Nodes related to site(s) of adherence ± PG, CN, SP, PD, PH T1-2N+ Preferable Not indicated for T1 PG, CN, SP, PD, PH Optional: Splenic hilum T3-4N+ Preferable As for T3N0, T4N0 As for T1-2N+ and T4N0 PG perigastric, CN celiac, SP suprapancreatic, PH porta hepatis, PD pancreaticoduodenal, PEN perioesophageal, MN mediastinal This table was published in Clinical Radiation Oncology, fourth Edition, Leonard et al., Page 929, Copyright Elsevier a Use preoperative imaging (CT, barium swallow), surgical clips, and post-operative imaging (CT, barium swallow) b For tumours with 5 cm margins confirmed pathologically, treatment of residual stomach is optional, especially if this would result in substantial increase in normal tissue morbidity c Optional node inclusion for T2-3N0 lesions if adequate surgical node dissection (D2) and at least 10–15 nodes are examined pathologically 15 Gastric Cancer
- 189. 186 Fig. 15.4 Nodal distribution and clinical target volumes for adjuvant radiotherapy for gas- tric cancer Paraesophageal Nodes Splenic Hilar Nodes Periesophageal Nodes Pancreaticoduodenal Nodes Gastric remnant/perigastric Nodes Celiac Nodes Portahepatic Nodes Superior mesenteric nodes Nodes along the splenic artery Duodenum J. Tey et al.
- 190. 187 15.4 Clinical Target Volumes for a Patient with T1N1M0 Adenocarcinoma of the Gastric Cardia Post Total Gastrectomy 15 Gastric Cancer
- 191. 188 Coverage of esophagojenunal anastomosis Coverage of hepatogastric ligament Coverage of celiac artery Coverage of splenic hilum J. Tey et al.
- 192. 189 15.5 Clinical Target Volumes for a Patient with T3N3M0 Adenocarcinoma of the Gastric Body Post Distal Gastrectomy 15 Gastric Cancer
- 193. 190 Coverage of remnant stomach Coverage of splenic hilum Coverage of Celiac artery Coverage of gastrojejunal anastomosis J. Tey et al.
- 194. 191 15.6 Clinical Target Volumes for a Patient with T2N1M0 Adenocarcinoma of the Antrum/Pylorus Post Distal Gastrectomy 15 Gastric Cancer
- 195. 192 Coverage of gastrojejunal anastomosis Coverage of remnant stomach Coverage of hepatogastric ligament Coverage of duodenal stump Optional coverage of splenic hilum 15.7 Plan Assessment • In advanced cases, we typically prioritise normal structure constraints, specifi- cally spinal cord, kidneys, and liver over full coverage of the tumour. • Ideally, when using 3D conformal technique, 100% of PTV45 should receive ≥42.75 Gy (95% of prescribed dose) as per ICRU 62. If using IMRT, 98% of PTV should receive ≥42.75 Gy (95% of prescribed dose) as per ICRU 83. • Critical normal organs at risk (OAR) surrounding the CTV need to be outlined. Dose constraints are outlined in Table 15.9. Table 15.10: From the above trials, it may be argued that adjuvant chemoradio- therapy should be reserved for patients with involved margins, pT3 or T4, less than D2 resection. In ARTIST trial, patients with node-positive disease benefited from addition of radiotherapy but this benefit was not demonstrated in ARTIST II. J. Tey et al.
- 196. 193 Table 15.9 Dose limitations of OAR in radiation therapy for upper abdominal malignancies OAR Dose limitation End point Rate (%) Spinal cord • Dmax = 50 • Dmax = 60 • Dmax = 69 Myelopathy • 0.2 • 6 • 50 Whole liver • Mean dose 30–32 • Mean dose 42 Classical RILD • 5 • 50 Small intestine • V45 195 cc (Entire potential space within peritoneal cavity) Grade ≥ 3 acute toxicity • 10 Heart • Mean dose 26 (Pericardium) • V30 46% (pericardium) • V25 10% (whole heart) Pericarditis Long-term cardiac mortality • 15% • 15% • 1 Bilateral whole kidneys • Mean dose 15–18 • Mean dose 28 Clinically relevant renal dysfunction • 5 • 50 15 Gastric Cancer
- 199. 196 References 1. Cancer today [Internet]. Gco.iarc.fr. 2022 [cited 10 March 2022]. http://gco.iarc.fr/today/ online-analysis-map 2. UpToDate [Internet]. Uptodate.com. 2022 [cited 10 March 2022]. https://www.uptodate. com/contents/adjuvant-and-neoadjuvant-treatment-of-gastric-cancer?search=stomach%20 cancersource=search_resultselectedTitle=3~150usage_type=defaultdisplay_rank=3 3. UpToDate [Internet]. Uptodate.com. 2022 [cited 10 March 2022]. https://www.uptodate.com/ contents/clinical-features-diagnosis-and-staging-of-gastric-cancer?search=stomach%20cance rtopicRef=2523source=related_link 4. Matzinger O, Gerber E, Bernstein Z, Maingon P, Haustermans K, Bosset J, et al. EORTC- ROG expert opinion: radiotherapy volume and treatment guidelines for neoadjuvant radia- tion of adenocarcinomas of the gastroesophageal junction and the stomach. Radiother Oncol. 2009;92(2):164–75. 5. National Comprehensive Cancer Network. Gastric Cancer (version 2.2022) [Internet]. NCCN. 2022 [cited 10 March 2022]. https://www.nccn.org/professionals/physician_gls/pdf/ gastric.pdf 6. Hartgrink H, van de Velde C. Status of extended lymph node dissection: Locoregional control is the only way to survive gastric cancer. J Surg Oncol. 2005;90(3):153–65. 7. Gunderson L, Tepper J. Clinical radiation oncology. 4th ed. Philadelphia: Elsevier; 2016. 8. Smalley S, Benedetti J, Haller D, Hundahl S, Estes N, Ajani J, et al. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012;30(19):2327–33. 9. Lee J, Lim D, Kim S, Park S, Park J, Park Y, et al. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in com- pletely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012;30(3):268–73. 10. Park S, Lim D, Sohn T, Lee J, Zang D, Kim S, et al. A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial. Ann Oncol. 2021;32(3):368–74. 11. Cunningham D, Allum W, Stenning S, Thompson J, Van de Velde C, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20. 12. Cats A, Jansen E, van Grieken N, Sikorska K, Lind P, Nordsmark M, et al. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018;19(5):616–28. 13. Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357(18):1810–20. 14. Bang Y, Kim Y, Yang H, Chung H, Park Y, Lee K, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised con- trolled trial. Lancet. 2012;379(9813):315–21. J. Tey et al.
- 200. 197 16 Pancreatic Cancer Marsha Reyngold and Christopher Crane Contents 16.1 General Principles of Target Delineation and Planning 197 References 207 16.1 General Principles of Target Delineation and Planning • Intensity modulated radiation therapy (IMRT) is becoming a standard technique for treatment of pancreatic adenocarcinoma in a variety of settings (neoadjuvant, adjuvant, and definitive). 3D-CRT may be appropriate for palliation and in the neoadjuvant setting, as long as the appropriate volume can be treated to the target dose while respecting normal tissue constraints. Ablative approaches in the definitive setting require the use of stereotactic body radiotherapy (SBRT) or image-guided techniques. • IV contrast-enhanced pancreatic protocol simulation CT helps with accurate tar- get and organ-at-risk delineation for all settings. Unless contraindicated, it is particularly useful for treating in the context of surgically altered anatomy and is critical for doses exceeding 50 Gy in EQD2. Typical pancreas protocol IV con- trast administration consists of two phases with 150 cc of iodinated contrast medium administered at the rate of 5 cc/s with 35 s (late arterial) and 90 s (portal venous) delay from start of scan. M. Reyngold · C. Crane (*) Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA e-mail: ReyngolM@mskcc.org; cranec1@mskcc.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_16
- 201. 198 • Motion management helps to lower doses to organs at risk (OARs) while maxi- mizing target coverage and is required for any ablative approaches. Gating (whether deep- inspirational breath hold or expiratory gating) is preferred, but an internal target volume (ITV) approach may be used as an alternative based patient factors and available technology. Gating requires metal fiducials or metal stent. • Patients are immobilized in a custom alpha-cradle with arms extended above the head if tolerable. • Suggested target volumes and relevant OARs are listed in the following tables, organized by setting/dose. • Ablative and non-ablative fractionation schemes may be appropriate in a particu- lar setting based on the treatment intent, available technology, and patient anatomy. • Treatment of high-risk resectable or borderline resectable disease with pre- operative intent requires lower doses, and therefore, less complex technology, but attention should be paid to adequate margins to fully encompass all micro- scopic disease as well as radiographically occult extension of disease along the vasculature (Table 16.1). Fractionation schemes including 25 Gy in 5 fractions, 30 Gy in 10 fractions, 36 Gy in 12 fractions, and 50.4 Gy in 28 fractions may be appropriate. • Unresectable tumors should be treated with ablative doses (BED10 ≥ 100 Gy) if motion management techniques and image-guidance are available (Table 16.2). The choice of the fractionation scheme is often driven by the available technol- ogy. However, it is critical that the trend for fewer fractions, which is in part driven by the resource-intensive nature of stereotactic planning and delivery, is balanced by radiobiologic and dosimetric considerations and results in a dose that is ablative (BED10 ≥ 100 Gy) [1]. Due to the proximity of the radiosensitive luminal GI tract OARs to the target, the ability to achieve an ablative dose often requires hypofractionated courses that exceed five fractions. We recommend Table 16.1 Target volumes for treatment in the neoadjuvant setting for borderline resectable dis- ease (see Fig. 16.1) Target volumes Definition and description GTV all gross disease on imaging, including the primary tumor (typically hypointense), paying particular attention to the extension along the vessels, and all suspicious nodes ITV- optional If using the ITV approach, use the guidelines for GTV delineation on all phases of the 4D-CT CTV Given the infiltrative nature of PDAC, adequate margin is critical, and should include at least 1 cm uniform expansion on all gross disease + coverage of CA and SMA basins + additional margin along vessels if there is any uncertainty regarding tumor extension + coverage of splenic hilum for body/tail lesions + optional coverage of porta hepatis basins for head of the pancreas lesions PTV PTV margin is based on the motion management technique used (if any) and should be at least 0.5 cm. For cases treated with free breathing (FB) and without an ITV, expansions of 1–1.5 cm in the superior-inferior dimension is recommended M. Reyngold and C. Crane
- 202. 199 Table 16.2 Target volumes for neoadjuvant/definitive setting for unresectable disease (see Fig. 16.2) Target volumes Definition and description GTV All gross disease on imaging, including the primary tumor (typically hypointense), paying particular attention to the extension along the vessels, and all suspicious nodes ITV-optional If using the ITV approach, use the guidelines for GTV delineation on all phases of the 4D-CT CTVhigh dose Corresponds to GTV or ITV if used without additional margin CTVmicroscopic dose Given the infiltrative nature of PDAC, adequate margin is critical, and should include at least 1 cm uniform expansion on all gross disease (to ensure coverage of peripancreatic nodes) + coverage of CA and SMA basins + splenic hilum basin (body/tail lesions only) + additional margin along vessels if there is any uncertainty regarding tumor extension Optional: Coverage of the porta hepatis basin (for head of the pancreas tumors) PTVhigh dose Uniform expansion 0–0.5 cm followed by subtraction of any overlapping critical OAR with additional safety margin as below. Ablative doses are preferred when possible • For 56 Gy in 28 fractions, or 33 Gy in 5 fractions Subtract stomach and small bowel without additional margin • For 50 Gy in 10 fractions, 67.5 Gy in 15 fractions or 75 Gy in 25 fractions Subtract stomach and small bowel with an additional uniform expansion margin of 0.5 cm. Can use 0.7 cm for long interface between the target and the given OAR (see Fig. 16.2) PTVmicroscopic dose PTV margin is based on the motion management technique used (if any) and should be at least 0.5 cm. For cases treated with FB and without an ITV, expansions of 1–1.5 cm in the superior-inferior dimension is recommended Notable OAR volumes Applicable for doses ≥ 60 Gy in 25 fractions (or BED equivalent) Stomach- proximal duodenum PRV Stomach and duodenum segments 1 and 2 + 0.3 cm (0.5 cm for long interface between target and OAR) Small bowel PRV All other small bowel + 0.3 cm (0.5 cm for long interface between target and OAR) See [1] for more detailed information on contouring for ablative cases 75 Gy in 25 fractions for tumors within 1 cm of the OARs and 67.5 Gy in 15 fractions for tumors more than 1 cm. 50 Gy in five fractions may be selectively used for tumors 2 cm away from the OARs. Extensive contact between tumor and OARs may preclude effective target coverage with the treatment dose. In those cases (either as determined after attempted ablative treatment planning or empirically judged based on the experience of the treating radiation oncology), non-ablative treatments of 50.4–56 Gy in 28 fractions or low dose SBRT approach of 33Gy in 5 fractions may be used. 16 Pancreatic Cancer
- 203. 200 a b c d e Biliary stent PV/SMV confluence Biliary stent PV/SMV confluence CHA CHA CA SMA Fig. 16.1 Volumes for a 2.9 cm adenocarcinoma in the head of the pancreas causing biliary and pancreatic duct dilatation s/p placement of the plastic biliary drain, partial encasement of the PV/ SMV and possible abutment of the common hepatic artery (CHA) with a 1.6 × 1.1 cm portacaval node treated with pre-operative intent. Volumes shown include GTV (red), GTV node (maroon), CTV (gold), PTV (red), stomach/proximal duodenum (light green), small bowel (dark green), large bowel (orange). (a)Axial and coronal views at the isocenter. Note asymmetrical margins with 1.5 cm superior-inferior margin to account for diaphragmatic motion used for treatment with free breathing. (b–e) Axial slices from most superior to most inferior aspects of the GTV. Given some haziness around CHA it was included in the GTV (b). CTV includes peripancreatic, CA (c), SMA (d, e) and porta hepatis nodes M. Reyngold and C. Crane
- 204. 201 a b c =A =! Fig. 16.2 Volumes for a 3.8 cm pancreatic head tumor with near occlusion of the SMV, abutment of PV and tumor tracking along the SMA to the celiacomesenteric trunk treated definitively with 75 Gy in 25 fractions with daily CBCT guidance and DIBH. Volumes shown include GTV (red), PTVhigh dose (maroon), PTVmicroscopic dose (gold), stomach/proximal duodenum (light green), stomach/proximal duodenum PRV (blue), small bowel (dark green), small bowel PRV (yellow) and large bowel (orange). (a) Axial, sagittal and coronal views at the isocenter obtained in the arte- rial phase. Note the restricted margins compared to pre-op case. (b, c) Axial slices showing target and OAR contours. (b) Given the infiltrative nature of PDAC over-contouring of the GTV to include the surrounding pancreas parenchyma may be reasonable, especially when supported by additional diagnostic imaging and/or other sources of data. (c) In regions of direct contact or close proximity of the GTV to a critical OAR, the PTV is designed to exclude the OAR with an addi- tional safety margin that exceeds PRV expansion margin (arrows) 16 Pancreatic Cancer
- 205. 202 Table 16.3 Target volumes for treatment in the adjuvant setting (see Fig. 16.3) Target volumes Definition and description GTV Not applicable CTV Post-operative bed and pancreatojejunostomy (PJ) Nodal basins including peripancreatic, CA, SMA, paraaortic, PV (head tumors), and splenic (body/tail) RTOG 0848 stepwise contouring approach to create CTV from ROIs ROIs: • CA (proximal 1–1.5 cm) • SMA (proximal 2.5–3 cm) • Portal vein (PV: starts at confluence of SMV and splenic vein) • PJ • Aorta (superiorly to most cephalad of CA, PV, or PJ contours; inferiorly to bottom L2, or as low as L3 to cover pre-op GTV) • Tumor bed (based on review of pre-op imaging, pathology report, surgical clips if placed for that purpose only) Expansions: • Expand PV, PJ, CA, SMA by 1.0 cm • Expand aorta by 2.5–3.0 cm on the right, 1.0 cm on the left, 2–2.5 cm anteriorly, 0.2 cm posteriorly CTV = Expansions 1 + 2, confirm that tumor bed is encompassed PTV PTV margin is based on the motion management technique used (if any) and should be at least 0.5 cm. For cases treated with FB and without an ITV, expansions of 1–1.5 cm in the superior-inferior dimension is recommended • For adjuvant field design, the RTOG 0848 contouring atlas provides a stepwise contouring approach based on identifiable regions of interest (ROI) that were chosen on the basis of ease of identification and reproducibility on imaging studies [2]. However, smaller fields targeting the post-operative bed, CA and SMA may be appropriate in clinical scenarios with dose-limiting OARs (Table 16.3). • Suggested dose constraints are listed in Table 16.4. M. Reyngold and C. Crane
- 208. 205 Fig. 16.3 Volumes for a patient with pT3N1 adenocarcinoma of the head of the pancreas s/p pancreaticoduodenectomy. Volumes shown include ROIs designated in the contouring atlas (light green), CTV (pink) and PTV (yellow). (a–f) Representative axial slices are shown. (g) Representative parasagittal and corresponding axial slices illustrate superior and inferior aspects of the PTV a b c PV Aorta PV Aorta CA PV Aorta CA 16 Pancreatic Cancer
- 209. 206 d e f Aorta SMA PV Aorta PJ Aorta SMA Fig. 16.3 (continued) M. Reyngold and C. Crane
- 210. 207 References 1. Reyngold M, Parikh P, Crane CH. Ablative radiation therapy for locally advanced pancreatic cancer: techniques and results. Radiat Oncol. 2019;14(1):95. 2. Goodman KA, Regine WF, Dawson LA, Ben-Josef E, Haustermans K, Bosch WR, et al. Radiation Therapy Oncology Group consensus panel guidelines for the delineation of the clini- cal target volume in the postoperative treatment of pancreatic head cancer. Int J Radiat Oncol Biol Phys. 2012;83(3):901–8. g Fig. 16.3 (continued) 16 Pancreatic Cancer
- 211. 209 17 Hepatocellular Carcinoma Yun Chiang, Laura A. Dawson, Sameh A. Hashem, and Jason Chia-Hsien Cheng Contents 17.1 General Principles of Planning and Target Delineation 210 Further Reading 216 Y. Chiang Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan e-mail: b93401108@ntu.edu.tw L. A. Dawson Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, UHN, Toronto, ON, Canada e-mail: Laura.Dawson@rmp.uhn.ca S. A. Hashem Afia Radiotherapy and Nuclear Medicine Center, Amman, Jordan e-mail: sameh.hashem@afia.jo J. C.-H. Cheng (*) Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan e-mail: jasoncheng@ntu.edu.tw © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_17
- 212. 210 17.1 General Principles of Planning and Target Delineation • Step-and-shoot intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy, with limited number or range of gantry angles to reduce low-dose spread of normal liver, have been the standard techniques for HCC. SBRT with ≤5–6 fractions is preferable in cases with safe bowel sparing, available facilities of high dose rate, adequate immobilization, and image guid- ance. Hypofractionated treatment is sometimes used due to the proximity of tar- geted tumor to luminal gastrointestinal tissues. • In addition to a history and physical, laboratory examinations, a liver function assessment and imaging studies should be obtained for diagnosis, staging, and planning. Patients should undergo a contrast-enhanced (preferably tri-phasic [arterial, portal-venous, and delayed phases]) computed tomography (CT) scan of the liver, with 3–5 mm slice thickness. Multi-phase dynamic magnetic reso- nance imaging (MRI) scans can be used if the required breath hold for image acquisition is possible or CT contrast is contraindicated. With image fusion, MRI scans may be complimentary to CT scans for target delineation. Positron emis- sion tomography (PET) images with 18F-fluorodeoxyglucose (18F-FDG) or other tracers, such as 11C-acetate and 11C-choline, may be helpful in localizing the viable tumor(s) of individual cases such as patients with residual/recurrent tumor(s) at previous lipiodol retention and/or radiofrequency ablation areas. • Half-body or whole-body immobilization with respiratory control is needed for better reproducibility. Devices such as a vacuum bag or chest board may be used to immobilize a patient, preferably with arms up, during simulation and used throughout the course of treatment. This will enable reproducibility and allow spatial freedom of beam directions. The systems for immobilization should be made of materials not attenuating radiation doses and should not interfere with the gantry positions that may be required for coplanar and non-coplanar beams. • Respiratory motion management using a number of techniques is frequently needed to minimize imaging artifacts from changes in liver positioin due to breathing. Active breath hold helps reduce the treated volume and is preferable to patients who can hold breath for more than 30 s. Abdominal compression is used for patients who could not tolerate breath hold and might result in deforma- tion of abdomen or organ shape. Delineation of target volumes is most often done on multi-phasic, multi-modality images, obtained in breath hold (i.e., simi- lar to diagnostic images for HCC). Image-guided radiation therapy (IGRT) is required to account for changes in the intra-/inter-fractional liver position. In patients who cannot tolerate breath control, the use of passive abdominal com- pression devices combined with four-dimensional CT (4DCT) provides informa- tion about internal organ motion and can compensate for liver position changes. Gated treatment takes longer duration for the selected inspiratory or expiratory window and may also be useful for patients that cannot tolerate breath control. • CT simulation with IV contrast to obtain multi-phase imaging is required. This should be obtained with the patient in the treatment position and respiratory coordination. Fusion of the different phase images and/or diagnostic images will aid in the delineation of gross tumor volume (GTV). Usually the viable HCC is Y. Chiang et al.
- 213. 211 best visualized (brightest) on the arterial-phase CT scan, with less enhancement seen relative to the liver on venous and delayed phase images. Portal-phase CT scan is used with the intrahepatic vessel distribution for anatomical boundaries of treated tumor, especially with the deformed liver shape under immobilization and respiratory control. Tumor invasion into the vascular structures is best observed on portal-venous phase CT scan. The extent of tumor invasion to infe- rior vena cava is better demonstrated on delayed-phase CT scan. • Under specific circumstances for SBRT, only visible tumor will be targeted as GTV. More commonly, GTV would be enlarged to constitute the clinical target volume (CTV) based on the clinical risk of microscopic spread within the bound- ary of liver parenchyma, such as around previous radiofrequency ablation zone or embolized zone. CTV may fluctuate in size and position because of respira- tory motion and organ dynamics. Suggested CTV for high-risk regions are detailed in Table 17.1 (CTVmacroscopic and CTVmicroscopic) (Figs. 17.1, 17.2, 17.3, and 17.4). Table 17.1 Suggest target volumes at the GTV and CTV regions Target volumes Definition and description GTVa Liver tumor: Intrahepatic enhancing tumor on arterial- phase contrast CT with washout on venous- or delayed-phase CT Lipiodol retaining tumor: Lipiodol (white) contiguous to the enhancing tumor Ablated refractory tumor: Arterial enhancing tumor adjacent to the hypodense ablated zone Vascular tumor thrombus: Arterial enhancing thrombus with washout on venous-phase CT CTVmacroscopica Liver tumor: The intrahepatic enhancing tumor on arterial-phase contrast CT Embolized zone contiguous to the enhancing tumor included in GTV Arterial enhancing tumor adjacent to the hypodense ablated zone Arterial enhancing vascular tumor thrombus CTVmicroscopic (elective)b (optional according to clinical indication/protocol) 3–5 mm margin around intrahepatic GTVc 2–3 mm margin around the tumor thrombus GTV within the vessel Bland thrombus adjacent to tumor thrombus GTV Radiofrequency ablation zone adjacent to GTV Embolized zone not directly adjacent to the GTV CTV should not cross natural barriers such as the surface/boundary of the liver PTV CTV (or GTV/CTVmacroscopic) + 5–20 mm (may be asymmetric), depending on immobilization and respiration control The internal organ motion and the setup error form the basis of PTV 4DCT acquired from all respiratory phases may help define PTV and cover the extent of internal organ motion a GTV/CTVmacroscopic. For example, to be treated to 45–54 Gy in 3–6 fractions. Note that the “safe” dose may need to be reduced if limited by normal tissues b Elective/microscopic CTV. For example, to be treated to 24–30 Gy in 3–6 fractions. Note that author L.A.D. does not routinely recommend a microscopic CTV around the GTV c The additional margin around the intrahepatic GTV may be treated to macroscopic/higher doses if safe 17 Hepatocellular Carcinoma
- 214. 212 Fig. 17.1 Residual hepatocellular carcinoma after transcatheter arterial chemoembolization and radiofrequency ablation. Tri-phasic contrast-enhanced CT simulation (from left to right: no con- trast phase, T1-weighted contrast-enhanced MRI image, arterial phase and venous [delayed] phases), obtained with breath-hold coordination for liver immobilization. The GTV (in red) includes the contrast enhancing tumor and the invaded IVC thrombosis. The CTV (in green) includes a 5-mm margin within liver boundary and 3-mm intravascular margin around the GTV Y. Chiang et al.
- 215. 213 Fig. 17.2 Recurrent hepatocellular carcinoma with partial inferior vena cava (IVC) thrombosis after repeated radiofrequency ablation (RFA). Tri-phasic contrast-enhanced CT simulation (from left to right: no contrast phase, T1-weighted contrast-enhanced MRI image, arterial phase and venous [delayed] phases), obtained with breath-hold coordination for liver immobilization. The CTV (in green) includes the contrast enhancing tumor and the tumor thrombus (GTV in red) as well as a 5-mm margin around the GTV within liver boundary and previous radiofrequency ablated zone (if clinically needed) 17 Hepatocellular Carcinoma
- 216. 214 Fig. 17.3 Recurrent hepatocellular carcinoma after surgery and radiofrequency ablation (RFA) with high risk of bile duct injury by RFA. Tri-phasic contrast-enhanced CT simulation (from left to right: no contrast, arterial, portal, and venous [delayed] phases), obtained with breath-hold coor- dination for liver immobilization. The CTV (in green) includes the contrast enhancing tumor (GTV in red) and a 5-mm margin of liver parenchyma and 3-mm margin of intra-vascular space around the GTV Y. Chiang et al.
- 217. 215 Fig. 17.4 Hepatocellular carcinoma refractory to sorafenib treatment with progression of portal vein and middle hepatic vein thromboses. Tri-phasic contrast-enhanced CT simulation (from left to right: no contrast, arterial, portal, and venous [delayed] phases), obtained on breath-hold coor- dination for liver immobilization. The CTV (in green) includes the contrast enhancing tumor (GTV in red) and a three-dimensional 5-mm margin around the GTV within liver boundary 17 Hepatocellular Carcinoma
- 218. 216 Further Reading Cheng JC, et al. Local radiotherapy with or without transcatheter arterial chemoemboliza- tion for patients with unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2000;47:435–42. Hong TS, et al. Interobserver variability in target definition for hepatocellular carcinoma with and without portal vein thrombus: radiation therapy oncology group consensus guidelines. Int J Radiat Oncol Biol Phys. 2014;89:804–13. Jabbour SK, et al. Upper abdominal normal organ contouring guidelines and atlas: A Radiation Therapy Oncology Group consensus. Pract Radiat Oncol. 2014;4:82–9. Kim TH, et al. Proton beam radiotherapy vs. radiofrequency ablation for recurrent hepatocellular carcinoma: A randomized phase III trial. J Hepatol. 2021;74:603–12. Lukovic J, et al. MRI-based upper abdominal organs-at-risk atlas for radiation oncology. Int J Radiat Oncol Biol Phys. 2020;106:743–53. Park HC, et al. Consensus for radiotherapy in hepatocellular carcinoma from the fifth Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014): current practice and future clinical trials. Liver Cancer. 2016;5:162–74. Tse RV, et al. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol. 2008;26:657–64. Wang MH, et al. Impact factors for microinvasion in patients with hepatocellular carcinoma: pos- sible application to the definition of clinical tumor volume. Int J Radiat Oncol Biol Phys. 2010;76:467–76. Yoon SM, et al. Efficacy and safety of transarterial chemoembolization plus external beam radio- therapy vs sorafenib in hepatocellular carcinoma with macroscopic vascular invasion. A ran- domized clinical trial. JAMA Oncol. 2018;4:661–9. Zeng ZC, et al. Consensus on stereotactic body radiation therapy for small-sized hepatocellular carcinoma at the seventh Asia-Pacific Primary Liver Cancer Expert Meeting. Liver Cancer. 2017;6:264–74. Y. Chiang et al.
- 219. 217 18 Rectal Cancer Jacob A. Miller, Jose G. Bazan, Erqi L. Pollom, Albert C. Koong, and Daniel T. Chang Contents 18.1 Diagnostic Workup Relevant for Target Volume Delineation 218 18.2 Simulation and Daily Localization 220 18.3 Target Volume Delineation and Treatment Planning 220 18.4 Plan Assessment 233 Further Reading 234 J. A. Miller · E. L. Pollom · D. T. Chang (*) Department of Radiation Oncology, Stanford University, Stanford, CA, USA e-mail: jacobm3@stanford.edu; erqiliu@stanford.edu; dtchang@stanford.edu J. G. Bazan Department of Radiation Oncology, The Ohio State University, Columbus, OH, USA e-mail: jose.bazan2@osumc.edu A. C. Koong Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA e-mail: akoong@mdanderson.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_18
- 220. 218 18.1 Diagnostic Workup Relevant for Target Volume Delineation • Physical exam is an important part of the staging and treatment planning process. For palpable tumors, note the distance to the anal verge. Sphincter function should be noted at the time of exam. • For low-lying tumors, direct visualization is necessary to determine the relation- ship to the dentate line, as the dentate line is not palpable. • Endorectal ultrasound (EUS) can be used to determine the depth of invasion of the primary tumor, as well as to assess the status of nearby lymph nodes, but it may under or over stage patients in approximately 20% of cases. • MRI is now a standard imaging modality for preoperative staging to detect inva- sion into the mesorectal fat (T3) or adjacent structures (T4), to assess lymph node status, verify distance from the anal verge, and to assess operability with negative margins (Fig. 18.1). • PET/CT can be helpful for delineating gross disease (Fig. 18.2). However, areas of low radiotracer uptake on PET/CT should not supercede physical, endoscopic, or CT/MRI findings. Fig. 18.1 Axial T2-weighted sequences without fat suppression for staging of rectal cancer. The mesorectal fat surrounds the rectum and is enclosed within the mesorectal fascia (yellow arrows). In the left panel, the tumor was staged as an early T3 tumor with minimal invasion into the perirec- tal fat. The distance from the mesorectal fascia is more than 1 cm (red arrow). In the middle panel, a more extensive example of a T3 tumor is shown with a tumor that approaches within 2 mm of the mesorectal fascia (large white arrow). In the right panel, a sagittal view is shown. A mesorectal lymph node is visible (thin white arrow). The estimated distance of the tumor from the anal verge is 4.5 cm J. A. Miller et al.
- 221. 219 a b Fig. 18.2 A patient with clinical T4N0 rectal adenocarcinoma, with invasion into the cervix. Co-registered CT and PET images illustrate the utility of PET in target volume delineation. (a) The GTV (red) is seen on representative axial, sagittal, and coronal views, on both the treatment plan- ning CT and PET. (b) Additional axial slices of the co-registered CT and PET are shown 18 Rectal Cancer
- 222. 220 18.2 Simulation and Daily Localization • Most patients treated with 3D conformal radiotherapy can be simulated prone on a belly board to displace bowel. If IMRT is planned, we recommend supine posi- tioning in a body mold to ensure setup reproducibility. A radio-opaque marker can be placed at the anal verge, and surgical scars should be wired. • CT simulation with intravenous contrast and ≤3 mm slice thickness. Oral con- trast may be helpful to delineate small bowel. PET/CT simulation or fusion with diagnostic PET/CT or MRI may aid in target delineation. • Bladder filling/emptying may be considered, particularly if IMRT is used. A full bladder may limit the volume of bowel in the pelvis, whereas an empty bladder may be more reproducible. • We recommend image guidance with daily orthogonal kilovoltage imaging and weekly cone-beam CT scans (to assess soft tissue) to verify alignment during treatment, depending on setup reproducibility. 18.3 Target Volume Delineation and Treatment Planning • Prior to the cone-down volume, conventional 3D conformal radiotherapy for rec- tal cancer involves a PA field and two opposed lateral fields (Figs. 18.3 and 18.4). • Traditional borders for the PA field are: superior—L5/S1 interspace; inferior— the inferior edge of the obturator foramen or 3 cm below the GTV, whichever is more distal; lateral—1.5–2 cm lateral to the pelvic brim. • Borders for the lateral fields include: superior—same as PA field; inferior— same as PA field; anterior—posterior margin of the pubic symphysis (bony land- mark for internal iliac nodes) for T1–T3 disease or at least 1 cm anterior to the Fig. 18.3 Standard fields for a clinical T3N1b rectal cancer treated with preoperative long-course chemoradiotherapy. A 3D conformal three-field plan is used. The PA field (left panel) and left lat- eral field (right panel) are shown. The CTV-SR is shown in red. The patient was simulated prone on a belly board, allowing the small bowel (purple) to fall anteriorly away from the CTV. The bladder is shown in yellow J. A. Miller et al.
- 223. 221 Fig. 18.4 Standard fields for a pathologic T3N2a rectal cancer treated with postoperative long- course chemoradiotherapy following an abdominoperineal resection. A 3D conformal three-field plan is used. The PA field (left panel) and left lateral field (right panel) are shown. The CTV-SR is shown in red. The field includes the perineal scar with margin. The patient was simulated prone on a belly board, allowing the small bowel (purple) to fall anteriorly away from the CTV. Note that more small bowel is in the pelvis in the postoperative setting anterior edge of the pubic symphysis (bony landmark for external iliac nodes) for T4 disease; posterior—1 to 1.5 cm posterior to the posterior edge of the bony sacrum. • With CT-based planning, the borders described above can be modified to ensure adequate coverage of the planning target volumes (PTV). Target volumes includ- ing primary and nodal gross tumor volumes (GTV), clinical target volumes (CTV), and the PTV should be delineated on every applicable slice of the planning CT. • The primary gross tumor volume (GTV-P) is defined as all gross disease on physical examination, endoscopy, and imaging. • The nodal GTV (GTV-N) includes all visible perirectal, mesorectal, and involved iliac lymph nodes. Include any lymph node in doubt as GTVN in the absence of a biopsy. For low-lying rectal tumors, attention should be paid to the inguinal lymph nodes (Fig. 18.10). For tumors with anterior invasion into adjacent organs, attention should also be paid to the external iliac lymph nodes. • The high-risk CTV (CTV-HR) should include the GTV with a minimum 1.5–2 cm superior and inferior margin, as well as the entire rectum, mesorectum, and presacral space (Table 18.1). • The standard-risk CTV (CTV-SR) should cover the entire CTVHR, mesorectum, and bilateral internal iliac lymph nodes. The CTV-SR should also include the bilateral external iliac and obturator nodes for patients with T4 tumors with ante- rior organ involvement (bladder, cervix, prostate). If the primary tumor extends inferiorly into the anal canal, the bilateral external iliac and inguinal lymph nodes should be included into CTV-SR (Table 18.1) (Figs. 18.5, 18.6, 18.7, 18.8, 18.9, and 18.10). 18 Rectal Cancer
- 224. 222 Table 18.1 Suggested target volumes for gross and microscopic disease in the preoperative set- ting (Figs. 18.5, 18.6, 18.8, 18.9, and 18.10) Target volumes Definition and description Gross tumor volume (GTV) Primary (GTV-P): all gross disease on physical examination, endoscopy, and imaging Regional lymph nodes (GTV-N): all visible perirectal, presacral, and involved iliac nodes. Include any lymph node in doubt as GTV in the absence of a biopsy. For low-lying rectal tumors, attention should also be paid to the inguinal nodes High risk clinical target volume (CTV-HR) CTV-HR should cover the GTV-P and GTV-N with 1.5–2 cm margin expansion superiorly and inferiorly, excluding uninvolved bone, muscle, and air. For grossly involved external iliac or inguinal nodes, a minimum 10–15 mm GTV to CTV margin should be included Include the entire rectum, mesorectum, and presacral space in the transverse plane at these levels. A 1–2 cm margin into adjacent organs (e.g., bladder, prostate, cervix) should be added for T4 tumors Visible mesorectal nodes on CT, MRI, and PET/CT should be included Standard risk clinical target volume (CTV-SR) Include the CTVHR, entire mesorectum, and bilateral internal iliac lymph nodes. Include the external iliac and obturator nodes for T4 tumors with anterior organ involvement. Include the externa lilac and inguinal lymph nodes in cases with anal canal involvement Superior: Rectum and mesorectum, up to the L5/S1 interspace or 2 cm superior to gross disease, whichever is most cephalad Inferiorly: Pelvic floor or at least 2 cm inferior to gross disease, whichever is most caudad Lymph nodes: To cover the internal iliac nodes, a 0.7–cm margin around the internal iliac vessels should be drawn (excluding muscle and bone) To cover the external iliac nodes (for T4 lesions), an additional 1 cm margin anterolaterally around the vessels should be drawn. Any adjacent small nodes should be included For tumors that extend into the anal canal, the bilateral inguinal nodes should be covered (Table 18.4) A 1.8-cm wide volume between the external and internal iliac vessels should be drawn to cover the obturator nodes Anterior: A margin of 1–1.5 cm should be added into bladder to account for changes in bladder and rectal filling Planning target volume (PTV) Each CTV should be expanded by 0.5–1 cm, depending on the physician’s comfort level with setup accuracy, frequency of imaging, and the use of IGRT J. A. Miller et al.
- 225. 223 Fig. 18.5 Representative images for a patient with clinical T3N1b rectal adenocarcinoma treated with preoperative long-course chemoradiotherapy. This patient was simulated prone (note the anterior displacement of the small bowel) with PET/CT simulation and 2.5 mm slice thickness. The CT images are rotated 180° for viewer orientation. CTV-SR (cyan), CTV-HR (orange), GTV-N (red, shaded), and GTV-P (red, shaded) are shown 18 Rectal Cancer
- 226. 224 Fig. 18.6 Representative images for a patient with clinical T4N0 rectal adenocarcinoma with gross invasion into the cervix treated with preoperative long-course chemoradiotherapy. CTV-SR (cyan), CTV-HR (orange), and GTV-P (red, shaded) are shown. Note that in this case, the CTV-SR covers the external iliac nodal region due to T4 disease J. A. Miller et al.
- 227. 225 Fig. 18.7 Representative images for a patient with pathologic T3N2a rectal adenocarcinoma treated with postoperative long-course chemoradiotherapy. This patient underwent an abdomino- perineal resection (APR) without preoperative chemoradiotherapy. The primary tumor extended from 2–5 cm from the anal verge. The patient was simulated prone. The CT images are rotated 180° for viewer orientation. CTV-SR (cyan) and CTV-HR (orange) are shown. In this case, due to the absence of small bowel near the postoperative bed, the GTV-HR was boosted to a total dose of 55.8 Gy. However, if a portion of bowel was near the boost volume, the dose could be reduced 18 Rectal Cancer
- 228. 226 Fig. 18.8 Representative images for a patient with clinical T3N0 rectal adenocarcinoma treated with short-course preoperative radiotherapy. This patient was simulated prone (note the anterior displacement of the small bowel) with PET/CT simulation with 2.5 mm slice thickness. The CT images are rotated 180° for viewer orientation. CTV-SR (cyan) and GTV (red, shaded) are shown J. A. Miller et al.
- 229. 227 Fig. 18.9 Representative images for a patient with clinical T2N0M1a rectal adenocarcinoma with a 2 cm non-regional right common iliac lymph node confirmed by PET/CT. This patient underwent preoperative long-course chemoradiotherapy. CTV-SR (cyan), CTV-HR (orange), GTV-N (red, shaded), and GTV-P (red, shaded) are shown 18 Rectal Cancer
- 230. 228 Fig. 18.10 Representative images for a patient with clinical T3N2a low-lying rectal adenocarci- noma (2 cm superior to the anal verge) with a grossly involved left inguinal lymph node confirmed by PET/CT. The patient underwent preoperative long-course chemoradiotherapy with IMRT for coverage of the bilateral external iliac and inguinal nodes. CTV-SR (cyan), CTV-HR (orange), GTV-N (red, shaded), GTV-P (red, shaded), and CTV-N (green, 10 mm GTV-N to CTV-N margin) are shown • Target volume delineation in the postoperative setting is similar to the preopera- tive setting. In the setting of abdominoperineal resection, the entire surgical bed, including the perineal scar, should be included (Table 18.2). • The RTOG anorectal contouring atlas provides a detailed consensus contouring descriptions of three elective CTVs that should be considered in patients with rectal and anal cancers. CTV-A includes the perirectal, presacral, and internal J. A. Miller et al.
