Basics And Physics of Brachytherapy
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Brachytherapy is a form of radiotherapy that involves placing nuclides within or in contact with the target area, and it can be classified into low, medium, or high dose rates. Important distinctions exist between brachytherapy and external beam radiotherapy, particularly regarding dose rate, dose gradients, and treatment fractionation approaches. Different types of implants and radionuclides are used, including sealed sources for brachytherapy, which can significantly affect clinical outcomes.
Basics And Physics of Brachytherapy
- 2. Brachytherapy Definitions • Brachytherapy: Radiotherapy delivered using nuclides placed within or in contact with the target volume. • Sealed Source: Fully encapsulated. • Low Dose Rate (LDR): < 2 Gy/h. • Temporary • Permanent • Medium Dose Rate (MDR): 2–12 Gy/h. • Almost never used for clinical treatment. • High Dose Rate (HDR): > 12 Gy/h. • Pulse Dose Rate (PDR): HDR treatment for a few minutes every hour, such that the dose rate averaged over days is in the LDR range. • Unsealed Source: Brachytherapy using freely floating radionuclides (injected into a specific location, or administered systemically).
- 3. A Note on Brachytherapy • Biologically speaking, there are several major differences between brachytherapy and EBRT: • Dose Rate: EBRT (excluding TBI) is usually performed at high dose rate. Brachy may be HDR, LDR or PDR. • Dose Gradient: Most EBRT plans attempt to achieve a uniform dose within the target volume. Brachy always produces steep dose gradients. • Fractionation: Brachy is performed in far fewer fractions compared to EBRT. • LDR implants may be performed in a single procedure (especially permanent implants).
- 4. Brachytherapy: Dose Rate Effects To a first approximation, the LDR survival curve is equal to the survival curve of many small fractions of EBRT/HDR. • This is the biological rationale for the use of PDR therapy. Classic Dose-Rate Effect: LDR treatment results in decreased cell killing and no shoulder on the survival curve, compared to HDR/EBRT. • The magnitude of this effect directly correlates with the amount of sublethal damage repair (SLDR) in that cell type. • This is responsible for differential sparing of normal tissue with LDR, and is the biological rationale for the superiority of LDR. • Intrafraction repair goes from 0 to 100 % between dose rates of 1 Gy/min and 0.01 Gy/min (60 cGy/h). Inverse Dose-Rate Effect: In some rapidly cycling cells, cell killing actually increases between ~154 and ~37 cGy/h. This is a cell cycle effect. • At 154 cGy/h the cell cycle is completely arrested, so radioresistant S-phase cells are radioresistant. • At 37 cGy/h the cell cycle is allowed to progress into the radiosensitive G2/M, causing cell killing. • This is another rationale for the superiority of LDR, proliferating cancer cells sensitize themselves but non-proliferating cells do not. Very Low Dose Rate: Below the “critical dose rate”, fast-growing cells are able to repopulate faster than they are killed. • For example, mouse jejunum treated at <0.54 cGy/min (32 cGy/h) shows very little killing. • Permanent implants have an extremely low dose rate. Therefore they are ineffective on rapidly proliferating tumors. • A typical I-125 prostate seed implant has a dose rate of ~7 cGy/h. • Fortunately, prostate CA is a very slowly proliferating tumor.
- 5. Dose-rate to cell survival curve that illustrates the general improvement in cell kill with increasing dose rate with the exception of the region containing the inverse dose-rate effect.
- 6. Dose Rate and Clinical Endpoints • Mazeron did two studies on interstitial LDR implants: one on the oral cavity and one on the breast. • Oral Cavity: Dose rates <50 cGy/h were associated with less necrosis, with similar local control as long as total dose was adequate. • Breast: Between 30 and 90 cGy/h, higher dose rates were associated with improved local control. • Typical temporary implant LDR dose rates are 50–60 cGy/h to the prescription point. However, higher or lower dose rates may be used depending on clinical judgment and implant geometry. • Higher dose rate = more efficacy, more toxicity. • Permanent implant LDR dose rates are variable, and mostly depend upon which isotope is being used. • Shorter half-life = higher dose rate. • Dose rate effects are largely irrelevant for HDR, as the dose rate is too high to allow intrafraction repair or reassortment.