- 231. 229 Table 18.2 Suggested target volumes in the postoperative setting (Fig. 18.7) Target volumes Definition and description Clinical target volume for gross disease or positive margin (CTV-P) Areas of known microscopically involved margin or macroscopic residual disease plus a 1–2 cm margin, excluding uninvolved bone, muscle, or air High risk clinical target volume (CTV-HR) Remaining rectum (if applicable), mesorectal bed, and presacral space axially at these levels, excluding uninvolved bone, muscle, or air. For undissected grossly involved external iliac or inguinal nodes, a minimum 10–15 mm GTV to CTV margin should be included Standard risk clinical target volume (CTV-SR) Include the CTV-HR, entire mesorectum, and bilateral internal iliac lymph nodes. Include the external iliac and obturator nodes for T4 tumors with anterior organ involvement. Include the externa lilac and inguinal lymph nodes in cases with anal canal involvement Superior: Remaining rectum and mesorectum (usually up to L5/S1) with at least 1 cm margin superior to the anastomosis, whichever is most cephalad Inferior: Pelvic floor or at least 1 cm below the anastomosis or rectal stump, whichever is most caudad. In cases following abdominoperineal resection, the surgical bed extending down to the wired perineal scar should be included Lateral: 0.7-cm margin around the internal iliac vessels, excluding muscle and bone To cover the external iliac nodes (for T4 lesions), an additional 1 cm margin anterolaterally around the vessels should be drawn. Any adjacent small nodes should be included For tumors involving the anal canal, the bilateral inguinal nodes should be covered (Table 18.4) A 1.8-cm wide volume between the external and internal iliac vessels should be drawn to cover the obturator nodes Anterior: 1–1.5 cm margin should be added into bladder to account for changes in bladder and rectal filling Planning target volume (PTV) Each CTV should be expanded by 0.5–1 cm, depending on the physician’s comfort level with setup accuracy, frequency of imaging, and the use of IGRT iliac regions and should be covered in all patients with rectal cancer. CTV-B includes the external iliac nodes (covered only for primary rectal tumors that invade into adjacent organs (T4 disease) or extend inferiorly into the anal canal). CTV-C includes the inguinal region (covered only for primary rectal tumors that extend inferiorly into the anal canal). A detailed description of CTV-A is pro- vided in Table 18.3. • More recent international consensus guidelines suggest a common set of pelvic subsites/subvolumes that differ from the terminology of the RTOG anorectal contouring atlas. In particular, major distinctions include recommendations for including the abdominal (cranial) presacral space, ischiorectal fossa, anterior vs. posterior (obturator vs. internal iliac) lateral lymph nodes, and the cranial border for the lateral lymph nodes. Based on these guidelines, consideration may be made for omitting the lateral lymph nodes superior to the cranial border of the 18 Rectal Cancer
- 232. 230 Table 18.3 Description of the borders of CTV-A in the RTOG anorectal contouring atlas Clinical target volume Key highlights CTV-A: lower pelvis Inferior: 2 cm below gross disease, including the entire mesorectum down to the pelvic floor Lateral: does not need to extend more than a few millimeters beyond the levator muscles unless there is tumor extension into the ischiorectal fossa. For T4 tumors, should include 1–2 cm margin around identified areas of invasion CTV-A: mid-pelvis Includes the rectum, mesorectum, internal iliac region, and 1 cm margin into the bladder for daily variation in bladder filling Posterolateral: Extends to the pelvic sidewall muscles or bone (when muscles are absent) Anterior: at least 1 cm into the posterior bladder. Should also include at least the posterior portion of the internal obturator vessels Recommend 7–8 mm margin in soft tissue around the internal iliac vessels. CTV should be trimmed off uninvolved muscle and bone CTV-A: upper pelvis Superior (perirectal component): Should be at the rectosigmoid junction or at least 2 cm cephalad to macroscopic disease in the rectum/perirectal nodes, whichever is most cephalad. The entire length of the rectum should be included Superior (nodal coverage): should be at the bifurcation of the common iliac vessels into the external/internal iliacs, approximately at the sacral promontory Recommend 7–8 mm margin in soft tissue around the internal iliac vessels, but at least 1 cm anteriorly, especially if vessels or small nodes are seen in this area. CTV should be trimmed off uninvolved muscle and bone mesorectum for T3N0 tumor without invasion of the mesorectal fascia, and for omitting the anterior lateral lymph nodes for T3N0-1 tumors in select scenarios. • The Australasian GI Trials Group Atlas describes seven elective regions to be considered when treating anal cancer, some of which are applicable for rectal cancers: mesorectum, presacral space, internal iliac nodes, ischiorectal fossa, obturator nodes, external iliac nodes, and inguinal nodes. Table 18.4 is a sum- mary of the definitions of these regions. • There are multiple acceptable approaches to dose prescription for rectal cancer. In the preoperative setting, the most common prescription dose is 45 Gy at 1.8 Gy/fraction to the PTVSR, followed by a sequential cone-down boost of 5.4 Gy at 1.8 Gy/fraction to a total of 50.4 Gy to the PTVHR. For clinical T4 tumors, the PTVHR may instead be boosted to a total dose of 54–55.8 Gy in 30–31 fractions. Grossly involved lymph nodes that will not be resected (e.g., inguinal) should be boosted to approximately 60 Gy in 30 fractions, whereas nodes that will be resected can be treated to 50.4 Gy (Table 18.5). • The 3D conformal technique uses opposing lateral fields with a PA field (Figs. 18.3 and 18.4). If treating external iliac lymph nodes with this technique, the anterior border of the lateral fields should be approximately 1 cm anterior to the anterior border of the pubic symphysis. • When treating with IMRT, simultaneous integrated boosts can be considered. Table 18.4 lists several suggested dose and fractionation schemes for various settings. J. A. Miller et al.
- 235. 233 Table 18.5 Suggested dose and fractionation schemes for rectal cancer PTV-SR PTV-HR Preoperative T3 or N+ 45 Gy at 1.8 Gy/fx, OR 45 Gy at 1.8 Gy/fx (SIB) 50.4 Gy at 1.8 Gy/fx (CD), OR 50 Gy at 2 Gy/fx (SIB) Preoperative T4 N0-2b 45 Gy at 1.8 Gy/fx, OR 45.9 Gy at 1.7 Gy/fx (SIB) 54–55.8 Gy at 1.8 Gy/fx (CD), OR 54 Gy at 2 Gy/fx (SIB) Preoperative (short course) T3-4 or N+ 25 Gy at 5 Gy/fx Postoperative (negative margins) 45 Gy at 1.8 Gy/fx, OR 45.9 Gy at 1.7 Gy/fx (SIB) 54–55.8 Gy at 1.8 Gy/fx (CD), OR 54 Gy at 2 Gy/fx (SB) Postoperative (gross disease or positive margin) 45 Gy at 1.8 Gy/fx, OR 45.9 Gy at 1.7 Gy/fx (SIB) 54–59.4 Gy at 1.8 Gy/fx (CD), OR 54–60 Gy at 2 Gy/fx (SIB and/or CD) fx fraction, CD (sequential) cone-down, SIB simultaneous integrated boost • With growing interest in total neoadjuvant therapy, patients may receive sys- temic therapy prior to radiation. Until further outcome data are available, the pre-chemotherapy primary and nodal tumor volumes should be used to define target volumes. Nodes that were initially suspicious for involvement should be included in the boost volume, and threatened radial margins prior to chemother- apy should be included in the high-dose volumes even in the setting of a major or complete response to chemotherapy. 18.4 Plan Assessment • Ideally, at least 95% of each PTV should receive 100% of the prescription dose. In addition, the maximum dose in the PTV should be 110%. • When evaluating plans with a sequential boost to gross disease, each individual plan should be scrutinized before the “plan sum” to assess for hot spots or undercoverage of each individual PTV. • The organs-at-risk include the small bowel, large bowel, bladder, femoral heads, iliac crest, and external genitalia. Uniform consensus guidelines for contouring the small and large bowel, bladder, and femoral heads are available from an RTOG consensus panel. Suggested dose constraints from QUANTEC and RTOG 0822 are listed in Table 18.6. 18 Rectal Cancer
- 236. 234 Table 18.6 Dose constraints for organs-at-risk Organ-at-risk Constraints Small bowel QUANTEC V15Gy 120cc (individual loops) V45Gy 195cc (entire potential space within peritoneal cavity) RTOG 0822 V35Gy 180 cc V40Gy 100 cc V45 Gy 65 cc Dmax 50 Gy Bladder QUANTEC Dmax 65 Gy V65Gy 50% RTOG 0822 V40Gy 40% V45Gy 15% Dmax 50 Gy Femoral heads RTOG 0822 V40Gy 40% V45Gy 15% Dmax 50 Gy Further Reading Daly ME, Murphy JD, Mok E, Christman-Skieller C, Koong AC, Chang DT. Rectal and bladder deformation and displacement during preoperative radiotherapy for rectal cancer: are current margin guidelines adequate for conformal therapy? Pract Radiat Oncol. 2011;1(2):85–94. Garofalo MC Hong T, Bendell J, et al. RTOG 0822: a phase II evaluation of preoperative chemo- radiotherapy utilizing intensity modulated radiation therapy (IMRT) in combination with capecitabine and oxaliplatin for patients with locally advanced rectal cancer. 2014. http://www. rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=0822. Accessed on January 31, 2014. Gay HA, Barthold HJ, O'Meara E, et al. Pelvic normal tissue contouring guidelines for radiation therapy: a Radiation Therapy Oncology Group consensus panel atlas. Int J Radiat Oncol Biol Phys. 2012;83(3):353–62. Marks LB,Yorke ED, Jackson A, et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys. 2010;76(3):10–9. Myerson RJ, Garofalo MC, El Naqa I, et al. Elective clinical target volumes for conformal therapy in anorectal cancer: a radiation therapy oncology group consensus panel contouring atlas. Int J Radiat Oncol Biol Phys. 2009;74(3):824–30. Ng M, Leong T, Chander S, et al. Australasian Gastrointestinal Trials Group (AGITG) contouring atlas and planning guidelines for intensity-modulated radiotherapy in anal cancer. Int J Radiat Oncol Biol Phys. 2012;83(5):1455–62. TaylorA, RockallAG, Reznek RH, Powell ME. Mapping pelvic lymph nodes: guidelines for delin- eation in intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2005;63(5):1604–12. Valentini V, Gambacorta MA, Barbaro B, et al. International consensus guidelines on clinical tar- get volume delineation in rectal cancer. Radiother Oncol. 2016;120(2):195–201. J. A. Miller et al.
- 237. 235 19 Anal Cancer Jacob A. Miller, Jose G. Bazan, Erqi L. Pollom, Albert C. Koong, and Daniel T. Chang Contents 19.1 Anatomy and Patterns of Spread 235 19.2 Diagnostic Workup Relevant for Target Volume Delineation 236 19.3 Simulation and Daily Localization 238 19.4 Target Volume Delineation and Treatment Planning 238 19.5 Plan Assessment 247 References 248 19.1 Anatomy and Patterns of Spread • The anal canal is about 4 cm in length and extends from the anorectal ring proxi- mally (palpable border of the anal sphincter and puborectalis muscle) to the anal verge distally. J. A. Miller · E. L. Pollom · D. T. Chang (*) Department of Radiation Oncology, Stanford University, Stanford, CA, USA e-mail: jacobm3@stanford.edu; erqiliu@stanford.edu; dtchang@stanford.edu J. G. Bazan Department of Radiation Oncology, The Ohio State University, Columbus, OH, USA e-mail: jose.bazan2@osumc.edu A. C. Koong Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA e-mail: akoong@mdanderson.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_19
- 238. 236 Table 19.1 Lymphatic drainage of the anal canal Location of primary tumor Draining lymphatics Distal anal canal, perianal skin, and anal verge Superficial inguinal Femoral External iliac Anal canal just proximal to dentate line Internal pudendal Hypogastric Obturator Inferior and middle hemorrhoidal Proximal anal canal and distal rectum Perirectal Superior hemorrhoidal • The anal verge is the junction of the nonkeratinized squamous epithelium of the distal anal canal and the keratinized hair-bearing perianal skin. • Embryologically, the dentate line (or pectinate line) is formed by the junction of the endoderm proximally and the ectoderm distally, leading to important differ- ences in both histology and lymphatic drainage. • The dentate line demarcates the transition from the columnar epithelium of the proximal anal canal to the squamous epithelium of the distal anal canal. • Squamous cell carcinomas that arise proximal to the anal verge are managed as anal canal cancers, whereas squamous cell carcinomas that arise distal to the anal verge are managed as perianal skin cancers. • The primary draining lymphatics of the anal canal include the perirectal, internal iliac (hypogastric), and superficial inguinal lymph nodes. The pattern of drainage depends on the location of the primary tumor within the anal canal (Table 19.1). 19.2 Diagnostic Workup Relevant for Target Volume Delineation • Physical examination is an important part of the staging and planning process, and should include detailed assessment of the characteristics of the primary tumor (size, location relative to anal verge, anal sphincter function, invasion of adjacent structures via pelvic examination) as well as an assessment of inguinal lymph nodes. • Inguinal lymph nodes that are suspicious for metastatic involvement but border- line in size should be biopsied to confirm metastasis, as nearly 50% of suspicious nodes are related to reactive hyperplasia. • PET/CT is recommended both for staging and treatment planning to assist in delineating extent of gross disease (Fig. 19.1). • Areas of low uptake on PET should not supersede physical examination findings or abnormalities seen on CT or MRI. J. A. Miller et al.
- 239. 237 Fig. 19.1 An example of delineating the GTV-P (red) using the co-registered simulation CT and diagnostic PET on representative axial, sagittal, and coronal images. In the lower three panels, additional axial slices of the co-registered CT and PET are shown 19 Anal Cancer
- 240. 238 19.3 Simulation and Daily Localization • The patient should be simulated supine with arms on chest in a body mold. Prone positioning with a belly board can be used to allow for anterior displacement of the bowel, but this is not as reproducible and complicates bolus placement. A radiopaque marker should be placed at the anal verge. • CT simulation with intravenous contrast and ≤3 mm slice thickness should be performed to delineate the pelvic blood vessels and gross tumor volume. If PET/ CT is available, a PET/CT fusion should be performed to aid in target volume delineation. MRI may also be useful. • Bladder filling/emptying should be considered. A full bladder may keep bowel from migrating into the pelvis, while an empty bladder may be more reproducible. • We recommend image guidance with daily orthogonal kilovoltage imaging and weekly cone-beam CT scans (to assess soft tissue) to verify alignment during treatment. Cone beam CTs may be done more frequently if there is significant variation in bladder and/or rectal filling. 19.4 Target Volume Delineation and Treatment Planning • Conventional 3D conformal radiotherapy for anal canal cancers is complex due to the need to irradiate the pelvis and inguinal lymph nodes. The “thunderbird” technique was historically the most common method used to treat anal cancer. An example of the thunderbird technique compared to an IMRT plan is shown in Fig. 19.2. A detailed description of thunderbird technique variations is described by Gilroy et al. [1] c d a b Fig. 19.2 Dose distributions for a photon/electron thunderbird technique (panel (a) and (b)) and intensity-modulated radiotherapy plan (panel (c) and (d)) J. A. Miller et al.
- 241. 239 • RTOG 0529 has established the feasibility of IMRT in a multi-institution setting and demonstrated lower rates of grade 2 or higher hematologic toxicity and lower rates of grade 3 or higher gastrointestinal or dermatologic toxicity when compared to historical controls in the RTOG 9811 trial, which utilized 3D con- formal radiotherapy [2, 3]. However, accurate target volume delineation is criti- cal, as delineation that is non-compliant with consensus guidelines is associated with an increased risk of disease recurrence (Table 19.2) [4–6]. Table 19.2 Suggested target volumes for gross and microscopic disease Target volumes Definition and description Gross tumor volumes (GTV-P, GTV-N) Primary (GTV-P): all gross disease on physical examination and imaging Regional nodes (GTV-N): all nodes ≥1.5 cm, PET-positive, and/or biopsy-proven. Include any lymph nodes in doubt as GTV-N in the absence of biopsy. Lymph nodes that are ≤3 cm (GTV-Na) may be distinguished from those that are 3 cm (GTV-Nb) Clinical target volumes for gross disease (CTV-P, CTV-N) CTV-P is the GTV-P with a 1.5–2.5 cm margin expansion excluding uninvolved bone, muscle, or air. The CTV-N is the GTV-N with a 1.0–1.5 cm margin expansion excluding uninvolved bone, muscle, or air High risk clinical target volume (CTV-HR) Should cover CTV-P, CTV-N, the entire mesorectum, perirectal lymph nodes, and bilateral internal iliac lymph nodes inferior to the inferior border of the sacroiliac joint. If the inguinal or external iliac nodes are involved, these regions should be included in CTV-HR. Similarly, the upper internal iliac nodes should be included if involved To cover the internal iliac nodes, a 0.7-cm margin around the internal iliac vessels should be drawn (excluding muscle and bone) [4, 7] To cover the external iliac nodes (for either inguinal or external iliac node-positive disease), an additional 1 cm margin anterolaterally around the vessels should be drawn. Any adjacent small nodes should be included [4, 7] To cover the inguinal nodes (for inguinal or external iliac node-positive disease), the entire inguinal compartment should be contoured, including small vessels and adjacent lymph nodes bounded by muscle and bone (Table 19.4). A 1.8-cm wide volume between the external and internal iliac vessels should be drawn to cover the obturator nodes [7] Anteriorly, a margin of 1–1.5 cm should be added into bladder to account for changes in bladder and rectal filling [4, 8] Low risk clinical target volume (CTV-LR) Should cover the uninvolved internal iliac lymph nodes superior to the inferior border of the sacroiliac joint, as well as the uninvolved external iliac and inguinal lymph nodes To cover the internal iliac nodes, a 0.7-cm margin around the internal iliac vessels should be drawn (excluding muscle and bone) [4, 7] To cover the external iliac nodes, an additional 1 cm margin anterolaterally around the vessels should be drawn. Any adjacent small nodes should be included [4, 7] To cover the inguinal nodes, the entire inguinal compartment should be contoured, including small vessels and adjacent lymph nodes bounded by muscle and bone (Table 19.4) Planning target volumes (PTV) Each CTV should be expanded by 0.5–1 cm, depending on the physician’s comfort level with setup accuracy, frequency of imaging, and the use of IGRT 19 Anal Cancer
- 242. 240 Table 19.3 Elective nodal regions described in RTOG anorectal contouring atlas [4] Clinical target volume Key highlights CTV-A (perirectal, presacral, internal iliac regions) Lower pelvis: The inferior border should be 2 cm below gross disease, including the entire mesorectum. The volume does not need to extend more than a few millimeters beyond the levator muscles unless there is extension into the ischiorectal fossa Mid pelvis: Includes the rectum, mesorectum, internal iliac nodes, and 1 cm margin into the bladder for daily variation in bladder filling. Posterolaterally, the volume extends to the pelvic sidewall muscles or bone (when muscles are absent). At minimum, the posterior portion of the internal obturator vessels should be included. A 7–8 mm margin in soft tissue around the internal iliac vessels should be drawn. The volume should be trimmed off uninvolved muscle and bone Upper pelvis: The most superior extent should be at the bifurcation of the common iliac vessels into the external/internal iliacs, approximately at the sacral promontory Recommend 7–8 mm margin in soft tissue around the internal iliac vessels, but at least 1 cm anteriorly, especially if vessels or small nodes are seen in this area. CTV should be trimmed off uninvolved muscle and bone CTV-B (external iliac region) The border between the inguinal and external iliac region is somewhat arbitrary. The consensus was that the border should be set at the level of the inferior extent of the internal obturator vessels (bony landmark: the upper edge of the superior pubic rami) Recommend 7–8 mm margin in soft tissue around the iliac vessels, but at least 1 cm anteriorly, especially if vessels or small nodes are seen in this area. CTV should be trimmed off uninvolved muscle and bone CTV-C (inguinal region) The most inferior extent should be 2 cm below the saphenous/femoral junction. The border between CTV-B and CTV-C is approximately the upper border of the superior pubic rami The entire inguinal compartment should be contoured, including small vessels and lymph nodes. CTV should be trimmed off uninvolved muscle and bone • Detailed contouring atlases available include the RTOG anorectal contouring atlas and the Australasian GI Trials Group Atlas [4, 5]. • The RTOG anorectal contouring atlas describes three CTV regions that should be included for all patients with anal canal cancer [4]. CTV-A includes the peri- rectal, presacral, and internal iliac regions. CTV-B includes the external iliac nodes. CTV-C includes the inguinal region. Table 19.3 provides a more detailed description of these regions. • The Australasian GI Trials Group Atlas describes seven elective regions to be considered when treating anal cancer: mesorectum, presacral space, internal iliac nodes, ischiorectal fossa, obturator nodes, external iliac nodes, and inguinal nodes [5]. Table 19.4 is a summary of the definitions of these regions. • Disagreement exists among anal cancer contouring guidelines (RTOG, AGITG, BNG) with respect to contouring the inguinal lymph nodes. Recent data indicate that 10–29% of involved inguinal lymph nodes appear to be situated outside of recommended nodal borders [9]. To adequately cover this nodal chain, a 2 cm J. A. Miller et al.
- 245. 243 Table 19.5 Suggested dose and fractionation schemes for anal canal cancer Target volume RTOG 9811 [3] RTOG 0529 [2]/Transaustralian [5] PTV-P T1N0: 45–50.4 Gy at 1.8 Gy/fraction T2N0: 50.4 Gy at 1.8 Gy/fraction N+ or T3-T4: 54–59.4 Gy at 1.8 Gy/ fraction T1N0: Not included on RTOG 0529 T2N0: 50.4 Gy at 1.8 Gy/fraction N+ or T3-T4: 54 Gy at 1.8 Gy/ fraction PTV-N 54–59.4 Gy at 1.8 Gy/fraction 50.4 Gy at 1.68 Gy/fraction if node ≤3 cm 54 Gy at 1.8 Gy/fraction if node 3 cm PTV-HR 45 Gy at 1.8 Gy/fraction T2N0: 42 Gy at 1.5 Gy/fraction N+ or T3-T4: 45 Gy at 1.5 Gy/ fraction PTV-LR 30.6–36 Gy at 1.8 Gy/fraction Alternatively, 40 Gy at 1.6 Gy/fraction SIB may be used A low-risk PTV was not used on RTOG 0529 radial margin around the femoral vessels, 1 cm radial margin around the saphe- nous/femoral junction, and 3 cm medial/lateral margin along the lower inguinal ligament is necessary. The caudal border of the inguinal CTV should be the level of the anal margin. • There are multiple techniques and methods of dose prescription for anal cancer, and the exact dose and fractionation will vary based on which technique is used. The current recommendations are based on the treatment plan used in RTOG 9811 [3] (Table 19.5). • Figure 19.3 shows a case example of a clinical T2N0 anal canal cancer treated with definitive chemoradiotherapy with an IMRT plan. The PTV-LR and PTV-HR were treated simultaneously to 40 Gy (1.6 Gy/fx) and 45 Gy (1.8 Gy/fx) in 25 fractions, respectively. Then, the PTV-P was boosted sequentially to 50.4 Gy (1.8 Gy/fx) in 28 total fractions. • Figure 19.4 shows a case example of a clinical T3N1a anal canal cancer with bilateral inguinal nodal involvement treated with definitive chemoradiotherapy with an IMRT plan. The PTV-LR and PTV-HR were treated simultaneously to 40 Gy (1.6 Gy/fx) and 45 Gy (1.8 Gy/fx) in 25 fractions, respectively. Then, the PTV-P and PTV-N were boosted sequentially to 54 Gy (1.8 Gy/fx) in 30 total fractions. • Figure 19.5 shows a case of a pathologic T1 (1.0 cm) clinical N0M0 squamous cell carcinoma of the perianal skin (anal margin), which was resected with a 0.1cm close margin. The patient was treated with postoperative radiotherapy to the postoperative bed and inguinal lymph nodes alone with an IMRT plan. The PTV-HR and PTV-P were treated simultaneously to 45 Gy (1.8 Gy/fx) in 25 fractions. Then, the PTV-HR was boosted sequentially to 55.8 Gy (1.8 Gy/fx) in 31 total fractions. 19 Anal Cancer
- 246. 244 Fig. 19.3 (a) Representative images of a patient with T2N0 anal canal cancer treated with defini- tive chemoradiotherapy. This patient was simulated supine using PET/CT simulation with a 2.5 mm slice thickness. CTV-LR (cyan), CTV-HR (orange), CTV-P (green), and GTV-P (red, shaded) are shown. (b) Magnified image of the lower pelvis showing CTV-LR (cyan), CTV-HR (orange), CTV-P (green), and GTV (red, shaded) a b J. A. Miller et al.
- 247. 245 a b Fig. 19.4 (a) Representative images of a patient with T3N1a anal canal cancer with bilateral inguinal lymph node involvement. This patient was simulated supine using PET/CT simulation with a 2.5 mm slice thickness. CTV-LR (cyan), CTV-HR (orange), CTV-P and CTV-N (green), and GTV-P and GTV-N (red, shaded) are shown. Note that the bilateral inguinal and external iliac nodes are included in CTV-HR due to bilateral inguinal involvement. (b) Magnified image of the lower pelvis showing CTV-HR (orange), CTV-P (green), CTV-N (green), GTV-P (red, shaded), and GTV-P (red, shaded) 19 Anal Cancer
- 248. 246 Fig. 19.5 Representative images of a patient with a pathologic T1 (1.0 cm) clinical N0M0 squa- mous cell carcinoma of the perianal skin (anal margin), which was resected with a 0.1 cm close margin. This patient was simulated supine using CT simulation with a 2.5 mm slice thickness. The perianal surgical bed with a 1.5–2 cm margin (CTV-P, green) and at-risk inguinal lymph nodes (CTV-HR, orange) were treated given concern for microscopic residual disease and the potential for nodal metastasis J. A. Miller et al.
- 249. 247 19.5 Plan Assessment • Ideally, at least 95% of each PTV should receive 100% of the prescription dose. In addition, the maximum dose in the PTV should not exceed 10%. • When evaluating plans with a sequential boost to gross disease, each individual plan should be scrutinized before the “plan sum” to assess for hot spots or under- coverage of each individual PTV. • The organs-at-risk include the small bowel, large bowel, bladder, femoral heads, iliac crest, and external genitalia. Uniform consensus guidelines for contouring the small and large bowel, bladder, and femoral heads are available from an RTOG consensus panel [10]. Suggested dose constraints from QUANTEC and RTOG 0529 are listed in Table 19.6 [2, 11]. • Pelvic bone marrow is emerging as an important organ-at-risk with respect to minimizing acute hematologic toxicity in patients receiving concurrent chemo- Table 19.6 Dose constraints for organs-at-risk Organ-at-risk Constraints Small bowel QUANTEC V15Gy 120 cc (individual loops) V45Gy 195 cc (entire potential space within peritoneal cavity) RTOG 0529 V30Gy 200 cc V35Gy 150 cc V45Gy 20 cc Dmax 50 Gy Large bowel RTOG 0529 V30Gy 200 cc V35Gy 150 cc V45Gy 20 cc Bladder QUANTEC Dmax 65 Gy V65Gy 50% RTOG 0529 V35Gy 50% V40Gy 35% V50Gy 5% Femoral heads RTOG 0529 V30Gy 50% V40Gy 35% V44Gy 5% Iliac crest RTOG 0529 V30Gy 50% V40Gy 35% V50Gy 5% External genitalia RTOG 0529 V20Gy 50% V30Gy 35% V40Gy 5% 19 Anal Cancer
- 250. 248 radiotherapy for anal cancer [12–14]. Currently, the pelvic bones serve as a sur- rogate for the pelvic bone marrow. Delineation of the pelvic bone marrow structure is described by Mell et al. [15]. The pelvic bone marrow structure con- sists of 3 sub-sites: the lumbosacral spine, the ilium, and the low pelvis. • We suggest that potential dose constraints for the pelvic bone marrow should include mean dose 28 Gy, V10 90% and V20 75%. However, these con- straints have not been validated prospectively and should not supercede other planning objectives. The lumbosacral spine may be the most active sub-site of the pelvic bone marrow [12, 13, 16], and limiting dose to this site may be suffi- cient to reduce hematologic toxicity. References 1. Gilroy JS, Amdur RJ, Louis DA, Li JG, Mendenhall WM. Irradiating the groin nodes with- out breaking a leg: a comparison of techniques for groin node irradiation. Med Dosim. 2004;29(4):258–64. 2. Kachnic LA, Winter K, Myerson RJ, et al. RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 2013;86(1):27–33. 3. Ajani JA, Winter KA, Gunderson LL, et al. Fluorouracil, mitomycin, and radiotherapy vs fluo- rouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA. 2008;299(16):1914–21. 4. Myerson RJ, Garofalo MC, El Naqa I, et al. Elective clinical target volumes for conformal therapy in anorectal cancer: a radiation therapy oncology group consensus panel contouring atlas. Int J Radiat Oncol Biol Phys. 2009;74(3):824–30. 5. Ng M, Leong T, Chander S, et al. Australasian Gastrointestinal Trials Group (AGITG) con- touring atlas and planning guidelines for intensity-modulated radiotherapy in anal cancer. Int J Radiat Oncol Biol Phys. 2012;83(5):1455–62. 6. Rouard N, Peiffert D, Rio E, et al. Intensity-modulated radiation therapy of anal squamous cell carcinoma: relationship between delineation quality and regional recurrence. Radiother Oncol. 2019;131:93–100. 7. Taylor A, Rockall AG, Reznek RH, Powell ME. Mapping pelvic lymph nodes: guide- lines for delineation in intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2005;63(5):1604–12. 8. Daly ME, Murphy JD, Mok E, Christman-Skieller C, Koong AC, Chang DT. Rectal and blad- der deformation and displacement during preoperative radiotherapy for rectal cancer: are cur- rent margin guidelines adequate for conformal therapy? Pract Radiat Oncol. 2011;1(2):85–94. 9. Dapper H, Schiller K, Münch S, et al. Have we achieved adequate recommendations for target volume definitions in anal cancer? A PET imaging based patterns of failure analysis in the context of established contouring guidelines. BMC Cancer. 2019;19(1):742. 10. Gay HA, Barthold HJ, O'Meara E, et al. Pelvic normal tissue contouring guidelines for radia- tion therapy: a Radiation Therapy Oncology Group consensus panel atlas. Int J Radiat Oncol Biol Phys. 2012;83(3):353–62. 11. Marks LB, Yorke ED, Jackson A, et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys. 2010;76(3):10–9. 12. Bazan JG, Luxton G, Kozak MM, et al. Impact of chemotherapy on normal tissue complication probability models of acute hematologic toxicity in patients receiving pelvic intensity modu- lated radiation therapy. Int J Radiat Oncol Biol Phys. 2013;87(5):983–91. J. A. Miller et al.
- 251. 249 13. Bazan JG, Luxton G, Mok EC, Koong AC, Chang DT. Normal tissue complication prob- ability modeling of acute hematologic toxicity in patients treated with intensity-modulated radiation therapy for squamous cell carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 2012;84(3):700–6. 14. Mell LK, Schomas DA, Salama JK, et al. Association between bone marrow dosimetric parameters and acute hematologic toxicity in anal cancer patients treated with concur- rent chemotherapy and intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2008;70(5):1431–7. 15. Mell LK, Kochanski JD, Roeske JC, et al. Dosimetric predictors of acute hematologic toxicity in cervical cancer patients treated with concurrent cisplatin and intensity-modulated pelvic radiotherapy. Int J Radiat Oncol Biol Phys. 2006;66(5):1356–65. 16. Rose BS, Liang Y, Lau SK, et al. Correlation between radiation dose to (1)(8)F-FDG- PET defined active bone marrow subregions and acute hematologic toxicity in cer- vical cancer patients treated with chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2012;83(4):1185–91. 19 Anal Cancer
- 252. 251 20 Postoperative Therapy for Cervical, Vaginal, and Endometrial Cancer Karen Tye, Loren K. Mell, and Dominique Rash Contents 20.1 Introduction 251 20.2 Diagnostic Workup Relevant for Target Volume Delineation 252 20.3 Simulation and Daily Localization 253 20.4 Target Volume Delineation and Treatment Planning 254 20.5 External Beam Plan Assessment 260 References 261 20.1 Introduction Intensity-modulated radiation therapy (IMRT) has become the treatment of choice for adjuvant radiotherapy for patients with gynecological cancers, particularly cer- vical and endometrial malignancies [1–3]. A Phase III randomized trial comparing patient reported outcomes and quality of life (QOL) scores in patients who received pelvic radiation with IMRT versus 3D conformal radiation therapy demonstrated significant reduction in acute GI and GU toxicity as well as better QOL with IMRT. Additionally, IMRT has been demonstrated to reduce the volume of irradi- ated bone marrow in cervical and endometrial cancer patients who undergo postop- erative pelvic radiotherapy (RT), producing a clinically significant reduction in acute and chronic toxicity [4, 5]. K. Tye · L. K. Mell (*) · D. Rash Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA e-mail: ktye@health.ucsd.edu; lmell@ucsd.edu; drash@health.ucsd.edu © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_20
- 253. 252 Target delineation is an essential component of IMRT treatment in cervical and endometrial cancer patients. Multiple consensus guidelines for clinical target vol- ume (CTV) delineation have been published in recent years [6–9]. The treatment paradigm varies by disease site: • For cervical cancer, surgery is preferred over radiation therapy for early stage disease. Radiation therapy is delivered following surgery in patients with high- risk features such as size ≥4 cm, lymphovascular space invasion (LVSI), deep cervical stromal involvement, positive margins, or locally advanced disease including parametria or lymph node involvement [10, 11]. • For endometrial cancer, treatment consists of upfront surgery, consisting of a total abdominal or laparoscopic hysterectomy and bilateral salpingo- oophorectomy (TAH or TLH-BSO) when possible. Radiation therapy is deliv- ered following surgery in women with adverse pathologic features including high-grade disease deep myometrial invasion, cervical stromal extension, and regional lymph node involvement [12]. Postoperative RT is recommended for endometrial cancer patients at high risk for recurrence in the lymph nodes, including stage I-II non-endometrioid histology or grade 3 endometrioid adenocarcinoma with deep myometrial invasion [13–15]. Whole pelvis RT is strongly considered for patients with stage III–IV disease to reduce the risk of pelvic and para-aortic recurrences [16–19]. A phase III randomized trial comparing vaginal cuff brachytherapy (VCB) and chemotherapy to pelvic RT alone for high-intermediate and high-risk early stage endometrial cancer patients did not demonstrate superiority with the addition of chemotherapy to VCB compared to pelvic RT [20]. Acute toxicity was greater with chemotherapy. As such, whole pelvis RT remains an effective, well-tolerated and appropriate adjuvant treatment in high-risk early stage endometrial carcinomas of all histologies. Traditionally, most endometrial cancer patients undergoing adjuvant RT received pelvic irradiation. However, low risk, early stage patients undergoing surgical stag- ing who are found to have negative nodes may undergo vaginal brachytherapy alone [21].Foradditionaldetails,pleaserefertothechapteronimageguidedbrachytherapy. 20.2 Diagnostic Workup Relevant for Target Volume Delineation • All gynecologic cancer patients should undergo a complete history and physical examination including a pelvic exam and evaluation of the inguinal and supracla- vicular lymph nodes as part of initial diagnosis and staging. Standard radio- graphic workup in these patients includes a computed tomography (CT) scan to assess the extent of local disease involvement and sites of extrauterine spread. K. Tye et al.
- 254. 253 • During the pelvic exam, special attention should be given to evaluation of the vaginal vault, rectovaginal septum, and bilateral parametria and sidewalls. Exam under anesthesia is indicated if patient discomfort prohibits a thorough examination. • Patients suspected to have urinary bladder or rectal involvement should undergo cystoscopy or rectosigmoidoscopy. • Positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) of the pelvis are useful in selected patients to delineate any residual gross tumor volume or involved lymph nodes. PET/CT is of particu- lar use in diagnostic workup of cervical cancer, to assess for para-aortic nodal spread and distant metastasis [22]. 20.3 Simulation and Daily Localization • Gynecologic cancer patients undergoing postoperative pelvic IMRT are simu- lated in the supine position. Immobilization of the lower body (and upper body in the setting of extended field radiation), such as with a cradle or Vac-Lok device, is recommended. • CT simulation with ≤3 mm slice thickness is the recommended simulation approach and is performed with (comfortably) full and empty bladder scans which can be fused to generate an integrated target volume (ITV). • Intravenous contrast is recommended to identify the patient’s vasculature as a surrogate for the lymph nodes, unless medically contraindicated. • Consider use of oral contrast to opacify the small bowel as a critical organ at risk. • Patients are encouraged to empty their rectum the morning of simulation and for daily treatment. Use of rectal enema may be considered. • An internal vaginal marker to identify the apex of the vagina and an introitus marker are standard. • Whenever possible, it is desirable to simulate patients in both the empty and full bladder state, to account for changes in target position due to bladder filling and emptying, such as with an internal target volume (ITV) (Fig. 20.1). Patients should be treated consistently in either a full bladder or empty bladder state to minimize the impact of bladder filling on target motion. • Daily orthogonal planar imaging (MV or kV) is recommended for setup. • Weekly imaging with cone beam CT (CBCT) should be done at minimum to verify treatment setup; daily CBCT to monitor variations in bladder and bowel filling can also be done. 20 Postoperative Therapy for Cervical, Vaginal, and Endometrial Cancer
- 255. 254 Fig. 20.1 An example of internal target volume (ITV) to planning target volume (PTV) expan- sion. Target volumes are drawn both on a scan with a full bladder (cyan) and empty bladder (yel- low) then combined to make an ITV (red), which is then expanded and included in the PTV (dark blue) 20.4 Target Volume Delineation and Treatment Planning • Delineated target volumes in cervical and uterine cancer patients undergoing adjuvant pelvic IMRT include multiple CTVs (CTV1, CTV2, and CTV3), to allow for anisotropic CTV to PTV expansions (Fig. 20.2). See Table 20.1 for a detailed description of these components, which were used on TIME-C randomized clini- cal trial. • Regarding CTV1, the anterior portion of the uterosacral ligament is removed dur- ing a radical hysterectomy. Consequently, the mesorectal fascia is used as a sur- rogate structure for the posterior border of the vaginal cuff and parametrium CTV [10]. • Vaginal boost can be considered if at higher risk for recurrence due to factors such as cervical stromal invasion, supracervical hysterectomy, extensive LVSI, or extensive vaginal involvement. K. Tye et al.
- 256. 255 Fig. 20.2 A patient with International Federation of Gynecology and Obstetrics (FIGO) stage IB1 cervical cancer who underwent a radical hysterectomy and pelvic lymphadenectomy. Pathology revealed deep cervical stromal invasion as well as 3 of 15 positive nodes. She was treated with adjuvant intensity-modulated pelvic radiation therapy and concurrent cisplatin. Three clinical tar- get volumes (CTV) are shown: CTV1 (green), CTV2 (blue), and CTV3 (red) • In endometrial cancer patients, CTV3 is modified to include the presacral region when there is cervical stromal invasion (Fig. 20.3). • Extended field RT (i.e., pelvic-para-aortic fields) are often used when patients have pathologic involvement of para-aortic or high common iliac nodes. In this case, the upper border of the CTV may extend to the T12-L1 or L1-L2 inter- space, or the renal vasculature (Fig. 20.4). 20 Postoperative Therapy for Cervical, Vaginal, and Endometrial Cancer
- 257. 256 Table 20.1 Target volumes used in cervical/endometrial cancer patients undergoing postopera- tive pelvic IMRT Target volumes Definition and description GTV Not applicable in most settings unless patient is found to have residual gross disease at the time of radiation treatment CTV1 Vaginal cuff Includes any fat and soft tissue anterior and posterior to the vaginal cuff between the bladder and rectum CTV2 Paravaginal/parametrial tissues, proximal vagina (excluding the cuff) CTV3 Includes common iliaca and external and internal iliac nodal regions The common iliac and external and internal iliac regions are defined by including the pelvic vessels plus a 7-mm expansion (excluding bone, muscle, and bowel) as well as all suspicious lymph nodes, lymphoceles, and pertinent surgical clips Soft tissues between the internal and external iliac vessels along the pelvic sidewall are included Presacral nodes: The presacral area consists of the soft tissues anterior (minimum 1.0 cm) to the S1–S2 vertebrae Upper extent: 7 mm inferior to L4–5 interspace Lower extent: superior aspect of femoral head (lower extent of external iliacs) and paravaginal tissues at level of vaginal cuff (lower extent of internal iliacs) Cervical: In patients with suspected uterosacral involvement, the entire presacral region is included Endometrial: The presacral region is included for patients with cervical stromal involvement Inguinal nodes: In cases with distal 1/3 vaginal involvement, inguinal nodes will be contoured continuously from external iliac nodes to 2 cm caudal to the saphenous/ femoral junction PTV1 CTV1 + 15 mm PTV2 CTV2 + 10 mm PTV3 CTV3 + 7 mm IMRT intensity-modulated radiation therapy, GTV gross tumor volume, CTV clinical target vol- ume, PTV planning target volume. The final PTV is then generated by the union of the PTV1, PTV2, and PTV3: PTV=PTV1 ∪ PTV2 ∪ PTV3 If an ITV approach is used, CTV1 and CTV2 should be contoured on both the empty and full blad- der scans and subsequently fused to generate an ITV. A 7 mm expansion on the ITV can be used to generate the PTV, which will be combined with PTV3 for the final PTV a To the level of L4–5 which will not include the entire common iliac nodal region in many patients; for patients undergoing extended field radiation for involved para-aortic disease, CTV3 should be extended to the level of the renal hilum or 2–3 cm above the highest involved node K. Tye et al.
- 258. 257 Fig. 20.3 The clinical target volume (CTV3) (red) is modified in endometrial cancer patients with cervical stromal invasion to include the presacral region Fig. 20.4 Sagittal cross-section of a planning computed tomography with overlaid prescription isodose in colorwash in a patient with endometrial cancer undergoing postoperative extended field radiation therapy. Planning target volume is shown in light green, extending to the superior border of L1 20 Postoperative Therapy for Cervical, Vaginal, and Endometrial Cancer
- 259. 258 Fig. 20.5 Several planning target volumes (PTV) are generated in the postoperative endometrial cancer patient described in Fig. 20.3. The final PTV used for treatment planning is generated by combining PTV1, PTV2, and PTV3 (and internal target volume (ITV), if defined). The resultant PTV (red) is shown in the figure encompassing CTV1 (green), CTV2 (blue), and CTV3 (yellow) • Modified extended fields with upper borders between L4-L5 and L1-L2 may be used in patients with extensive pelvic nodal or high common iliac nodal involvement. • Planning target volumes (PTVs) are created for each CTV (see Table 20.1 for CTV to PTV margins), and the final PTV used for treatment planning is gener- ated by combining the individual PTVs (Fig. 20.5). Different CTV to PTV expansions are used for each CTV component based on its degree of internal organ motion and setup uncertainty. • A boost of 5–15 Gy may be added for gross nodal disease or parametrial involvement; this may be done sequentially or by an integrated boost (Fig. 20.6). K. Tye et al.
- 260. 259 Fig. 20.6 A patient with FIGO stage IB endometrioid adenocarcinoma s/p robotic assisted lapa- roscopic hysterectomy who was found at the time of CT simulation to have an enlarged para-aortic lymph node. She was treated with extended field IMRT. An ITV technique was used. The superior border of CTV3 (green) was modified to include the renal hilum and the GTV of gross nodal dis- ease is contoured (red). This was given a planned SIB boost 5940 cGy with 4760 cGy in 28 frac- tions to the other nodes 20 Postoperative Therapy for Cervical, Vaginal, and Endometrial Cancer
- 261. 260 20.5 External Beam Plan Assessment • Ideally at least 95% of the PTV should receive 100% of the prescription dose and ≥99% of the PTV will receive ≥90% of the prescription dose. • The dose maximum should occur within the PTV and dose areas 100% of the prescription dose outside of the PTV should be minimized. • Organs at risk (OAR) used in treatment planning include the bowel, bladder, and rectum and femoral heads. In patients undergoing adjuvant chemotherapy, the pelvic bone marrow (BM) should be included as this technique has been shown to help reduce the risk of hematologic toxicity [2] (Fig. 20.7). See Table 20.2 for detailed descriptions for delineation of the OARs as well as dose constraints used in gynecological cancer patients undergoing pelvic IMRT treatment planning. • The bowel contour should include the entire peritoneal space encompassing the bowel such that the superoinferior boundaries extend 1.5 cm superior to the cau- dal aspect of the PTV and inferiorly to the rectosigmoid junction. In the anterior- posterior direction, the bowel should be delineated from the anterior abdominal wall to the most posterior extent of bowel. The bilateral bowel edges serve as the left-right boundaries. c a b Fig. 20.7 Contours for organs at risk including bowel ((a), orange), rectum ((b), brown), bladder ((b), yellow), and bone marrow ((c), green) on representative computed tomography slices K. Tye et al.
- 262. 261 Table 20.2 Organ at risk (OAR) and dose constraints from University of California San Diego guidelines and TIME-C protocol Organ Definition and description Dose constraints Bowel Outermost loops of bowel from the level of the L4–5 interspace to the sigmoid flexure. Includes the sigmoid colon and ascending/descending colon present in the pelvis V35 Gy 35% V45 Gy 200 cc Rectum Defined by the outer rectal wall from the level of the sigmoid flexure to the anus V45 Gy 50% Bladder Defined by the outer bladder wall V45 Gy 35% Bone marrow The pelvic bones serve as a surrogate for the pelvic bone marrow. Regions included are the os coxae, L5 vertebral body, entire sacrum, acetabulae, and proximal femora The superior extent of the contour should be at the level of the superior border of L5 or the iliac crest (whichever is more superior) Inferior extent: ischial tuberosities V10 Gy 90% V20 Gy 75% V40 Gy 37% Femoral heads Entire femoral head excluding the femoral neck V30 Gy 15% V50 Gy 5% Kidneys The outer organ contour should be delineated and filled in, treating the right and left kidneys as a solid continuous structure V18 Gy 50% Spinal cord The spinal cord will be contoured from the level of T10/T11 to the L1/L2 interspace Dmax 45 Gy Duodenum The duodenum should be contoured and filled in, treating the organ as a solid continuous structure, from the distal stomach to the jejunum V40 Gy 50% V55 Gy 5 cc References 1. Klopp AH, Yeung AR, Deshmukh S, et al. Patient-reported toxicity during pelvic intensity- modulatedradiationtherapy:NRGOncology-RTOG1203.JClinOncol.2018;36(24):2538–44. 2. Wright JD, Deutsch I, Wilde ET, et al. Uptake and outcomes of intensity-modulated radiation therapy for uterine cancer. Gynecol Oncol. 2013;130(1):43–8. 3. Osborn V, Schwartz D, LeeYC, et al. Patterns of care of IMRT usage in postoperative manage- ment of uterine cancer. Gynecol Oncol. 2017;144(1):130–5. 4. Klopp AH, Moughan J, Portelance L, et al. Hematologic toxicity in RTOG 0418: a phase 2 study of postoperative IMRT for gynecologic cancer. Int J Radiat Oncol Biol Phys. 2013;86(1):83–90. 5. Vitzthum LK, Park H, Zakeri K, et al. Risk of pelvic fracture with radiation therapy in older patients. Int J Radiat Oncol Biol Phys. 2020;106(3):485–92. 6. Klopp A, Smith BD, Alektiar K, et al. The role of postoperative radiation therapy for endo- metrial cancer: executive summary of an American Society for Radiation Oncology evidence- based guideline. Pract Radiat Oncol. 2014;4(3):137–44. 7. Small W Jr, Mell LK, Anderson P, et al. Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy in postoperative treatment of endometrial and cervical cancer. Int J Radiat Oncol Biol Phys. 2008;71(2):428–34. 20 Postoperative Therapy for Cervical, Vaginal, and Endometrial Cancer
- 263. 262 8. Murakami N, Norihisa Y, Isohashi F, et al. Proposed definition of the vaginal cuff and para- colpium clinical target volume in postoperative uterine cervical cancer. Pract Radiat Oncol. 2016;6(1):5–11. 9. Small W, Bosch WR, Strauss JB, et al. Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiation therapy in postoperative treatment of endome- trial and cervical cancer. Int J Radiat Oncol Biol Phys. 2014;71(2):428–34. 10. Sedlis A, Bundy BN, Rotman MZ, et al. A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: a Gynecologic Oncology Group Study. Gynecol Oncol. 1999;73(2):177–83. 11. Peters WA, Liu PY, Barrett RJ, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high- risk early-stage cancer of the cervix. J Clin Oncol. 2000;18(8):1606–13. 12. Keys HM, Roberts JA, Brunetto VL, et al. A phase III trial of surgery with or without adjunc- tive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004;92:744–51. 13. Creutzberg CL, Nout RA, Lybeert ML, et al. Fifteen-year radiotherapy outcomes of the randomized PORTEC-1 trial for endometrial carcinoma. Int J Radiat Oncol Biol Phys. 2011;81(4):631–8. 14. Blake P, Swart AM, et al. Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis. Lancet. 2009;373(9658):137–46. 15. Onsrud M, Cvancarova M, Hellebust TP, et al. Long-term outcomes after pelvic radiation for early-stage endometrial cancer. J Clin Oncol. 2013;31(31):3951–6. 16. National Comprehensive Cancer Network. Cervical cancer (version 1.2020). http://www.nccn. org/professionals/physician_gls/pdf/cervical.pdf. Accessed March 4, 2020. 17. National Comprehensive Cancer Network. Uterine neoplasms (version 5.2019). http://www. nccn.org/professionals/physician_gls/pdf/uterine.pdf. Accessed March 4, 2020. 18. de Boer SM, Powell ME, Mileshkin L, et al. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an interna- tional, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018;19(3):295–309. 19. Matei D, Filiaci V, Randall ME, et al. Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer. N Engl J Med. 2019;380(24):2317–232. 20. Randall ME, Filiaci V, McMeekin DS, et al. Phase III trial: adjuvant pelvic radiation therapy versus vaginal brachytherapy plus paclitaxel/carboplatin in high-intermediate and high-risk early stage endometrial cancer. J Clin Oncol. 2019;37(21):1810–8. 21. Nout RA, Smit VT, Putter H, et al. Vaginal brachytherapy versus pelvic external beam radio- therapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open- label, non-inferiority randomised trial. Lancet. 2010;375:816–20. 22. Palaniswamy SS, Borde CR, Subramanyam P. 18F-FDG PET/CT in the evaluation of cancer cervix: where do we stand today? Nucl Med Commun. 2018;39(7):583–92. K. Tye et al.
- 264. 263 21 Definitive Therapy for Cervical, Vaginal, and Endometrial Cancer Casey W. Williamson and Loren K. Mell Contents 21.1 Introduction 263 21.2 General Principles of Workup, Imaging, and Staging 264 21.3 CT Simulation for Treatment Planning 264 21.4 General Principles of Target Delineation 265 21.5 Organs at Risk 267 21.6 Plan Assessment 269 21.7 Image-Guided Treatment Delivery 269 21.8 Cervical Cancer 269 21.9 Vaginal Cancer 272 21.10 Endometrial Cancer 274 References 276 21.1 Introduction IMRT is fast becoming a widely used radiation approach for definitive treatment of gynecologic cancers. Although no large randomized trials comparing IMRT to con- ventional techniques have been conducted for this population, evidence from numerous phase II trials and controlled studies support the effectiveness and reduced toxicity with IMRT in patients with an intact uterus. Moreover, phase III protocols C. W. Williamson · L. K. Mell (*) Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA e-mail: cwwillia@health.ucsd.edu; lmell@ucsd.edu © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_21
- 265. 264 have begun to incorporate IMRT as a standard treatment approach for definitive therapy, indicating its widespread acceptance. However, 3D conformal techniques remain in common use for this population, and delineation of targets and organs at risk (OARs) are also important for defining fixed beam arrangements and evaluating the dosimetry with conventional treatment plans. In contrast to the postoperative setting, application of IMRT in patients with an intact uterus is complicated by even greater mobility of targets and OARs. Moreover, treatment intensity is generally higher, with radiation often given with concurrent chemotherapy and followed by brachytherapy and/or nodal boosts, with higher overall doses delivered. Thus, nor- mal tissue dose is a particularly critical factor in determining both treatment toler- ance and risk for high grade late complications. Advanced technologies play a prominent role in defining targets and OARs in this context, which remains an active area of investigation. 21.2 General Principles of Workup, Imaging, and Staging • All patients should undergo a complete history and physical examination with attention on pelvic exam to size and location of tumor, extent of vaginal exten- sion, and presence of urethral, parametrial, and/or sidewall involvement. Exam under anesthesia may be necessary if patient is unable to otherwise tolerate a thorough examination. • If there is clinical suspicion for bowel or bladder involvement, pelvic MRI and proctosigmoidoscopy and/or cystoscopy are indicated. • Dynamic contrast-enhanced MRI is the optimal method for detecting cervix invasion and myometrial invasion, with an accuracy of 85–93% [1], and has been shown to be superior to CT and physical examination for determining tumor size and extent of invasion [2]. • The sensitivity of MRI for detecting lymph node metastases is 27–66% with specificity 73–94% in surgically staged patients [3]. However, PET/CT is prefer- able if available, with sensitivity and specificity for assessing regional lymph node metastases ranging from 50–100% and 87–100%, respectively [3]. • Radiologic workup with whole-body PET/CT is preferred for patients with at least International Federation of Gynecology and Obstetrics (FIGO) stage IB disease, given its greater sensitivity than CT [4], and is now admissible for FIGO staging purposes [5]. • FIGO has published staging systems for cervical, endometrial, and ovarian can- cers [5, 6]. There are also TNM staging systems produced by the American Joint Committee on Cancer [7]. 21.3 CT Simulation for Treatment Planning • CT simulation should be obtained with the patient in a supine position with a customized immobilization cradle to minimize treatment setup error. Scans should be obtained with slice thickness ≤3 mm. C. W. Williamson and L. K. Mell
- 266. 265 • The degree of bladder and rectal fullness at simulation should ideally replicate that which will be observed during daily treatment. Empty and full bladder scans may be fused to generate an integrated target volume (ITV). • Treatment can be delivered with either a (comfortably) full or empty bladder and it is recommended to use a consistent bladder filling state (i.e., always full or always empty) for both the simulation scan used for treatment planning, and for daily treatment. Treatment with an empty bladder may be more reproducible and reduces the absolute variation in bladder volume, whereas treatment with a full bladder can displace bowel from the treatment field and improve bowel dosim- etry [8]. • Bowel preparation with an enema can be used to achieve simulation with an empty rectum. • Given that the patient’s pelvic vasculature serves as a surrogate for lymph node location, simulation with intravenous contrast is recommended, unless medically contraindicated. • Tools for improving target volume delineation include placement of fiducial markers prior to CT simulation or placing radiopaque markers in the vaginal apex and introitus at the time of simulation. • Patients with disease involving the distal one-half of the vagina (or vaginal pri- mary) should also receive bilateral inguinal RT, in which case CT simulation can be performed in the “frog-leg” position to minimize skin fold toxicity. 21.4 General Principles of Target Delineation • IMRT is increasingly used as a standard modality for gynecologic malignancies in the definitive setting. Evidence demonstrates excellent outcomes and an improved toxicity profile, with improvements in gastrointestinal (GI) and hema- tologic toxicities, as well as reduced risk of pelvic fractures, compared to 3D conformal techniques [9–15]. • Multiple ongoing clinical trials utilize IMRT, with their respective protocols delineating specific treatment planning requirements [16–20]. • Fusion of pre-treatment PET/CT with CT simulation is recommended to assist in delineation of gross tumor volume (GTV). • See dedicated sections below for target delineation for cervical, vaginal, and endometrial cancers, respectively, with definitions described in Table 21.1. These recommendations are derived from the protocol for the multi-institutional coop- erative group phase III NRG-GY006 clinical trial [16]. Note there are varying standards across trials and institutions. • Accurate target delineation is of critical importance for IMRT planning. International consensus guidelines for contouring definitive cervix cases have been published [21]. • Interactive online sample cases are available on educational websites, such as eContour [22], to assist with contouring. • An MRI study using injected iron oxide particles suggested that 95% of pelvic (common iliac, internal iliac, medial and anterior external iliac, and obturator) 21 Definitive Therapy for Cervical, Vaginal, and Endometrial Cancer
- 267. 266 Table 21.1 Target delineation for cervical cancer (per NRG-GY006 protocol) [16] Name Details GTV All visible gross disease as assessed by clinical information, physical examination, radiographic studies, endoscopic examination, and biopsy results CTV1 GTV + cervix + uterus CTV2 Parametria and upper third of the vagina (or upper half if the vagina is clinically involved) CTV3 Common, external iliac, internal iliac, and presacral lymph nodes. The upper border should start the aortic bifurcation (approximately L4–L5 interspace). Presacral nodes should be included to the S2–S3 interspace; below this point this nodal volume can be separated into two structures. External iliac nodes should be included to the top of the femoral heads. If there is distal vaginal involvement, the inguinal nodes should be included (from the external iliac nodes to 2cm caudal to the saphenous/femoral junction). If para-aortic nodes are involved, an extended field should be used, extending the superior border to the L1/L2 interspace or 3cm cranial to gross disease. CTV3 should be obtained by placing a 7mm margin around the vessels with inclusion of any adjacent visible lymph nodes, lymphoceles, or surgical clips. This volume should be modified to exclude bone, muscle, and bowel, and should not extend inferior to the ischial tuberosities CTV_boost Gross pelvic lymph nodes. If the patient will receive a parametrial boost, this area should be included ITV If an ITV approach is to be used, CTV1 should be delineated on both the full and empty bladder scans and combined to generate the ITV CTV_4500 or CTV_4760 CTV1 + CTV2 + CTV3 + ITV PTV1 CTV1 + 15 mm uniform expansion PTV2 CTV2 + 10 mm uniform expansion PTV3 CTV3 + 5 mm uniform expansion PTV4 ITV + 7 mm uniform expansion PTV_boost CTV_boost + 5 mm uniform expansion PTV_4500 or PTV_4760 PTV1 + PTV2 + PTV3 + PTV4 + PTV_boost. This should be trimmed up to 3 mm from the skin surface, if necessary, to spare skin. The CTV should be fully encompassed by the PTV lymph nodes are located within 7 mm of the pelvic vasculature [23]. However, inguinal nodal basins should be delineated using an anatomic compartment approach given greater range of potential lymph node location with respect to the vessels [24]. • Common problems with target delineation observed in multi-center trials include: – – Inadequate margin around the vasculature/clinical target volume (CTV) that is too close to the vessels – – Insufficient coverage around the internal iliac vasculature inferior and poste- rior in the pelvis – – Insufficient coverage around the obturator vasculature inferior and anterolat- erally in the pelvis – – Insufficient coverage of the presacral region – – Unnecessary extension of the CTV into the sacral hollows C. W. Williamson and L. K. Mell
- 268. 267 21.5 Organs at Risk • Standard organs at risk (OARs) include the bowel, rectum, bone marrow, blad- der, and femoral heads. Recommended dose constraints for these structures are outlined in Table 21.2. Table 21.2 Organ at risk definition (per NRG-GY006 protocol) [16] OAR Description Dose constraints All patients Dosimetric parameter Per protocol Variation acceptable Bowel space Bowel space should be contoured beginning from the axial slice 1cm above the superior-most slice containing PTV (if not present at this level, then beginning from its most superior extent) and extending to its most inferior extent in the pelvis. The distal descending colon and sigmoid colon should not be included. The volume should include the outermost extent of bowel loops plus any space within the abdominal cavity the bowel may occupy. Individual loops of bowel should not be separately contoured. Rectum should be contoured separately (next row) V45 (cc) DMax (Gy) D30% (Gy) ≤200 ≤59.4 ≤40 ≤250 ≤62.1 ≤50 Rectum The outer rectal wall should be contoured and filled in and treated as a solid continuous structure, spanning the level of the sigmoid flexure to the anus D50% (Gy) D60% (Gy) DMax (Gy) ≤45 ≤30 ≤50 ≤54 ≤50 ≤55 Bone marrow The outer bone contour should be delineated and filled in, treated as a solid continuous structure. The os coxae, L4 and L5 vertebral bodies, entire sacrum, acetabulae, and proximal femora should be included. The inferior-most extent should be the level of the ischial tuberosities Dmean (Gy) V10 (%) V20 (%) ≤27 ≤85.5 ≤66 ≤29 ≤90 ≤75 Bladder The outer wall of the entire bladder should be contoured and filled in, treating the organ as a solid continuous structure D50% (Gy) DMax (Gy) ≤45 ≤50 ≤55 ≤57.5 Femoral heads The outer contours of bilateral femoral heads should be delineated and filled in, treated as solid continuous structures, not including the femoral necks D15% (Gy) DMax (Gy) ≤30 ≤50 ≤50 ≤55 Extended field patients [17] Bilateral kidney The outer organ contour of each kidney should be delineated and filled in, treated as a solid continuous structure D50% (Gy) ≤18 ≤20 Spinal cord Should be contoured from T10/T11 to the L1/L2 interspace D0.03cc (Gy) ≤45 ≤47.5 Duodenum Should be contoured from the outer border and filled in from the distal stomach to the jejunum D0.03cc D50% (Gy) ≤56 ≤40 ≤60 ≤50 Liver Should be contoured from the outer border and filled in D50% (Gy) ≤25 ≤30 21 Definitive Therapy for Cervical, Vaginal, and Endometrial Cancer
- 269. 268 Fig. 21.1 Organs at risk for pelvic IMRT: Representative slices from a patient with FIGO IIIC2 cervical cancer (starting superiorly from the L2/L3 interspace). Contoured are the bladder (yellow), rectum (light green), sigmoid (light brown), bone marrow (pink), bowel space (orange), left kidney (blue), right kidney (green), left formal head (blue), right femoral head (green), spinal canal (orange) • Figure 21.1 shows representative axial CT slices with OARs contoured for a patient with FIGO IIIC2 cervical cancer treated with extended field RT. • Normal tissue complication probability (NTCP) modeling studies have estab- lished validated dose constraints for bowel [25] and bone marrow [26] in cervical cancer patients undergoing chemoradiotherapy. • IMRT has been shown to reduce GI toxicity [10, 11] and hematologic toxicity [11], and may improve patient-reported GI and urinary toxicity. C. W. Williamson and L. K. Mell
- 270. 269 • PET/CT can be used to segment active subregions of bone marrow, where dose accumulation has been correlated with higher rates of hematologic toxicity [27]. Moreover, this approach can reduce the overall bone and bone marrow dose [28]. Sparing metabolically active marrow with IMRT has been found to reduce neu- tropenia and improve chemotherapy tolerance in prospective clinical trials [11, 29]. 21.6 Plan Assessment • Ideally, at least 95% of the PTV should receive 100% of the prescription dose, and ≥99% of the PTV should receive at least 90% of the prescrip- tion dose. • The dose maximum should occur within the PTV and dose areas 100% of the prescription dose outside of the PTV should be minimized. • Knowledge-based planning workflows are useful to help achieve optimal dosimetry for more complicated IMRT plans in patients with cervical can- cer [30]. 21.7 Image-Guided Treatment Delivery • Patients treated with conventional beam arrangements should undergo at least weekly imaging with MV ports. • Daily bony imaging with kV or cone beam CT (CBCT) can facilitate reduction of planning margins to 5 mm around the nodal CTV [31, 32]. • Patients treated with IMRT should undergo image guidance with at least weekly CBCT. CBCT with each fraction is recommended, whenever feasible, to check for large variation in target position due to changes in rectal or bladder filling or uterine motion. 21.8 Cervical Cancer • Regional lymphatic spread typically follows a stepwise pattern by spreading to pelvic nodes before para-aortic nodes. The cervix drains the paracervical lymph nodes which in turn drain into the obturator, internal iliac, and external iliac basins, followed by common iliac and para-aortic nodes. • Patients with lesions involving the distal vagina are at risk for inguinal nodal metastases. • Delineated target volumes include a GTV and multiple clinical target volumes (CTVs). See Table 21.1 for detailed descriptions of these volumes. 21 Definitive Therapy for Cervical, Vaginal, and Endometrial Cancer
- 271. 270 • If para-aortic nodes are involved, an extended field technique should be employed by extending the cranial border of CTV superiorly to the L1/L2 interspace or 3 cm cranial to the superior-most involved node. • PTVs are created for each CTV and the final PTV used for treatment planning is the combination of all PTVs. Different CTV-PTV expansions are used for each CTV component based on its degree of internal organ motion and setup uncer- tainty (29), which have been validated in a separate cohort [30]. Figure 21.1 shows representative axial CT slices for a patient with FIGO IIIC2 disease. • A typical dose prescription is 45 Gy in 25 fractions to the node-negative pelvis, or 47.6 Gy in 28 fractions if there is nodal disease, with a simultaneous inte- grated boost (SIB) to involved nodes to 59.4 Gy. • The nodal boost dose and/or dose per fraction may need to be reduced to respect bowel tolerance; note there are acceptable variations in dose prescription in practice. • A parametrial boost may be added at the discretion of the treating physician for parametrial involvement as long as that side is not to receive a SIB within the parametrial boost field. Conventional AP/PA fields for a parametrial boost include the sacroiliac joints (upper border), bottom of the obturator foramen (lower border), and obturator internus muscle (lateral borders) with a 4–5 cm midline block. A typical dose prescription is 6–10 Gy in 3–5 fractions. • Brachytherapy boost is standard towards the end of or following the completion of EBRT. See the following chapter for further discussion. • Figure 21.2 shows sample slices from the CT simulation scan for a patient with IB1 cervical cancer treated with pelvic IMRT. • Figure 21.3 shows sample slices from the CT simulation scan for a patient with IIIC2 cervical cancer treated with extended field IMRT. C. W. Williamson and L. K. Mell
- 272. 271 Fig. 21.2 Representative slices from the CT simulation plan for a patient with FIGO IB1 cervical squamous cell carcinoma who had undergone a large size cold knife cone biopsy. The patient’s pre-treatment PET/CT was fused to the planning CT. Shown are CTV1 (blue), CTV2 (orange), and CTV3 (red). She received 45 Gy in 25 fractions to the pelvis with concurrent cisplatin followed by an HDR intracavitary boost of 28 Gy in 4 fractions 21 Definitive Therapy for Cervical, Vaginal, and Endometrial Cancer
- 273. 272 Boost CTV to treat FDG-avid PALN CTV3 trimmed to exclude bowel, muscle CTV3 split inferior to S3 Started CTV3 at L1/L2 Fig. 21.3 Representative slices from the CT simulation scan for a patient with FIGO IIIC2 cervi- cal squamous cell carcinoma with parametrial involvement and PET/CT-positive para-aortic lymph nodes. Planning was done on an empty bladder and the PET/CT was fused to the planning CT scan. Shown are the primary GTV (yellow), nodal GTV (orange), CTV1 (pink), CTV2 (pur- ple), and CTV3 (cyan). The prescribed plan was for 47.6 Gy in 28 fractions to the pelvis with an SIB boost to gross nodes to 59.4 Gy although bowel tolerance limited the boost dose to 58 Gy for bowel-adjacent nodes to be followed by HDR brachytherapy boost 21.9 Vaginal Cancer • Vaginal cancer primaries are a relatively rare entity, as any tumor involvement of either cervix or vulva results in classification of cervical or vulvar cancer, respec- tively. There is a lack of prospective data to guide management specifically for vaginal cancers. The recommended treatment approach is individualized and often follows guidelines for cervical cancer. • Definitive RT, consisting of EBRT and brachytherapy, is an excellent treatment option for stage I disease, although definitive surgery is an option for select C. W. Williamson and L. K. Mell
- 274. 273 patients with non-bulky, distal, non-urethral disease. Definitive chemoradiation therapy is a standard for stages II-IVA [33–35]. • The standard EBRT approach is pelvic RT with coverage of the entire vagina. • Patients with disease involving the distal one-half of the vagina should receive bilateral inguinal RT. • Temporary fiducial markers can be used to delineate the vaginal apex and introi- tus at the time of CT simulation. • A typical EBRT dose prescription is 45 Gy in 25 fractions to the pelvis and entire vagina, typically followed by a brachytherapy boost (e.g., 6 Gy × 4 fractions). • Figure 21.4 shows sample slices from a CT simulation for a patient with stage IVA (T4N0M0) squamous cell carcinoma of the distal posterior vagina with rec- tal involvement, treated with pelvic IMRT. Fig. 21.4 Representative slices from CT simulation scan for a patient with a stage IVA (T4N0M0) squamous cell carcinoma of the distal posterior vagina with concern for rectal involvement. Contours shown are CTV1 (light green), CTV2 (orange), and CTV3 (purple). The pelvis received 45 Gy in 25 fractions, followed by an HDR brachytherapy boost of 21.5 Gy in 3 fractions 21 Definitive Therapy for Cervical, Vaginal, and Endometrial Cancer
- 275. 274 21.10 Endometrial Cancer • The uterus is bordered anteriorly by the bladder and posteriorly by the rectum. It is covered by peritoneal reflections and is divided into the fundus, isthmus, and cervix. • The uterine wall consists of an outer smooth muscle layer (the myometrium) and an inner layer of glandular epithelium (endometrium). • The uterus is supported by five ligaments: broad, round, cardinal, uterosacral, and vesicouterine. • Nodal areas at risk for uterine cancer patients include the obturator, external iliac, internal iliac, common iliac, and para-aortic lymph nodes. • Lesions involving the uterine fundus can spread directly to the para-aortic nodes. • The incidence of pelvic and para-aortic lymph node involvement varies accord- ing to risk categories (low, medium, and high), as well as tumor size and depth of invasion, as defined in the Gynecologic Oncology Group (GOG) 33 trial [36] • Hysterectomy is standard treatment for patients who are surgical candidates, with consideration for adjuvant RT based on pathologic risk features. • For medically inoperable patients, standard treatment is definitive RT with brachytherapy, with or without EBRT. EBRT alone can be considered for patients who are ineligible for or refuse brachytherapy [37–39]. Patients with recurrent disease may also be candidates for EBRT. • For patients to be treated with EBRT + brachytherapy, a standard EBRT dose is 45 Gy in 25 fractions. • For patients treated with EBRT alone, pelvic RT can be followed by a cone-down boost to the uterus and cervix. SBRT can be considered if the patient is unable to receive brachytherapy. • Target delineation is similar to pelvic RT for cervical cancer (Table 21.1). – – GTV includes all gross disease based on all available clinical and radio- logic data. – – The CTV is divided into three subregions: CTV1, CTV2, and CTV3 a. CTV1: GTV + entire uterus b. CTV2: paravaginal/parametrial tissues plus 3cm of the proximal vagina c. CTV3: same as in the postoperative setting (see postoperative chapter) – – In patients with distal one-third vaginal involvement, the inguinal nodes should be contoured continuously from the external iliac nodes to 2 cm cau- dad to the saphenous/femoral function. – – If para-aortic nodes are involved, an extended field technique should be employed by extending the cranial border of CTV3 in a similar fashion to that described in Table 21.1. – – Each CTV should be expanded differentially to form PTV1, PTV2, and PTV3 (15 mm, 7–10 mm, and 5–7 mm margins, respectively). • An additional boost of 5–15 Gy may be added for gross nodal disease or parame- trial involvement, which may be done with an SIB or a sequential approach. • Figure 21.5 shows a pre-treatment MRI from a patient with medically inoperable FIGO stage IB endometrial cancer demonstrating deep myometrial invasion. • Figure 21.6 shows sample slices from the CT simulation scan for the same patient who was treated with definitive radiation therapy. C. W. Williamson and L. K. Mell
- 276. 275 Fig. 21.5 Sagittal (left) and coronal (right) pre-treatment pelvic MRI from a patient with a medi- cally inoperable FIGO IA endometrial cancer with a 7.0 × 4.7 × 0.5 cm mass in the anterior body/ lower uterine segment involving more than 50% of the myometrium and extending into the upper cervix Boost CTV to treat gross node Fig. 21.6 Representative slices from CT simulation scan for a patient with FIGO stage IB medi- cally inoperable endometrial cancer with pelvic adenopathy (same patient as Fig. 21.5). The pre- treatment pelvic MRI was fused to the CT simulation scan. Shown are CTV1 (red), nodal CTV (dark blue), and CTV Boost (light blue). She received 50.4 Gy in 28 fractions to the pelvis with a boost to the suspicious pelvic lymph node to a total of 56.4 Gy and an HDR brachytherapy boost of 20 Gy in 5 fractions with an intracavitary applicator 21 Definitive Therapy for Cervical, Vaginal, and Endometrial Cancer
- 277. 276 References 1. Frei KA, et al. Prediction of deep myometrial invasion in patients with endometrial cancer: clinical utility of contrast-enhanced MR imaging-a meta-analysis and Bayesian analysis. Radiology. 2000;216:444–9. 2. Mitchell DG, et al. Early invasive cervical cancer: tumor delineation by magnetic resonance imaging, computed tomography, and clinical examination, verified by pathologic results, in the ACRIN 6651/GOG 183 intergroup study. J Clin Oncol. 2006;24:5687–94. 3. Kitajima K, Murakami K, Kaji Y, Sakamoto S, Sugimura K. Established, emerging and future applications of FDG-PET/CT in the uterine cancer. Clin Radiol. 2011;66:297–307. 4. Grigsby PW, Siegel BA, Dehdashti F. Lymph node staging by positron emission tomography in patients with carcinoma of the cervix. J Clin Oncol. 2001;19:3745–9. 5. Bhatla N, et al. Revised FIGO staging for carcinoma of the cervix uteri. Int J Gynecol Obstet. 2019;145:129–35. 6. Creasman W. Revised FIGO staging for carcinoma of the endometrium. Int J Gynecol Obstet. 2009;105:109. 7. Amin MB. AJCC cancer staging system. 8th ed. Chicago: Am. Jt. Commitee Cancer; 2017. 8. Chen VE, et al. The impact of daily bladder filling on small bowel dose for intensity modulated radiation therapy for cervical cancer. Med Dosim. 2019;44:102–6. 9. Hasselle MD, et al. Clinical outcomes of intensity-modulated pelvic radiation therapy for car- cinoma of the cervix. Int J Radiat Oncol. 2011;80:1436–45. 10. Gandhi AK, et al. Long-term clinical outcome and late toxicity of intensity modulated versus conventional pelvic radiation therapy for locally advanced cervix carcinoma: updated results from a prospective randomized study. Int J Radiat Oncol. 2015;93:E257–8. 11. Mell LK, et al. Bone marrow-sparing intensity modulated radiation therapy with concurrent cisplatin for stage IB-IVA cervical cancer: an international multicenter phase II clinical trial (INTERTECC-2). Int J Radiat Oncol Biol Phys. 2017;97:536–45. 12. Lin AJ, et al. Intensity modulated radiation therapy and image-guided adapted brachytherapy for cervix cancer. Int J Radiat Oncol Biol Phys. 2019;103:1088–97. 13. Marnitz S, et al. Role of surgical versus clinical staging in chemoradiated FIGO stage IIB-IVA cervical cancer patients—acute toxicity and treatment quality of the uterus-11 multicenter phase III intergroup trial of the German Radiation Oncology Group and the Gynecologic C. Int J Radiat Oncol. 2016;94:243–53. 14. Berger T, et al. Importance of technique, target selection, contouring, dose prescription, and dose-planning in external beam radiation therapy for cervical cancer: evolution of practice from EMBRACE-I to II. Int J Radiat Oncol Biol Phys. 2019;104:885–94. 15. Vitzthum LK, et al. Risk of pelvic fracture with radiation therapy in older patients. Int J Radiat Oncol Biol Phys. 2020;106:485–92. 16. Testing the addition of a new anti-cancer drug, triapine, to the usual chemotherapy treat- ment (cisplatin) during radiation therapy for advanced-stage cervical and vaginal cancers. NRG-GY006. Available at https://clinicaltrials.gov/ct2/show/NCT02466971. 17. Atezolizumab before and/or with chemoradiotherapy in immune system activation in patients with node positive stage IB2, II, IIIB, or IVA cervical cancer. NRG-GY017. Available at https://clinicaltrials.gov/ct2/show/NCT03738228. 18. Mileshkin A, et al. A phase III trial of adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone: Outback (ANZGOG0902/GOG0274/RTOG1174). J Clin Oncol. 2014;32:5632. 19. Monk BJ, et al. CALLA: efficacy and safety of durvalumab with and following concurrent chemoradiotherapy (CCRT) versus CCRT alone in women with locally advanced cervical can- cer: a phase III, randomized, double-blind, multicenter study. J Clin Oncol. 2019;37:5597. 20. Pötter R, et al. The EMBRACE II study: the outcome and prospect of two decades of evolution within the GEC-ESTRO GYN working group and the EMBRACE studies. Clin Transl Radiat Oncol. 2018;9:48–60. C. W. Williamson and L. K. Mell
- 278. 277 21. Lim K, et al. Consensus guidelines for delineation of clinical target volume for intensity- modulated pelvic radiotherapy for the definitive treatment of cervix cancer. Int J Radiat Oncol Biol Phys. 2011;79:348–55. 22. Sherer MV, et al. Development and usage of econtour, a novel, three-dimensional, image- based web site to facilitate access to contouring guidelines at the point of care. JCO Clin Cancer Inf. 2019;19:41. https://doi.org/10.1200/CCI.19.00041. 23. Taylor A, Rockall AG, Reznek RH, Powell MEB. Mapping pelvic lymph nodes: guide- lines for delineation in intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2005;63:1604–12. 24. Kim CH, Olson AC, Kim H, Beriwal S. Contouring inguinal and femoral nodes; how much margin is needed around the vessels? Pract Radiat Oncol. 2012;2:274–8. 25. Simpson DR, et al. Normal tissue complication probability analysis of acute gastrointestinal toxicity in cervical cancer patients undergoing intensity modulated radiation therapy and con- current cisplatin. Int J Radiat Oncol. 2012;83:e81–6. 26. Rose BS, et al. Normal tissue complication probability modeling of acute hematologic toxicity in cervical cancer patients treated with chemoradiotherapy. Int J Radiat Oncol. 2011;79:800–7. 27. Rose BS, et al. Correlation between radiation dose to 18F-FDG-PET defined active bone mar- row subregions and acute hematologic toxicity in cervical cancer patients treated with chemo- radiotherapy. Int J Radiat Oncol Biol Phys. 2012;83:1185–91. 28. Li N, et al. Feasibility of atlas-based active bone marrow sparing intensity modulated radiation therapy for cervical cancer. Radiother Oncol. 2017;123:325–30. 29. Mell LK, et al. Phase 1 trial of bone marrow sparing intensity modulated radiation therapy with concurrent cisplatin and gemcitabine in stage IB-IVA cervical cancer. Int J Radiat Oncol. 2016;96:S14. 30. Li N, et al. Highly efficient training, refinement, and validation of a knowledge-based plan- ning quality-control system for radiation therapy clinical trials. Int J Radiat Oncol Biol Phys. 2017;97:164–72. 31. Khan A, et al. Optimized planning target volume for intact cervical cancer. Int J Radiat Oncol. 2012;83:1500–5. 32. Williamson CW, et al. Prospective validation of a high dimensional shape model for organ motion in intact cervical cancer. Int J Radiat Oncol. 2016;96:801–7. 33. Tran PT, et al. Prognostic factors for outcomes and complications for primary squamous cell carcinoma of the vagina treated with radiation. Gynecol Oncol. 2007;105:641–9. 34. Frank SJ, Jhingran A, Levenback C, Eifel PJ. Definitive radiation therapy for squamous cell carcinoma of the vagina. Int J Radiat Oncol Biol Phys. 2005;62:138–47. 35. Miyamoto DT, Viswanathan AN. Concurrent chemoradiation for vaginal cancer. PLoS One. 2013;8:e65048. 36. Creasman WT, et al. Surgical pathologic spread patterns of endometrial cancer: a gynecologic oncology group study. Cancer. 1987;60:2035–41. 37. Fishman DA, et al. Radiation therapy as exclusive treatment for medically inoperable patients with stage I and II endometrioid carcinoma of the endometrium. Gynecol Oncol. 1996;61:189–96. 38. Podzielinski I, et al. Primary radiation therapy for medically inoperable patients with clinical stage I and II endometrial carcinoma. Gynecol Oncol. 2012;124:36–41. 39. van der Steen-Banasik E, et al. Systemic review: radiation therapy alone in medical non- operable endometrial carcinoma. Eur J Cancer. 2016;65:172–81. 21 Definitive Therapy for Cervical, Vaginal, and Endometrial Cancer
- 279. 279 22 Image-Guided Brachytherapy Christine H. Feng and Jyoti Mayadev Contents 22.1 General Principles 280 22.2 Cervical Cancer 280 22.2.1 Initial Evaluation and Applicator Choice 280 22.2.2 Implant Evaluation 281 22.2.3 Volume Delineation 281 22.2.4 Treatment Planning 282 22.3 Endometrial Cancer 284 22.3.1 Postoperative Adjuvant Treatment 284 22.3.2 Medically Inoperable Endometrial Cancer 287 22.3.3 Locally Recurrent Endometrial Cancer 287 22.4 Vaginal Cancer 289 22.4.1 Initial Evaluation and Applicator Choice 289 22.4.2 Implant Evaluation 289 22.4.3 Volume Delineation 289 22.4.4 Treatment Planning 290 22.5 Vulvar Cancer 291 References 291 C. H. Feng · J. Mayadev (*) Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA e-mail: chf013@health.ucsd.edu; jmayadev@health.ucsd.edu © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_22
- 280. 280 22.1 General Principles • All patients should undergo a complete history and physical examination includ- ing a pelvic examination during initial diagnosis and staging. Standard radio- graphic workup in these patients includes a contrast-enhanced computed tomography (CT) scan, PET/CT and/or pelvic MRI to assess the extent of local disease involvement and sites of metastatic spread. • Brachytherapy treatment planning and delivery guidance is given by the American Brachytherapy Society (ABS) [1] and GEC-ESTRO [2–4]. • Applicator choice should consider histopathologic diagnosis, tumor size, topog- raphy, extension to nearby organs, and response to radiotherapy or chemoradio- therapy when applicable. • Brachytherapy is the standard central boost technique for cervical and uterine cancer patients and other techniques including stereotactic body radiotherapy (SBRT) are options only in the context of a clinical trial or in patients who refuse brachytherapy. • All patients should be counseled on long-term toxicities of brachytherapy and use of a vaginal dilator if not having regular vaginal intercourse. • Follow-up should be coordinated within a multidisciplinary team. 22.2 Cervical Cancer • The use of brachytherapy in definitive treatment improves local control, disease- free survival (DFS), and overall survival (OS) [5–7]. • Brachytherapy should be initiated Week 3–5 of external beam radiation (EBRT). • Total treatment time should be 56 days or less. • In the postoperative setting, patients with a positive vaginal margin should receive brachytherapy following EBRT. 22.2.1 Initial Evaluation and Applicator Choice • Full history and physical exam • Labs: CBC, CMP (chemistry, LFTs, BUN, Cr) • Radiographic studies: – – Contrast-enhanced CT chest/abdomen/pelvis at diagnosis – – Whole body PET/CT recommended at diagnosis – – Pelvic MRI (along with cystoscopy and/or sigmoidoscopy) at diagnosis if concerns regarding bladder and/or rectal invasion – – Pelvic MRI recommended for brachytherapy planning in patients with larger (4 cm) tumors C. H. Feng and J. Mayadev
- 281. 281 • Brachytherapy applicator dependent on tumor size, parametrial extension, vagi- nal extension: – – Intracavitary alone: tumor size 4 cm, 1 cm vaginal involvement, non-bulky parametrial disease – – Hybrid intracavitary/interstitial: tumor size 3–5 cm, parametrial disease, irreg- ular tumor topography, difficulty meeting organs-at-risk (OAR) constraints – – Interstitial alone: tumor size 5 cm, 1 cm vaginal involvement, bulky para- metrial disease, difficulty meeting OAR constraints • Transabdominal or transrectal ultrasound (US) can be used to guide tandem placement. • Transrectal US can also be useful in cases where a tandem tract needs to be cre- ated or to guide needle placement for hybrid/interstitial cases. • Additional considerations for patients with pre-existing fistula(s): – – Vesico-vaginal fistula: consider diverting nephrostomy tubes – – Rectovaginal fistula: divert prior to initiation of radiation 22.2.2 Implant Evaluation • Thin-slice CT or MRI with applicator for 3D treatment planning. • Tandem should be placed in cervix and uterus. – – If using ring, the ring should be flush against the cervix. – – If using ovoids, tandem should bisect the ovoids. – – Ensure vaginal packing does not displace ring or ovoids • If using interstitial needles, review for tumor coverage and proximity to critical structures. 22.2.3 Volume Delineation • Target structures and OAR delineation for intact cervical cancer are in Table 22.1. • Ensure full dose coverage of uterus in cases with uterine extension. Table 22.1 Intact cervical cancer brachytherapy target volumes and OARs (Figs. 22.1 and 22.2) Structure Description GTV Macroscopic tumor at time of brachytherapy seen on MRI HRCTV GTV, cervix, macroscopic extension or parametrial involvement at time of brachytherapy IRCTV(3) HRCTV + 1 cm margin, can include initial disease extension at diagnosis (often used in Europe, less commonly used in the United States) Bladder Contour outer bladder wall Rectum Contour outer rectal wall from above the anal sphincter to level of transition into the sigmoid Sigmoid Contour outer sigmoid wall from rectosigmoid flexure to 2 cm superior to uterus and parametria 22 Image-Guided Brachytherapy
- 282. 282 HR CTV HR CTV IR CTV IR CTV GTV GTV Fig. 22.1 Suggested image-guided brachytherapy target volumes from the Groupe Européen de Curiethérapie and the European Society for Radiotherapy Oncology (Haie-Meder et al. [2]). HRCTV high-risk clinical target volume, IRCTV intermediate-risk clinical target volume, GTV gross tumor volume. (Used with permission) • If using CT for planning, target volumes often overestimate extent of disease. • If using MRI for planning, definition of the GTV is possible. For postoperative cervical cancer with a positive vaginal margin, the upper 1/3 of the vagina should be treated. 22.2.4 Treatment Planning • Common dose and fractionation schedules for intact cervical cancer are in Table 22.2. • Postoperative cervical cancer with positive vaginal margin is typically treated with EBRT to 45 Gy in 25 fractions followed by vaginal cuff brachytherapy to 15 Gy in 3 fractions dosed to the surface of the upper vagina. • Planning dosimetry goals are in Table 22.3. C. H. Feng and J. Mayadev
- 283. 283 c d a b Fig. 22.2 FIGO IIB cervical cancer. Sagittal views of (a) PET/CT with FDG-avid tumor posterior to bladder (blue arrow) and (b) T2-weighted pelvic MRI showing posterior cervical tumor (red arrow). (c) Tandem and ovoids applicator with HRCTV in red, rectum in brown, sigmoid in magenta, bladder in yellow. (d) Applicator with dose distribution. 1050 cGy in green, 700 cGy in orange, 400 cGy in cyan Table 22.2 Intact cervical cancer HDR EQD2 for common dose and fraction schedules Total EBRT (Gy) # HDR fractions HRCTV dose per fraction (Gy) Total HRCTV dose (Gy) Total HRCTV EQD210 (Gy) 45 4 7.0 28.0 83.9 45 5 5.5 27.5 79.8 45 5 6 30 81.8 45 3 8.0 24.0 80.3 Dose contribution from EBRT is assumed to be prescription dose (45 Gy) and doses are cumulative EQD2 (α/β = 10 for target, α/β = 3 for normal tissues) for HDR and physical doses for PDR/LDR 22 Image-Guided Brachytherapy