- 7. Brachytherapy: Choice of Nuclide and Implant • Ra-226 was used for many decades but is almost never used anymore due to risk of radon leakage. • Permanent LDR implants generally use I-125, Pd-103, or less commonly Au-198. • Temporary LDR implants may use Au-198, Ir-192, Cs-137, Co-60 or others. • HDR implants almost always use Ir-192. • Implants are classified as interstitial (such as prostate or breast brachy) or intracavitary (such as GYN brachy). Unsealed Sources • I-131 is a beta-emitter that is taken up by thyroid tissue as well as differentiated thyroid cancers. • Bone-seeking nuclides include Sr-89, Sm-153 and Ra-223 and are used to treat widespread bony metastases. • P-32 is a beta-emitter that can be used to treat the lining of a cyst, joint space, or body cavity.
- 11. Definitions • AAPM TG-43: Task Group Report 00 of the American Association for Physics in Medicine. • Activity (A): Amount of radioactive material. • Units: 1 Curie (Ci) = 3.7 x 1010 Becquerel (Bq) • Radius (r): aka distance, depth. • Dose Rate (D ): not to be confused with total dose (D) • Initial Dose Rate (D0) • Exposure Rate Constant (Γ), aka Gamma Constant: Exposure rate per millicurie of isotope at 1 cm distance. • Exposure Rate (X ) = ΓA • Milligrams Radium Equivalent (mgRaEq): • 1 mgRaEq = 8.25 R -cm2 -h-1 -mg-1 exposure rate • Air kerma strength (SK): Kerma (kinetic energy released in matter) measured in air @ 1 m. • 1 U = 1 cGy -cm-2 -h-1 = 1 μGy -m-2 -h-1 • Proportional to Activity. • Dose rate constant (Λ): Dose rate to water for 1U air kerma strength at 1 cm (cGy -cm-2 -h-1 /U). • Low Dose Rate (LDR): 0.4–2 Gy/h • Medium Dose Rate (MDR): 2–12 Gy/h • High Dose Rate (HDR): >12 Gy/h • Pulse Dose Rate (PDR): HDR fractionated over time to approximate LDR dose rates. Details of the units and activities along with dosimetry can be found in AAPM TG-43.
- 12. The Historical Role of Radium • 226Ra brachytherapy was used for many decades prior to 60Co, 137Cs, 192Ir, or megavoltage X- rays. • Radium sources consist of radium chloride powder placed within a doublesealed platinum tube. • 226Ra comes to a secular equilibrium with 222Rn and its decay products by emitting alpha rays. • This results in accumulation of multiple radioactive daughter nuclides emitting alphas, betas and gammas. • The encapsulation is designed to absorb everything except for the gammas. • Average photon energy 0.83 MeV (range 0.18–2.29 MeV). • 226Ra is no longer used because of the risk of radon gas leakage and other safety concerns. • Many LDR brachytherapy systems are based on “milligrams radium equivalent” (mgRaEq). • For a source of activity A and gamma constant Γ: Radium Equivalent (mCi) = ΓA x mg x Ra x Eq / 8.25 R/cm 2 /hr
- 13. Production of Radionuclides • Naturally Occurring: Byproducts of uranium decay, these nuclides can be mined from the Earth. • 226-Ra, 223-Ra, 222-Rn among others. • Fission Byproduct: Obtained from nuclear reactors. • 137-Cs, 131-I, 90-Sr among others. • Neutron Bombardment: Creates beta-minus emitters. Cyclotrons can produce high intensity proton and neutron flux. Nuclear reactors can produce very high intensity neutron flux. • 198-Au, 192-Ir, 153-Sm, 125-I, 103-Pd, 89-Sr, 60-Co, 32-P among others. • Proton Bombardment: Creates beta-plus emitters, often used for PET imaging. Protons are accelerated by a cyclotron. • 123-I, 18-F, 15-O, 11-C, 3-H among others. • Daughter Elution: A longer-lived mother nuclide (“cow”) decays into a shorter-lived daughter nuclide (“milk”) that can be repeatedly eluted for clinical use. This is an example of transient equilibrium. • 90-Y, 99m-Tc among others.