- 284. 284 Table 22.3 Cervical cancer brachytherapy target volume and OAR goals Structure Dosimetric parameter Ideal Goal EQD23 (Gy) Maximum constraint EQD23 (Gy) HRCTV (EQD210) D90% (Gy) ≥80 – Bladder D2cc (Gy) ≤80 ≤90 Rectum D2cc (Gy) ≤65 ≤75 Sigmoid D2cc (Gy) ≤70 ≤75 22.3 Endometrial Cancer • Brachytherapy can be used in the postoperative adjuvant, recurrent, and medi- cally inoperable settings for uterine cancer. • Upfront surgery is standard for patients who have operable endometrial cancer. • Lymph node assessment should be considered in patients with FIGO grade 2–3 disease, 2 cm gross disease intraoperative, and/or 50% myometrial invasion. 22.3.1 Postoperative Adjuvant Treatment • Adjuvant radiation therapy reduces risk of local recurrence in patients with adverse pathologic features including high-grade disease, deep myometrial inva- sion, cervical stromal extension, LVSI, and regional lymph node involve- ment [8–12]. • Treatment recommendations for adjuvant therapy are in Table 22.4. • Vaginal brachytherapy should commence within 12 weeks of surgery, only after pelvic exam to assess for cuff healing. • Vaginal brachytherapy boost following EBRT should commence within 2 weeks of finishing EBRT. 22.3.1.1 Initial Evaluation and Applicator Choice • Full history and physical exam • Labs: CBC, CMP (chemistry, LFTs, BUN, Cr) • Radiographic studies: – – Clinical stage I patients do not require routine imaging workup – – Contrast-enhanced CT chest/abdomen/pelvis for patients with locally advanced disease 22.3.1.2 Implant Evaluation • Thin-slice CT with applicator for 3D treatment planning. • Vaginal cylinder should be largest diameter tolerated by patient. • Verify applicator is flush with apex of the vaginal cuff and achieves mucosal contact. • Verify vaginal length. C. H. Feng and J. Mayadev
- 285. 285 Table 22.4 Adjuvant treatment recommendations for endometrial cancer AJCC stage GRADE LVSI PLND Cervical involvement Chemo Pelvic EBRT Brachytherapy IA 1 Any Any N/A No No No 2 No Any N/A No No No Yes Any N/A No No Yes 3-Adeno Any Any N/A No Noa Yes 3-PS/ CC Any Any N/A No/ Yes Yes No Any Any N/A Yes No Yes IB 1 No Any N/A No No No Yes Any N/A No No Yes 2 No Any N/A No No Yes Yes Any N/A No No Yes 3-Adeno No Any N/A No Noa Yes Yes Any N/A No Yes No 3-PS/ CC Any Any N/A Yes Yes No Any Any N/A Yes No Yes II 1–2 No No Yes No No Yes Yes No Yes No Yes Yes 1–2 No Yes Yes No No Yes Yes Yes Yes No No Yes 3-Adeno Any Any Yes No Yes Yes 3-PS/ CC Any Any Yes Yes No Yes Any Any Yes Yes Yes Yes IIIA 1 Any Any No Yes No/Yes No Any Any Yes Yes Yes Yes 2–3 No Any No Yes Yes No Yes Any Any Yes Yes Yes Any Any Yes Yes Yes Yes IIIB Any Any Any Any Yes Yes Yes IIIC1 1 Any Any No Yes Yes No Any Any Yes Yes Yes Yes 2–3 No Any No Yes Yes No Yes Any Any Yes Yes Yes Any Any Yes Yes Yes Yes IIIC2 1 Any Any No Yes N/A No Any Any Yes Yes N/A Yes 2–3 No Any No Yes N/A No Yes Any Any Yes N/A Yes LVSI = lymphovascular space invasion, PLND = pelvic lymph node dissection, PS = papillary serous histology, CC = clear cell histology EFRT depends on uterine risk factors and LN status/risk of involvement a Denotes patients eligible for GOG 249 and pelvic RT should be considered 22 Image-Guided Brachytherapy
- 286. 286 22.3.1.3 Volume Delineation • Brachytherapy alone: upper 1/3 to 1/2 of vagina depending on tumor characteristics • Brachytherapy following EBRT: upper 1/3 to 1/2 of vagina 22.3.1.4 Treatment Planning • Common dose and fractionation schedules for postoperative endometrial cancer are in Table 22.5. Table 22.5 Common dose and fractionation schedules for postoperative endometrial cancer (A) Vaginal cuff brachytherapy alone schedules Prescription point # Fractions Dose per fraction (Gy) 0.5 cm Depth from vaginal surface 3 7 4 5.5 5 5 6 2.5 Vaginal surface 4 8.5 5 6 6 4 (B) Vaginal cuff brachytherapy boost schedules after EBRT (See Fig. 22.3) EBRT dose and fractionation Prescription point # HDR fractions Dose per fraction (Gy) 45 Gy in 25 fractions Surface 3 5 50.4 Gy in 28 fractions Surface 2 6 a b Fig. 22.3 Vaginal cuff brachytherapy applicator with (a) small air gap (red arrow) at apex and (b) without air gaps C. H. Feng and J. Mayadev
- 287. 287 Table 22.6 Inoperable uterine cancer definitive radiotherapy recommendations AJCC stage Grade EBRT Brachytherapy I 1 No Yes 2–3 Yes II Any Pelvic RT Yes IIIC1 Any Pelvic RT Yes IIIC2 Any EFRT Yes 22.3.2 Medically Inoperable Endometrial Cancer • Definitive radiotherapy consisting of brachytherapy +/− EBRT is standard treatment. • EBRT alone is not preferred, and should only be offered to patients who refuse or are ineligible for brachytherapy. • Treatment recommendations for definitive therapy are in Table 22.6. 22.3.2.1 Initial Evaluation and Applicator Choice • Full history and physical exam. • Labs: CBC, CMP (chemistry, LFTs, BUN, Cr). • Radiographic studies: Pelvic MRI at baseline recommended to determine full extent of disease. • Patients with uterine width 4 cm may be treated with a tandem and cylinder or tandem and ring. • Patients with uterine width 4 cm will require a double tandem applicator. 22.3.2.2 Implant Evaluation • Thin-slice CT with applicator for 3D treatment planning. • For single tandem, ensure tandem is in the uterus and reaches fundus. • For double tandem, ensure tandems are in the uterus, ideally with tips in the bilateral cornu for optimal dose distribution. 22.3.2.3 Volume Delineation • Use MRI to guide GTV delineation. • CTV should include the entire uterus, cervix, and upper 1–2 cm of the vagina. 22.3.2.4 Treatment Planning • Common dose and fractionation schedules for postoperative endometrial cancer are in Table 22.7. 22.3.3 Locally Recurrent Endometrial Cancer • For patients without prior radiotherapy or with an out-of-field recurrence, sal- vage radiotherapy is recommended for vaginal or pelvic recurrences. 22 Image-Guided Brachytherapy
- 288. 288 Table 22.7 Common dose and fractionation schedules for inoperable uterine cancer (A) Brachytherapy alone schedules # HDR fractions Dose per fraction (Gy) EQD210 (Gy) 4 8.5 52.4 5 8 60 5 7.3 52.6 6 6.4 52.5 6 6 48 (B) Brachytherapy boost schedules following EBRT (See Fig. 22.4) EBRT dose and fractionation # HDR fractions Dose per fraction (Gy) EQD210 (Gy) 45 Gy in 25 fractions 2 8.5 70.5 3 6.5 71.1 3 6.3 69.9 4 5.2 70.6 5 5 75 50.4 Gy in 28 fractions 2 6 65.6 6 3.75 75.3 c a b Fig. 22.4 Medically inoperable endometrial cancer with Y applicator brachytherapy following EBRT. (a) Sagittal view with applicator in place. HRCTV in red, rectum in brown, sigmoid in blue, bladder in yellow. (b) Axial view with applicator in place and HRCTV in red. (c) Axial view with dose distribution. 780 cGy in yellow, 520 cGy in orange, 390 cGy in cyan, 260 cGy in green – – EBRT: 45 Gy in 25 fractions. – – Brachytherapy: total EQD2 of 70–80 Gy. – – For patients previously treated with pelvic radiation who present with a vagi- nal recurrence, salvage surgery could be considered. If surgery is unable to be performed, salvage radiotherapy may consist of reduced-dose EBRT and brachytherapy +/− chemotherapy. – – Reduced-dose EBRT: 30.6–36 Gy in 17–20 fractions. – – Brachytherapy dosing depends on normal tissue tolerance and prior dose. • For patients previously treated with pelvic radiation who have a non-vaginal pel- vic recurrence, salvage radiotherapy may consist of reduced-dose EBRT and/or SBRT +/− chemotherapy. C. H. Feng and J. Mayadev
- 289. 289 – – Reduced-dose EBRT: 30.6–36 Gy in 17–20 fractions. – – Consider boosting gross disease with EBRT or SBRT depending on normal tissue tolerance and prior dose. 22.4 Vaginal Cancer • Brachytherapy as a part of definitive organ-preserving treatment improves over- all survival [13]. • Definitive radiation is the preferred approach for patients with Stage I disease, with surgery as an option in select non-bulky stage I patients with distal non- urethral disease. • Definitive chemoradiation is the preferred approach for stage II-IVA. 22.4.1 Initial Evaluation and Applicator Choice • Full history and physical exam. • Labs: CBC, CMP (chemistry, LFTs, BUN, Cr). • Radiographic studies: – – Contrast-enhanced CT chest/abdomen/pelvis for initial staging – – Pelvic MRI (along with cystoscopy and/or sigmoidoscopy) at diagnosis if concerns regarding bladder and/or rectal invasion • Interstitial brachytherapy is the standard approach, with exception of very small tumors with thickness ≤5 mm where intracavitary applicators may be considered. • Transrectal US can help guide interstitial needle placement and avoid placing needles into bowel. • Perform digital rectal exam at conclusion of interstitial procedure to ensure no catheters are perforating rectum. 22.4.2 Implant Evaluation • Thin-slice CT or MRI with applicator for 3D treatment planning. – – Diluted contrast can be placed into bladder and rectosigmoid region to assist with organ visualization. • If using interstitial needles, review for tumor coverage and proximity to critical structures, especially rectum and bowel. 22.4.3 Volume Delineation • Pelvic MRI can help determine superior and paravaginal extent to disease. • Target structures and OAR delineation for vaginal cancer are in Table 22.8. • Vaginal target volumes depend on the extent of initial involvement, treatment response, and presence of multifocal disease or discontinuous spread. 22 Image-Guided Brachytherapy
- 290. 290 22.4.4 Treatment Planning • Common dose and fractionation schedules for vaginal cancer are in Table 22.9. • Planning dosimetry goals are in Table 22.10. • Total dose goal should be 70–80 Gy depending on location within the vagina and surrounding normal structures, such as the urethra. For example, the proximal vagina dose could be 75–80 Gy, but the distal vaginal dose should be decreased to 70–75 Gy. • For patients with multifocal spread or discontinuous disease, it is reasonable to treat the entire vaginal length to an equivalent dose of 60 Gy and boost areas of gross residual tumor to 70–80 Gy. Table 22.9 Common dose and fractionation schedules for primary vaginal cancer EBRT dose and fractionation # HDR fractions HRCTV dose per fraction (Gy) HRCTV EQD210 (Gy) 45 Gy in 25 fractions 3 7 74.1 4 6 76.3 5 4.5–5.5 71.5–79.8 9 3 76.8 10 3 73.6 50.4 Gy in 28 fractions 3 7 79.4 5 4–5 72.9–80.9 Table 22.10 Primary vaginal cancer brachytherapy target volume and OAR goals (See Fig. 22.5) Structure Dosimetric parameter Ideal goal EQD23 (Gy) Maximum constraint EQD23 (Gy) HRCTV (EQD210) D90% (Gy) Lower 1/3 Vagina: 70–75 – Upper 2/3 Vagina: 75–80 Bladder D2cc (Gy) ≤80 ≤90 Rectum D2cc (Gy) ≤65 ≤75 Sigmoid D2cc (Gy) ≤75 ≤75 Table 22.8 Primary vaginal cancer brachytherapy target volumes and OARs Structure name Description GTV Macroscopic tumor at time of brachytherapy seen on MRI HRCTV GTV + 1 cm margin in lateral, inferior, and superior directions IRCTV HRCTV + microscopic extension in vagina (includes all initial disease) Bladder Contour outer bladder wall Rectum Contour outer rectal wall from above the anal sphincter to level of transition into the sigmoid Sigmoid Contour outer sigmoid wall from recto-sigmoid flexure to 2 cm superior to uterus and parametria C. H. Feng and J. Mayadev
- 291. 291 c a b Fig. 22.5 Distal vaginal cancer with interstitial implant. (a) Sagittal view with applicator in place. HRCTV in red, rectum in brown, urethra in magenta, bladder in yellow. (b) Axial view with appli- cator in place. (c) Axial view with dose distribution. 600 cGy in yellow, 500 cGy in orange, 300 cGy in blue, 200 cGy in cyan 22.5 Vulvar Cancer • Concurrent chemoradiotherapy is the preferred approach for stage II-IVA, with consideration of brachytherapy boost for patients with vaginal extension or who poorly tolerate the initial phase of EBRT. • Brachytherapy is not standard in treatment of stage I disease except in medically inoperable patients. References 1. Albuquerque K, Hrycushko BA, Harkenrider MM, Mayadev J, Klopp A, Beriwal S, et al. Compendium of fractionation choices for gynecologic HDR brachytherapy—an American Brachytherapy Society Task Group Report. Brachytherapy. 2019;18(4):429–36. https://doi. org/10.1016/j.brachy.2019.02.008. 2. Haie-Meder C, Pötter R, Van Limbergen E, Briot E, De Brabandere M, Dimopoulos J, et al. Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (I): concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol. 2005;74(3):235–45. 3. Pötter R, Haie-Meder C, Van Limbergen E, Barillot I, De Brabandere M, Dimopoulos J, et al. Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy - 3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiolo. Radiother Oncol. 2006;78(1):67–77. 4. Dimopoulos JCA, Petrow P, Tanderup K, Petric P, Berger D, Kirisits C, et al. Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (IV): basic principles and param- eters for MR imaging within the frame of image based adaptive cervix cancer brachytherapy. Radiother Oncol. 2012;103(1):113–22. https://doi.org/10.1016/j.radonc.2011.12.024. 5. Mayadev J, Viswanathan A, Liu Y, Li C-S, Albuquerque K, Damato AL, et al. American Brachytherapy Task Group Report: a pooled analysis of clinical outcomes for high-dose-rate brachytherapy for cervical cancer. Brachytherapy. 2017;16(1):22–43. https://www.sciencedi- rect.com/science/article/pii/S1538472116300150?via%3Dihub. 6. Han K, Milosevic M, Fyles A, Pintilie M, Viswanathan AN. Trends in the utilization of brachy- therapy in cervical cancer in the United States. Int J Radiat Oncol. 2013;87(1):111–9. https:// www.sciencedirect.com/science/article/pii/S0360301613005956?via%3Dihub. 22 Image-Guided Brachytherapy
- 292. 292 7. Robin TP, Amini A, Schefter TE, Behbakht K, Fisher CM. Disparities in standard of care treatment and associated survival decrement in patients with locally advanced cervical can- cer. Gynecol Oncol. 2016;143(2):319–25. https://www.sciencedirect.com/science/article/pii/ S0090825816314123?via%3Dihub. 8. Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD, et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004;92(3):744–51. http://www.ncbi.nlm.nih.gov/pubmed/14984936. 9. Naumann RW, Coleman RL. The use of adjuvant radiation therapy in early endometrial cancer by members of the Society of Gynecologic Oncologists in 2005. Gynecol Oncol. 2007;105(1):7–12. https://linkinghub.elsevier.com/retrieve/pii/S0090825806009164. 10. Randall ME, Filiaci V, McMeekin DS, von Gruenigen V, Huang H, Yashar CM, et al. Phase III trial: adjuvant pelvic radiation therapy versus vaginal brachytherapy plus paclitaxel/car- boplatin in high-intermediate and high-risk early stage endometrial cancer. J Clin Oncol. 2019;37(21):1810–8. http://ascopubs.org/doi/10.1200/JCO.18.01575. 11. Creutzberg CL, Nout RA, Lybeert MLM, Wárlám-Rodenhuis CC, Jobsen JJ, Mens J-WM, et al. Fifteen-year radiotherapy outcomes of the randomized PORTEC-1 trial for endome- trial carcinoma. Int J Radiat Oncol. 2011;81(4):e631–8. http://www.ncbi.nlm.nih.gov/ pubmed/21640520 12. Kong A, Johnson N, Kitchener HC, Lawrie TA. Adjuvant radiotherapy for stage I endo- metrial cancer: an updated cochrane systematic review and meta-analysis. J Natl Cancer Inst. 2012;104(21):1625–34. https://academic.oup.com/jnci/article-lookup/doi/10.1093/ jnci/djs374. 13. Orton A, Boothe D, Williams N, Buchmiller T, Huang YJ, Suneja G, et al. Brachytherapy improves survival in primary vaginal cancer. Gynecol Oncol. 2016;141(3):501–6. http://www. ncbi.nlm.nih.gov/pubmed/27036631. C. H. Feng and J. Mayadev
- 293. 293 23 Vulvar Cancer Allison E. Garda, Loren K. Mell, and Ivy A. Petersen Contents 23.1 Introduction 293 23.2 General Principles 294 23.3 IMRT for Vulvar Cancer 294 23.4 Simulation 295 23.5 Image Registration 295 23.6 Target Delineation 295 23.7 Prescription Recommendations 300 23.8 Organs at Risk 301 23.9 Image-Guided Radiation Therapy 302 References 302 23.1 Introduction Vulvar cancer is one of the most complex disease sites to treat with radiation ther- apy, due to the large treatment volumes and relatively high rates of morbidity, par- ticularly with intensive chemoradiation for advanced stages. Intensity modulated radiation therapy (IMRT) is now widely used in the community and in A. E. Garda · I. A. Petersen (*) Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA e-mail: Garda.Allison@mayo.edu; petersen.ivy@mayo.edu L. K. Mell Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA e-mail: lmell@ucsd.edu © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_23
- 294. 294 contemporary clinical trial protocols, due to reduced rates of morbidity and high treatment efficacy in most published series compared to historical techniques. Publication of consensus contouring guidelines has advanced the quality of treat- ment delivery, and evolving treatment planning recommendations have helped stan- dardize approaches across institutions. 23.2 General Principles • The treatment of vulvar cancer consists of upfront surgery, typically radical vul- vectomy or wide local excision in select patients with small well-lateralized tumors. Most patients undergo lymph node evaluation with either inguinofemo- ral dissection or sentinel lymph node biopsy, particularly those found to have tumor invasion 3 mm, lymphovascular space invasion (LVSI) and/or high-grade disease. • Radiation therapy (RT) is typically delivered following surgery in patients with high-risk features including LVSI, tumor invasion 5 mm, surgical margins 8 mm, microscopically positive margins, grade 3 disease, and/or positive lymph nodes [1–3]. Data suggests smaller margins (e.g., 5 mm) may be used as indica- tion for adjuvant therapy [4–6]. • Patients presenting with unresectable disease are candidates for preoperative RT [7, 8]. At many centers, these patients also receive concomitant chemotherapy [9–11]. Patients with unresectable locally advanced disease have high rates of clinical and pathologic response to chemoradiation [12], which is an area of active investigation in a recently completed prospective Phase II clinical trial [13]. • The standard RT approach in vulvar cancer patients consists of pelvic-inguinal irradiation. Brachytherapy has a limited role in vulvar cancer patients, apart from women with a positive vaginal margin or those with medically inoperable disease. 23.3 IMRT for Vulvar Cancer • Given the large volumes irradiated and the growing experience using intensity- modulated RT (IMRT) in patients with gynecologic cancer, IMRT is receiving increasing attention in the treatment of vulvar cancer. The recently completed Gynecology Oncology Group (GOG) 0279 trial of definitive chemoradiation in locally advanced disease mandates IMRT [13]. • Dosimetric and preliminary clinical studies have reported superior normal tissue sparing and lower rates of acute and chronic toxicities in patients with vulvar cancer receiving IMRT compared to those undergoing conventional approaches [14–17]. Long-term outcome in these patients, however, remains limited. • Consensus recommendations for contouring and treatment planning, including a pictorial contouring atlas, have been published [18]. A. E. Garda et al.
- 295. 295 23.4 Simulation • Patients with vulvar cancer undergoing IMRT should be simulated in the supine position using a modest frog-leg position with customized immobilization of the upper and lower body, with the goal of reducing skin folds. • Since the patient’s vasculature serves as a surrogate for the lymph nodes, it is helpful to perform an IV contrast-enhanced computed tomography (CT) simulation. • The anus should be marked with a fiducial marker at the time of simulation. • To assist in delineation of the tumor, radiopaque wire is used to identify gross disease or surgical scars. • It is advisable to simulate all patients with 0.5–1 cm bolus placed over the vulva, particularly in patients treated preoperatively or with gross disease. Bolus over the groins should be considered in cases of clinically evident skin involvement. • Simulation scans should be obtained with full and empty bladder and an internal target volume (ITV) should be generated [19] for locally advanced cases, espe- cially in those with vaginal, urethral, and/or anal involvement. If rectum is dis- tended 3.5 cm at the time of simulation, simulation should be repeated after bowel preparation. 23.5 Image Registration • In patients undergoing preoperative or definitive radiotherapy, positron-emission tomography (PET)-CT is helpful for delineation of the gross tumor vol- ume (GTV). • Gadolinium-enhanced pelvic MRI with and without vaginal gel is useful to help delineate the full extent of primary tumor and evaluate relationship between tumor and adjacent normal tissues. 23.6 Target Delineation • Delineated target volumes in vulvar cancer patients include a gross tumor vol- ume (GTV) (in preoperative or definitive setting) and two clinical target volumes (CTV). CTV1 encompasses the GTV (if applicable), uninvolved vulvar tissue, and adjacent soft tissues. CTV2 includes the pelvic and inguinofemoral lymph nodes bilaterally. CTV3 includes boost volumes to either primary and/or nodal disease. Each CTV is then expanded to create planning target volumes (PTVs). • See Table 23.1 for a detailed description of target volumes. • See Table 23.2 for a description of boost target volumes. • See Figs. 23.1 and 23.2 for pictorial atlas of contours in the definitive and post- operative setting, respectively. 23 Vulvar Cancer
- 296. 296 Table 23.1 Target volumes used in vulvar cancer patients undergoing IMRT Target volumes Definition and description GTV Primary tumor defined on physical exam, CT or PET/CT imaging (preoperative/ definitive only) Pelvis and inguinal lymph nodes: All nodes ≥1.5 cm, biopsy proven, and/or with FDG avidity CTV1 GTV plus remaining uninvolved vulva and adjacent soft tissues as indicated below: If GTV extends beyond vulva, CTV1 includes this region plus 1-cm margin If primary tumor involves vagina: gross disease plus 3 cm of vagina If primary tumor involves anus, anal canal, or bladder: gross disease plus 2 cm of anus or bladder If primary tumor is periurethral: gross disease plus 2 cm of urethra If primary tumor extends to mid or proximal urethra: entire urethra and bladder neck included If primary tumor is preclitoral: gross disease plus 2 cm and cover suspensory ligament of the clitoris (extends to pubic bone) Bone and muscle should be excluded unless directly involved by tumor If no skin involvement, CTV1 should be cropped from the skin by 3–5 mm CTV2 Bilateral pelvic and inguinofemoral lymph node regions The pelvic lymph nodes (common iliac,a external iliac, internal iliac, and obturator nodal regions) are defined by including the pelvic vessels plus a 7 mm expansion excluding uninvolved bone, muscle, and bowel The presacral area should be included in patients with vaginal involvement and consists of the soft tissues anterior (minimum 1.0 cm) to the S1–S3 vertebrae In patients with anal/rectal involvement, the perirectal lymph nodes should also be included Inguino-femoral lymph node compartment begins superiorly where the external iliac artery leaves the bony pelvis to become the femoral artery with the inferior border 2 cm below the sapheno-femoral junction or at the level of the lesser trochanter; laterally, medial border of the iliopsoas; medially, lateral border of adductor longus or medial end of pectineus; posteriorly, iliopsoas muscle laterally and anterior aspect of the pectineus muscle; medially and anteriorly, the anterior edge of the sartorius muscle. No margin is added posterior or lateral to femoral vessels. Any visualized lymph nodes in adjacent fat/soft tissues should be included.b PTV1 CTV1 + 5–10 mmc PTV2 CTV2 + 5–7 mmc The final PTV is then generated by the union of the PTV1 and PTV2: PTV = PTV1 ∪ PTV2 and may be needed to be cropped back from the skin surface in the inguinal nodal region IMRT intensity-modulated radiation therapy, GTV gross tumor volume, PET positron-emission tomography, CT computed tomography, CTV clinical target volume, PTV planning target volume a To the level of L4–5 which will not include the entire common iliac nodal region in many patients. At some centers in patients with negative pelvic lymph nodes, the common iliacs are not included, and the upper extent of the treatment volume is limited to the bottom of the sacroiliac joints b The inguino-femoral lymph nodes should be considered as a region or compartment, rather than a margin around vessels c This expansion to PTV assumes daily image guidance with CBCT matched to soft tissues. Consider increasing margins to 1 cm if daily cone beam CT (CBCT) is not used A. E. Garda et al.
- 297. 297 Table 23.2 Target volumes used for boost to primary tumor and involved lymph nodes Target volumes Definition and description GTV Primary tumor defined on physical exam, CT or PET/CT imaging Pelvis and inguinal lymph nodes: All nodes ≥1.5 cm, biopsy proven, and/or PET avidity CTV3 GTVprimary + 2 cm and anatomically confined to CTV1 PTV3 CTV3 + 5–7 mma GTVnode + 5 mma GTV gross tumor volume, PET positron-emission tomography, CT computed tomography, CTV clinical target volume, PTV planning target volume a This expansion to PTV assumes daily image guidance with CBCT matched to soft tissues. Consider increasing margins to 1 cm if daily CBCT is not used 1 cm bolus covering vulva Marker at anal verge Wire demarcating tumor at time of sim Wire demarcating extent of tumor at time of sim Fig. 23.1 Definitive radiotherapy. The patient had FIGO Stage IIIB vulvar cancer confined to the vulva, which was deemed unresectable based on proximity to the urethral meatus and vagina, and two FDG-avid right inguinal lymph nodes. She was treated with definitive IMRT and concurrent chemotherapy. The GTV for the primary lesion is outlined in blue. CTV1 (cyan) includes the entire vulva, excluding adjacent bone and muscle. CTV2 (magenta) includes the pelvic and inguinal- femoral lymph nodes. The pelvic lymph nodes and primary were treated to 45 Gy in 25 fractions. The bilateral inguinal-femoral regions were treated to 50 Gy in 25 fractions. PTV3 included the FDG-avid right inguinal lymph nodes (yellow) plus 5 mm and was treated with a simultaneous integrated boost to 62.5 Gy in 25 fractions. CTV3 (orange) was the primary GTV plus 2 cm expan- sion confined to CTV1 and was treated with a sequential boost of 14 Gy in 7 fractions (total dose 64 Gy in 32 fractions). PTV expansions were all 5 mm due to use of daily CBCT 23 Vulvar Cancer
- 298. 298 Fig. 23.2 Postoperative radiotherapy. The patient had FIGO Stage IIIA vulvar cancer (preopera- tive primary outlined in blue). She underwent wide local excision, dissection of grossly enlarged left inguinal lymph node (preoperative node outlined in yellow), and bilateral sentinel lymph node dissection at an outside institution. Final pathology showed a 4 cm moderately differentiated squa- mous cell carcinoma with 0.4 cm depth of invasion without lymphovascular space invasion. Pathologic margins were 7 mm. A 3 cm left non-sentinel inguinal lymph node was involved with- out extranodal extension. Two right and one left sentinel lymph nodes were negative for malig- nancy. She was treated with adjuvant IMRT and concurrent chemotherapy. Pelvic and right inguinal-femoral lymph nodes (magenta) were treated to 45 Gy, vulva (cyan) was treated to 50 Gy, and left inguinal-femoral lymph nodes (orange) were treated to 55 Gy, all in 25 fractions. PTV expansions were all 5 mm due to the use of daily CBCT • Figure 23.3 depicts contours from consensus guidelines [18] and indicates the extent of variation in target delineation amongst clinicians with expertise in IMRT. Note that a contouring atlas is available on the NRG Oncology web- site [20]. A. E. Garda et al.
- 299. 299 a b Fig. 23.3 Consensus contour (yellow), modified consensus contour (red), and individual contours from 14 different physicians for a locally advanced vulvar case (case 1) (a) and postoperative case (case 2) (b). The modified consensus contour was retracted from the space between the vulva and groin (white arrow) and skin surface (blue arrow) when it was believed to be at low risk. (From Gaffney et al. [18], reproduced with permission) 23 Vulvar Cancer
- 300. 300 23.7 Prescription Recommendations • Table 23.3 provides suggested dose and fractionation schemes. • A primary site boost is typically given sequentially with IMRT, direct electron field, or interstitial brachytherapy, depending on response and location of disease. • When using a sequential boost for definitive treatment, consider rescanning and adjusting the target volume prior to starting the boost phase of treatment. • Using IMRT, grossly involved lymph nodes can be boosted using a simultaneous integrated boost (SIB). A common SIB scheme involves delivery of 45 Gy in 25 fractions to the pelvis, with 2.25 Gy per fraction to positive pelvic lymph nodes (plus PTV margin) and 2.5 Gy per fraction to positive inguinal lymph nodes (plus PTV margin). Table 23.3 Suggested dose fractionation schemes Radiotherapy timing PTV1 PTV2 PTV3 Preoperative 45–50.4 Gy/25–28 fractions 45–50.4 Gy/25–28 fractions 57.6 Gy/32 fractions [12] Definitive 45–50.4 Gy/25–28 fractions 45–50.4 Gy/25–28 fractions Primary: 59.4–70.2 Gy/33–39 fractions Lymph nodesa : 59.4–70.2 Gy/33–39 fractions Adjuvant 45–50.4 Gy/25–28 fractionsb 45–50.4 Gy/25–28 fractions Gross residual disease: For ENE: 64–66 Gy/32–33 fractions 54–64 Gy/30–32 fractions PTV planning target volume, ENE extranodal extension a If using simultaneous integrated boost to lymph nodes, use EQD2 dose equivalent in 25 fractions b Consider higher dose for close/positive margins or lymphovascular space invasion A. E. Garda et al.
- 301. 301 23.8 Organs at Risk • See Table 23.4 for detailed descriptions of the organs at risk (OARs) used in vulvar cancer and Table 23.5 for dose constraints for OARs. • Organs at risk used in the treatment planning process typically include the bowel, bladder, rectum, anus, and bilateral femoral heads. In women undergoing che- motherapy, the pelvic bone marrow (BM) may also be included. • Small bowel constraints are given priority over coverage of the lymph node SIB volume. Table 23.4 Organs at risk (OAR) in radiotherapy for vulvar cancer Organ Definition and description Bowel bag Abdominal contents excluding muscle and bones. Inferiorly, contours start at the most inferior small or large bowel loop or above the anorectum, whichever is most inferior. Extend contours at least 2 cm above the superior most portion of the PTV Rectum Outer wall of the rectum contoured beginning inferiorly at the level of the ischial tuberosity and superiorly to where the rectum loses its round shape and connects anteriorly with the sigmoid Anus Outer wall of the anus contoured inferiorly from the anal verge identified by radiopaque marker placed at time of simulation to the level of the ischial tuberosity in the axial plane. The anal canal is approximately 4 cm in length Sigmoid Bowel contoured inferiorly where the anorectum contour ends and ending when connecting to the ascending colon laterally Bladder Outer bladder wall contoured inferiorly from the bladder base and ending superiorly at the bladder dome Bone marrow Pelvic bones serve as a surrogate for the pelvic bone marrow Regions included are the os coxae, L5 vertebral body, entire sacrum, acetabulae, and proximal femora Proximal femurs Femoral head and neck contoured inferiorly from the lowest level of the ischial tuberosities and superiorly to the top of the ball of the femur, including the trochanters PTV planning target volume 23 Vulvar Cancer
- 302. 302 Table 23.5 Normal tissue dose constraints for vulvar cancer radiotherapy Critical structure Recommendationa Small bowel Max ≤52 Gyb ≤30% to receive ≥40 Gy 195 cm3 to receive ≥45 Gy Rectum ≤80% to receive ≥40 Gy Anus ≤80% to receive ≥40 Gy, Max ≤65 Gyc Bladder ≤35% to receive ≥45 Gy Femoral heads ≤50% to receive ≥30 Gy ≤35% to receive ≥45 Gy ≤5% to receive ≥44 Gy Bone marrow ≤37% to receive ≥40 Gy ≤90% to receive ≥10 Gy ≤80% to receive ≥20 Gy PTV planning target volume a Based on constraints from RTOG 1203 [21] and RTOG 0529 [22], as recommended in consensus guidelines [18], and currently in use at Mayo Clinic in Rochester, MN b Small bowel is given priority over coverage of the PTV (pelvic lymph node boost) volume c May not be met in case of tumors immediately adjacent to or involving the anus 23.9 Image-Guided Radiation Therapy • Daily image guidance typically includes a combination of kV and/or CBCT imaging. CBCT is preferred for daily localization and matching with soft tissue. References 1. Gaffney DK, Du Bois A, Narayan K, et al. Patterns of care for radiotherapy in vulvar cancer: a Gynecologic Cancer Intergroup study. Int J Gynecol Cancer. 2009;19(1):163–7. 2. Heaps JM, FuYS, Montz FJ, Hacker NF, Berek JS. Surgical-pathologic variables predictive of local recurrence in squamous cell carcinoma of the vulva. Gynecol Oncol. 1990;38(3):309–14. 3. Homesley HD, Bundy BN, Sedlis A, Adcock L. Radiation therapy versus pelvic node resection for carcinoma of the vulva with positive groin nodes. Obstet Gynecol. 1986;68(6):733–40. 4. Baiocchi G, Mantoan H, de Brot L, et al. How important is the pathological margin distance in vulvar cancer? Eur J Surg Oncol. 2015;41(12):1653–8. 5. Nooij LS, van der Slot MA, Dekkers OM, et al. Tumour-free margins in vulvar squamous cell carcinoma: does distance really matter? Eur J Cancer. 2016;65:139–49. 6. Chan JK, Sugiyama V, Pham H, et al. Margin distance and other clinico-pathologic prognostic factors in vulvar carcinoma: a multivariate analysis. Gynecol Oncol. 2007;104(3):636–41. 7. Acosta AA, Given FT, Frazier AB, Cordoba RB, Luminari A. Preoperative radiation therapy in the management of squamous cell carcinoma of the vulva: preliminary report. Am J Obstet Gynecol. 1978;132(2):198–206. 8. Boronow RC. Combined therapy as an alternative to exenteration for locally advanced vulvo- vaginal cancer: rationale and results. Cancer. 1982;49(6):1085–91. A. E. Garda et al.
- 303. 303 9. LandoniF,ManeoA,ZanettaG,etal.Concurrentpreoperativechemotherapywith5-fluorouracil and mitomycin C and radiotherapy (FUMIR) followed by limited surgery in locally advanced and recurrent vulvar carcinoma. Gynecol Oncol. 1996;61(3):321–7. 10. Moore DH, Thomas GM, Montana GS, Saxer A, Gallup DG, Olt G. Preoperative chemoradia- tion for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group. Int J Radiat Oncol Biol Phys. 1998;42(1):79–85. 11. Thomas G, Dembo A, DePetrillo A, et al. Concurrent radiation and chemotherapy in vulvar carcinoma. Gynecol Oncol. 1989;34(3):263–7. 12. Moore DH, Ali S, Koh WJ, et al. A phase II trial of radiation therapy and weekly cisplatin chemotherapy for the treatment of locally-advanced squamous cell carcinoma of the vulva: a gynecologic oncology group study. Gynecol Oncol. 2012;124(3):529–33. 13. ClinicalTrials.gov. Gynecologic Oncology Group 0279: radiation therapy, gemcitabine hydro- chloride, and cisplatin in treating patients with locally advanced squamous cell cancer of the vulva. n.d.. https://ClinicalTrials.gov/show/NCT01595061. Accessed 26 Mar 2020. 14. Bloemers MC, Portelance L, Ruo R, Parker W, Souhami L. A dosimetric evaluation of dose escalation for the radical treatment of locally advanced vulvar cancer by intensity-modulated radiation therapy. Med Dosim. 2012;37(3):310–3. 15. Beriwal S, Heron DE, Kim H, et al. Intensity-modulated radiotherapy for the treatment of vul- var carcinoma: a comparative dosimetric study with early clinical outcome. Int J Radiat Oncol Biol Phys. 2006;64(5):1395–400. 16. Beriwal S, Coon D, Heron DE, et al. Preoperative intensity-modulated radiotherapy and che- motherapy for locally advanced vulvar carcinoma. Gynecol Oncol. 2008;109(2):291–5. 17. Beriwal S, Shukla G, Shinde A, et al. Preoperative intensity modulated radiation therapy and chemotherapy for locally advanced vulvar carcinoma: analysis of pattern of relapse. Int J Radiat Oncol Biol Phys. 2013;85(5):1269–74. 18. Gaffney DK, King B, Viswanathan AN, et al. Consensus recommendations for radia- tion therapy contouring and treatment of vulvar carcinoma. Int J Radiat Oncol Biol Phys. 2016;95(4):1191–200. 19. Small W Jr, Mell LK, Anderson P, et al. Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy in postoperative treatment of endometrial and cervical cancer. Int J Radiat Oncol Biol Phys. 2008;71(2):428–34. 20. https://www.nrgoncology.org/ciro-gynecologic. Accessed 26 Mar 2020. 21. Klopp AH, Yeung AR, Deshmukh S, et al. Patient-reported toxicity during pelvic intensity- modulated radiation therapy: NRG oncology-RTOG 1203. J Clin Oncol. 2018;36(24):2538–44. 22. Kachnic LA, Winter K, Myerson RJ, et al. RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 2013;86(1):27–33. 23 Vulvar Cancer
- 304. 305 24 Advanced Technologies and Treatment Techniques for Gynecologic Malignancies Casey W. Williamson, Whitney Sumner, and Loren K. Mell Contents 24.1 General Principles 305 24.2 Image Guidance 306 24.3 Bone Marrow-Sparing IMRT 307 24.4 Adaptive Re-planning 308 24.5 Proton Therapy 309 24.6 Stereotactic Body Radiation Therapy (SBRT) 310 24.6.1 Cervical Cancer 310 24.6.2 Endometrial Cancer 311 References 311 24.1 General Principles • Outcomes for locoregionally advanced gynecologic malignancies remain subop- timal and toxicities can limit treatment delivery. Methods to intensify treatment and to reduce toxicity are both needed. • Intensity-modulated RT (IMRT) has become an accepted standard modality for definitive and postoperative external beam RT (EBRT) for cervical and endome- trial cancer although there is still some controversy regarding routine implemen- tation given limited prospective, randomized data. C. W. Williamson · W. Sumner · L. K. Mell (*) Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA e-mail: cwwillia@health.ucsd.edu; wsumner@health.ucsd.edu; lmell@health.ucsd.edu; lmell@ucsd.edu © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_24
- 305. 306 • Daily image-guided IMRT (IG-IMRT) improves localization of the targets and the organs at risk (OARs) and can enable more conformal treatment plans while maintaining tumoricidal doses. • Adaptive re-planning can account for changes in tumor and patient anatomy throughout the treatment course to potentially further improve target coverage and reduce dose to OARs. • Bone marrow-sparing IMRT can reduce hematologic toxicity. • SBRT can be used as a boost for definitive therapy for patients who are ineligible for brachytherapy or who refuse brachytherapy. SBRT can also enable delivery of high dose RT to previously irradiated areas or to localized areas of recurrence or limited sites of metastasis. • Proton therapy may reduce toxicity due primarily to rapid dose fall-off distal to the target although high quality directly comparative data with conventional RT and/or IMRT are limited. 24.2 Image Guidance • IMRT allows for sophisticated and conformal treatment planning which can reduce the volume of irradiated area. However, this requires accurate delineation of target structures and OARs as well as appropriate management of organ motion and setup uncertainty. Pelvic organs are in motion both during and between treatment fractions. • IG-IMRT has been associated with improvement in both hematologic and gastro- intestinal toxicity compared to IMRT alone [1, 2] – – Daily on-board orthogonal kV images can be used to align bony anatomy at the time of treatment to the initial positioning at computed tomography (CT) simulation. – – Cone-beam CT (CBCT) can be acquired daily and allows for improved iden- tification of rectal and bladder filling status in comparison to the time of simu- lation. With application of a shape model-based planning target volume (PTV) expansion strategy and image guidance with daily CBCT, target coverage within the 95% isodose cloud is excellent [3]. – – Figure 24.1 shows an example of pre-treatment daily CBCT identifying changes in bladder and rectal filling resulting in movement of the uterine fun- dus outside the PTV. C. W. Williamson et al.
- 306. 307 Fig. 24.1 Comparison between patient anatomy and coverage of the planning target volume (PTV, pink line) at the time of CT simulation (left column) and on cone-beam CT before one of the patient’s daily treatments (right column). The patient received treatment for a FIGO 2009 IIB cervical cancer with pelvic and para-aortic involvement. Changes in filling status of the bladder and rectum resulted in a portion of the uterine fundus falling outside the PTV (white arrow) 24.3 Bone Marrow-Sparing IMRT • IMRT can be used to spare bone marrow for patients undergoing pelvic RT and has been shown to reduce hematologic toxicity [2, 4]. • A variety of approaches have been implemented – – PET/CT-based IG-IMRT can be used by contouring pelvic bones and defining active bone marrow as regions within bones with standardized uptake volume (SUV) greater than the mean SUV within bones, then applying dose con- straints to the bone marrow [2, 5]. 24 Advanced Technologies and Treatment Techniques for Gynecologic Malignancies
- 307. 308 Pelvic bone marrow constraints, with hard constraints based on NTCP modeling: [6] • Soft constraint: mean ≤27 Gy, V10(%) ≤85.5%, V20(%) ≤66% • Hard constraint: mean ≤29 Gy, V10(%) ≤90%, V20(%) ≤75% Active bone marrow constraints: • Soft constraint: mean ≤28.5 Gy, V10(%) ≤90%, V20(%) ≤70% • Hard constraint: mean ≤30 Gy, V10(%) ≤90%, V20(%) ≤75% – – An atlas-based approach is also feasible and offers an advantage if PET/CT is unavailable [5]. – – Another option in the absence of PET/CT is to demarcate bone marrow as the low-density regions within bones on the simulation CT and to then apply dose constraints [4]. 24.4 Adaptive Re-planning • Adaptive re-planning can be subdivided into three major categories: offline between treatment fractions, online immediately prior to a treatment fraction, or in real-time during treatment delivery. • Several adaptive strategies have been proposed and can be considered – – A “plan-of-the-day” technique which generates a patient-specific library of treatment plans corresponding to different target volumes and organ motion, with pre-treatment CBCT used to select the library plan most similar to the target and OAR configuration each day. – – Scheduled re-planning can be done with weekly magnetic resonance imag- ing (MRI). – – Deformable image registration can be used to model accumulated dose to targets and OARs. • Offline adaptive RT (ART) – – Offline ART, e.g., generating a new treatment plan between treatment frac- tions, should be considered for patients who experience significant weight loss or substantial change in target size. – – Repeat simulation may be required if re-planning cannot be performed on imaging acquired in the treatment room. – – Deformable image registration can be utilized to create new plans based on pre-treatment imaging and/or interim diagnostic imaging (e.g., MRI, positron emission tomography (PET)/CT). – – Advanced treatment planning systems can allow for automated dose monitor- ing and dose-volume metrics that can be reviewed offline to guide decision- making regarding the need for re-planning. • Online ART – – Variation in rectum and bladder filling can lead to both target and OAR dis- placement that may not be captured on CT simulation. – – Emerging technologies allow for integration of iterative CBCT for dose cal- culation and daily re-planning based on pre-treatment imaging [7] or for MRI-based online re-planning [8]. C. W. Williamson et al.
- 308. 309 24.5 Proton Therapy • Proton therapy takes advantage of a relatively gradual dose build-up and a sharp dose fall-off distal to the target compared to photons. • Protons may therefore allow for decreased dose to OARs, particularly distal to incident treatment fields as well as decreased integral dose while preserving ade- quate dose to the targets. • Treatment of para-aortic nodes and re-irradiation are additional scenarios in which proton therapy may present advantages over IMRT. • Dosimetric and early clinical studies suggest improvement in dose to nearby normal structures including bowel, bladder, and bone marrow with protons com- pared to IMRT [9]. • Protons may also allow for improved ovarian sparing in pre-menopausal women, e.g., sparing one ovary to a mean dose of 15 Gy [10]. • For definitive management, target dosing should be the same as with photon therapy (accounting for an assumed relative biological effectiveness (RBE) of 1.1 for protons). • See the definitive EBRT chapter for gross tumor volume (GTV) and clinical target volume (CTV) delineation. PTVs are beam-specific based on range uncer- tainty. Avoid beam arrangements that result in critical structures in the field distal to the target. Figure 24.2 shows sample images from a patient treated with intensity- modulated proton therapy (IMPT). • Proton therapy can be considered as a boost alternative for patients who are unable to receive brachytherapy, as protons can have dosimetric advantages in the bladder, bowel, femoral heads, and the rectum compared to VMAT. For example, the boost CTV can be determined using MRI obtained after 3 weeks of chemoradiation and a dose of 30 Gy/Gy equivalent in 5 fractions then adminis- tered in lieu of brachytherapy [11]. • However, it should be noted that high quality prospective evidence is lacking at present and the link between improved dosimetry and clinically meaningful reduc- tion in toxicity and/or the ability to deliver intensified therapy remains unproven. Fig. 24.2 Representative cross-sectional images of an intensity-modulated proton therapy (IMPT) plan for a 39-year-old woman with FIGO 2009 IIB cervical cancer with involvement of pelvic nodes. The patient had a history of active lupus nephritis leading to hemodialysis and she was referred for proton therapy given concern for increased risk of radiation-induced bowel injury. The pelvis received 39.6 Gy in 22 fractions and the gross nodal disease was boosted to a total of 51.6 Gy. She then received a brachytherapy boost of 30 Gy in 4 fractions. Dose is shown in color wash with legend in absolute dose (bottom right) 24 Advanced Technologies and Treatment Techniques for Gynecologic Malignancies
- 309. 310 24.6 Stereotactic Body Radiation Therapy (SBRT) 24.6.1 Cervical Cancer • For patients with locoregionally advanced cervical cancer, standard of care is daily fractionated EBRT with concurrent cisplatin-based chemotherapy followed by a brachytherapy boost with a final 2 Gy equivalent dose (EQD2) dose to the target of 80–95 Gy. • SBRT is a specialized EBRT modality which allows for high doses to be deliv- ered in 1–5 fractions. Target visualization, accurate tumor and OAR delineation, and high-fidelity setup with image guidance are crucial. • Lymph nodes can be boosted with SBRT [12]. • SBRT can also be considered in the setting of re-irradiation for recurrent disease or for treating limited sites of metastasis [12–15]. • Some patients are not candidates for brachytherapy due to severe medical comor- bidities and some patients refuse brachytherapy, especially patients at risk for posttraumatic stress disorder [16]. • SBRT can allow for conformal delivery of a high dose boost – – However, a recent phase II trial investigating the use of SBRT (28 Gy in 4 fractions) as a replacement for brachytherapy closed prematurely due to con- cern for higher than expected toxicity and lower than expected 2-year local control, progression-free survival, and overall survival [17]. Brachytherapy remains the standard of care for eligible patients. – – A five-fraction regimen (e.g., 27.5 Gy in 5 fractions) following 45 Gy to the pelvis could also be considered for patients who will not receive brachyther- apy, which results in an EQD2 of 80 Gy (α/β = 10). Figure 24.3 shows images from a patient treated with an SBRT boost following EBRT. Fig. 24.3 Representative images from a stereotactic body radiation therapy (SBRT) boost given in lieu of brachytherapy for a 52-year-old woman with FIGO 2009 IB1 cervical cancer who was not a surgical candidate and not a candidate for brachytherapy due to comorbidities. She received external beam radiation to the pelvis to 45 Gy in 25 fractions followed by an SBRT boost of 30 Gy in 5 fractions. Dose is shown in color wash with legend in absolute dose (bottom right). Fiducial markers were placed prior to simulation (white arrow) C. W. Williamson et al.
- 310. 311 • Determination of dose and fractionation should take into account target size, prior RT to the area, and tolerance of nearby OARs. For a 5 fraction regimen, dose per fraction is typically in the 4–8 Gy range [18, 19]. Fractions of 8–15 Gy per fraction have also been reported [20, 21]. • Total EQD2 should be calculated for the treated area. 24.6.2 Endometrial Cancer • SBRT has also been considered as an alternative modality for boost delivery in the setting of postoperative endometrial cancer [22–24]. • Lymph nodes can also be boosted with SBRT as above. • Re-irradiation or metastasis-directed SBRT can also be considered. • A retrospective series of patients with recurrent, persistent, or oligometastatic foci treated with a median 24 Gy (range 10–50) in a median of 4 (range 1–6) fractions showed 1 year and 3 year local control rates of 80% and 68%, with more favorable control in smaller tumors [25]. The rate of grade ≥2 toxicity was 4.3% with only one grade 3 event and no grade 4 or 5 toxicities. References 1. LiangY, et al. Prospective study of functional bone marrow-sparing intensity modulated radia- tion therapy with concurrent chemotherapy for pelvic malignancies. Int J Radiat Oncol Biol Phys. 2013;85:406. https://doi.org/10.1016/j.ijrobp.2012.04.044. 2. Mell LK, et al. Bone marrow-sparing intensity modulated radiation therapy with concur- rent cisplatin for stage IB-IVA cervical cancer: an international multicenter phase II clinical trial (INTERTECC-2). Int J Radiat Oncol Biol Phys. 2017;97:536. https://doi.org/10.1016/j. ijrobp.2016.11.027. 3. Williamson CW, et al. Prospective validation of a high dimensional shape model for organ motion in intact cervical cancer. Int J Radiat Oncol. 2016;96:801–7. 4. Huang J, Gu F, Ji T, Zhao J, Li G. Pelvic bone marrow sparing intensity modulated radiother- apy reduces the incidence of the hematologic toxicity of patients with cervical cancer receiving concurrent chemoradiotherapy: a single-center prospective randomized controlled trial. Radiat Oncol. 2020;15:180. https://doi.org/10.1186/s13014-020-01606-3. 5. Yusufaly T, et al. A multi-atlas approach for active bone marrow sparing radiation therapy: implementation in the NRG-GY006 trial. Int J Radiat Oncol Biol Phys. 2020;108:1240–7. 6. Rose BS, et al. Normal tissue complication probability modeling of acute hematologic toxic- ity in cervical cancer patients treated with chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2011;79:800. https://doi.org/10.1016/j.ijrobp.2009.11.010. 7. Ahunbay EE, et al. Online adaptive replanning method for prostate radiotherapy. Int J Radiat Oncol Biol Phys. 2010;77:1561. https://doi.org/10.1016/j.ijrobp.2009.10.013. 8. Visser J, et al. Dosimetric comparison of library of plans and online MRI-guided radiother- apy of cervical cancer in the presence of intrafraction anatomical changes. Radiat Oncol. 2019;14:126. 24 Advanced Technologies and Treatment Techniques for Gynecologic Malignancies
- 311. 312 9. Lin LL, et al. Initial report of pencil beam scanning proton therapy for posthysterectomy patients with gynecologic cancer. Int J Radiat Oncol Biol Phys. 2016;95:181. https://doi. org/10.1016/j.ijrobp.2015.07.2205. 10. Vyfhuis MAL, et al. Preserving endocrine function in premenopausal women undergoing whole pelvis radiation for cervical cancer. Int J Part Ther. 2019;6:10. https://doi.org/10.14338/ ijpt-d-19-00061.1. 11. Clivio A, et al. Intensity modulated proton beam radiation for brachytherapy in patients with cervical carcinoma. Int J Radiat Oncol Biol Phys. 2013;87:897. https://doi.org/10.1016/j. ijrobp.2013.08.027. 12. Hasan S, et al. Stereotactic body radiation therapy (SBRT) for pelvic or para-aortic recurrence from gynecologic malignancies. Int J Radiat Oncol. 2015;87:897. https://doi.org/10.1016/j. ijrobp.2015.07.1241. 13. Llewelyn M, Taylor A. Re-irradiation of cervical and endometrial cancer. Curr Opin Oncol. 2017;29:343. https://doi.org/10.1097/CCO.0000000000000392. 14. Mesko S, et al. Clinical outcomes for stereotactic ablative radiotherapy in oligometastatic and oligoprogressive gynecological malignancies. Int J Gynecol Cancer. 2017;27:403. https://doi. org/10.1097/IGC.0000000000000869. 15. Kunos CA, et al. Phase I trial of carboplatin and gemcitabine chemotherapy and stereotactic ablative radiosurgery for the palliative treatment of persistent or recurrent gynecologic cancer. Front Oncol. 2015;5:126. 16. Kirchheiner K, et al. Posttraumatic stress disorder after high-dose-rate brachytherapy for cervical cancer with 2 fractions in 1 application under spinal/epidural anesthesia: inci- dence and risk factors. Int J Radiat Oncol Biol Phys. 2014;89:260. https://doi.org/10.1016/j. ijrobp.2014.02.018. 17. Albuquerque K, et al. A phase II trial of stereotactic ablative radiation therapy as a boost for locally advanced cervical cancer. Int J Radiat Oncol Biol Phys. 2020;106:464. https://doi. org/10.1016/j.ijrobp.2019.10.042. 18. Deodato F, et al. Stereotactic radiotherapy in recurrent gynecological cancer: a case series. Oncol Rep. 2009;22:415–9. 19. Rwigema JCM, et al. Stereotactic body radiation therapy for abdominal and pelvic oligo- metastases: dosimetric targets for safe and effective local control. Pract Radiat Oncol. 2015;5:e183–91. 20. Kunos C, Brindle JM, Debernardo R. Stereotactic radiosurgery for gynecologic cancer. J Vis Exp. 2012;62:3793. https://doi.org/10.3791/3793. 21. Choi C, et al. Image-guided stereotactic body radiation therapy in patients with isolated para- aortic lymph node metastases from uterine cervical and corpus cancer. Int J Radiat Oncol Biol Phys. 2009;74:147. 22. Kemmerer E, et al. Use of image-guided stereotactic body radiation therapy in lieu of intra- cavitary brachytherapy for the treatment of inoperable endometrial neoplasia. Int J Radiat Oncol Biol Phys. 2013;85:129. https://doi.org/10.1016/j.ijrobp.2012.02.058. 23. Jones R, et al. Dosimetric feasibility of stereotactic body radiation therapy as an alternative to brachytherapy for definitive treatment of medically inoperable early stage endometrial cancer. Radiat Oncol. 2014;9:164. https://doi.org/10.1186/1748-717X-9-164. 24. Dalwadi SM, et al. Definitive chemoradiation followed by stereotactic body radiotherapy boost for inoperable endometrial cancer. J Radiat Oncol. 2019;8:329. https://doi.org/10.1007/ s13566-019-00403-0. 25. Reshko LB, et al. Stereotactic body radiation therapy (SBRT) in recurrent, persistent or oligo- metastatic gynecological cancers. Gynecol Oncol. 2020;159:611. https://doi.org/10.1016/j. ygyno.2020.10.001. C. W. Williamson et al.
- 312. 313 25 Prostate Adenocarcinoma Daniel Gorovets, Brandon S. Imber, Neil Desai, and Michael J. Zelefsky Contents 25.1 General Principles of Planning and Target Delineation 313 Further Reading 323 25.1 General Principles of Planning and Target Delineation • Intensity-modulated radiation therapy (IMRT) is the standard technique for external beam radiation therapy (EBRT) for prostate adenocarcinoma. IMRT is used in both the definitive setting (alone or combined with brachytherapy) and post-operatively (adjuvant or salvage). Various fractionation schemes exist; how- ever, all approaches rely on accurate target delineation and image-guided treat- ment delivery to maximize tumor control and minimize toxicities. This chapter will describe common treatment approaches and provide walk-throughs of typi- cal scenarios in the radiotherapeutic management of prostate cancer. D. Gorovets (*) · B. S. Imber · M. J. Zelefsky Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA e-mail: gorovetd@mskcc.org; imberb@mskcc.org; zelefskm@mskcc.org N. Desai Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX, USA e-mail: neil.desai@utsouthwestern.edu © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_25
- 313. 314 • Following pathological confirmation, initial case workup includes digital rectal examination, urinary and erectile function scores, and relevant labs (i.e. PSA +/− additional studies if ADT is planned). At MSKCC, mpMRI is recom- mended for all patients (unless contraindicated) to identify potentially under- sampled high-grade disease, determine prostate volume, define the dominant tumor size/location, evaluate extent of extra-prostatic disease (EPE) and seminal vesicle invasion (SVI), as well as identify gross disease requiring dose escalation post-operatively. • Choice between various treatment regimens depends on factors such as NCCN risk group, MRI findings, age, comorbidities, urinary function, and patient preference. • Simulation: At MSKCC, MR-only simulation and treatment planning as described by Tyagi et al. is preferred for all definitive treatments and for post-op gross local recurrences. Alternatively, a 2 mm slice thickness CT simulation can be fused with a 3 T MRI in the treatment position to help delineate the pros- tate CTV. – – For definitive treatments, three fiducial markers (base, mid-gland, apex) +/− rectal spacer (if no posterior EPE) are placed at least 5 days prior to sim. If dose escalation is planned for suspected post-op gross local recur- rences, fiducial markers can be placed at the time of biopsies. – – Empty rectum: Low fat-low residue diet, fiber supplement, and simethicone are started 1 week before sim and continued through treatment; An enema is administered 3 h before sim +/− treatments as needed. – – Full bladder: 16 oz of water 45 min prior to sim + treatments. – – To delineate the urethra as an avoidance structure, a Foley catheter is placed for stereotactic body radiation therapy (SBRT) sims and when EBRT is com- bined with a brachytherapy boost. Alternatively, MR-based urethral delinea- tion can be used as described by Zakian et al. – – Position: Supine with leg/pelvis immobilization. SBRT setups should be vali- dated and may include frame or frameless systems. At MSKCC, patients are immobilized with a thermoplastic mold that extends from mid-abdomen to mid-thigh and conforms to the inner leg. A knee cushion is used to provide additional stability. – – Sim Borders: L2 to mid-femur. – – Isocenter: Prostate or prostate bed; if treating lymph nodes: top of femo- ral heads. • Image fusion of MRI to simulation CT can be improved by matching of the blad- der/prostate interface (often affected by “pitch” variations between MRI/CT) as well as bony anatomy and fiducials (requires specific MRI sequence, such as T1 SPGR or 3D BFFE). • Clinical target volumes (CTV) should be delineated on every slice of the plan- ning CT or MRI. Planning target volumes (PTV) depend on fractionation scheme, image guidance, and institutional standards. A general description of target vol- umes and margins is indicated in Table 25.1. • Volume walk-throughs: see Figs. 25.1, 25.2, 25.3, 25.4, and 25.5. D. Gorovets et al.
- 317. 318 Seminal Vesicles Base Spacer CTV within levator ani Mid-gland Bladder interface AFS Foley to delineate urethra for SBRT Apex Stop CTVpros contours on slice above GUD Good slice to start contouring CTVpros Fig. 25.1 Definitive prostate CTV (orange) delineation. This series of representative images from a 2-mm slice thickness CT simulation (left) fused with a T2 MRI (right) demonstrates general boundary discrimination. It begins at the SVs and proceeds caudally to the apex. Not all slices are shown. Note that hydrogel rectal spacer is best visualized on T2 MRI, however, Atluri et al. dem- onstrated that the addition of iodinated contrast can facilitate MRI-independent spacer delineation D. Gorovets et al.
- 318. 319 Fig. 25.2 Three-dimensional projection of CTV in various views for quality assessment. Note the appearance of a relatively globular gland underneath a winged structure representing the seminal vesicles superiorly. Cross-referencing of these projections to axial contours allows for detection of common misinterpretations of anatomy, i.e., extending too far into the GUD will produce exten- sion of the pedestal structure inferiorly. Moreover, gross irregularities in the overall structure may reflect overcorrection from slice to slice that is not anatomically faithful, especially when averag- ing organ deformation and motion during treatment 25 Prostate Adenocarcinoma
- 319. 320 Initiate CTV above Gud 8- 12 mm below VUA Caudal bladder above VUA Cover peri-prostatic clips Laterally bounded by levator ani and then obturator internii superiorly Superior to symphsis, gradually pull anterior border to 3mm into bladder End superiorly at level of vas deferens or 1-2 cm above public symphsis, Do not extend soley to cover hemostatic clips. Cover residual SV Poterior borter = anorectal surface Anterior borter pupic symphysis Fig. 25.3 Post-prostatectomy target delineation. Representative images from 2-mm slice thick- ness simulation CT with full bladder protocol begin caudally and proceed cranially. Note that manual modification of the PTV (red) after expansion is shown alongside the initial CTV (blue). This helps avoid overdosing the rectum by excessive draping of the “dumbbell” shape cranially at the anterolateral rectum D. Gorovets et al.
- 320. 321 Fig. 25.4 Three-dimensional projection of PTV in orthogonal views for quality assessment. As opposed to an intact prostate treatment plan, the contours for a post-operative plan will necessarily approximate the bladder and rectum to cover areas of potential microscopic residual disease. These areas include the anterior perirectal space, the vesicoureteral anastomosis (VUA), and the new spaces created at the posterior bladder interface with the pelvic floor and VUA. The overlap of PTV margin with rectum (green) and bladder (yellow) is highlighted here. A gradual tapering of the anterior PTV boundary superior to the pubic symphysis is ensured by inspection of the 3D projection. Smoothing out this transition avoids abrupt changes in dose distribution that are sus- ceptible to errant targeting based on day-to-day changes in bladder volume despite a full bladder protocol 25 Prostate Adenocarcinoma
- 321. 322 Initiate CTVnodes at aortic bifurcation Bifurcation into internal and external ilias Gross nodal boost GTV (red), PTV (pink) Pre-sacral coverage ends at S2/S3 Ext. iliac coverage ends at femoral heads Pre-sacaral coverage starts at L5/S1 Coverage of the common iliacs CTVpros includes entire SVs in this case Stop CTVnodes at public symphysis Spacer Stop CTVpros contours on slice above GUD a b Fig. 25.5 (a, b) Pelvic lymph node target delineation. Representative images from a 2-mm slice thickness CT simulation scan are provided beginning cranially and proceeding caudally. Note that a 3 T MRI in the treatment position was fused to help delineate the CTVpros (orange) and rectal spacer (magenta). This patient had regional lymph node disease (T1cN1M0, GS 4 + 4, PSA 22) treated with moderately hypofractionated IG-IMRT and 2 years of Lupron and Abiraterone. Radiation consisted of 26 fraction dose-painting: elective pelvis to 4680 cGy (CTVnodes: green; PTVnodes: blue), gross right pelvic lymph node to 5720 cGy (GTVboost: red; PTVboost: pink), and prostate/SVs to 7020 cGy (CTVpros: orange; PTVpros: red) D. Gorovets et al.
- 322. 323 Further Reading Atluri PS, et al. Addition of iodinated contrast to rectal hydrogel spacer to facilitate MRI- independent target delineation and treatment planning for prostate cancer. Pract Radiat Oncol. 2019;9(6):e528–33. McLaughlin PW, et al. Radiographic and anatomic basis for prostate contouring errors and meth- ods to improve prostate contouring accuracy. Int J Radiat Oncol Biol Phys. 2010;76(2):369–78. Excellent demonstration of the anatomic features useful in determining boundaries to the CTV and demonstrating common errors in anatomic interpretation. Particularly useful are the com- parisons of MRI to CT scan images. Pollack A et al. RTOG 0534 protocol information: a phase III trial of short-term androgen depriva- tion with pelvic lymph node or prostate bed only radiotherapy (SPPORT) in prostate cancer patients with a rising PSA after radical prostatectomy. See Section 6.0 Radiation Therapy. General approach to both the postoperative fossa and pelvic lymph nodes are demonstrated in this protocol. 2010. RTOG website. http://www.rtog.org/ClinicalTrials/ProtocolTable/ StudyDetails.aspx?action=openFileFileID=4642. Poortmans P, et al. Guidelines for target volume definition in post-operative radiotherapy for prostate cancer, on behalf of the EORTC Radiation Oncology Group. Radiother Oncol. 2007;84(2):121–7. EORT guidelines for postoperative target delineation. Note that here, we more closely approximate RTOG guidelines for therapy. Tyagi N, et al. Clinical workflow for MR-only simulation and planning in prostate. Radiat Oncol. 2017;12:119. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513123/. Zakian KL, et al. Comparison of motion-insensitive T2-weighted MRI pulse sequences for visual- ization of the prostatic urethra during MR simulation. Pract Radiat Oncol. 2019;9(6):e534–40. Describes technique to delineate the urethra on MRI. 25 Prostate Adenocarcinoma
- 323. 325 26 Bladder Cancer Ariel E. Marciscano and Marisa A. Kollmeier Contents 26.1 General Principles of Planning and Target Delineation 325 26.2 Three-Dimensional Conformal Radiation Therapy (3D-CRT) 326 26.3 Intensity-Modulated Radiation Therapy (IMRT) 328 26.4 Simulation and Planning 331 26.5 MSKCC Guidelines 332 References 334 26.1 General Principles of Planning and Target Delineation • Organ-preservation with bladder-sparing trimodality therapy (TMT) is a standard definitive treatment option for node-negative, muscle-invasive bladder cancer (MIBC). TMT involves maximal, and ideally complete, TURBT followed by con- current chemoradiotherapy [1–3]. For node positive bladder cancer, systemic che- motherapy is the mainstay of therapy; however, for patients with disease confined to the pelvis/para-aortic nodes, chemoradiation is a reasonable therapeutic option. • RTOG/NRG protocols have classically used three-dimensional conformal radia- tion therapy (3D-CRT). Future NRG studies, including the phase III SWOG/ NRG 1806 study (NCT03775265), permit intensity-modulated radiation therapy (IMRT) for concurrent chemoradiotherapy. A. E. Marciscano Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA e-mail: arm7007@med.cornell.edu M. A. Kollmeier (*) Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA e-mail: kollmeim@mskcc.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_26
- 324. 326 • The use of IMRT is increasingly utilized to minimize dose to adjacent normal tissue, especially bowel—particularly, when dose constraints cannot be achieved with 3D-CRT-based planning. When using IMRT, it is essential to account for organ motion which may be accomplished by image-guidance. • There is no consensus on optimal field design [4, 5] (whole bladder +/− prostate, partial bladder, elective nodal coverage) or dose/fractionation regimen (daily fractionation [6], BID hyperfractionation [6, 7], hypofractionation [8]). • Definitive treatment should include the use of radiosensitizing therapy for all eligible patients.Various chemotherapy regimens [1, 6, 7] and hypoxia-modifying agents [9] have been studied. In general, the most commonly used radiosensitiz- ers are cisplatin, fluorouracil (5 FU)/mitomycin C, or gemcitabine. • The use of adjuvant radiotherapy for high-risk bladder cancer following radical cystectomy is under investigation [10, 11]. In general, this approach is most appropriate for pT3, pN+, and/or positive surgical margins. Additionally, the use of intraoperative radiation therapy may be appropriate for some cystectomy- eligible patients with locally advanced disease who are anticipated to have a need for adjuvant local therapy due to positive surgical margins. • Organs at risk (OARs) include: small bowel, large bowel, rectum, and femo- ral heads. 26.2 Three-Dimensional Conformal Radiation Therapy (3D-CRT) • Recent RTOG studies (0712, 0926) have included a small pelvic field (defined as CTV4140) which includes the entire bladder, prostate and prostatic urethra (in men), proximal urethra (in women), and regional lymphatics followed by a cone down to a whole bladder field (defined as CTV6120) which includes the entire bladder and any gross tumor volume. Protocol OAR constraints are displayed in Table 26.1. • The small pelvic field is generally planned as a four-field box arrangement (Table 26.2, Fig. 26.1). • The whole bladder field is generally planned as a four-field box or parallel opposed laterals (Table 26.2). • A randomized study comparing standard whole-bladder radiation therapy versus reduced high-dose volume radiation therapy (RHDVRT) reported no significant reduction in late toxicity and non-inferiority of locoregional control with RHDVRT as compared with whole-bladder radiation therapy [12].A two-phase sequential boost or single-phase concomitant boost approach can be used for RHDVRT (Fig. 26.2). Table 26.1 Doses constraints for 3D-CRT selective bladder preservation RTOG 0712/0926 OAR constraints for 3D-CRT-based selective bladder preservation Rectum V30Gy 50% (0712) or V55Gy 50% (0926) V55Gy 10% (0712) Femoral heads V50Gy 20% (0712) Dmax 45 Gy (0712, 0926) Small bowel D45Gy 300 cm3 A. E. Marciscano and M. A. Kollmeier
- 325. 327 Table 26.2 Field design for 3D-CRT selective bladder preservation Small pelvic field Designed to cover entire bladder and regional pelvic nodes as well as prostate/prostatic urethra in men and proximal urethra in women using four-field box arrangement AP/PA fields: Superior extent to S1/S2 junction (anterior) and inferior extent 1 cm below obturator foramen. Laterally, extend field 1.5 cm beyond bony pelvis (at widest diameter). Block femoral heads Parallel opposed lateral fields: Same superior/inferior extent as AP/PA field. Anteriorly, 1 cm anterior to symphysis pubis or 1.5 cm anterior to CTV whole bladder volume. Posteriorly, extend 3 cm beyond CTV whole bladder volume (see below). Consider anterior block to minimize dose to small bowel Recommend contouring of pelvic nodes to ensure standard fields encompass intended lymphatics at risk, adjust borders as necessary Whole bladder field CTV whole bladder field includes entire bladder and any gross tumor volume (GTV) PTV whole bladder includes 0.5 cm isotropic expansion on CTV whole bladder with exception of 1.5 cm superiorly Field design for whole bladder may consider four-field box or opposed lateral field to optimize target coverage and OAR sparing, multi-leaf collimation to optimize conformality a b Fig. 26.1 AP (a) and lateral (b) DRR images for 3D-CRT small pelvic field for selective bladder preservation. Field design outlined in red; targets and organs at risk as follows: bladder (yellow), prostate/seminal vesicles (magenta), pelvic nodes (green), rectum (brown), femoral heads (white) a b Fig. 26.2 Schematic representation of target delineation for reduced high-dose volume radiation therapy (RHDVRT) per BC2001 randomized non-inferiority trial via (a) two-phase bladder-boost “cone down” technique or (b) single-phase simultaneous integrated boost (SIB) technique 26 Bladder Cancer
- 326. 328 26.3 Intensity-Modulated Radiation Therapy (IMRT) • Target volumes with IMRT are similar to 3D-CRTand include the whole bladder, prostate, and prostatic urethra in men/proximal urethra in women with or without nodal coverage. • Daily bladder target motion variability introduces significant uncertainty that must be accounted for with PTV margin, daily setup, and image-guidance. • In addition to accounting for consistency in bladder filling volume, it is also criti- cal to assess variability in adjacent organs at risk (OARs). The daily variation in the positioning of the small/large bowel in the superior, anterior, and lateral directions as well as the position of the large bowel/sigmoid and rectum in the posterior and lateral orientations. • IMRT offers a reduction in dose to OARs directly adjacent to the high-dose PTV, including the small and large bowel. • IMRT offers an opportunity to optimize sparing of normal bladder for partial bladder/reduced volume irradiation and potentially permit dose-escalation to the TURBT bed [13–15]. • Please see Table 26.3 for summary of target volumes for IMRT for bladder cancer. • Please see clinical vignettes and IMRT-based treatment fields for patients with localized MIBC including (1) initial pelvic field (Fig. 26.3) and sequential blad- der boost (Fig. 26.4); or (2) bladder-only field (Fig. 26.5). • Common conventional dose-fractionation prescriptions are: 64–66.6 Gy deliv- ered in 32–37. Elective treatment of the regional nodes (including CTV bladder) is generally 39.6–45 Gy delivered in 1.8 Gy fractions prior to sequential bladder boost of 19.8–21.6 Gy in 1.8 Gy fractions. Table 26.3 Field design for selective bladder preservation using intensity-modulated radiation therapy (IMRT) planning Initial pelvic field • Designed to cover entire bladder and regional pelvic nodes as well as prostate/prostatic urethra in men using four-field box arrangement • GTV = any gross disease and/or tumor bed as defined by fiducials or post-TURBT imaging • CTV bladder = whole bladder (including GTV) + prostate/prostatic urethra (men) or proximal urethra (women) • PTV bladder = CTV bladder + 1.5 cm • CTV pelvis = includes bilateral pelvic nodal regions (perivesical, internal iliac, external iliac, presacral, distal common iliac) • PTV pelvis = CTV pelvis + 8–10 mm on vessels (corresponding to nodal regions) • If electing to treat pelvic nodes combine PTV bladder + PTV pelvis to create composite PTV for initial pelvic field Bladder-boost field • GTV/CTV bladder boost = any gross disease and/or tumor bed as defined by fiducials or post-TURBT imaging • PTV bladder boost = CTV + 1 cm isotropic expansion A. E. Marciscano and M. A. Kollmeier
- 327. 329 e f g c d a b Fig. 26.3 Initial pelvic IMRT field for 56-year-old gentleman with cT2N0 high-grade urothelial muscle-invasive bladder carcinoma involving right posterolateral bladder wall. Representative images of initial pelvic field with targets and PTV contoured in axial (a–e), coronal (f) and sagittal (g) plane 26 Bladder Cancer
- 328. 330 c a b Fig. 26.4 Bladder-boost pelvic IMRT field for 56-year-old gentleman with cT2N0 high-grade urothelial muscle-invasive bladder carcinoma involving right posterolateral bladder wall. Bladder = cyan. TURBT bed = yellow. PTV boost = blue. Rectum = magenta. Bowel = green. Arrows = fiducials. (a) axial (b) sagittal and (c) coronal plane Fig. 26.5 Concurrent chemoradiation with bladder-only IMRT for 82-year-old man with locally advanced, unresectable muscle-invasive disease at right anterolateral bladder wall. PTV = red. GTV = yellow. Bowel = green, Rectum = orange. Prostate = blue. Axial (a–c), coronal (d), and sagittal (e) representative CT slices with targets contoured for IMRT-based bladder-only treatment a b A. E. Marciscano and M. A. Kollmeier
- 329. 331 26.4 Simulation and Planning • CT-based simulation in supine position with appropriate pelvic immobilization device is recommended. • Reproducible bladder filling and verification with image-guidance is critical to effective and safe delivery of IGRT for MIBC [16]. • Image-guidance may vary by institution. For the initial phase, daily KV imaging matched to bone and at least weekly CBCTs to verify bladder position are per- formed. For the boost phase, daily KV imaging matched to fiducials and/or CBCT daily is appropriate. When fiducials are not present, daily CBCT is rec- ommended for the boost phase. e c d Fig. 26.5 (continued) 26 Bladder Cancer
- 330. 332 26.5 MSKCC Guidelines • At our institution, definitive trimodality therapy generally involves maximal TURBT with bladder mapping and placement of gold fiducial markers placed at the periphery of the TUR bed. • Following TUR with fiducial placement, a CT-based simulation is performed with empty bladder. The choice of an empty bladder is for both consistency and reduction of the initial bladder target volume. Oral contrast is used to delineate bowel. IV contrast for simulation purposes should be used with caution in patient with compromised renal function or those planned for nephrotoxic chemotherapy. • During Week 3–4 of concurrent chemoradiation, a CT-based re-simulation is performed with full bladder in order to plan the cone down phase. The choice of a full bladder is to displace bowel and uninvolved bladder walls from bladder boost target. • The prescription for the initial phase of treatment is 4500 cGy delivered in 25 daily fractions (180 cGy/fraction) and the targets for the initial phase of treat- ment are: bladder (whole), prostate/prostatic urethra, regional pelvic nodes (obturators/perivesical, external iliac, internal iliac, presacral, common iliac [to aortic bifurcation]). • The prescription for the cone down phase of treatment is 2160 cGy delivered 12 daily fractions (cumulative dose to PTV boost is 6660 cGy over 37 fractions). The target for the cone down phase of treatment includes the TURBT bed as defined by the fiducial markers with a 1 cm margin. • In selected patients, hypofractionated regimens (55 Gy over 20 fractions) may be used. Target volumes include the bladder/prostatic urethra and any gross tumor with a 1.5 cm circumferential margin with daily CBCT for image-guidance. Radiosensitizing chemotherapy is utilized when clinically appropriate. Selected patients may include those with poor performance status or very elderly patients, cystectomy-ineligible patients with multifocal disease, or palliation for locally advanced disease. • For node-positive patients, the initial phase may include a simultaneous inte- grated boost (SIB) to dose-escalate gross adenopathy. Generally, a SIB dose of 5625 cGy delivered in 25 daily fractions (225 cGy/fraction) to gross nodal dis- ease (PTV = GTV + 5 mm margin) respecting normal tissue tolerance is appro- priate. See Figs. 26.6 and 26.7 for case example of locally advanced node positive bladder cancer. A. E. Marciscano and M. A. Kollmeier
- 331. 333 e f g h c d a b Fig. 26.6 Initial pelvic fields with simultaneous integrated boost for 51-year-old male with cT2N+ locally advanced urothelial bladder carcinoma w/ 5.0 × 2.8 cm mass along left posterolat- eral wall s/p maximal TURBT. Sagittal (a), coronal (b), and axial (c–h) CT slices with targets contoured for IMRT-based treatment 26 Bladder Cancer
- 332. 334 e f g h c d a b Fig. 26.7 Bladder-boost fields for 51-year-old male with cT2N+ locally advanced urothelial blad- der carcinoma w/ 5.0 × 2.8 cm mass along left posterolateral wall s/p maximal TURBT. Axial (a–f), coronal (g), and sagittal (h) CT slices with targets and organs at risk contoured for IMRT- based bladder boost References 1. James ND, et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder can- cer. N Engl J Med. 2012;366(16):1477–88. 2. Mak RH, et al. Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014;32(34):3801–9. 3. Huddart RA, et al. Patient-reported quality of life outcomes in patients treated for muscle- invasive bladder cancer with radiotherapy +/- chemotherapy in the BC2001 phase III ran- domised controlled trial. Eur Urol. 2019;77:260. 4. Tan MP, et al. The intensity-modulated pelvic node and bladder radiotherapy (IMPART) trial: a phase II single-centre prospective study. Clin Oncol. 2019;32:93. 5. Tunio MA, et al. Whole-pelvis or bladder-only chemoradiation for lymph node- negative invasive bladder cancer: single-institution experience. Int J Radiat Oncol Biol Phys. 2012;82(3):e457–62. 6. Coen JJ, et al. Bladder preservation with twice-a-day radiation plus fluorouracil/cisplatin or once daily radiation plus gemcitabine for muscle-invasive bladder cancer: NRG/RTOG 0712-a randomized phase II trial. J Clin Oncol. 2019;37(1):44–51. 7. Mitin T, et al. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil- cisplatin with selective bladder preservation and adjuvant chemotherapy for A. E. Marciscano and M. A. Kollmeier
- 333. 335 patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013;14(9):863–72. 8. Choudhury A, et al. Phase II study of conformal hypofractionated radiotherapy with concur- rent gemcitabine in muscle-invasive bladder cancer. J Clin Oncol. 2011;29(6):733–8. 9. Hoskin PJ, et al. Radiotherapy with concurrent carbogen and nicotinamide in bladder carci- noma. J Clin Oncol. 2010;28(33):4912–8. 10. Zaghloul MS, et al. Adjuvant sandwich chemotherapy plus radiotherapy vs adjuvant chemo- therapy alone for locally advanced bladder cancer after radical cystectomy: a randomized phase 2 trial. JAMA Surg. 2018;153(1):e174591. 11. Baumann BC, et al. Bladder cancer patterns of pelvic failure: implications for adjuvant radia- tion therapy. Int J Radiat Oncol Biol Phys. 2013;85(2):363–9. 12. Huddart RA, et al. Randomized noninferiority trial of reduced high-dose volume versus stan- dard volume radiation therapy for muscle-invasive bladder cancer: results of the BC2001 trial (CRUK/01/004). Int J Radiat Oncol Biol Phys. 2013;87(2):261–9. 13. Kang JJ, et al. Whole versus partial bladder radiation: use of an image-guided hypofraction- ated IMRT bladder-preservation protocol. Am J Clin Oncol. 2018;41(2):107–14. 14. Hafeez S, et al. Prospective study delivering simultaneous integrated high-dose tumor boost (/=70 Gy) With image guided adaptive radiation therapy for radical treatment of localized muscle-invasive bladder cancer. Int J Radiat Oncol Biol Phys. 2016;94(5):1022–30. 15. Kollmeier MA, et al. Image-guided intensity modulated radiation therapy (IMRT) for bladder cancer: toxicity and early outcomes. Int J Radiat Oncol Biol Phys. 2014;90(1):S463. 16. Adil K, et al. Anisotropic bladder planning target volume in bladder radiation therapy. Pract Radiat Oncol. 2019;9(1):24–8. 26 Bladder Cancer
- 334. 337 27 Testicular Seminoma Brandon S. Imber, Daniel Gorovets, Sean M. McBride, and Michael J. Zelefsky Contents 27.1 General Principles of Planning and Target Delineation 337 References 343 27.1 General Principles of Planning and Target Delineation • In almost all cases, initial management of testicular cancer involves a radical inguinal orchiectomy. Post-operative management depends on histological sub- type and extent of disease. • Post-operative radiation is generally only considered for pure seminomas (most common type of testicular germ cell tumor, highly radiosensitive) and rarely considered for non-seminomatous germ cell tumors (less common, less radiosensitive). • Prior to any treatment, adequate workup should be performed to ensure pure seminoma, including detailed history and physical exam, serum tumor markers (AFP, β-hCG, and LDH), chemistry panel, testicular ultrasound, and CXR [1]. Following radical inguinal orchiectomy for a pure seminoma, serum tumor markers should be repeated, and additional staging studies should be performed B. S. Imber · D. Gorovets (*) · S. M. McBride · M. J. Zelefsky Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA e-mail: imberb@mskcc.org; gorovetd@mskcc.org; mcbrides@mskcc.org; zelefskm@mskcc.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_27
- 335. 338 including CT chest/abdomen/pelvis +/− brain MRI (if indicated). All patients planned for testicular cancer treatment should be offered fertility evaluation and sperm banking. • Laterality of testicular seminoma and prior surgery influences pattern of spread [2]. – – Right sided seminoma tends to drain to the paracaval, precaval, and aortoca- val nodes. – – Left sided seminoma tends to drain to the lateroaortic and preaortic nodes. – – Pelvic, external iliac or inguinal nodes may be at risk in patients with prior scrotal or inguinal surgery [3]. • Patients with stage I pure seminoma have several options. Generally, post- orchiectomy surveillance is strongly preferred. However, based on results from MRC TE 10 [4] and TE18 [5], those patients with stage I seminoma who refuse surveillance can receive adjuvant radiotherapy to para-aortic lymph nodes alone (i.e., PA strip, see Table 27.1 and Fig. 27.1) to a dose of 20–25.5 Gy unless there is prior inguinal or scrotal violation. Another non-inferior adjuvant option is 1–2 cycles of carboplatin [1, 8]. • Patients with stage II pure seminoma can be treated using a dogleg field (see Table 27.2 and Figs. 27.2 and 27.3) to either 30 Gy (stage IIA) or 36 Gy (stage IIB) [1]. Alternatively, primary chemotherapy can be used, typically consisting of etoposide/cisplatin +/− bleomycin for 3–4 cycles. • At our institution, standard radiation simulation parameters for testicular semi- noma include a 2 mm slice thickness CT with the patient positioned supine with arms up. An alpha cradle is used for immobilization. IV contrast is often used for stage II patients to help delineate gross nodal disease. If the patient has a staging Table 27.1 Suggested target volumes for stage I testicular seminoma Target volume Definition based on CT imaging and vascular anatomy (see Fig. 27.1) Definition based on anatomic landmarks CTV • Contour inferior vena cava and aorta from 2 cm below top of kidney superiorly down to the bifurcation of iliac vessels inferiorly • Superior border: top of T11 (Note: some sources recommend top of T12) [6] • Expand IVC contour by 1.2 cm and aorta contour by 1.9 cm • Inferior border: bottom of L5 • Combine the two volumes and then subtract off of bone, muscle, and bowel • Lateral borders: edge of transverse processes (typically 10 cm width); For left sided seminoma: nodal mapping studies suggest that it is optional to cover the left renal hilum [7]. PTV [20–25.5 Gy in 1.5–2.0 Gy per fraction] • Expand the final CTV by 0.5 cm + 0.7 cm to block edge See [6] for more detailed information B. S. Imber et al.