- 14. Sealed Source Properties • Classically, source strength is measured as activity (Ci or Bq) or milligrams radium equivalent (mgRaEq). • Two sources with the same Activity (Ci) may emit very different amounts, energies and types of radiation due to encapsulation and filtration. Hence, their dose rate may be different. • Source strength is specified as air kerma rate at a distance of 1 m as mentioned above. (1 U = 1 μGy/h/m2). Unsealed Source Properties • Unsealed sources do not have to worry about encapsulation so they simply are specified as nuclide, activity, and chemical formulation. (ie elemental vs. colloidal vs. antibody-bound). • An unsealed source will have separate physical and biological half-lives. • Effective half-life equation:
- 15. Implant Instrumentation and Technique (Ircu-38 and 58) An intracavitary implant is placed within an applicator such that the sources do not directly contact tissue. • Tandem and ovoids (ie, Fletcher-Suit) • Ring and tandem • Vaginal cylinder • Partial breast balloon brachytherapy • Endobronchial An interstitial implant is inserted into tissue. • Template-based catheters • Free-hand catheters • Permanent seeds Other types • Surface applicator (eye plaque, intraoral, skin) • Intravascular • Intraoperative Unsealed sources may be given systemically (oral, intravenous) or injected in a specific location (intracystic, intra-articular).
- 16. Brachytherapy Dose Rate • LDR implants deliver dose over days (temporary) to months (permanent). • Temporary LDR implants: Typical dose rates are approx. ~60 cGy/h or 1 cGy/min. • Permanent implant dose rates are much lower, but total dose is very high such as in prostate seed implants (120–145 Gy). • Normal tissue sparing effect due to sublethal damage repair (SLDR). • HDR implants typically deliver dose over a few minutes, with typical dose rates >50 cGy/min (>3,000 cGy/h). • Like external beam RT, fractions are given over a time scale shorter than that of DNA repair. • Computer-controlled HDR afterloaders allow for detailed optimization of dwell positions and times. • Geometric normal tissue sparing is used to make up for loss of biological normal tissue sparing. • PDR is a method that uses an HDR afterloader to deliver fractions every hour or so, to approximate LDR dose rates.
- 23. Loading Patterns: Basic Principles • In a uniformly loaded catheter, the center will receive more dose than the ends. • Therefore if you want a homogenous dose, you need peripheral loading – more source strength at the ends. • This is true for both LDR and HDR.
- 24. Classical Dose Systems (Interstitial) • Prior to computer planning era, pre-calculated tables were used to calculate how much radium was needed to load an implant. These are of mainly historical interest. Paterson-Parker (Manchester): • Different dose-loading tables for single plane, two-plane, and volume implants. • Peripherally loaded – non-uniform loading. • Uniform dose within implanted volume. • Crossed ends – needles/catheters run perpendicular to each other. Quimby • Different dose-loading tables for single plane, two-plane, and volume implants. • Uniform loading. • Central hot spot within implanted volume. • Crossed ends – needles/catheters run perpendicular to each other. Paris • Volume implants with multiple parallel needles or catheters. • Uniform loading, identical for all needles. • Uniform spacing of all needles. • Central hot spot within implanted volume. • Parallel ends – no crossing of needles. Other • Prostate – computer planning is preferred over fixed systems.
- 25. Classical Dose Systems (Intracavitary) Fletcher-Suit (named after Gilbert Fletcher and Herman Suit) • Dose is prescribed to Point A: • 2 cm superior to the top of the ovoids as seen on a lateral film, and • 2 cm lateral to the tandem, in a direction perpendicular to the tandem as seen on an AP film. This is supposed to represent the paracervical triangle where the uterine vessels cross the ureter. • Revised Point A is 2 cm superior to the flange: • Unlike classical Point A, this point can be visualized on AP film alone (no need for laterals). • Point H is the prescription point used by the American Brachytherapy Society. • Find the intersection between the tandem and a line drawn between the mid-dwell positions of both ovoids. • Move cephalad along the tandem by 2 cm plus the radius of the ovoids. • Then, move lateral by 2 cm. • This is intended to be the same point as classical Point A, but with more reproducible delineation. • However, it is a bit lower than classical Point A. • Typical LDR dose rate is 50–60 cGy/h to Point A. • Additional dose measurements at: • Point B is 3 cm lateral to Point A (5 cm from midline), represents the obturator nodes. • Point P is the bony pelvic sidewall, either at the level of Point A or at the top of the acetabulum. • Bladder Point is defined by the posterior extent of the bladder directly behind the Foley catheter. • Vaginal Point is defined by the posterior extent of the vaginal packing, at the level of the midpoint of both ovoids. • Rectal Point is defined as 5 mm posterior to the vaginal point.
- 26. Definitions of Point A: Point A is the typical prescription point for cervical brachytherapy. • The original definition is 2 cm lateral to the tandem and 2 cm above the top of the ovoids. • The revised definition is 2 cm lateral to the tandem and 2 cm above the top of the flange.
- 27. Rules of Thumb
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