- 336. 339 Fig. 27.1 Volumes for clinical stage I seminoma based on vascular anatomy. Volumes for clinical stages IA, IB, and IS (CTV = red, PTV = blue); slices are superior to inferior 27 Testicular Seminoma
- 337. 340 PET scan, this can also be fused with the simulation CT scan. The contralateral intact testicle should be shielded with a clamshell. • 3D-CRT is the standard treatment approach for seminoma with AP/PA fields based on bony anatomic landmarks or vascular anatomy.A general description of target volumes and margins is indicated in Tables 27.1 and 27.2. See [6] for more detailed information. • In the case of prior inguinal or scrotal surgery, the ipsilateral inguinal and iliac regions should be included in the field. If there was penetration of the scrotum, consider electron boost to the scrotum and scar. Fig. 27.1 (continued) B. S. Imber et al.
- 338. 341 Table 27.2 Suggested target volumes for stage II testicular seminoma Target volume and dosing Definition based on CT imaging and vascular anatomy (see Fig. 27.2) Definition based on anatomic landmarks CTVinitial • Create CTVvessels: Same IVC/aorta contours and expansions as per Table 27.1. Next, contour common iliac vessels, proximal internal iliac vessels (until takeoff of superior gluteal), and external iliac vessels down to the upper border of the acetabulum and expand by 1.2 cm respecting anatomic boundaries • Superior border: top of T11 (Note: some sources recommend top of T12) [6] • Create CTVnodes: Contour gross nodal disease (GTV) and expand by 0.8 cm respecting anatomic boundaries • Inferior border: top of the acetabulum (Note: some sources recommend middle or bottom of the obturator foramen) [6] • Combine CTVvessels and CTVnodes to form CTVinitial • Lateral border: tips of transverse processes of lumbar vertebra (typically L3 with consideration of kidney location) and extending to cover lateral acetabular edge at inferior extent of the field PTVinitial [20–25.5 Gy in 1.5–2.0 Gy per fraction] • Expand CTVinitial by 0.5 cm + 0.7 cm to block edge • For left sided seminoma: nodal mapping studies suggest that it is optional to cover the left renal hilum [7] PTVconedown [Boost volume to receive total of 30–36 Gy in 2 Gy per fraction] (see Fig. 27.3) • Expand CTVnodes by 0.5 cm + 0.7 cm to block edge • Ensure 2 cm margin on all visible gross adenopathy See [6] for more detailed information 27 Testicular Seminoma
- 339. 342 Fig. 27.2 Inferior portion of dogleg field based on vascular anatomy. Initial dogleg field with CTV in red and PTV in blue with slices projected superior to inferior. Note that the superior por- tion of the field is as per Fig. 27.1 B. S. Imber et al.
- 340. 343 Fig. 27.3 Boost volumes. Example boost contours for a male with stage IIA disease. Note that GTV = yellow, CTV = red, PTV = blue, and that slices are superior to inferior References 1. Gilligan T, Lin DW, Aggarwal R, et al. Testicular cancer, Version 2.2020, NCCN Clinical Practice Guidelines in oncology. J Natl Compr Cancer Netw. 2019;17:1529–54. 2. Paly JJ, Efstathiou JA, Hedgire SS, et al. Mapping patterns of nodal metastases in seminoma: rethinking radiotherapy fields. Radiother Oncol. 2013;106:64–8. 3. McMahon CJ, Rofsky NM, Pedrosa I. Lymphatic metastases from pelvic tumors: anatomic classification, characterization, and staging. Radiology. 2010;254:31–46. 4. Fosså SD, Horwich A, Russell JM, et al. Optimal planning target volume for stage I testicular seminoma: a medical research council randomized trial. medical research council testicular tumor working group. J Clin Oncol. 1999;17:1146. 5. Jones WG, Fossa SD, Mead GM, et al. Randomized trial of 30 versus 20 Gy in the adju- vant treatment of stage I Testicular Seminoma: a report on Medical Research Council Trial TE18, European Organisation for the Research and Treatment of Cancer Trial 30942 (ISRCTN18525328). J Clin Oncol. 2005;23:1200–8. 27 Testicular Seminoma
- 341. 344 6. Wilder RB, Buyyounouski MK, Efstathiou JA, et al. Radiotherapy treatment planning for tes- ticular seminoma. Int J Radiat Oncol Biol Phys. 2012;83:e445–52. 7. Dinniwell R, Chan P, Czarnota G, et al. Pelvic lymph node topography for radiotherapy treat- ment planning from ferumoxtran-10 contrast-enhanced magnetic resonance imaging. Int J Radiat Oncol Biol Phys. 2009;74:844–51. 8. Mead GM, Fossa SD, Oliver RTD, et al. Randomized trials in 2466 patients with stage I semi- noma: patterns of relapse and follow-up. J Natl Cancer Inst. 2011;103:241–9. B. S. Imber et al.
- 342. 345 28 Brain Metastases Christophe Marques, Julie Jang, Fahad Momin, Michael Reilly, and Eric L. Chang Contents 28.1 Whole Brain Radiation Therapy Versus Stereotactic Radiosurgery 345 28.2 WBRT: General Principles of Planning and Target Delineation 346 28.3 SRS: General Principles of Planning and Target Delineation 351 References 354 28.1 Whole Brain Radiation Therapy Versus Stereotactic Radiosurgery • The choice of whole brain radiation therapy (WBRT) versus stereotactic radio- surgery (SRS) is beyond the scope of this manual, but depends on a number of factors, including number and volume of brain metastases and performance sta- tus. Several prognostic tools, including molecular graded prognostic assessment, are available to aid in decision-making. • Generally, SRS offers better preservation of neurocognitive function and quality of life, whereas WBRT improves the distant and overall control rates of intracra- nial metastases. C. Marques (*) · J. Jang · F. Momin · M. Reilly · E. L. Chang Department of Radiation Oncology, Norris Cancer Center, Keck School of Medicine of USC, Los Angeles, CA, USA e-mail: Christophe.Marques@med.usc.edu; Julie.Jang@med.usc.edu; Fahad.Momin@med.usc.edu; Michael.Reilly@med.usc.edu; Eric.Chang@med.usc.edu © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_28
- 343. 346 28.2 WBRT: General Principles of Planning and Target Delineation • See Table 28.1 for clinical scenarios and variations in technique. Dose fraction- ations are included in Table 28.2. • Strategies to preserve neurocognitive function include addition of memantine and/or hippocampal avoidance WBRT (HA-WBRT). • Non-contrast treatment-planning CT scan from vertex to upper cervical spine (axial slice thickness ≤2.5 mm) is performed with the patient supine and head in neutral position, using a thermoplastic mask for immobilization, with field of view 600 mm. Table 28.1 Suggested WBRT fields Conventional WBRT Leptomenin- geal disease Lymphoma/ leukemia Scalp spar- ing HA-WBRT Clinical scenario • Diffuse brain metastases (numerous or “too many to count”) • Leptomen- ingeal dis- ease • CNS pro- phylaxis for ALL • Cosmetic outcome is a priority (technique may result in a “reverse Mohawk”) • Diffuse brain metastases (numerous or “too many to count”) • PCI for SCLC • CNS leuke- mia (high- risk) • PCI for SCLC • Exclusion: lesion is within 5 mm from hippocampus Fields 3D-CRT with lateral opposed beams rotated slightly off-axis (RAO/LAO) to avoid divergence into the lenses IMRT/VMAT Target volumes and margins Entire cra- nial contents Entire cranial contents Entire cranial contents Entire cra- nial contents CTV: whole brain parenchyma to foramen magnum + optic nerves + optic nerves PTV: CTV minus (hippo- campi + 5 mm expansion), no setup margin + retroorbital region + retroorbital region Normal structure constraints: + lamina cri- bosa + retina Brain metastases: +/− whole globe if ocu- lar involve- ment • hippocampi D100% ≤9 Gy, Dmax ≤16 Gy C. Marques et al.
- 344. 347 Table 28.1 (continued) Conventional WBRT Leptomenin- geal disease Lymphoma/ leukemia Scalp spar- ing HA-WBRT Field edges Sup: 2 cm flash MLC edge set at outer table of the calvarium • optic nerves and chiasm Dmax ≤30 Gy Post: 2 cm flash +/− posterior neck MLC block to protect soft tissue PCI for SCLC: • hippocampi D100% ≤7.5 Gy, Dmax ≤13.5 Gy Inf: bottom of C1 • optic nerves and chiasm Dmax ≤25 Gy Ant: MLC block from 2 cm flash to anterior aspect of C1, blocking parotid and lenses Cover temporal lobes and cribriform plate Cover tempo- ral lobes and cribriform plate with additional margin 8–10 mm for penumbra and daily setup Cover tempo- ral lobes and cribriform plate with additional margin 8–10 mm for penumbra and daily setup Cover poste- rior 1/3 of the globes if no ocular involvement on slit lamp examination or entire bilat- eral globes if ocular involvement Table 28.2 WBRT dose and fractionation Clinical scenario Dose and fractionation WBRT, LMD 30 Gy in 10 fractions (most common), 37.5 Gy in 15 fractions (RTOG), 30 Gy in 12 fractions, 20 Gy in 5 fractions (poor prognosis) WBRT reirradiation 20–25 Gy in 10 fractions and a time interval of at least 4–6 months PCI fort SCLC 25 Gy in 10 fractions (most common) CNS prophylaxis for ALL 12 Gy in 8 fractions CNS leukemia (high-risk) ≥18 Gy in 9–10 fractions (dose based on intensity of systemic therapy) 28 Brain Metastases
- 345. 348 • 3D-CRT with opposed lateral photon beams of energy 6 MV is used typically with a multileaf collimator (MLC) block (Figs. 28.1 and 28.2). • For hippocampal avoidance, inverse-planned IMRT relies on a planning CT scan fused to a gadolinium contrast-enhanced MRI scan (using the three-dimensional spoiled gradient sequence with axial slice thickness 1.25–1.5 mm to define the hippocampal avoidance region) (Fig. 28.3) [1]. • Orthogonal films for setup verification are done weekly with MV imaging. Daily kV is usually reserved for IMRT-based WBRT. c d a b Fig. 28.1 Standard WBRT fields as described in Table 28.1 with lateral opposed beams rotated slightly off-axis (RAO/LAO) to avoid divergence into the lenses. (a) Beam’s eye view showing coverage of the cribriform plate (blue) with MLCs blocking the lenses (green), (b) mid-cranium axial view illustrating coplanar anterior field edges, (c) axial view showing adequate coverage of the cribriform plate and avoidance of the lenses, (d) axial view illustrating adequate coverage of the temporal lobes. Note: the isocenter can also be placed midline at the level of the canthus, allow- ing no beam divergence to the eyes or lenses C. Marques et al.
- 346. 349 c d a b Fig. 28.2 Variations of the standard WBRT fields accounting for differing clinical situations as described in Table 28.1. (a) Conventional WBRT, (b) larger fields used for leptomeningeal disease with red arrow showing greater distance from the cribriform plate compared to (a), (c) fields cover- ing the posterior orbits for CNS leukemia/lymphoma, (d) scalp-sparing technique with MLC edges set at the outer table of the calvarium 28 Brain Metastases
- 347. 350 Fig. 28.3 Hippocampal avoidance WBRT illustrated with axial slices of CT and fused postcontrast three- dimensional spoiled gradient MRI from the caudal to cranial direction. Per RTOG 0933 contour guidelines, only the subgranular zone (SGZ) portion of the hippocampi is contoured (red) and a 5 mm volumetric expansion margin (blue) is applied to create a hippocampal avoidance zone. The PTV consists of the entire brain tissue (yellow) minus the 5 mm expanded hippocampi (blue). Also shown are the optic nerves (yellow) and chiasm (orange) C. Marques et al.
- 348. 351 28.3 SRS: General Principles of Planning and Target Delineation • Clinical scenarios employing SRS include single-fraction and fractionated SRS (2–5 fractions) for intact brain metastases and post-resection cavity (Table 28.3, Figs. 28.4 and 28.5). Dose fractionation depends on target size or volume and distance from critical structures (Table 28.4). • Instruments include the frame-based or frameless cobalt-based Leksell Gamma Knife® or LINAC-based systems. • Target volume delineation and treatment planning using a volumetric contrast- enhanced T1-weighted MRI scan (1–2 mm slices) is preferred (or contrast- enhanced CT scan if unable to tolerate MRI or patient has an incompatible implanted device). A thin-slice CT is acquired and co-registered for LINAC- based SRS. • For LINAC-based SRS, daily imaging is required. Table 28.3 Suggested SRS target volume delineation using two different methods [2, 3] Target GTV CTV Unresected brain metastases Contrast enhancing lesion on T1-weighted sequence MRI GTV + 0 mm Postoperative gross total resection cavity (method 1) [2] n/a • 2 mm expansion margin around the resection cavity borders visualized on postcontrast MRI Postoperative gross total resection cavity (method 2) [3] n/a • Entire contrast enhancing region, surgical cavity, and surgical tract seen on postoperative MRI • 5–10 mm margin along the bone flap beyond the initial region of preoperative tumor contact (if initial tumor was in contact with the dura) • 1–5 mm margin along the bone flap (if initial tumor was NOT in contact with the dura) • 1–5 mm margin along the venous sinus (if initial tumor was in contact with a venous sinus) 28 Brain Metastases
- 349. 352 Fig. 28.4 Single-fraction SRS to a 24 mm left temporal lobe surgical cavity, after gross total resection of a 33 mm metastasis from primary rectal cancer with preoperative dural contact but no venous sinus contact. Method 1 shows the contours as described by Soltys et al. [2], CTV delinea- tion (red) = MRI T1 post-gadolinium enhancement and surgical cavity (blue) + 2 mm uniform expansion margin. Method 2 shows the contours as described by Soliman et al. [3], CTV delinea- tion (red) = MRI T1 post-gadolinium enhancement, surgical cavity, and surgical tract (blue) + 10 mm margin along the bone flap. Single-fraction SRS was chosen due to the small cavity size (3 cm) and sufficient distance from delicate brain structures. Patient was treated using Leksell Gamma Knife® by Elekta, hence PTV = CTV + 0 mm expansion margin. Contoured struc- tures shown include the right optic nerve (yellow), left optic nerve (orange), and the brain- stem (cyan) C. Marques et al.
- 350. 353 Fig. 28.5 Multiple isocenter single-fraction SRS to new brain metastases from primary breast cancer, ranging from 6 to 20 mm (volume ranging from 0.07 to 1.92 cm3 ) in a patient who received prior WBRT 30 Gy in 10 fractions. Lesion 1 is located in the right parietal lobe, lesion 2 in the left parietal lobe, lesion 3 in the right temporal lobe, and lesion 4 in the left cerebellum. Single-fraction treatment was chosen due to the smaller tumor sizes (less than 3 cm) and sufficient distance from delicate brain structures. For all lesions, GTV delineation (red) = MRI T1 post-gadolinium enhancement. Patient was treated using Leksell Gamma Knife® by Elekta, hence PTV and CTV used 0 mm expansion from GTV Table 28.4 SRS dose and organ at risk constraints for different fractionation schemes (based on Alliance A071801 trial) [4] 1 Fraction 3 Fractions 5 Fractions PTV dose (postop cavity) 20 Gy (4.2 cm3 ) 27 Gy (30 cm3 ) 30 Gy (≥30 cm3 to 5 cm) 18 Gy (≥4.2 to 8.0 cm3 ) 17 Gy (≥8.0 to 14.4 cm3 ) 15 Gy (≥14.4 to 20 cm3 ) 14 Gy (≥20 to 30 cm3 ) 12 Gy (≥30 cm3 to 5 cm) PTV dose (unresected metastases) 24 Gy (1 cm) 27 Gy 30 Gy 22 Gy (≥1.0 to 2.0 cm) 18 Gy (≥2.0 to 3.0 cm) 15 Gy (≥3.0 to 4.0 cm) Brainstem constraint V12 Gy 1 cm3 23.1 Gy max 28 Gy max V18 Gy 0.5 cm3 V23 Gy 0.5 cm3 Optic apparatus constraint 9 Gy max 17.4 Gy max 23 Gy max V13.8 Gy 0.2 cm3 V20 Gy 0.2 cm3 28 Brain Metastases
- 351. 354 References 1. Gondi V, Tolakanahalli R, Mehta MP, Tewatia D, Rowley H, Kuo JS, et al. Hippocampal- sparing whole-brain radiotherapy: a “how-to” technique using helical tomotherapy and linear accelerator-based intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2010;78(4):1244–52. https://doi.org/10.1016/j.ijrobp.2010.01.039. 2. Soltys SG, Adler JR, Lipani JD, Jackson PS, Choi CY, Puataweepong P, et al. Stereotactic radiosurgery of the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys. 2008;70(1):187–93. https://doi.org/10.1016/j.ijrobp.2007.06.068. 3. Soliman H, Ruschin M, Angelov L, Brown PD, Chiang VLS, Kirkpatrick JP, et al. Consensus contouring guidelines for postoperative completely resected cavity stereotactic radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys. 2018;100(2):436–42. https://doi.org/10.1016/j. ijrobp.2017.09.047. 4. Clinicaltrials.gov. n.d.. https://clinicaltrials.gov/ct2/show/NCT04114981. C. Marques et al.
- 352. 355 29 Benign Tumors of the CNS Rupesh Kotecha, Samuel T. Chao, Erin S. Murphy, and John H. Suh Contents 29.1 General Principles of Radiotherapy Planning and Target Volume Delineation 356 29.2 Patient Positioning, Immobilization, and Simulation 356 29.3 Normal Structures 357 29.3.1 Low-Grade Astrocytic and Oligodendroglial Tumors 362 29.3.2 Meningioma 364 29.3.3 Vestibular and Non-Vestibular Schwannoma 365 29.3.4 Pituitary Tumors 368 29.3.5 Glomus Tumors/Paraganglioma 372 R. Kotecha Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA e-mail: rupeshk@baptisthealth.net S. T. Chao · E. S. Murphy · J. H. Suh (*) Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland, OH, USA Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA e-mail: chaos@ccf.org; murphye3@ccf.org; suhj@ccf.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_29
- 353. 356 29.1 General Principles of Radiotherapy Planning and Target Volume Delineation • In the management of patients with benign primary brain tumors, a detailed his- tory, neurologic-focused physical examination, appropriate laboratory investiga- tions (including assessment of hormonal function), visual field and visual acuity testing, audiometric assessment, and baseline neurocognitive function are all key to determine the appropriate treatment modality. Maximal safe surgical resection, with an objective of a gross total resection, remains the standard-of-care for patients whoaremedicallyoperableandhavesurgicallyaccessibletumors.Multidisciplinary care is highly recommended for all patients with benign primary brain tumors. • Definitive radiation therapy is used for patients with a variety of primary brain tumors, including pituitary adenomas, meningiomas, and vestibular and non- vestibular schwannomas. The radiation therapy approach to more aggressive variants of these tumors or malignant tumors is discussed elsewhere in this textbook. • A variety of radiotherapy techniques are used in patients with benign primary brain tumors, including 3D-conformal radiotherapy (3D-CRT), fractionated ste- reotactic radiosurgery (FSRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), stereotactic radiosurgery (SRS), as well as proton beam radiotherapy (PBT). • Accurate delineation of the target volumes as well as the key organs-at-risk (OARs) is key to individualizing the best treatment option for each patient and creating an optimal radiotherapy treatment plan. Essential to this process is the ability to obtain treatment planning MR images close to the time of CT simula- tion with sequences that best allow for visualization of the tumor (i.e. T1-post contrast or FLAIR images) as well as normal anatomy (i.e. T1 images to delin- eate the hippocampus or 3D T2 or CISS sequences to delineate cranial nerves). 29.2 Patient Positioning, Immobilization, and Simulation • Patients with benign primary brain tumors are typically simulated in the supine position with arms extending parallel to the body and shoulders in a natural position. • For patients undergoing CT simulation and treatment, an indexed 3-point thermo- plastic mask is used for immobilization; however, a 5-point thermoplastic mask can be used for patients with base-of-skull tumors or with tumors close to the opticapparatusinwhichneckpositioningcanbereinforcedwiththeextendedmask. • For patients undergoing MRI simulation and treatment, a clam shell mask is used. • The head and chin are placed in a neutral position, unless specific instructions for base-of-skull positioning are required. • Axial CT simulation images are obtained at 1 mm slice thickness (SRS, FSRT, or PBT) or 2 mm slice thickness (3D-CRT, IMRT, or VMAT) through the entire head of the patient and down to the level of the shoulders. R. Kotecha et al.
- 354. 357 • Co-registration of diagnostic MR imaging is strongly recommended for target volume delineation for primary brain tumors, unless there is a clear medical or clinical contraindication. • IV contrast is used, unless medical or clinical contraindication, to delineate pri- mary tumors, resected tumor cavities, or to aid with fusion to pre-treatment MR imaging. 29.3 Normal Structures • OARs are delineated on the treatment planning CT scan with aid of pre-treat- ment MR imaging. • Planning risk volumes (PRVs) can be created for tumors abutting nearby critical organs for aid in dosimetric planning and dose assessment at the time of plan evaluation. • A list of normal contours delineated for most benign primary brain tumors is provided in Table 29.1. • Examples of contours of key OARs for primary intracranial cases are provided in Figs. 29.1, 29.2, 29.3 and 29.4. • Brain • Uninvolved brain (brain—GTV or CTV, depending on clinical scenario) • Brainstem (brainstem core, brainstem surface) • Spinal cord • Right cochlea • Left cochlea • Right globe • Left globe • Right lens • Left lens • Right optic nerve • Left optic nerve • Optic chiasm • Right retina • Left retina • Right lacrimal gland • Left lacrimal gland • Right temporal lobe • Left temporal lobe • Right hippocampus • Left hippocampus • Hypothalamus • Pituitary Table 29.1 List of suggested organs-at-risk for primary brain tumors 29 Benign Tumors of the CNS
- 355. 358 Fig. 29.1 Representative slices of a CT simulation (brain window/level) for a patient demonstrat- ing key OARs to delineate for patients with primary brain tumors. Structures best delineated using this contrast setting include the brainstem, optic chiasm, and intracranial components of the optic nerves. Additionally, this helps to visualize the retinal component of the globe. The right hippo- campus is in yellow and the left hippocampus in brown; these are delineated using an axial T1 MRI but visualized on the CT scan (see corresponding Fig. 29.4). The brainstem is in pink and separated into a brainstem core and a brainstem surface (typically a 3 mm peripheral rind). The hypothala- mus (dark brown) is located in front of the brainstem and behind the optic chiasm (olive green). Each of the optic nerves (right magenta and left in purple) approximates the respective globe contours. The lacrimal glands (teal) are located on lateral aspect of each of the globes R. Kotecha et al.
- 356. 359 Fig. 29.2 Representative slices of the CT simulation for patient in Fig. 29.1 demonstrating key OARs to delineate for patients with primary brain tumors (soft tissue window/level). Structures best delineated using this contrast setting include the optic nerves as they traverse the optic canals as well as the orbital components of these nerves (right optic nerve in magenta and left optic nerve in purple), as well as the globes and lacrimal gland 29 Benign Tumors of the CNS
- 357. 360 Fig. 29.3 Representative slices of the CT simulation (bone window/level) demonstrating the right and left cochlea, which are best identified and delineated. Based on the patient’s head position, these structures may not be located on the same axial slices as shown in this example R. Kotecha et al.
- 358. 361 Fig. 29.4 Representative slices of the CT simulation (brain window/level setting) and treatment planning MRI (T1 post-contrast) used to delineate the right (yellow) and left (brown) hippocampus for treatment planning. It is important to note that these contours represent the subgranular zone of the hippocampus (not the entire structure) and can be visualized as hypointense gray matter. The superior-most slice begins where the hypointense gray matter borders the atrium of the lateral ventricle and approximates the splenium of the corpus callosum, while the inferior-most slice ends at the inferior extent of the temporal horn of the lateral ventricle 29 Benign Tumors of the CNS
- 359. 362 29.3.1 Low-Grade Astrocytic and Oligodendroglial Tumors Patients with low-grade diffuse astrocytomas (IDH-mutated) and oligodendroglio- mas should undergo maximal safe resection for diagnosis and molecular character- ization. Gross total resection should be attempted if this can be safely performed. • Patients are treated with conventionally fractionated radiation therapy to a dose of 54 Gy in 30 fractions (Table 29.2 and Fig. 29.5); chemotherapy is recom- mended for patients with grade 2 or higher tumors with certain high-risk features. • Multi-modality therapy is recommended for IDH-wild type tumors (akin to malignant gliomas given their natural history and prognosis). • Stereotactic radiosurgery is not recommended for these tumors in the upfront setting, except for select patients with pilocytic astrocytomas. Table 29.2 Recommended target volumes for astrocytic and oligodendroglial tumors Tumor type GTV definition Suggested CTV expansions PTV expansions Grade I pilocytic astrocytoma For unresected tumors, the GTV will be delineated by the post-contrast T1 MRI For resected tumors, the GTV will include the post-operative cavity 0–0.5 cm, reduced around natural anatomic barriers to tumor spread 0–0.3 cm, depending on the radiotherapy technique and daily patient positioning technology 0–1 mm: SRS or HSRT 1–3 mm: Conventionally fractionated radiotherapy Ganglioglioma For unresected tumors, the GTV will be delineated by the post-contrast T2 or FLAIR MRI For resected tumors, the GTV will include the post-operative cavity and residual tumor 1 cm, reduced around natural barriers to tumor spread 0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology Grade II low-grade diffuse glioma (DH-mutated) For unresected tumors, the GTV will be delineated by the post-contrast T2 or FLAIR MRI For resected tumors, the GTV will include the post-operative cavity and residual tumor 1 cm, reduced around natural barriers to tumor spread 0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology R. Kotecha et al.
- 360. 363 Fig. 29.5 Representative treatment planning CT images (brain window/ level) and corresponding MR images (post-contrast FLAIR) for a patient with an oligodendroglioma after a left frontotemporoparietal craniotomy with partial resection with involvement of the left insula and portions of the operculum as well as extending into the left centrum semiovale. The GTV (red) was outlined using the FLAIR residual disease and the post-operative cavity. A 1.0 cm expansion was used to generate the CTV (yellow), with anatomic restriction out of the posterior fossa, skull, and other midline structures, and a 0.3 cm expansion to generate the PTV (blue) 29 Benign Tumors of the CNS
- 361. 364 29.3.2 Meningioma • Meningiomas represent the most common primary intracranial tumors in adults and a majority (70%) are benign and can be treated definitively with radio- therapy (Table 29.3). • For patients with Grade 1 meningiomas who undergo subtotal resection in areas at high-risk for symptomatic progression, adjuvant therapy can be considered. For the remainder, repeat surgery and radiation therapy are considered in the set- ting of disease recurrence. • In addition to the use of a treatment planning MRI for target volume delinea- tion, CT evaluation is strongly recommended to decide whether to include any periosteal and bone changes within the GTV (Table 29.4 and Figs. 29.6, 29.7 and 29.8). Table 29.3 Recommended techniques and dose/fractionation schedules for Grade 1 meningiomas Radiation technique Suggested dose/fractionation SRS 14–16 Gy in 1 fraction FSRT 20–24 Gy in 4 fractions 25 Gy in 5 fractions Conventionally fractionated radiotherapy 52.2–54 Gy at 1.8–2 Gy/fraction 50.4 Gy at 1.8 Gy/fraction for optic nerve sheath meningiomas Table 29.4 Recommended target volumes for Grade 1 meningiomas Tumor type GTV definition Suggested CTV expansions PTV expansions Grade 1 meningioma (unresected) Tumor delineated on planning MRI and CT simulation 0–0.5 cm, reduced around natural anatomic barriers to tumor spread 0–0.3 cm, depending on the radiotherapy technique and daily patient positioning technology 0–1 mm: SRS or HSRT 1–3 mm: Conventionally fractionated radiotherapy Grade 1 meningioma (recurrent) Post-operative cavity, residual enhancing tumor including suspicious dural and/or bone involvement, and prior dural attachment Anatomically constrained 0–0.5 cm expansion 0–0.3 cm, depending on the radiotherapy technique and daily patient positioning technology 0–1 mm: SRS or HSRT 1–3 mm: Conventionally fractionated radiotherapy R. Kotecha et al.
- 362. 365 Fig. 29.6 Representative treatment planning MR images (axial, coronal, and sagittal T1 post- contrast) for a patient with a right frontal convexity extra-axial homogenously enhancing menin- gioma. The delineated tumor in red represents the GTV and no CTV or PTV expansions were added as this patient was treated with single fraction frame-based SRS. The bottom row of images displays the prescription isodose line (green) of 14 Gy as well as the 8 Gy (teal) and 4 Gy (blue) isodose lines 29.3.3 Vestibular and Non-Vestibular Schwannoma • Patients with vestibular or non-vestibular schwannomas can be treated with radi- ation therapy in the definitive setting, as adjuvant treatment for patients with partially resected tumors, or rare cases for those with recurrent disease (Table 29.5 and Figs. 29.9 and 29.10). 29 Benign Tumors of the CNS
- 363. 366 Fig. 29.7 Representative treatment planning CT images (brain window/level) for a patient with a right cavernous sinus meningioma treated to a dose of 52.2 Gy in 29 fractions. The GTV is outlined in red and was delineated using a treatment planning MRI; a 2 mm margin was added to create the PTV (yellow). Colorwash isodose lines are overlayed, including the prescription dose (52.2 Gy, dark red) and 45 Gy (orange), 30 Gy (green), and 15 Gy (blue). Key organs-at-risk are also delin- eated, including the brainstem (purple), chiasm (light blue), adjacent cranial nerves (blue), carotid artery (dark blue), and right cochlea (coral) Fig. 29.8 Representative treatment planning CT images (brain window/level) and corresponding MR images for a patient with a massive sellar and suprasellar Grade 1 meningioma, with signifi- cant residual disease after attempted debulking. The tumor is outlined in maroon and a 3 mm expansion was used to create the PTV. Organs-at-risk visualized in these slices include the brain- stem (purple) as well as both globes R. Kotecha et al.
- 364. 367 Table 29.5 Radiotherapy techniques and target volumes for vestibular and non-vestibular schwannomas Radiation technique Suggested dose/ fractionation Relevant target volumes SRS 12–13 Gy in 1 fraction GTV: Tumor as delineated on planning MRI and CT simulation CTV: None PTV: Technique dependent, typically 0–1 mm FSRT 20 Gy in 4 fractions 25 Gy in 5 fractions GTV: Tumor as delineated on planning MRI and CT simulation CTV: None PTV: Technique dependent, typically 0–1 mm Conventionally fractionated radiotherapy 46.8–54 Gy at 1.8–2 Gy/fraction GTV: Tumor as delineated on planning MRI and CT simulation CTV: None PTV: Technique dependent, typically 0–3 mm Fig. 29.9 Representative treatment planning MR images (axial T1 post-contrast) for a patient with a right cerebellopontine angle vestibular schwannoma (brown). The tumor compresses the right middle cerebellar peduncle and right side of the pons as well extends into the fundus of the internal auditory canal (orange star). Of note, there is compression of the brainstem (blue) and also compression of the right cisternal trigeminal nerve (red) as well as moderate partial effacement of the fourth ventricle. In this case, GTV is brown and no CTV or PTV expansions were used 29 Benign Tumors of the CNS
- 365. 368 Fig. 29.10 Representative axial and coronal treatment planning MR images (T1 post-contrast) for a patient with a left cerebellopontine schwannoma. Note that the tumor extends into the internal auditory canal. Key organs-at-risk are delineated including the brainstem (blue) and cochlea (teal). The tumor is covered by the prescription isodose line (12.5 Gy, dark red) as well as a higher iso- dose line (20 Gy, orange) in the center of the tumor and the lower isodose line (5 Gy, green) Table 29.6 Recommend techniques and dose/fractionation schedules for pituitary adenomas Radiation technique Suggested dose/fractionation SRS Non-functional: 15–16 Gy in 1 fraction Functional/secretory: 18–25 Gy in 1 fraction (preferred 20 Gy) based on optic nerve/chiasm tolerance Conventionally fractionated radiotherapy Non-functional: 45–50.4 Gy at 1.8–2 Gy/fraction Functional/secretory: 54–55.8 Gy at 1.8–2 Gy/fraction 29.3.4 Pituitary Tumors • Non-functional pituitary adenomas are typically treated with SRS, HSRT, or conventionally fractionated radiation therapy in the adjuvant or salvage setting, after resection (Table 29.6). • Functional pituitary adenomas may be treated with hormonal therapy, or resec- tion, depending on the tumor subtype, prior to consideration of radiation therapy. • High-resolution, thin-slice MR images of the pituitary gland in the coronal and sagittal planes are useful when delineating the target volumes (Table 29.7 and Figs. 29.11, 29.12 and 29.13). Due to the differential enhancement patterns of adenomas and the normal pituitary gland, tumors are best seen in the early phase of the gadolinium-enhanced dynamic imaging and appear as a hypointense lesion against the hyperintense background of the normally enhancing pituitary gland. R. Kotecha et al.
- 366. 369 Table 29.7 Recommended target volumes for pituitary adenomas Tumor type GTV definition Suggested CTV expansions PTV expansions Unresected Focal residual Focal recurrent disease Tumor delineated on planning MRI and CT simulation 0–0.5 cm, reduced around natural anatomic barriers to tumor spread 0–0.3 cm, depending on the radiotherapy technique and daily patient positioning technology 0–1 mm: SRS or HSRT 1–3 mm: Conventionally fractionated radiotherapy Resected with residual or recurrent disease Tumor delineated on planning MRI and CT simulation 0–0.5 cm, reduced around natural anatomic barriers to tumor spread and to pre-operative disease extension 0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology Fig. 29.11 Representative axial, coronal, and sagittal treatment planning MR images (T1 post- contrast) for a patient with a growth-hormone secreting pituitary adenoma (top row). The tumor is outlined in green (GTV, no PTV expansion) abuts the medial margin of the right cavernous carotid and extends between the loops of the cavernous carotid laterally with cavernous sinus involvement superiorly. The optic chiasm is delineated in blue. This patient was treated with SRS to a dose of 24 Gy in 1 fraction with corresponding isodose lines for the prescription dose (24 Gy, green), 30 Gy (orange), 10 Gy (teal), and 8 Gy (blue). The dose to the chiasm, optic nerves, and brainstem was less than 8 Gy, each 29 Benign Tumors of the CNS
- 367. 370 Fig. 29.12 Pre-operative axial and coronal MR images (T1 post-contrast) for a patient with a non-secretory pituitary adenoma (top row) centered in the sella and extending into the suprasellar cistern displacing the optic chiasm and invading into the right cavernous sinus. Post-operative axial and coronal MR images (T1 post-contrast) after resection demonstrate residual tumor in the sella and right cavernous sinus R. Kotecha et al.
- 368. 371 Fig. 29.13 Representative treatment planning CT images (brain window/level) for a patient with a non- secretory pituitary adenoma after resection (see Fig. 29.12 for pre- and post-operative MR images). The GTV is outlined in coral with a 0.5 cm, anatomically restrained margin in teal, expansion for the CTV, and a 0.3 cm margin expansion for the PTV. Key organs-at-risk are delineated on the slices, including the brainstem (light blue), optic chiasm (red), and right and left optic nerves (light and dark orange) 29 Benign Tumors of the CNS
- 369. 372 Knowledge of the type of implanted material (muscle vs. fat vs. rotational nasal septal flap) is useful to differentiate tumor from implanted material. • For patients with macroadenomas, it is important to assess the extent of invasion into the cavernous sinus, and when this is difficult to visualize, it is recommended to include the entire cavernous sinus in the GTV. 29.3.5 Glomus Tumors/Paraganglioma • Glomus tumors represent rare neuroendocrine tumors that can occur at the skull base, head and neck, thorax, and abdomen and are typically named based on their origin site. • Treatment options include embolization, resection, and radiation therapy with high local control rates (Table 29.8). • Depending on the site of origin, careful assessment of the patient’s diagnostic MR and CT imaging is needed when delineating the target volume to detect potential invasion into the tympanic cavity, jugular foramen, petroclival region, cavernous sinus, or hypoglossal canal. • In addition to the use of a treatment planning MRI for target volume delineation, CT evaluation is strongly recommended to assess for potential bony erosion (Table 29.9 and Figs. 29.14 and 29.15). Table 29.8 Recommended techniques and dose/fractionation schedules for glomus tumors/ paragangliomas Radiation technique Suggested dose/fractionation SRS 14–16 Gy in 1 fraction FSRT 25 Gy in 5 fractions Conventionally fractionated radiotherapy 50.4–54 Gy at 1.8–2 Gy/fraction Table 29.9 Recommended target volumes for glomus tumors/paragangliomas GTV definition Suggested CTV expansions PTV expansions Tumor delineated on planning MRI and CT simulation 0–0.5 cm, reduced around natural anatomic barriers to tumor spread 0–0.3 cm, depending on the radiotherapy technique and daily patient positioning technology 0–1 mm: SRS or HSRT 1–3 mm: Conventionally fractionated radiotherapy R. Kotecha et al.
- 370. 373 Fig. 29.14 Representative treatment planning MR images (first column, T2-weighted SPACE sequence), treatment planning CT images (second column, soft tissue window/level), and dosimet- ric treatment plan for a patient with a right-sided glomus tumor centered at the carotid bifurcation with splaying of the internal and external carotid arteries. The GTV (red) was delineated using the treatment planning MRI co-registered to the treatment planning CT scan with a 3 mm expansion used to create the PTV (turquoise). This elderly patient was treated to a dose of 25 Gy in 5 fractions and colorwash isodose lines are overlayed (third column), including the prescription dose (25 Gy, red), 110% isodose volume (27.5 Gy dark green), 80% isodose volume (20 Gy, light green), and 50% isodose volume (12.5 Gy, purple). Key nearby organs-at-risk, including the parotids, subman- dibular glands, oral cavity, and oropharyngeal wall are visualized on selected slices 29 Benign Tumors of the CNS
- 371. 374 Fig. 29.15 Representative treatment planning CT images (bone window/level) for a patient with a recurrent left-sided glomus tumor after embolization and resection, with recurrent disease centered in the left jugular bulb, treated to a dose of 54 Gy in 30 fractions. Co-registration of the patient’s MR images at initial diagnosis and at the time of recurrence was used to generate the GTV (red) which consisted of the initial extent of disease at first diagnosis, post-operative changes and tumor bed, and recurrent disease, with coverage to the skull base. A 0.3 cm margin expansion was used to create the PTV (blue). Key organs-at-risk are delineated on the slices, including the brainstem (orange), man- dible (green), left parotid (pink), right parotid (light orange), spinal cord with PRV (green and violet, respective), oropharyngeal wall (brown), oral cavity (yellow), and lips (pink) R. Kotecha et al.
- 372. 375 30 Malignant Tumors of the CNS Rupesh Kotecha, Samuel T. Chao, Erin S. Murphy, and John H. Suh Contents 30.1 General Principles of Radiotherapy Planning and Target Volume Delineation 375 30.2 Patient Positioning, Immobilization, and Simulation 376 30.3 Normal Structures 377 30.4 High-Grade Glioma 382 30.4.1 Meningioma and Hemangiopericytoma 383 30.1 General Principles of Radiotherapy Planning and Target Volume Delineation • In the management of patients with malignant primary brain tumors, a detailed history, neurologic-focused physical examination, appropriate laboratory inves- tigations (including assessment of hormonal function as well as baseline blood R. Kotecha Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA e-mail: rupeshk@baptisthealth.net S. T. Chao · E. S. Murphy · J. H. Suh (*) Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland, OH, USA Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA e-mail: chaos@ccf.org; murphye3@ccf.org; suhj@ccf.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_30
- 373. 376 counts for patients undergoing chemotherapy), visual field and visual acuity testing, audiometric assessment, and baseline neurocognitive function are all important. Maximal safe surgical resection, with an objective of a gross-total resection, remains the standard-of-care for patients who are medically inopera- ble and have surgically accessible tumors. • Definitive radiation therapy is used for patients who undergo a biopsy alone and adjuvant radiotherapy for the majority of patients after resection. The radiation therapy approach to benign variants of these tumors is discussed elsewhere in this textbook. • A variety of radiotherapy techniques are used in patients with malignant primary brain tumors, including 3D-conformal radiotherapy (3D-CRT), fractionated ste- reotactic radiosurgery (FSRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), stereotactic radiosurgery (SRS), as well as proton beam radiotherapy (PBT). • Accurate delineation of the target volumes as well as the organs-at-risk is key to determining the best treatment option for each patient and creating an optimal radiotherapy treatment plan. Essential to this process is the ability to obtain treat- ment planning MR images close to the time of CT simulation with sequences that best allow for visualization of the tumor (i.e. T1-post contrast or FLAIR images) as well as normal anatomy (i.e. T1 images to delineate the hippocampus or 3D T2 or CISS sequences to delineate cranial nerves). 30.2 Patient Positioning, Immobilization, and Simulation • Patients with malignant primary brain tumors are typically simulated in the supine position with arms extending parallel to the body and shoulders in a natu- ral position. • For patients undergoing CT simulation and treatment, an indexed 3-point ther- moplastic mask is used for immobilization; however, a 5-point thermoplastic mask can be used for patients with base-of-skull tumors or with tumors close to the optic apparatus in which neck positioning can be reinforced with the extended mask. • For patients undergoing MRI simulation and treatment, a clam shell mask is used. • The head and chin are placed in a neutral position, unless specific instructions for base-of-skull positioning are required. • Axial CT simulation images are obtained at 1 mm slice thickness (SRS, FSRT, or PBT) or 2 mm slice thickness (3D-CRT, IMRT, or VMAT) through the entire head of the patient and down to the level of the shoulders. R. Kotecha et al.
- 374. 377 • Co-registration of diagnostic MR imaging is strongly recommended for target volume delineation for primary brain tumors, unless there is a clear medical or clinical contraindication. • IV contrast can be used to delineate primary tumors, resected tumor cavities, or to aid with fusion to pre-treatment MR imaging. 30.3 Normal Structures • Organs-at-risk are delineated on the treatment planning CT scan with aid of pre- treatment MR imaging. • Planning risk volumes (PRVs) can be created for tumors abutting nearby critical organs for aid in dosimetric planning and dose assessment at the time of plan evaluation. • A list of normal contours delineated for most primary brain tumors is provided in Table 30.1. • Examples of contours of key organs-at-risk for primary intracranial cases are provided in the “Benign Tumors of the CNS chapter” Figs. 30.1, 30.2, 30.3 and 30.4. • Brain • Uninvolved brain (brain—GTV or CTV, depending on clinical scenario) • Brainstem (brainstem core, brainstem surface) • Spinal cord • Right cochlea • Left cochlea • Right globe • Left globe • Right lens • Left lens • Right optic nerve • Left optic nerve • Optic chiasm • Right retina • Left retina • Right lacrimal gland • Left lacrimal gland • Right temporal lobe • Left temporal lobe • Right hippocampus • Left hippocampus • Hypothalamus • Pituitary Table 30.1 List of suggested organs-at-risk for primary brain tumors 30 Malignant Tumors of the CNS
- 375. 378 Fig. 30.1 Representative slices of a contrast- enhanced treatment planning CT for a patient with a right temporal anaplastic astrocytoma, with a satellite right parietal lesion. Treatment planning MRIs (not shown) were co-registered to the planning CT to generate the target volumes. Two sequential radiotherapy volumes were used in this patient, the first (PTV1, orange) to 50.4 Gy and the final volume (PTV2, yellow) to 59.4 Gy. The GTV1 (red) was delineated using the post-contrast FLAIR image, with a 1.5 cm anatomically constrained expansion used to create the CTV1 (green) and 0.3 cm expansion created for the PTV1 (orange). The GTV2 (brown) was delineated using the post-contrast T1 image and included the resection cavity, with a 1 cm anatomically constrained expansion used to create the CTV2 (pink) and 0.3 cm expansion created for the PTV2 (yellow). Note that the anatomically constrained expansions do not cross midline, extend into the pre-pontine cistern, skull, or extend past the tentorium into the posterior fossa R. Kotecha et al.
- 376. 379 Fig. 30.2 Representative slices of the treatment planning MRI (post-contrast FLAIR) for a patient with a left frontal non-enhancing anaplastic astrocytoma after gross-total resection. This patient was treated to a dose of 59.4 Gy in 33 fractions. The GTV (red) was delineated using the post- contrast FLAIR image and included the resection cavity. A 1.5 cm anatomically constrained expansion used to create the CTV (pink) and 0.3 cm expansion created for the PTV (blue). Of note, the left (brown) and right (hippocampal) contours are seen on the inferior most treatment planning image presented (although these were delineated on a co-registered T1 post-contrast MRI) 30 Malignant Tumors of the CNS
- 377. 380 Fig. 30.3 Representative slices of the treatment planning MRI (post- contrast FLAIR and post-contrast T1) for a patient with a right parietal glioblastoma after a subtotal resection. Two sequential radiotherapy volumes were used in this patient, the first (PTV1, orange) to 46 Gy and the final volume (PTV2, yellow) to 60 Gy. The GTV1 (red) was delineated using the post-contrast FLAIR image, with a 2 cm anatomically constrained expansion used to create the CTV1 (pink) and 0.3 cm expansion created for the PTV1 (orange). The GTV2 (brown) was delineated using the post-contrast T1 image, with a 2 cm anatomically constrained expansion used to create the CTV2 (orange) and 0.3 cm expansion used to create the PTV2 (yellow) R. Kotecha et al.
- 378. 381 Fig. 30.4 Representative slices of a contrast-enhanced treatment planning CT for an elderly, poor-risk patient with a large glioblastoma centered in the right frontal region treated with a hypo- fractionated course of radiotherapy alone. The GTV (red) was delineated using the post-contrast T1 MRI co-registered to the planning CT scan. A 0.5 cm margin was used to create the CTV (pink), and although anatomically constrained, importantly, it includes tracks at risk for potential contralateral tumor spread such as the genu of the corpus callosum (green star). A 0.3 cm expan- sion was used to create the PTV (light orange). Representative organs-at-risk including the bilat- eral globes, retina, optic nerves, chiasm, and brainstem are also visualized on certain slices 30 Malignant Tumors of the CNS
- 379. 382 30.4 High-Grade Glioma • Patients with high-grade astrocytoma and oligodendroglioma undergo maximal safe resection for diagnosis and molecular characterization as well as to safely remove as much gross disease as feasible. • Patients are treated with conventionally fractionated radiation therapy to a dose of 59.4–60 Gy along with chemotherapy, either in the concurrent or adjuvant setting (Table 30.2 and Figs. 30.1, 30.2 and 30.3). • Poor-risk, elderly, or frail patients with high-grade gliomas can be treated with hypofractionated radiotherapy schedules, including 40.05 Gy in 15 fractions or Table 30.2 Recommended target volumes for high-grade glioma Tumor type Recommended dose/ fractionation GTV definition Suggested CTV expansions PTV expansions Anaplastic glioma (enhancing tumor) Sequential Cone Down: PTV1: 50.4 Gy at 1.8 Gy/fraction PTV2 59.4 Gy at 1.8 Gy/fraction Simultaneous Integrated Boost: PTV1: 54.45 Gy at 1.65 Gy/fraction PTV2: 59.4 Gy at 1.8 Gy/fraction GTV1 is defined by the T2 or FLAIR volume GTV2 is defined by the post-operative cavity and residual tumor by the post-contrast T1 MRI CTV1 is defined by a 1.5 cm expansion, reduced around natural barriers to tumor spread CTV2 is defined by a 1.0 cm expansion, reduced around natural barriers to tumor spread 0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology Anaplastic glioma (non- enhancing tumor) IDH-wild type diffuse astrocytoma PTV1: 59.4 Gy at 1.8 Gy/fraction GTV is defined by the post-operative cavity volume and residual tumor by T2 or FLAIR CTV is defined by a 1.5 cm expansion, reduced around natural barriers to tumor spread 0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology Glioblastoma PTV1: 46 Gy at 2 Gy/ fraction PTV2: 60 Gy at 2 Gy/ fraction (sequential cone down) PTV1: 50–51 Gy at 1.67–1.7 Gy/fraction PTV2: 60 Gy at 2 Gy/ fraction (simultaneous integrated boost) GTV1 is defined by the T2 or FLAIR volume GTV2 is defined by the post-operative cavity and residual tumor by the post-contrast T1 MRI CTV1 is defined by a 2 cm expansion, reduced around natural barriers to tumor spread CTV2 is defined by a 2 cm expansion, reduced around natural barriers to tumor spread 0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology R. Kotecha et al.
- 380. 383 Tumor type Recommended dose/ fractionation GTV definition Suggested CTV expansions PTV expansions Gliosarcoma PTV1: 46 Gy at 2 Gy/ fraction PTV2: 60 Gy at 2 Gy/ fraction (sequential cone down) PTV1: 50–51 Gy at 1.67–1.7 Gy/fraction PTV2: 60 Gy at 2 Gy/ fraction (simultaneous integrated boost) GTV1 is defined by the T2 or FLAIR volume GTV2 is defined by the post-operative cavity and residual tumor by the post-contrast T1 MRI CTV1 is defined by a 1.5–2 cm expansion, reduced around natural barriers to tumor spread CTV2 is defined by a 1.5–2 cm expansion, reduced around natural barriers to tumor spread 0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology Table 30.2 (continued) 25 Gy in 5 fractions, with reduced margins (0.5–1 cm), with or without chemo- therapy (Table 30.2 and Figs. 30.4, 30.5, 30.6). • Treatment paradigms for patients with gliosarcoma mirror those for those with glioblastoma (Fig. 30.7). 30.4.1 Meningioma and Hemangiopericytoma • Meningiomas represent the most common primary intracranial tumors in adults with fewer than 30% of tumors classified as atypical (WHO grade II) or malig- nant (WHO grade III). • Adjuvant radiation therapy can be considered for patients who undergo a gross- total resection of WHO grade II meningioma and is recommended for patients who undergo a subtotal resection (Table 30.3 and Fig. 30.8). • For patients with a WHO III meningioma, adjuvant radiation therapy is recom- mended for all patients regardless of the extent of resection (Table 30.3 and Fig. 30.9). • Given that grade II and III meningiomas can involve bone and brain, it is impor- tant to note on image review and target volume delineation that skull and normal brain are not necessarily a natural barrier to tumor spread. For example, margins should include normal brain if there is brain invasion noted as part of operative or pathology findings. • Adjuvant radiation therapy is recommended for patients who undergo resection of a hemangiopericytoma. 30 Malignant Tumors of the CNS
- 381. 384 Fig. 30.5 Representative slices of the treatment planning MRI (post-contrast T1) for an elderly, poor-risk patient with a left posterior temporal glioblastoma. This patient did not any significant FLAIR volume extending outside of the contrast-enhanced tumor. Therefore, the patient was treated to a dose of 40 Gy in 15 fractions to a single volume. The GTV (brown) was delineated using the post-contrast T1 and included the resection cavity, residual tumor, and nearby satellite nodule. A 1.0 cm anatomically constrained expansion was used to create the CTV (green) and 0.3 cm expansion used to create the PTV (yellow). Note that the CTV is anatomically restricted from crossing the tentorium (red star) R. Kotecha et al.
- 382. 385 Fig. 30.6 Representative slices of the treatment planning MRI (post-contrast T1) for an elderly, poor-risk patient with a right cerebellar glioblastoma. This patient was treated to a dose of 30 Gy in 5 fractions. The GTV (red) was delineated using the post-contrast T1 and included the resection cavity following gross-total resection of the tumor. A 0.5 cm anatomically constrained expansion was used to create the CTV (pink), and 0.3 cm expansion was used to create the PTV (light orange). Of note, the cochlea and brainstem are visible on the axial MRI Fig. 30.7 Representative slices of the treatment planning MRI (post-contrast FLAIR and post- contrast T1) for a patient with a left temporal occipital gliosarcoma after gross-total resection. Two radiotherapy volumes were used in this patient, the first (PTV1, orange) to 46 Gy and the final volume (PTV2, purple) to 60 Gy. The GTV1 (green) was delineated using the post-contrast FLAIR image, with a 1.5 cm anatomically constrained expansion used to create the CTV1 (turquoise) and 0.3 cm expansion used to create the PTV1 (orange). The GTV2 (red) was delineated using the post-contrast T1 image, with a 1.5 cm anatomically constrained expansion used to create the CTV2 (pink) and 0.3 cm expansion used to create the PTV2 (purple). The brainstem is contoured in blue 30 Malignant Tumors of the CNS
- 383. 386 Fig. 30.7 (continued) R. Kotecha et al.
- 384. 387 Table 30.3 Recommended target volumes for grade II/III meningioma and hemangiopericytoma Tumor type Recommended dose/ fractionation GTV definition Suggested CTV expansions PTV expansions Grade II meningioma (upfront) PTV: 54–59.4 Gy at 1.8 Gy/fraction GTV is defined by The post-operative cavity, residual tumor including suspicious dural and/or bone involvement by the post-contrast T1 MRI CTV is defined by a 0.5 cm expansion, reduced around natural barriers to tumor spread 0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology Grade II meningioma (recurrent) PTV: 54–59.4 Gy at 1.8 Gy/fraction GTV is defined by The post-operative cavity, residual tumor including suspicious dural and/or bone involvement by the post-contrast T1 MRI. Evaluation of prior dural attachment at initial diagnosis is also recommended CTV is defined by a 0.5–1.0 cm expansion, reduced around natural barriers to tumor spread 0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology Grade III meningioma (upfront or recurrent) PTV: 59.4–60 Gy at 1.8–2 Gy/ fraction GTV is defined by The post-operative cavity, residual tumor including suspicious dural and/or bone involvement by the post-contrast T1 MRI. Evaluation of prior dural attachment at initial diagnosis is also recommended CTV is defined by a 1–1.5 cm expansion, reduced around natural barriers to tumor spread 0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology Hemangiopericytoma PTV: 59.4–60 Gy at 1.8–2 Gy/ fraction GTV is defined by The post-operative cavity, residual tumor including suspicious dural and/or bone involvement by the post-contrast T1 MRI CTV is defined by a 1.5 cm expansion, reduced around natural barriers to tumor spread, but include entirety of involved bone 0.3–0.5 cm, depending on frequency of IGRT, radiotherapy technique, and daily patient positioning technology 30 Malignant Tumors of the CNS
- 385. 388 Fig. 30.8 Representative slices of the treatment planning MRI (post-contrast T1) for a patient with an atypical (WHO grade II) parafalcine meningioma. Outlining the pre-operative extent of disease, including dural attachments is critical to delineating the post-operative target volumes for radiotherapy treatment planning. The post-surgical bed, original dural attachments, and residual nodularity at the medial margin of the surgical cavity involving the falx were included in the GTV (red). A 0.5 cm anatomically constrained margin was used to generate the CTV (pink) and a 0.3 cm expansion used to create the PTV (turquoise) R. Kotecha et al.
- 386. 389 Fig. 30.9 Axial, coronal, and sagittal T1 post-contrast MRI for a patient with a large left fronto- parietal parasagittal convexity malignant meningioma (WHO III) (top row). Outlining the pre- operative extent of disease, including dural attachments (brown) is critical to delineating the post-operative target volumes for radiotherapy treatment planning. Representative slices of the post-operative treatment planning T1 post-contrast T1 MRI (below) show the post-surgical bed and original dural attachments included in the GTV (red). A 1.0 cm anatomically constrained margin was used to create the CTV (green) and a 0.3 cm expansion used to create the PTV (blue) 30 Malignant Tumors of the CNS
- 387. 391 31 Hodgkin and Non-Hodgkin Lymphoma Avani D. Rao, Harold C. Agbahiwe, and Stephanie A. Terezakis Contents 31.1 General Principles of Tumor Volume Delineation and Field Setup 392 31.2 Principles of Involved-Site and Involved-Node Radiation Therapy 392 31.3 Case-Based Examples for Target Delineation 394 31.4 Contouring for Select Sites Including Extranodal Sites 400 31.4.1 General Principles of Patient Setup and TV Delineation for Inguinal/ Pelvic Region Lymphoma 400 31.4.2 General Principles of Patient Setup and TV Delineation for Gastric Lymphoma 400 31.4.3 General Principles of Patient Setup and TV Delineation for Orbital and Sinonasal Lymphoma 401 References 403 A. D. Rao Department of Advanced Radiation and Proton Therapy, Inova Schar Cancer Institute, Fairfax, VA, USA e-mail: Avani.Rao@umm.edu H. C. Agbahiwe Department of Radiation Oncology, Virginia Cancer Specialists, Fairfax, VA, USA e-mail: Harold.Agbahiwe@usoncology.com S. A. Terezakis (*) Department of Radiation Oncology, University of Minnesota, Minneapolis, MN, USA e-mail: sterezak@umn.edu © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_31
- 388. 392 31.1 General Principles of Tumor Volume Delineation and Field Setup • Delineation and field setup for radiation therapy (RT) for both Hodgkin (HL) and non-Hodgkin lymphoma (NHL) depend on the origin of the disease, the quality and patient positioning of pre-chemotherapy imaging, the use and response to systemic chemotherapy, as well as the extent of disease. • Extended-field radiation therapy (EFRT) was historically used as definitive man- agement without chemotherapy. With combined modality therapy allowing for reduction of treatment field size, involved-field radiation therapy (IFRT) then became standard therapy to treat smaller fields resulting in lower doses delivered to normal tissues compared to EFRT. • With the most recent effective curative regimens despite shrinking radiation fields, involved-site radiation therapy (ISRT) which further reduced volumes based on 3-dimensional (3D) anatomy, focusing on the original extent of disease with a margin to account for imaging limitations, has become the recommended standard [1–3]. • ISRT has emerged over the past decade due to ongoing efforts to minimize late effects of treatment and improve the quality of life of survivors [4]. • In practices where patients are seen by the radiation oncologist prior to diagnos- tic imaging, involved-node radiation therapy (INRT) technique may be employed. The principles of target volume delineation for INRT and ISRT are similar, with differences in the quality and accuracy of pre-chemotherapy imaging suggesting that the margins for ISRT should be larger to allow for uncertainties in contour- ing the clinical target volume (CTV). INRT is the common approach in Europe where optimal imaging is available, including a pre-chemotherapy PET-CT scan acquired in the same position as the radiotherapy treatment positioning [5–8]. As it is not yet a routine practice that optimal pre-treatment imaging is available, ISRT is the standard practice in most healthcare systems in North America. • Treatment doses to various subtypes of Hodgkin and non-Hodgkin lymphoma differ based on their histology, stage, and response to chemotherapy and are therefore out of the scope of this chapter on target volume selection/delineation and field setup. 31.2 Principles of Involved-Site and Involved-Node Radiation Therapy • Below is a summary of published guidelines for defining INRT and ISRT treat- ment volumes [1–3, 5]. A. D. Rao et al.
- 389. 393 • ISRT simulation must be based on a 3-dimensional simulation (CT simulator, PET/CT simulator, or a magnetic resonance imaging simulator). If the patient’s medical conditions permit, IV contrast should be used for accurate identification of the vessels. • When radiation therapy is performed as consolidation after chemotherapy, the pre- and post-chemotherapy FDG-PET and CT should be ideally fused with the simulation CT in the RT planning system. • ISRT planning incorporates the standard definitions and nomenclature as out- lined in the International Commission on Radiation Units and Measurements (ICRU) Report 83, with consideration of whether radiation therapy is used as a primary modality or as consolidation therapy [9]. • The gross tumor volume (GTV), CTV, internal target volume (ITV) when rele- vant, and planning target volume (PTV) should be delineated as follows using all the available imaging information including pre-chemotherapy imaging (contrast- enhanced CT and PET-CT as shown in the clinical examples discussed throughout this chapter). • Pre-chemotherapy GTV. • Post-chemotherapy GTV. • CTV: A volume encompassing the superior and inferior extent of the pre- chemotherapy GTV with the radial extent respecting and avoiding overtly unin- volved, normal structures (i.e. lungs, kidneys, muscles) based on clinical judgment. The CTV should also take into account the differences in pre- chemotherapy and post-chemotherapy imaging positioning and fusion accuracy, pattern of spread of disease, changes in the volume of disease since imaging, risk of subclinical involvement, and nearby structures. Typically, the superior and inferior extent of the CTV often extends 1–2 cm beyond the pre-chemotherapy GTV extent to account for these uncertainties. Nodal volumes that are more than 5 cm apart can be treated as separate fields. • ITV: Target motion should be accounted for using an ITV as defined in the ICRU Report 83 as the CTV with a margin to consider organ motion for an individual patient [9]. A 4D CT simulation can be useful to obtain the ITV margins. If unavailable, 1.5 to 2 cm margins may be necessary in the chest or upper abdomen where respiratory movement can be significant. • PTV: This margin should account for uncertainty in setup based on patient fac- tors or immobilization that varies across institutions. • The CTV for ISRT will generally be larger than that for INRT due to the lack of optimal imaging information. 31 Hodgkin and Non-Hodgkin Lymphoma
- 390. 394 • Radiotherapy may be used as a single modality for definitive treatment of certain indolent, early-stage NHLs, and early-stage nodular lymphocyte-predominant HL. In these scenarios, the CTV should be more generous given the concern of a larger extent of subclinical disease without pre-treatment with chemother- apy [1–3]. • For a reference of historical IFRT field borders, please refer to the chapter on HL and NHL in the previous edition of this handbook [10]. 31.3 Case-Based Examples for Target Delineation • Early-stage Hodgkin lymphoma (Fig. 31.1). • Advanced-stage Hodgkin lymphoma (Fig. 31.2). • Nodular lymphocyte-predominant Hodgkin lymphoma (Fig. 31.3). • Early-stage Diffuse Large B-cell Lymphoma of the Head and Neck (Fig. 31.4). • Follicular lymphoma of the groin (Fig. 31.5). Fig. 31.1 A 27-year-old male with Stage IIA, non-bulky, favorable-risk, nodular sclerosing Hodgkin lymphoma involving the left supraclavicular and mediastinal lymph node regions was treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A post- chemotherapy PET demonstrated a complete metabolic response (Deauville 2). Since he met cri- teria for the German Hodgkin Study Group H10, he was treated with 20 Gy of radiation therapy following completion of 2 cycles of ABVD. For target delineation, the pre-chemotherapy PET/CT was registered to the simulation CT. For target delineation, the pre-chemotherapy PET/CT was registered to the simulation CT. (a) Axial slices from cranial to caudal extent of his disease on pre- chemotherapy PET/CT with gross disease (pre-chemo GTV) contoured in red. (b) Corresponding axial slices in his post-chemotherapy simulation CT demonstrate the slight change in anatomy between scans due to the different arm positioning, hyperextended neck, and five-point mask retracting his shoulders at the time of simulation, differences that are accounted for by an ISRT contouring approach. The small volume post- chemotherapy residual disease (post-chemo GTV) is shown in pink and the ISRT CTV in green. This patient was treated with a breath-hold technique, so there is no expansion on the CTV to account for respiratory motion. Radiation ther- apy was prescribed to the CTV plus an institutionally specified PTV margin A. D. Rao et al.
- 391. 395 a b 31 Hodgkin and Non-Hodgkin Lymphoma
- 392. 396 c a b Fig. 31.2 A 31-year-old woman with Stage IIB with bulk nodular sclerosing Hodgkin lymphoma involving the cervical, supraclavicular, mediastinal, and bilateral hilar nodal regions received 2 cycles of ABVD and interim PET/CT demonstrated a complete metabolic response (Deauville 2). She received an additional 4 cycles AVD (Bleomycin dropped due to pulmonary toxicity) and subsequently was treated with consolidation radiation therapy due to initial bulky disease at presentation. For target delineation, the pre-chemotherapy PET/CT was registered to the simulation CT. (a) Axial slices from cranial to caudal extent of her disease on pre-chemotherapy PET/CT with gross disease (pre-chemo GTV) contoured in red. (b) On post-chemotherapy simulation CT, note the slight change in anatomy between scans due to the hyperextended neck and five-point mask retracting her shoulders at time of simulation, differences that are accounted for by an ISRT contouring approach. The small volume post-chemotherapy residual disease (post-chemo GTV) is shown in pink and the ISRT CTV in green. (c) The final ITV in red is shown overlaying the CTV in green and post-chemo GTV in pink, accounting for changes in anatomy due to respiration captured using 4-D CT at time of simulation. Radiation therapy was prescribed to the ITV plus an institutionally specified PTV margin A. D. Rao et al.
- 393. 397 a a b b Fig. 31.3 A 61-year-old man with Stage IIA nodular lymphocyte-predominant Hodgkin lym- phoma involving the right supraclavicular, subpectoral, and axillary lymph node regions treated with definitive radiation therapy alone. Patient was simulated with arms up, utilizing a wingboard. (a) The diagnostic PET/CT was registered to the simulation CT. (b) Corresponding axial slices of his simulation CT are shown with respect to the diagnostic PET/CT. Gross disease is contoured in red and the ISRT CTV in light green. Radiation therapy was prescribed to the institutionally pre- scribed PTV margin (blue) 31 Hodgkin and Non-Hodgkin Lymphoma
- 394. 398 a b Fig. 31.4 A 47-year-old woman with Stage IIA non-bulky, favorable diffuse large B-cell lymphoma of the left tonsil and left neck (level 2, 5.6 cm) received 3 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and subsequently presented for consolidation radiotherapy. She was simulated with her neck in extension and immobilized using a 5 point aquaplast mask. For target delineation, the pre- chemotherapy PET/CT was registered to the simulation CT. (a) Axial slices from cranial to caudal extent of her disease on pre-chemotherapy PET/CT demonstrate the gross disease (pre-chemo GTV) contoured in red. (b) Corresponding axial slices in her post-chemotherapy simulation CT demonstrate small volume post- chemotherapy residual disease (post- chemo GTV) contoured in red and the ISRT CTV contoured in green, covering the entire left tonsil and left neck nodal level of the involved lymph node, including 1–2 cm superior and inferior to the pre- chemotherapy extent of disease A. D. Rao et al.
- 395. 399 a a b b Fig. 31.5 A 70-year-old man with Stage IA non-bulky, grade I/II follicular lymphoma of the left inguinal/femoral region treated with definitive radiation therapy alone. For target delineation, the diagnostic PET/CT was registered to the simulation CT. (a) Axial slices from cranial to caudal extent of his disease on PET/CT (fused to the CT simulation) are shown (b) corresponding axial slices of his simulation CT alone. Gross disease is contoured in red and the ISRT CTV in light green. Radiation therapy was prescribed to the institutionally prescribed PTV margin (dark green). A bolus was used to increase superficial dose and improve dose coverage 31 Hodgkin and Non-Hodgkin Lymphoma
- 396. 400 31.4 Contouring for Select Sites Including Extranodal Sites 31.4.1 General Principles of Patient Setup and TV Delineation for Inguinal/Pelvic Region Lymphoma • Patients should be simulated in the “frog-leg” position for coverage of the ingui- nal region in order to separate the leg from the external genitalia and flatten any inguinal skin folds to minimize potential skin reactions. • Shield testicles with a clamshell and recommend sperm banking in men and consider the location of the ovaries for reproductive age women. • Modern radiation techniques, including 3DCRT and IMRT, are recommended. One may also need to add bolus to increase superficial dose and improve coverage. 31.4.2 General Principles of Patient Setup and TV Delineation for Gastric Lymphoma • Patients should fast 3–4 h prior to simulation and treatment in order to decrease gastric motility. Oral contrast should be used in all cases and IV contrast is rec- ommended if there are involved lymph nodes. • Patients should be simulated with arms up if using conformal radiation therapy and immobilized using a custom mold. Respiratory motion should be assessed using a 4D CT scan and treatment with deep inspiratory breath hold (DIBH) should be considered. • Modern radiation techniques, including 3DCRT and IMRT, are recommended to spare dose to the kidney and liver. Suggested target volumes for gastric lym- phoma radiation therapy are presented in Table 31.1. The PTV margin should be adjusted accordingly based on the results of 4D assessment. In some cases, 2 cm may not be adequate given the degree of stom- ach motion. Table 31.1 Suggested target volume delineation for gastric, orbital, and sinonasal lymphoma Origin Suggested target volume selection and delineation Gastric (Fig. 31.6) GTV = gross disease CTV = GTV + stomach from gastroesophageal to gastroduodenal junction PTV = CTV + 2 cm margin using 4D CT assessment of respiratory motion Orbital (Fig. 31.7) GTV = gross disease CTV = GTV + whole orbit PTV = CTV + 5-mm margin Sinonasal (Fig. 31.8) CTV = prechemo GTV + entire involved sinus(es) PTV = CTV + 4–5-mm margin depending upon setup technique A. D. Rao et al.
- 397. 401 a a b b Fig. 31.6 A 63-year-old woman with a Stage IIAE MALT lymphoma with diffuse gastric involve- ment and perigastric lymphadenopathy was treated with definitive radiation therapy alone. For target delineation, axial slices from the cranial to caudal extent of her disease on the (a) CT simula- tion and (b) 4DCT MIP (maximum intensity projection). Since the patient had diffuse gastric involvement, GTV = CTV. ISRT CTV is shown in red and ITV is shown in green with correspond- ing images. Radiation therapy was prescribed to the PTV margin (blue) 31.4.3 General Principles of Patient Setup and TV Delineation for Orbital and Sinonasal Lymphoma • The patient is simulated in the supine position with arms down and head immo- bilized using a thermoplastic mask. • For orbital lymphoma, one may treat with a superior-inferior wedge pair tech- nique, 3DCRT, or IMRT. Bolus may be added to increase superficial dose to localized soft tissue disease and consider a lacrimal gland shield if the prescribed dose is ≥30 Gy. • For limited indolent disease of the conjunctivae, treat with anterior electron beam setup or may consider electron/photon mixed energy; consider lens shield if tumor located in the periphery. • For sinonasal lymphomas, treatment with 3DCRT or IMRT is recommended given the higher doses delivered in the treatment of this disease depending on the histology and the number of surrounding critical structures. • Suggested target volumes for orbital and sinonasal lymphoma radiation therapy are presented in Table 31.1. Case examples are presented in Figs. 31.7 and 31.8. 31 Hodgkin and Non-Hodgkin Lymphoma
- 398. 402 Fig. 31.7 A 69-year-old woman with Stage IAE MALT lymphoma of the left lacrimal gland treated with definitive radiation therapy alone. For target delineation, axial slices from the cranial to caudal extent of her disease on the simulation CT are shown. Gross disease is contoured in red and the ISRT CTV in light green covers the whole orbit. Radiation therapy was prescribed to the institutionally prescribed PTV margin (blue) A. D. Rao et al.
- 399. 403 a a b b Fig. 31.8 A 56-year-old woman with Stage IAE diffuse large B-cell lymphoma of the left eth- moid/sphenoid sinus with extension across the nasal septum into the right nasal cavity. Superiorly, the mass is associated with erosive changes in the cribriform plate. Laterally, the mass erodes the left medial orbital wall and inferiorly, extends into the left maxillary sinus. The left frontal sinus was completely opacified. Patient was initially taken to surgery for resection of the mass for patho- logic confirmation with a near total resection. She then received 3 cycles of R-CHOP and was treated with consolidative radiation therapy. (a) Preoperative (and pre-chemotherapy) axial slices from cranial to caudal extent of her disease are shown. (b) On corresponding axial slices of her simulation CT there is no gross disease and the ISRT CTV in red covers the entirety of the involved sinuses. Radiation therapy was prescribed to the institutionally prescribed PTV margin (blue) References 1. Specht L, Yahalom J, Illidge T, et al. Modern radiation therapy for Hodgkin lymphoma: field and dose guidelines from the international lymphoma radiation oncology group (ILROG). Int J Radiat Oncol Bio Phys. 2014;89(4):854–62. 2. Illidge T, Specht L, Yahalom J, et al. Modern radiation therapy for nodal non-Hodgkin lym- phoma—target definition and dose guidelines from the international lymphoma radiation oncology group (ILROG). Int J Radiat Oncol Bio Phys. 2014;89(1):49–58. 31 Hodgkin and Non-Hodgkin Lymphoma
- 400. 404 3. Yahalom J, Illidge T, Specht L, et al. Modern radiation therapy for Extranodal lymphomas: field and dose guidelines from the international lymphoma radiation oncology group (ILROG). Int J Radiat Oncol Bio Phys. 2015;92(1):11–31. 4. Zhou R, Ng A, Constine LS, et al. A comparative evaluation of normal tissue doses for patients receiving radiation therapy for Hodgkin lymphoma on the childhood cancer survivor study and recent Children’s oncology group trials. Int J Radiat Oncol Bio Phys. 2016;95(2):707–11. 5. Girinsky T, van der Maazen R, Specht L, et al. Involved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma: concepts and guidelines. Radiother Oncol. 2006;79:270–7. 6. Girinsky T, Ghalibafian M. Radiotherapy of Hodgkin lymphoma: indications, new fields, and techniques. Semin Radiat Oncol. 2007;17:2006–222. 7. Girinsky T, Specht L, Ghalibafian M, et al. The conundrum of Hodgkin lymphoma nodes: to be or not to be included in the involved node radiation fields. The EORTC-GELA lymphoma group guidelines. Radiother Oncol. 2008;88:202–10. 8. Eich H, Muller R, Engenhart-Cabillic R, et al. Involved-node radiotherapy in early-stage Hodgkin’s lymphoma: definition and guidelines of the German Hodgkin study group (GHSG). Strahlenther Onkol. 2008;184:406–10. 9. DeLuca P, Jones D, Gahbauer R, et al. Prescribing, recording and reporting photon-beam intensity-modulated radiation therapy (IMRT). J ICRU. 2010;10:1–106. 10. Lee N, Lu J. Target volume delineation and field setup: a practical guide for conformal and intensity-modulated radiation therapy. Berlin, Heidelberg, Germany: Springer-Verlag; 2013. A. D. Rao et al.
- 401. 405 32 Soft Tissue Sarcoma Charles Catton, Amy Parent, Colleen Dickie, and Brian O’Sullivan Contents 32.1 General Principles of Planning and Target Delineation 405 32.1 General Principles of Planning and Target Delineation • Anatomic location, size, depth (with respect to the superficial fascia), and patho- logical features dictate the management of soft tissue sarcoma (STS). • Invasion is typically in the longitudinal direction within muscle and confined to the compartment of origin. Suspicious peritumoral changes, henceforth referred to as edema, may harbor microscopic disease. Edema is most often pronounced in the cranio-caudal dimension and should ordinarily be encompassed in the radiotherapy target volume. • STS generally respect barriers to tumor spread such as bone, interosseous mem- brane, and major fascial planes, and this concept should be exploited in tissue/ function preserving radiotherapy planning, especially in extremity lesions. • Retroperitoneal tumors commonly grow to a large size and initially displace but eventually invade adjacent organs and tissues. • In the event of an “unplanned” surgical resection with positive margins (surgical error), the RT target volume needs to generously include all disturbed muscle compartments in addition to any other tissues considered to be directly involved (see Figs. 32.1, 32.2, and 32.3). C. Catton · A. Parent · C. Dickie (*) · B. O’Sullivan Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada e-mail: charles.catton@rmp.uhn.ca; amy.parent@rmp.uhn.ca; colleen.dickie@rmp.uhn.ca; brian.osullivan@rmp.uhn.on.ca © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_32
- 402. 406 Fig. 32.1 A patient with a T1N0M0 Grade 3 dedifferentiated liposarcoma in the posterolateral thigh. This patient presented having had a previous unplanned excision of a superficial lesion where the fascia of the vastus lateralis was breached but did not involve the deeper compartment originally. CT simulation used 2.0-mm slice thickness. Notice the area of violated fascia due to previous surgical error. Shown are representative slices C. Catton et al.
- 403. 407 Fig. 32.2 Example of GTV, CTV, and PTV displayed in the sagittal view as well as an axial view of the disrupted fascia as a result of an unplanned excision with the corresponding planning CT target volumes • For preoperative planning target volume definition, CT simulation imaging fused with MR imaging should be performed, ideally with the patient in the treatment position, to help guide delineation of the gross tumor volume (GTV) and clinical target volume (CTV) (see Figs. 32.1 and 32.2). • For postoperative planning target volume definition after assumed complete sur- gical resection, there is no GTV to delineate. The location of the original GTV following the operation (GTVpostop) should be recreated in the planning CT data- set using preoperative CT/MRI imaging if available (see Figs. 32.4, 32.5, and 32.6). • Note: The stage classification has changed in the recently published eighth edi- tion of the TNM. Principle changes include different size thresholds for different anatomic sites and the elimination of depth in classification. • For preoperative cases, 50 Gy is ordinarily used and target volumes include the GTV and the CTV50 and should be delineated on every slice on the planning CT (see Figs. 32.1, 32.2, 32.7, and 32.8). • For postoperative RT delivery, 66 Gy is ordinarily used (60 Gy can be used in margin clear, low-grade cases) with an additional peripheral CTV volume for tissues with a lower risk of tumor infestation (see Figs. 32.4, 32.5, and 32.6). • For unresectable residual gross disease, 70 Gy in 2 Gy/fraction or equivalent dose fractionation is ordinarily used depending on the tolerance of the ana- tomic region. • Suggested GTV and CTV50 for preoperative IMRT of extremity STS are detailed in Table 32.1. 32 Soft Tissue Sarcoma
- 404. 408 Fig. 32.3 A patient who presented following an unplanned excision of a right-sided 3 cm (T1N0M0) pre-tibial pleomorphic undifferentiated sarcoma. The defect was closed with a split- thickness graft and both radial and deep margins were positive. The recommendation was for 50 Gy preoperative radiotherapy followed by wide re-excision with free-flap closure. The post-op GTV for this case is as described in Chap. 30 Table 30.2. The CTV50 and PTV50 radiotherapy target volumes follow Table 30.1 as described for the preoperative setting. CT simulation used 2.0- mm slice thickness. Axial and sagittal CT simulation views of the radiotherapy target volumes are shown. Gross disease has been excised and the postop GTV identifies the position of the original tumor reconstructed from a preoperative CT scan. A representative axial T2-weighted MRI image demonstrates the soft tissue defect and the relationship of the skin graft and positive deep margin to the periosteum. The CTV50 comprises a 3–4 cm radial expansion beyond the site of the positive margins at the edge of the skin graft, and deeply, includes the involved periosteum. The radial margins more closely approximate postoperative margins to account for the lack of a GTV and the contamination from intralesional surgery. A 5 mm bolus plug has been placed to fill the soft tissue defect anterior to the skin graft to provide adequate build-up on the deep periosteal margin. An axial preoperative CT and postoperative MRI view is shown to demonstrate the defect C. Catton et al.
- 405. 409 Fig. 32.4 A patient with a deep T3N0M0 Grade 3 pleomorphic rhabdomyosarcoma in the left thigh. This patient received postoperative RT for negative but close margins. CT simulation used 2.0-mm slice thickness. Edema was contoured at the superior aspect of the GTVpostop and included in the CTV56. Shown are representative slices. CTV56 is limited by the femoral head and bone throughout the target. In some cases where the subcutaneous tissues have been contaminated, bolus may be applied to the surgical scar for a component of the treatment (e.g., 50 Gy) 32 Soft Tissue Sarcoma
- 406. 410 Fig. 32.5 Sagittal CT simulation view of the radiotherapy target volumes for this postoperative STS case and corresponding preoperative and postoperative MRI. Note the CTV56 is defined by edema and the postoperative surgical changes. Where the target may appear coincidental in this scaled anatomic illustration, the usual margins were applied (e.g., 0.5- to 1-cm PTV expansion). In addition, the preoperative imaging was imported and co-registered with the postoperative RT plan- ning CT dataset in order to appreciate the original tumor extent for delineation of the GTVpostop C. Catton et al.
- 407. 411 Fig. 32.6 The digitally reconstructed skin rendered image displaying the surgical scar and the planning target volume (PTV56) shown in light blue that includes the surgical scar with a margin 32 Soft Tissue Sarcoma
- 408. 412 Fig. 32.7 A patient with a deep T3N0M0 grade 2 myxofibrosarcoma in the left lateral thigh. The patient received preoperative RT to minimize the necessary treatment volume. CT simulation used 2.0-mm slice thickness. The patient had extensive peritumoral edema extending superiorly and inferiorly that was included in the CTV50 and shown in representative slices. The CTV50 is limited by bone throughout the target. The PTV was 42 cm long exceeding the maximum machine capa- bilities for a single isocenter technique. Planning used a dual isocenter IMRT technique. The iso- centers are strategically placed to approximate the center of both adjoining volumes and cooptimized to ensure uniform PTV coverage. Axial, coronal, and sagittal CT views are shown with corresponding target volumes delineated C. Catton et al.
- 409. 413 Fig. 32.8 Sagittal CT simulation view and corresponding sagittal T2-weighted preoperative MRI image that demonstrates extensive longitudinal peritumoural edema. Note that the CTV50 is defined by edema and usual margins were applied (e.g., 0.5- to 1.0-cm PTV expansion). The preoperative imaging was imported and co-registered with the planning CT dataset in order to appreciate the edema extent for delineation of the CTV50 • Suggested GTVpostop and CTV66 for postoperative IMRT of extremity STS are detailed in Table 32.2. • Suggested GTV and CTV (dose 50–50.4 Gy) for preoperative IMRT of retroperi- toneal STS are detailed in Table 32.3 (Figs. 32.9 and 32.10). 32 Soft Tissue Sarcoma
- 410. 414 Table 32.1 Suggested target volumes for preoperative extremity STS Target volumes Definition and description GTV Primary: All gross disease on physical examination and imaging. T1-weighted contrast-enhanced MRI preferable. Co-registration of the MRI and planning CT is facilitated by immobilizing the patient in the treatment position CTV50* Includes all areas at risk of subclinical spread defined by the distance from the GTV or edema Includes the GTV + a 4-cm margin in the longitudinal dimensions and a 1.5-cm margin in the radial dimension limited to but including any anatomic barrier to tumor spread, such as bone or fascia Suspicious peritumoural edema, best demonstrated on T2-weighted MRI, may contain microscopic tumor cells and should be contoured separately with an adequate margin (usually 1–2 cm) For cases of “unplanned excision,” margins should include postop GTV or any residual GTV + all surgically manipulated and disturbed tissues and violated fascia + 4 cm longitudinally and 1.5 cm radially limited to but including any barrier to tumor spread PTV50* CTV50 + 0.5–1.0 cm, determined by individual institutional protocols and procedure *Suggested gross tumor dose is 2.0 Gy/fraction to 50 Gy Table 32.2 Suggested target volumes for postoperative extremity STS Target volumes Definition and description GTVpostop GTVpostop should identify the original site of the tumor Important to review and import presurgical imaging when contouring on the CT simulation scan for RT planning to ensure adequate coverage of the original tumor extent CTV66* CTV66 should encompass the entire GTVpostop + immediate area of surgical change with a 1- to 2-cm margin in the longitudinal plane and a 1.5-cm margin in the transverse plane. This may, but not always, include all surgically disturbed tissues, scars, and drain sites PTV66* CTV66 + 0.5–1.0 cm, determined by individual institutional protocols and procedure CTV56* Includes all areas at risk of subclinical spread defined by the distance from the GTVpostop and additional disturbed tissues Includes the GTVpostop + a 4-cm margin in the longitudinal dimensions and a 1.5-cm margin in the radial dimension limited to but including any anatomic barrier to disease spread; additional disturbed surgical tissues and any scars or drain sites are ordinarily included with a 1- to 2-cm margin if they are not included in the CTV66 Suspicious peritumoural edema should be contoured separately and included with an adequate margin. Like surgically disrupted tissue, it is best identified from a recent postoperative MRI scan Discussion with the surgeon and review of surgical and pathology reports will facilitate the decision about whether or not a seroma, lymphocele, or hematoma should be included PTV56* CTV56 + 0.5–1.0 cm, determined by individual institutional protocols and procedure The table describes single-phase simultaneous boost technique.An alternative is the more traditional- phased shrinking field technique that delivers 50 Gy in 25 fractions to all areas of subclinical disease followed by a boost to deliver the final 16 Gy in 8 fractions using a second radiotherapy plan *High-risk subclinical dose: 2.0 Gy/fraction to 66 Gy; for lower-risk subclinical regions 1.69 Gy/ fraction to 56 Gy delivered to the CTV56 C. Catton et al.
- 411. 415 Table 32.3 Suggested target volumes for retroperitoneal STS Target volumes Definition and description GTVa Primary: All gross disease on physical examination and imaging CTV Includes all areas at risk of subclinical spread defined by the distance from the GTV Includes the GTV + 2-cm margin in the longitudinal dimensions and a 0.5–2.0-cm margin in the radial dimension limited to but including any anatomic barrier to tumor spread and critical anatomy. For example, if the tumor is approximating an intact liver, 0.5 cm of the liver is included 2-cm margins are usually used posteriorly to include fatty tissues and vessels Ipsilateral kidney may be sacrificed provided the contralateral kidney has acceptable function. In such a case, dose to the uninvolved opposite kidney should be kept as low as reasonably achievable Other organs at risk include the small bowel, liver, spinal cord, and lungs PTV CTV + 0.5 cm, determined by individual institutional protocols and procedure a Suggested gross tumor dose range of 50 Gy/25 fractions to 50.4 Gy/28 fractions Fig. 32.9 An example of a right-sided T2bN0M0 Grade 3 undifferentiated pleomorphic retroperi- toneal sarcoma juxtaposed to the duodenum, the right kidney, and the iliac vessels. CT simulation used a 2.0-mm slice thickness. Representative slices are shown. Note the small amount of liver included in the CTV and PTV in the first three axial slices. Multifocal areas of calcifications within the tumor aided in daily image guidance for targeted IMRT. 4D CT simulation is encouraged 32 Soft Tissue Sarcoma
- 412. 416 Fig. 32.10 An axial, coronal, and sagittal display of the right-sided retroperitoneal sarcoma. Note the bowel displacement by the tumor, one of the major advantages of preoperative radiotherapy in this setting C. Catton et al.
- 413. 417 33 Pediatric Sarcoma Ethan B. Ludmir, Benjamin T. Cooper, and Arnold C. Paulino Contents 33.1 Background, Anatomy, and Patterns of Spread 417 33.2 Diagnostic Imaging for Target Volume Definition 419 33.3 Target Volume Delineation and Treatment Planning 419 33.4 Simulation, Immobilization, Treatment Devices, and Daily Localization 426 33.5 Plan Assessment 427 Further Reading 429 33.1 Background, Anatomy, and Patterns of Spread • Pediatric sarcomas are a heterogeneous group of diseases, including both sarco- mas of bone and soft tissue sarcomas (STS). Treatment algorithms for these dis- eases vary significantly by histology, stage and risk grouping, and even geographical site of practice (i.e., Europe versus the United States). • Ewing sarcoma (EWS) is the second-most-common pediatric bone tumor (the most common being osteosarcoma, for which radiotherapy does not generally play as central a role in treatment). Rhabdomyosarcoma (RMS) is the most com- mon pediatric STS. E. B. Ludmir · A. C. Paulino (*) Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA e-mail: EBLudmir@mdanderson.org; apaulino@mdanderson.org B. T. Cooper Department of Radiation Oncology, NYU Langone Health, New York, NY, USA e-mail: Benjamin.cooper@nyulangone.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_33
- 414. 418 • In the treatment of both EWS and RMS, the conventional treatment algorithm includes a combination of systemic chemotherapy and local therapy. Local ther- apy can include surgical resection and/or radiotherapy. • For unresectable EWS and RMS, radiotherapy alone is generally used for defini- tive local management, while radiotherapy can be delivered postoperatively in certain high-risk settings for both EWS and RMS. • EWS and RMS, like many sarcomas, can occur in virtually any anatomic loca- tion in the body. This precludes in-depth discussion for the purposes of this chap- ter regarding nuances of each specific anatomic location where these sarcomas may arise. • However, it is noteworthy that EWS most commonly occurs in the pelvis (25% of cases) followed by the femur (16% of cases). Patients with pelvic tumors are typically not amenable to resection and often dispositioned to definitive radio- therapy for local management of these tumors. • RMS has a wide distribution across anatomic primary sites in the body, most commonly in the head-and-neck (35%), followed by genitourinary system (20%), and then extremity (20%). Primary tumor location of RMS is dichoto- mized into favorable and unfavorable sites, which directly impacts staging, risk stratification, and treatment algorithms for RMS patients. Within the head-and- neck lesions, tumors are classified as being parameningeal (15% of all RMS cases), orbital (10%), or other head-and-neck locations (10%). Parameningeal lesions, which occur in one of the eight specific sites (middle ear, mastoid, nasal cavity, nasopharynx, infratemporal fossa, pterygopalatine fossa, paranasal sinuses, and parapharyngeal space [commonly abbreviated with the mnemonic “MMNNOOPP”]), have increased risk of direct extension into the central ner- vous system and are classified as unfavorable primary site tumors. • Generally, in considering local patterns of spread, uninvolved bone and intraos- seous membranes provide anatomic boundaries for microscopic spread. That said, tumor erosion and invasion of bone are not uncommon and should be evalu- ated on imaging (primarily CT-based imaging for assessment of bone). • As both EWS and RMS are often treated with chemotherapy before radiother- apy, post-chemotherapy volume reduction should be considered where pre- treatment imaging demonstrates tumor “pushing” on nearby structures and displacing them (especially lung, bladder, and bowel); post-chemotherapy imag- ing in these settings generally shows that these anatomic structures return to a more normal position after response to induction chemotherapy. In contrast, direct invasion into surrounding structures (identified on pre-chemotherapy imaging) should warrant at least some coverage with post-induction radiother- apy fields. • Nodal spread, while not commonly observed among most pediatric sarcomas, can be seen among select RMS cases, often by anatomic primary site. Extremity RMS has higher rates of nodal metastases and is often evaluated by sentinel node biopsy; certain genitourinary RMS (particularly paratesticular) patients may under surgical ipsilateral nerve-sparing retroperitoneal nodal dissection (generally reserved for patients 10 years old). While discussion regarding elective nodal coverage is ongoing in select contexts for RMS patients, elective nodal coverage is generally E. B. Ludmir et al.
- 415. 419 not recommended for most RMS and EWS patients. However, when nodal metas- tases are observed, it is recommended to ensure at least some radiotherapy cover- age of the entire nodal basin (not only the involved node/s). 33.2 Diagnostic Imaging for Target Volume Definition • A combination of diagnostic imaging techniques is helpful for both target vol- ume definition (gross tumor volume [GTV] and clinical tumor volume [CTV]) as well as staging. • CT imaging is particularly helpful for outlining bony involvement/erosion, and MRI provides excellent soft tissue delineation to assess extent of disease includ- ing intracranial invasion. Both modalities are commonly utilized for both EWS and RMS. • PET imaging has increasingly been utilized for both RMS and EWS at time of initial staging, with supporting literature for its adoption over other imaging techniques (such as bone scans). It may be helpful in identifying initially involved sites of disease pre-induction-chemotherapy. 33.3 Target Volume Delineation and Treatment Planning • In the treatment of EWS, target volumes are generally split into two categories: a volume defined by extent of disease at initiation presentation (GTV1, CTV1) and a generally smaller volume defined by post-chemotherapy (and sometimes post-surgery) residual disease (GTV2, CTV2). Additional margins added to the CTVs for set-up uncertainty leads to resultant planning target volumes (PTVs). Table 33.1 outlines general target volume definitions for EWS, while Table 33.2 provides suggested doses based on the Children’s Oncology Group (COG) AEWS1031 protocol. • RMS radiotherapy can be delivered as a single volume (dose-level) or as two dose-levels similar to EWS; generally volume reductions for boost doses beyond 36 Gy in the treatment of RMS are recommended for “pushing” tumors into the thoracic or pelvis (see similar discussion regarding EWS above). Full details regarding this are presented in the ongoing COG ARST1431 protocol (for intermediate- risk RMS), but invasive RMS lesions may still require complete coverage of the pre-chemotherapy volume with the maximum dose (often 50.4 Gy for gross disease), irrespective of response to chemotherapy. This is particularly relevant for parameningeal head-and-neck RMS lesions, where the GTV2 volume should generally include pre-chemotherapy extent of disease regardless of induction chemotherapy response. For lesions “pushing” into sur- rounding structures, cone-down beyond 36 Gy can be performed. Table 33.3 pro- vides general guidelines for target volume definitions for RMS; see the ongoing COG ARST1431 protocol for full details, which are beyond the scope of this chapter. 33 Pediatric Sarcoma
- 416. 420 Table 33.1 Ewing sarcoma target volume definitions Target volumes Definition and description Initial target volumes (pre-induction treatment) GTV1 Pre-chemotherapy extent of initial gross disease (including bone and soft tissue), including unresected enlarged/suspicious nodes. GTV1 may be modified if initial tumors extend into body cavities/spaces (pelvis, thorax) and subsequently regress with chemotherapy CTV1 GTV1 + 1–1.5 cm. CTV1 includes involved nodal basins (clinical or pathologic involvement) PTV1 CTV1 + set-up margin (institution- and image-guidance-specific, often 3–5 mm) Reduced target volumes (post-induction treatment) GTV2 Residual tumor after induction chemotherapy; however, all pre-chemotherapy extent of bony involvement is typically included in GTV2. Postoperatively, GTV2 defined as residual disease (bone or soft tissue), and site(s) of positive margins CTV2 GTV2 + 1–1.5 cm PTV2 CTV2 + set-up margin (institution- and image-guidance-specific, often 3–5 mm) GTV gross tumor volume; CTV clinical tumor volume; PTV planning tumor volume Table 33.2 Ewing sarcoma doses (all in doses of 1.8 Gy per daily fraction) Setting PTV1 (Gy) PTV2 (Gy) Definitive radiotherapy (all sites except vertebral) 45 10.8 Definitive radiotherapy—Vertebral 45 5.4 Extraosseous EWS with complete response to chemotherapy 50.4 0 Postoperative with microscopic residual disease (R1 resection) with 90% tumor necrosis on pathology 0 50.4 Postoperative with microscopic residual disease (R1 resection) with 90% tumor necrosis on pathology 50.4 0 Postoperative with gross residual disease (R2 resection) 45 10.8 PTV planning target volume; EWS Ewing sarcoma Table 33.3 Rhabdomyosarcoma target volume definitions Target volumes Definition and description GTV1 Pre-chemotherapy extent of initial gross disease (including bone and soft tissue), including unresected enlarged/suspicious nodes CTV1 GTV1 + 1 cm. CTV1 includes involved nodal basins (clinical or pathologic involvement) PTV1 CTV1 + set-up margin (institution- and image-guidance-specific, often 3–5 mm) GTV2 Residual tumor after induction chemotherapy, excluding areas where initial tumor “pushed” into surrounding structures such as the thorax or pelvis. However, pre-chemotherapy invasive disease (particularly in the context of parameningeal RMS of the head-and-neck) should generally be included in GTV2 irrespective of chemotherapy response CTV2 GTV2 + 1 cm PTV2 CTV2 + set-up margin (institution- and image-guidance-specific, often 3–5 mm) GTV gross tumor volume; CTV clinical tumor volume; PTV, planning tumor volume E. B. Ludmir et al.
- 417. 421 • While the staging, grouping, and risk stratification of RMS are beyond the scope of this chapter, it is noteworthy that conventional definitions of RMS histology are shifting. Whereas previously RMS was broadly divided by the two most common histologic subtypes, embryonal (lower risk) and alveolar (higher risk), this is now shifting to a molecular definition of histologic risk. For ongoing COG RMS protocols, molecular fusion status is being used instead of embryonal/alve- olar histology. Patients with translocations involving FOX01 (chromosome 13) are associated with higher-risk alveolar-histology natural histories; these fusions typically include PAX3-FOX01 and PAX7-FOX01 translocations, represented by t(2;13) and t(1;13), respectively. Data support fusion-negative alveolar-histology RMS to behave similarly to embryonal-histology RMS. Table 33.4 outlines gen- eral guidelines for RMS RT dosing. Table 33.4 Rhabdomyosarcoma doses (all in doses of 1.8 Gy per daily fraction) Group Fusion status (histology) Dose (Gy) I (R0 resection) Negative (embryonal) 0 I (R0 resection) Positive (alveolar) 36.0 II, node-negative (R1 [microscopic residual]) Either 36.0 (to pre- chemotherapy disease) II, node-positive (involved node, resected) Either 41.4 (to pre- chemotherapy site and nodal region) III, non-orbital and orbital if incomplete response after induction chemotherapy Either 50.4* III, orbital if complete response after induction chemotherapy Either 45.0** Special considerations III, per ongoing ARST1431 for tumors 5 cm in size pre-chemotherapy who do not achieve complete response to induction chemotherapy (protocol only) Either 59.4* III, per ongoing ARST1431 if radiographic or biopsy-proven complete response at week 9 after induction chemotherapy Either 36.0*** Extremity RMS, N0 (clinical and pathological), s/p amputation Either (including alveolar/ fusion-positive) 0 RMS rhabdomyosarcoma; N0 node-negative.*Per ongoing ARST1431, volume reduction can be performed after 36.0 Gy, such that PTV1 receives 36.0 Gy, and PTV2 receives the cone-down dose (either an additional 14.4 Gy or 23.4 Gy, depending on primary tumor size as above [5 cm cut- off]).**Per ongoing ARST1431, group III disease with complete response (either radiographic or biopsy-proven) at week 9 restaging (following induction chemotherapy) can be treated to a single dose-level to 36.0 Gy to the PTV1, without further boost or cone-down. Therefore, orbital prima- ries with week 9 complete response on ARST1431 may be treated to 36.0 Gy; see ARST1431 protocol for full details.***Per ongoing ARST1431, radiographic complete response by CT/MRI as well as complete metabolic response by FDG-PET or biopsy-proven absence of residual disease at week 9 restaging after induction chemotherapy allows for single dose-level treatment to 36.0 Gy to PTV1; see ARST1431 protocol for full details 33 Pediatric Sarcoma
- 418. 422 • Example cases of target volume delineation are highlighted in the cases below. Figures 33.1 and 33.2 highlight cases of EWS in the pelvis and thorax, respec- tively, highlighting two-volume target volume delineation conventional for the treatment of EWS with RT. Figures 33.3, 33.4, and 33.5 highlight cases of RMS; Fig. 33.1 A patient with Ewing sarcoma involving the pelvis. The post-induction-chemotherapy simulation CT is shown at left, and the pre-chemotherapy/pre-treatment MRI (T1 post-contrast sequence) is shown at right. Sample axial slices are shown at multiple axial levels. GTV1 (red) and GTV2 (green) are shown; CTVs are not shown but were contoured as GTV + 1.5 cm. Note that in the third row of images (inferior-most of the three axial slices shown), there was no residual dis- ease at that level and therefore no GTV2 is seen. Similarly at this level, GTV1 extension into the pelvis was reduced to account for tumor “pushing” and interval response to induction chemother- apy. PTV1 was treated to 45.0 Gy, and PTV2 was treated to a further 10.8 Gy for a total dose of 55.8 Gy E. B. Ludmir et al.
- 419. 423 Fig. 33.2 A patient with left posterior chest wall Ewing sarcoma. Axial CT simulation slices are shown. Note that a four-dimensional CT simulation was performed to account for full respiratory excursion/motion of the target volumes. GTV1 (red) and GTV2 (green) are shown; CTVs are not shown but were contoured as GTV + 1 cm. Note as well that the initial primary tumor occupied the posterior half of the left hemithorax; however, the GTV1 (red) reflects adaption of the GTV con- tour to account for “pushing” of the tumor into space now occupied by normal lung tissue post- induction chemotherapy. The GTV1 (red) still covers all sites of contact/involvement of the original primary tumor in the left hemithorax. PTV1 was treated to 45.0 Gy, and PTV2 was treated to a further 10.8 Gy for a total dose of 55.8 Gy Fig. 33.3 includes a case of parameningeal RMS with intracranial extension at diagnosis, often warranting early initiation of local therapy with a single high-dose volume. Figure 33.4 demonstrates principles and considerations of target volume delineation in the context of orbital RMS, and Fig. 33.5 highlights a case of extremity RMS with axillary (regional) adenopathy. 33 Pediatric Sarcoma
- 420. 424 Fig. 33.3 A patient with infratemporal fossa embryo- nal (fusion-negative) rhabdomyosarcoma, with intracranial extension and evidence of bone erosion. Axial slices from pre-treat- ment MRI (T1 post-contrast sequence) and CT simulation (soft tissue and bone windows) are shown. GTV (red) and CTV (green) are shown. CTV reflects a 1 cm expansion from the GTV. Note that intracranial extension (observed in the top two rows of axial slices). Bony erosion and destruction of the left mandible and left pterygoid plate are noted as well. Single dose-level used as patient was treated concurrent with initiation of chemotherapy due to intracranial extension. With a thermoplastic mask and daily kV image guidance, a 3 mm PTV margin was utilized. PTV was treated to 50.4 Gy E. B. Ludmir et al.
- 421. 425 Fig. 33.4 A patient with orbital embryonal (fusion-negative) rhabdomyosarcoma, with incom- plete response to induction chemotherapy. Axial slices from CT simulation and pre-treatment MRI (T1 post-contrast sequence) are shown. GTV (red) and CTV (green) are shown. CTV reflects a 1 cm expansion from the GTV; CTV extends beyond the bony orbit in certain slices due to poten- tial concern for bony erosion on staging CT (generally orbital RMS CTVs should not extend out- side the bony orbit absent bone erosion). Note that a rightward eye deviation is used to optimize sparing of both lens and optic nerve. Single dose-level used as GTV minimally responded to induc- tion chemotherapy; had primary tumor responded to induction chemotherapy, two dose-levels to 36 Gy and cone-down to 50.4 Gy would have been utilized. Patient was treated with a thermoplas- tic mask and daily kV image guidance, and a 3 mm PTV margin was utilized. PTV was treated to 50.4 Gy 33 Pediatric Sarcoma
- 422. 426 Fig. 33.5 A patient with right upper extremity alveolar (fusion-positive) rhabdomyosarcoma, with axillary nodal metastases. Axial slices from CT simulation in top panel show treatment to right hypothenar eminence primary site. Axial slices from CT simulation in bottom panels show treatment to the right axillary nodal basins where extensive FDG-avid adenopathy was identified on PET imaging; the complete nodal basin was contoured as the GTV (red) to ensure complete coverage of the nodal basin given multiple axillary nodes noted on staging PET imaging. For both the primary tumor site in the right hand and the right axillary nodal metastases, GTV (red) and CTV (green) are shown. Notably, the patient’s extensive axillary adenopathy responded partially to induction chemotherapy, but the primary tumor site minimally responded to induction chemo- therapy. The primary tumor site was therefore treated as a single dose-level to 50.4 Gy; had the primary site responded, two dose-levels to 36 Gy followed by a cone-down to 50.4 Gy would have been utilized. For the right axillary nodal disease, while the diffuse adenopathy in the right axillary basin achieved partial response to induction chemotherapy, the diffuse involvement of the basin resulted in the treating radiation oncologist to elect to cover the entire right axillary basin as a single dose-level as shown to 50.4 Gy. It is further noteworthy that no sites of disease in transit between the right hand and the right axillary were identified, and therefore no other parts of the right arm were treated in transit between the right hand and the right axilla 33.4 Simulation, Immobilization, Treatment Devices, and Daily Localization • Immobilization during simulation is highly variable and dependent on anatomic sites to be treated. For head-and-neck lesions, immobilization of head and shoul- der may be accomplished with thermoplastic mask. For thoracic lesions (includ- ing those involving thoracic vertebrae), arms are generally positioned up, with VacLok or similar cradle used in conjunction with wingboard. For pelvic lesions, E. B. Ludmir et al.
- 423. 427 immobilization of pelvis and upper legs can be accomplished with VacLok or similar cradle. Extremity lesions may be simulated with custom VacLok cradles and other devices; extremity lesions may warrant feet-first positioning and non- supine positioning in select cases. • Ifconcernexistsregardingrespiratorymotionoftargetvolumes,four-dimensional simulation can be considered to assess the extent of target volume excursion with respiration. • For pelvic lesions, particularly genitourinary lesions, bladder filling may also be a consideration; for prostate and bladder lesions, consistent bladder filling may be desirable and may be accomplished with daily ultrasound assessment of blad- der filling. Depending on the child’s age and ability to successfully fill (or empty) bladder, simulation with both full and empty bladder may provide a full extent of target volume excursion irrespective of bladder filling. • For male patients with pelvic and proximal leg sarcomas, frog-leg positioning may be utilized if a testicular shield will be employed. • Type and frequency of image guidance directly inform the CTV to PTV expan- sion. Many institutions utilize daily kV imaging for image guidance and conse- quently utilize 3–5 mm PTV expansions. Smaller PTVs can be considered depending on the type and frequency of image guidance, as well as proximity to critical structures (a common scenario among head-and-neck primary patients, where structures such as optic nerves, brainstem, and other structures are proxi- mate to the target volumes). • One additional consideration is that in addition to CT-based simulation, MR- based simulation may be used in conjunction with CT simulation to provide MRI data in the treatment position. • Finally, simulation and radiotherapy treatments may require daily sedation/anes- thesia for younger patients (typically patients younger than 8 years old). 33.5 Plan Assessment • While there is variability across clinical scenarios regarding plan assessment and acceptability, generally at least 95% of the PTV (or PTVs) should be covered by the prescription dose, with minimization of hotspots greater than 110% (at most 10% of the PTV getting 110% or greater). Conventional dose constraints per COG protocols for EWS and RMS are shown in Table 33.5; however, as pediatric patients carry profound risks of long-term toxicities from radiotherapy, efforts to maximize organ-at-risk (OAR) sparing should be made. To that end, while not discussed in the context of this chapter, modalities such as proton beam therapy may be considered for pediatric patients. Special considerations for proton beam therapy techniques, range uncertainties, beam arrangements, and more are beyond the scope of this chapter and should be discussed with expert physicists as well as physicians experienced with the use of proton beam therapy for pedi- atric malignancies. 33 Pediatric Sarcoma
- 424. 428 Table 33.5 Conventional normal tissue constraints Organ/tissue Volume (%) Dose (Gy) Brainstem Point max 54 Optic chiasm/optic nerve Point max 54 Spinal cord Point max 45 Lens Point max 6 Cochlea Point max 35 Heart 100 30 Lungs (bilateral) 20 20 100 15 Liver 100 23.4 50 30 Kidney (bilateral) 50 24 100 14.4 Small bowel 50 45 Bladder 100 45 Rectum 100 45 These represent general normal tissue constraints, including from COG protocols for EWS and RMS, as well as conventional institutional dose constraints; as per the text, given the long-term toxicities associated with pediatric RT, efforts should be made to optimize OAR sparing beyond these constraints. Certain clinical contexts may warrant exceeding these constraints, while others may warrant more rigorous sparing of the OAR than listed here • In addition to considerations regarding the use of photon-based techniques (such asintensity-modulatedradiotherapy)versusproton-basedtechniques,planassess- ment should inform how patients and their parents are counseled regarding acute and late effects of each pediatric radiotherapy plan. Considerations regarding secondary malignancies should be made (particularly relevant for EWS, which carries a higher-than-expected rate of secondary malignancies relative to most other pediatric cancers), as well as site-specific risks including: for head- and- neck sarcoma patients—dentofacial abnormalities, xerostomia, xerophthalmia, decreased visual acuity, cataractogenesis, facial asymmetry, endocrinopathies, and neurocognitive dysfunction; for extremity patients—epiphyseal closure and decreased bone growth/skeletal asymmetry; for patients receiving vertebral RT—decreased height as well as risk of kyphosis, lordosis, and scoliosis (mini- mized with coverage of the complete vertebral body for pre- pubescent children); for patients receiving thoracic RT—pneumonitis, pulmonary fibrosis, cardiac radiotoxicity; for patients receiving pelvic RT—cystitis, urinary incontinence or stricture, and infertility (which should also be considered depending on specific chemotherapeutics utilized, in particular cyclophosphamide). E. B. Ludmir et al.
- 425. 429 Further Reading Casey DL, ChiY-Y, Donaldson SS, et al. Increased local failure for patients with intermediate-risk rhabdomyosarcoma on ARST0531: A report from the Children’s Oncology Group. Cancer. 2019;125:3242–8. Donaldson SS. Ewing sarcoma: radiation dose and target volume. Pediatr Blood Cancer. 2004;42:471–6. Donaldson SS, Torrey M, Link MP, et al. A multidisciplinary study investigating radiotherapy in Ewing’s sarcoma: end results of POG #8346. Pediatric Oncology Group. Int J Radiat Oncol Biol Phys. 1998;42:125–35. Hawkins DS, Chi Y-Y, Anderson JR, et al. Addition of vincristine and irinotecan to vincristine, dactinomycin, and cyclophosphamide does not improve outcome for intermediate-risk rhab- domyosarcoma: a report from the Children’s Oncology Group. J Clin Oncol. 2018;36:2770–7. Ladra MM, Szymonifka JD, Mahajan A, et al. Preliminary results of a phase II trial of proton radiotherapy for pediatric rhabdomyosarcoma. J Clin Oncol. 2014;32:3762–70. Lin C, Donaldson SS, Meza JL, et al. Effect of radiotherapy techniques (IMRT vs. 3DCRT) on outcome in patients with intermediate-risk rhabdomyosarcoma enrolled in COG D9803 – a report from the Children’s Oncology Group. Int J Radiat Oncol Biol Phys. 2012;82:1764–70. Million L,Anderson J, Breneman J, et al. Influence of noncompliance with radiation therapy proto- col guidelines and operative bed recurrences for children with rhabdomyosarcoma and micro- scopic residual disease: a report from the Children’s Oncology Group. Int J Radiat Oncol Biol Phys. 2011;80:333–8. 33 Pediatric Sarcoma
- 426. 431 34 Pediatric Brain Tumors Benjamin T. Cooper, Ethan B. Ludmir, and Arnold C. Paulino Contents 34.1 Medulloblastoma 431 34.1.1 General Principles of Target Delineation and Radiation Treatment Planning 431 34.2 Ependymoma 436 34.2.1 General Principles of Target Delineation and Radiation Treatment Planning 436 34.3 Pure Germinoma 440 34.3.1 General Principles of Target Delineation and Radiation Treatment Planning 440 References 442 34.1 Medulloblastoma 34.1.1 General Principles of Target Delineation and Radiation Treatment Planning • Multiple different radiation delivery techniques can be used to successfully treat medulloblastoma including 3D conformal therapy, intensity modulated radiation therapy (IMRT), volumetric arc therapy (VMAT), and proton therapy. Regardless of treatment platform, careful volumetric target delineation is required. B. T. Cooper Department of Radiation Oncology, NYU Langone Health, New York, NY, USA e-mail: Benjamin.cooper@nyulangone.org E. B. Ludmir · A. C. Paulino (*) Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA e-mail: EBLudmir@mdanderson.org; apaulino@mdanderson.org © Springer Nature Switzerland AG 2022 N. Y. Lee et al. (eds.), Target Volume Delineation and Field Setup, Practical Guides in Radiation Oncology, https://doi.org/10.1007/978-3-030-99590-4_34
- 427. 432 • Comprehensive staging is critical in determining treatment dose and volume. All patients must undergo a comprehensive history and physical exam, a thin-cut (1–3 mm slice thickness) contrast-enhanced MRI of the brain both pre- and post- operatively, MRI of the spine with contrast, and CSF sampling to rule of dissemination. Patients with positive CSF cytology, gross metastasis, or ≥1.5 cm2 of residual disease in the tumor bed on postoperative MRI are classified as hav- ing high risk disease while those with no tumor spread (M0 disease) and 1.5 cm2 tumor bed residual are considered standard risk. • CT simulation, with or without anesthesia depending on patient cooperativity, should be done in a reproducible manner. This often consists of a full body Vac- Lok or alpha cradle immobilization system in addition to a standard brain mask with multiple markings for both triangulation and longitudinal spinal alignment. Many CT software packages allow for variable CT slice thickness by region and this can be helpful to allow thinner slices through the brain to allow detailed contouring and thicker slices throughout the spine to limit the amount of con- touring throughout the remainder of the body. The scan range should include all immobilization devices, include the top of the head cranially, and capture the gonads caudally. • Careful discussion should take place between the radiation oncologist and the anesthesiologist regarding anesthesia needs when making the mask. For exam- ple, if a patient is intubated to start treatment but is anticipated to be treated with a laryngeal mask airway (LMA) or even nasal cannula later in the treatment an oral airway can be added to ensure reproducible chin position and avoid the need to resimulate due to a loose mask. • Careful delineation of target and organ as risk (OAR) volumes should be done on every slice of the planning CT as seen in Figs. 34.1 and 34.2. The recommended target volumes for the craniospinal axis, tumor bed involved field boost, and whole posterior fossa boost are included in Tables 34.1 and 34.2. • When using proton therapy to treat a growing child, some have recommended treating the entire vertebral body to a dose up to 30 Gy when 36 Gy CSI is given [1]. Many radiation oncologists include the bone in the PTV with no further expansion to avoid intentionally giving dose to the esophagus and lungs (Fig. 34.3). However, there is limited [2] and early data [3] that intentionally covering the whole vertebral body may not be necessary and is the subject of an ongoing clinical trials (ClinicalTrials.gov Identifier: NCT03281889). • Care should be taken to identify the bottom of the thecal sac that is often, but not always, at the S2 vertebral level. Treating more inferiorly than necessary may increase exit dose to the gonads when using a single posterior photon field. This is not a concern with proton treatment. • There were increased failures on the 18 Gy craniospinal dose arm of Children’s Oncology Group (COG) ACNS0331 and 23.4 Gy craniospinal irradiation remains the standard of care for standard risk disease. This trial demonstrated the equivalence of an involved field boost to whole posterior fossa irradiation in patients with standard risk disease. Thus our recommendation is 23.4 Gy to the entire craniospinal axis followed by an involved field boost to 54 Gy for standard risk disease. B. T. Cooper et al.
- 428. 433 Fig. 34.1 A patient with standard-risk medulloblastoma. This patient was simulated using a 2.5 mm CT slice thickness. Note the coverage of the cribriform plate as part of the target volume (the cyan line is the PTV CSI, while the inner red line is the CTVCSI). Also note the PTVtbboost (orange line), CTVtbboost (green line), and GTV (red) contours Fig. 34.2 MRI slices fused to CT simulation images from the same patient who had a gross total resection of a medulloblastoma. This is an example of a tumor bed boost. The GTV (resection cavity) is shown in red, CTVtbboost in green, and PTVtbboost in orange. Notice the CTV is cropped at the tentorium 34 Pediatric Brain Tumors
- 429. 434 Table 34.1 Recommended target volumes for the craniospinal (CSI) portion of treatment Target volumes Definition and description GTV Tumor bed including all residual gross disease and the walls of the resection cavity as noted on MRI and areas of concern outlined by the neurosurgeon. Surgical defects not initially involved with tumor and caused by the procedure (the route to and from the tumor bed) are not considered part of this cavity. Any areas of gross disease in the spine should be outlined as well for consideration of a boost CTVCSI The entire volume contained by the dura matter and in contact with the cerebrospinal fluid is the CTV including any postoperative pseudomeningocele. The CTV is the entire vertebral body and canal (Fig. 34.3) in a growing child and the entire canal in a fully grown individual PTVCSI CTVCSI + 3–10 mm depending on comfort level of daily patient positioning and institutional experience Table 34.2 Recommended target volumes for the tumor bed boost within the posterior fossa Target volumes Definition and description GTV Tumor bed including all residual gross disease and the walls of the resection cavity as noted on MRI and areas of concern outlined by the neurosurgeon. Surgical defects not initially involved with tumor and caused by the procedure (the route to and from the tumor bed) are not considered part of this cavity. Any areas of gross disease in the spine should be outlined as well for consideration of a boost CTVtbboost CTVtbboost = GTV + a 1–1.5 cm anatomically confined margin. This should exclude barriers to spread such as the tentorium and limit the brainstem to a 2–3 mm margin in areas of tumor contact PTVtbboost CTVtbboost + 3–5 mm depending on daily imaging and institutional experience Fig. 34.3 Example of CTVspine displayed on bone windows of the spine in a growing child. The CTV could cut across the vertebral body in a fully grown child or an adult B. T. Cooper et al.
- 430. 435 • We recommend a margin of 1–1.5 cm from the tumor bed delineated on the post- operative MRI and limited by anatomic boundaries such as the skull and tento- rium cerebelli. Brainstem invasion can occur and we recommend including 2–3 mm of the brainstem in the CTV for tumors contacting the brainstem. However, if there was no contact on preoperative imaging or at surgery the brain- stem can be excluded from the CTV. A PTV margin of 3–5 mm is recommended based on institutional setup data and frequency of imaging. The authors use 3 mm with daily image guided radiotherapy. • Patients with M2 disease (intracranial subarachnoid disease) may receive boosts up to a total dose of 54 Gy to areas of supratentorial or posterior fossa metastatic disease. • Patients with M3 disease (spinal deposits of disease) are subdivided into those with diffuse disease and those with focal disease. Diffuse spinal disease is defined as radiographically visible multiple sites of disease in each of at least 3 out of 4 spinal regions (i.e., cervical, thoracic, lumbar, or sacral). • On the most recent COG high risk medulloblastoma protocol (ACNS 0332) dif- fuse spinal disease was prescribed 39.6 Gy, focal disease above the spinal cord 45 Gy, and focal disease below the spinal cord 50.4 Gy. • For high risk disease or patients that will not be getting chemotherapy, such as some adult patients not fit to get chemotherapy, we recommend 36 Gy to the craniospinal axis with a boost to 54 Gy. There have been many retrospective series examining the use of tumor bed boost in high risk disease without excess non-tumor bed posterior fossa failures although there are no randomized trials. • If the entire posterior fossa is to receive the boost, the CTV should include all structures below the tentorium cerebelli with the anterior border including the posterior clinoids (Table 34.3). The entire brainstem is included in the posterior fossa CTV. This is demonstrated at https://www.qarc.org/cog/ACNS0331Atlas. pdf as well as in Fig. 34.4. Table 34.3 Recommended target volumes for the entire posterior fossa Target volumes Definition and description GTV Tumor bed including all residual gross disease and the walls of the resection cavity as noted on MRI and areas of concern outlined by the neurosurgeon. Surgical defects not initially involved with tumor and caused by the procedure (the route to and from the tumor bed) are not considered part of this cavity. Any areas of gross disease in the spine should be outlined as well for consideration of a boost CTVpf CTVpf should include the entire posterior fossa. The entire brainstem is included in this volume and the borders are the base of skull anteriorly, the tentorium superiorly, and the foramen magnum inferiorly. Posteriorly and laterally the bone of the skull constrains this volume as seen in Fig. 34.4 PTVpf CTVpf + 3–5 mm depending on daily imaging and institutional experience 34 Pediatric Brain Tumors
- 431. 436 Fig. 34.4 A patient with high risk disease involving dissemination in the cerebellar folia requiring a whole posterior fossa boost. The CTVpf in blue encompasses the entire posterior fossa with the PTVpf in orange 34.2 Ependymoma 34.2.1 General Principles of Target Delineation and Radiation Treatment Planning • Similar to medulloblastoma, CT-based volumetric target delineation and plan- ning are required regardless of radiation therapy technique (3DCRT, IMRT, or proton therapy). • All patients should undergo high quality (1–3 mm slice thickness) pre- and post- operative MRI of the brain and total spine in addition to a detailed history and physical. • Unless medically contraindicated, MRI of the spine and CSF cytology should be obtained to rule out tumor dissemination though intracranial ependymoma is less likely (10%) to disseminate at diagnosis when compared to medulloblastoma. • Given that extent of resection is the most important prognostic factor for patients with intracranial ependymoma, re-resection should be entertained if possible with reasonable anticipated morbidity if residual disease is identified on postop- erative MRI. • CT simulation without contrast should be performed with 1–3 mm slice thick- ness to allow proper fusion, OAR delineation, and target delineation. The scan borders should include all immobilization devices and the entire cervical cord. • As with medulloblastoma, many of these children will require daily anesthesia and careful planning with the anesthesiology will allow construction of a mask that can reproducibly accommodate the necessary respiratory assist devices. B. T. Cooper et al.
- 432. 437 • The GTV is the postoperative resection cavity with special attention to the fora- men of Luschka and Magendie which are often involved in patients with intra- cranial ependymoma (Fig. 34.5). Speaking with the surgeon can be helpful to discuss any operative findings that are not readily apparent on MRI. • GTV to CTV margins have decreased over the past decade with the most recent COG trial ACNS 0831 treating patients with a CTV = GTV + 0.5 cm to a total dose of 54 Gy in 30 fractions (Table 34.4). • In order to minimize brainstem toxicity, the expansion of the CTV into the brain- stem was limited to 3 mm. Additionally, a conedown was prescribed in this trial for children older than 18 months to a total dose of 59.4 Gy that excluded the entire brainstem, optic chiasm, and cervical cord from the boost volume (Fig. 34.5). Fig. 34.5 This is a child with ependymoma and bilateral foramen of Luschka involvement show- ing the CTV54 (red) extending 3 mm into the brainstem (blue) but CTV59.4 (orange) completely excluding the brainstem. CTV59.4 would also exclude the cervical spinal cord and the optic chiasm Table 34.4 Recommended target volumes for infratentorial ependymoma Target volumes Definition and description GTV Tumor bed including all residual gross disease and the walls of the resection cavity as noted on MRI and areas of concern outlined by the neurosurgeon. Special attention should be paid to the foramina of Magendie and Luschka (Fig. 34.7) CTV54 and CTV59.4 CTV54 = GTV + 5–10 mm constrained by bone and tentorium. The CTV54 should not extend into the brainstem more than 3 mm. CTV59.4 as defined in ACSN 0831 was GTV + 5 mm excluding the entire brainstem, optic chiasm, and cervical cord PTVx PTV54,59.4 = CTV54,59.4 + 3–5 mm depending on daily imaging and institutional experience. However, it is understood that PTV will be under-dosed in some locations to respect cervical spinal cord and optic chiasm tolerance 34 Pediatric Brain Tumors
- 433. 438 • It is important to note that many pediatric radiation oncologists still advocate for larger margins (CTV = GTV + 1 cm) and a total dose of 54 Gy when treating patients not enrolled on ACNS 0831 and this is considered acceptable. • Given that extent of resection is the most important prognostic factor for patients with intracranial ependymoma, re-resection should be entertained if possible with reasonable anticipated morbidity if residual disease is identified on postop- erative MRI. • When treating to 59.4 Gy a two-phase treatment approach is suggested where a conedown at 54 Gy is employed to spare additional dose to the brainstem, optic chiasm, and cervical spinal cord. Essentially, regardless of inferior tumor extent, the PTV54 should not extend below the foramen magnum (Fig. 34.6). • The most recently published COG Ependymoma Protocol, ACNS 0831, speci- fied a goal cervical spinal cord D10% ≤ 57 Gy. They suggest during treatment of PTV59.4 the entire spinal cord volume should receive no more than 70% or 126 cGy per fraction during each of the last three treatments to achieve the rec- ommended maximum dose constraint. Fig. 34.6 Sagittal CT simulation scan demonstrating the CTV59.4 cropped to avoid the brainstem (orange) and not extend past the foramen magnum. CTV54 (red) needed to extend into the brain- stem and past the foramen magnum in this case due to tumor location B. T. Cooper et al.
- 434. 439 Fig. 34.7 Axial images for the same patient showing CTV59.4 in orange expanded 3 mm per insti- tutional standard to form PTV59.4 in purple. The brainstem (blue), cochlea (red and magenta), cervi- cal cord (green), temporal lobes (yellow and green), and the optic chiasm (light blue) are also outlined as organs at risk 34 Pediatric Brain Tumors
- 435. 440 34.3 Pure Germinoma 34.3.1 General Principles of Target Delineation and Radiation Treatment Planning • CT-based volumetric target delineation and planning are required regardless of radiation therapy technique (3DCRT, IMRT, or proton therapy). • All patients should undergo high quality (1–3 mm slice thickness) pre- and post- operative MRI of the brain and total spine in addition to a detailed history and physical. • Unless medically contraindicated MRI of the spine and CSF cytology should be obtained to rule out tumor dissemination though germinoma is less likely to dis- seminate to the spinal axis at diagnosis when compared to medulloblastoma. • Additionally, serum and CSF beta-human chorionic gonadotropin (β-hCG) and alpha-fetoprotein (AFP) levels are done to rule out a non-germinomatous germ cell tumor (NGGCT) component such as choriocarcinoma or endodermal sinus tumor. • Off protocol in North America, NGGCT is currently treated with CSI though investigation into a more limited treatment field is ongoing [4]. • Patients with any elevation of AFP are treated as NGGCT. • On ACNS 1123, the most recent COG trial for localized germ cell tumors, only patients with serum or CSF β-hCG ≤ 100 mIU/mL were treated as germinoma with patients with β-hCG 100 treated as NGGCT. • Construction of a face mask in the supine treatment position with standard brain triangulation marks is critical for setup reproducibility. If CSI is required for dis- seminated disease, the immobilization will be similar to patients with medullo- blastoma above. • Patients with involvement of only the suprasellar and pineal regions (bifocal ger- minoma) are treated as localized disease with the standard treatment approach of whole ventricular irradiation followed by an involved field boost to initial gross disease. • The target volume includes the prechemotherapy tumor volume, any residual disease and the ventricles. It is critical to outline the prechemotherapy disease at initial treatment planning because this boost volume will often extend outside of the normal ventricular volume. • The boost CTV is prechemotherapy GTV + 1–1.5 cm. • Inclusion of the prepontine cistern is optional but should be considered for patients that have undergone a third ventriculostomy and for patients with large suprasellar tumors (Figs. 34.8 and 34.9). • A whole ventricular contouring atlas was generated for ACNS 1123 and can be found at https://www.qarc.org/cog/ACNS1123_Atlas.pdf. • If radiation is being used as the sole treatment modality the whole ventricular volume is treated to 21–24 Gy with a boost to bring the total dose to the preche- motherapy volume to 45 Gy. Given the good prognosis of this disease and the B. T. Cooper et al.
- 436. 441 Fig. 34.8 T2 weighted MRI of patient with a germinoma illustrating the whole ventricle volume (lime green) and the boost volume (yellow). This patient underwent a third ventriculostomy so the prepontine cistern was electively covered Fig. 34.9 Axial images showing the whole ventricular CTV (red), whole ventricular PTV (blue), and the boost PTV (green). It is important to contour the prechemotherapy GTV prior to the whole ventricular volume as the boost volume often extends outside of the whole ventricular volume and if the boost and initial plan are not planned upfront the boost volume will not receive sufficient dose 34 Pediatric Brain Tumors
- 437. 442 desire for long term neurocognitive toxicity a fraction size of 1.5 Gy is often used though 1.8 Gy a fraction is not unreasonable. • When neoadjuvant chemotherapy is used, and the primary has a complete response, the dose to the whole ventricle is 21 Gy with a boost of 9 to 15 Gy to bring the total dose to the primary tumor to 30 to 36 Gy. Dose reduction of the whole ventricular volume to 18 Gy was studied in ACNS 1123. While there were no ventricular failures in the 74 evaluable patients treated with 18 Gy to the whole ventricular volume, the study failed to demonstrated noninferiority of this reduced dose compared to the design threshold of 95% 3-year progression free survival (https://doi.org/10.1093/neuonc/noab270). • Patients with a partial response or progressive disease will require a boost such that the total dose to the primary tumor is 36–45 Gy. References 1. Hoeben BA, et al. Management of vertebral radiotherapy dose in paediatric patients with can- cer: consensus recommendations from the SIOPE radiotherapy working group. Lancet Oncol. 2019;20(3):e155–66. 2. MacEwan I, et al. Effects of vertebral-body-sparing proton craniospinal irradiation on the spine of young pediatric patients with medulloblastoma. Adv Radiat Oncol. 2017;2(2):220–7. 3. De B, et al. Early axial growth outcomes of pediatric patients receiving proton craniospinal irradiation. J Pediatr Hematol Oncol. 2018;40(8):574–9. 4. Fangusaro J, et al. Phase II trial of response-based radiation therapy for patients with localized CNS Nongerminomatous germ cell tumors: a Children's oncology group study. J Clin Oncol. 2019;37(34):3283–90. B. T. Cooper et al.