astro guideline on brain mets
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This document summarizes guidelines for the radiotherapeutic and surgical management of patients newly diagnosed with brain metastases. It discusses various treatment modalities including whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and surgery. It reviews several studies comparing outcomes of different treatment approaches. The guidelines were developed by an international task group that systematically reviewed the literature to form consensus recommendations. Key findings included no clear survival benefit of adding SRS to WBRT for patients with multiple brain metastases, and that omitting WBRT after surgery or SRS for a limited number of metastases may be reasonable if patients are closely monitored.
astro guideline on brain mets
- 1. Journal presentation ABHIJIT DAS 1ST YEAR PGT, DEPT.. OF RADIATION ONCOLOGY AHRCC
- 3. • Brain metastases being a significant health care Problem, It is estimated that 20% to 40% of cancer patients will develop brain metastases during the course of their illness • Various modalities used : 1.WBRT 2.SRS(STEREOTACTIC RADIOSURGERY) 3.SURGERY 4. SUPPORTIVE CARE WITH DEXAMETHASONE
- 4. Purpose: To systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases IMPORTANCE: it was felt important to develop guidelines from an international perspective with international representation on the Brain Metastases Task Group. key questions are posed- Such as prognostic classification systems, radiotherapy fractionation schemes, comparison of surgery and radiosurgery, neurocognition as an outcome variable in decision-making, palliative supportive care, and radiation sensitizers.
- 5. METHODS AND MATERIALS The Guidelines Subcommittee of the Clinical Affairs and Quality Committee, in accordance with established ASTRO policy, recruited a Task Group These experts represent radiation oncology, neurosurgery, physicists, outcomes, and health services research systematically review the literature on the radiotherapeutic and surgical management for patients with newly diagnosed metastatic disease to the brain.
- 6. Email and conference A concensus formed from various publications, review articles Initial draft of manuscript reviewed again by 3 expert reveiwers Put on astro website Public comment as feedback Upon integration of the feedback, the document was then submitted to the ASTRO Board of Directors for their final review and approval in October 2011
- 7. Inclusion and exclusion: 1.Only randomized phase III trials pertinent to the management of newly diagnosed brain metastases were included. 2.Trials dealing with the use of WBRT, surgery, radiosurgery, chemotherapy, radiosensitizers, and palliative care alone were considered. 3.Trials that examined the use of prophylactic cranial irradiation were excluded. 4.all the radiosurgery trials used frame-based single fraction radiosurgery techniques with either a linear accelerator or gamma knife unit. MEDLINE (1966-Nov. 3, 2010), EMBASE (1980-2010 week 46), and the CENTRAL databases (issue 4, 2010)___1826 publications, 597 publications, and 425 publications A total of 36 randomized controlled trials were selected by international radiation oncology groups, ASTRO, Canadian Association of Radiation Oncology (CARO), European Society for Therapeutic Radiology and Oncology (ESTRO), and Trans-Tasman Radiation Oncology Group (TROG),
- 8. Result of public feedback: the literature search was further expanded to include nonrandomized studies (prospective or retrospective) dealing with the use of either radiosurgery or fractionated radiation to the postoperative surgical cavity. The MEDLINE (1947 to May week 2, 2011) -1549 nonrandomized publications EMBASE (1980-2011 week 20) -3721 nonrandomized publications. CENTRAL search -0 randomized controlled trials. Titles and abstracts were screened and a final total of 15 relevant publications were retrieved.
- 9. CLASS 1 CLASS II CLASS III AGE LESS THAN 65 Other than class I or class iii KPS >=70 <70 CONTROLLED PRIMARY 3 MONTHS STABILITY/ NEWLY diagnosed EXTRACRANIAL METASTASES Absent Class Median survival(MONTHS) I 7.1 II 4.2 III 2.3 prognostification
- 12. • Thus histology plays significant role in the treatment decisions and prognostification in the diagnosis specific GPA. • There is an insufficient data for protracted schedule in radioresistant tumours such as rcc and melanoma. • The revised GPA has found histology to be statistically significant based on retrospective data in a more recent era (1985-2007) compared with the database used to derive the RTOG RPA (1979-1993). The difference may be due to newer and more effective chemotherapy used to treat systemic disease. CAVEATS
- 14. WBRT AND SURGERY fraction WBRT+SUR G WBRT P value 40gy/20# NOORDIJK ET AL. 10 MONTHS 6 MONTHS .04 30gy/10# MINTZ ET AL. 5.6 MONTHS 6.3 MONTHS Non specifi ed 36gy/12# PATCHELL ET AL 40 WK 15 WK <.01 2 out of 3 study shows significant survival. Mintz et al reported a significant difference (P= .009) in the Cox regression analysis for mortality in patients having extracranial metastases versus no evidence of primary tumor. The benefit for surgery may be lost in patients with poor prognostic factors such as advanced extracranial disease or lower performance status. OVERALL SURVIVAL Mintz et al
- 15. WBRT AND SURGERY STUDY ORIGINAL SITE(%) OTHER PARTS OF BRAIN(%) WBRT +SURG 46 37 SURG 10 14 WBRT+ SURG(2 yr relapse rate) 59 42 SURG(do) 27 23 The first trial was small and not powered for survival. The second trial by the EORTC included patients randomized to receive postoperative WBRT.ALSO No prospective studies have evaluated whether resection of more than one metastasis conveys meaningful clinical benefit. benefit of excising multiple brain metastases causing mass effect has not been definitively proven with level 1 evidence. However, it was felt by the guideline authors that safe resection of multiple brain metastases causing mass effect should be included as an option for good prognosis patients. PATCHELL ET AL. EORTC 22952- 26001 Due to the paucity of randomized data, it is unknown whether the omission of postoperative WBRT (with a strategy of close radiographic and clinical follow-up and the use of salvage radiosurgery or WBRT at relapse) reduces neurocognitive decline compared with patients undergoing immediate postoperative WBRT. P< .001 P< .08
- 16. SRS, WBRT AND SURGERY In good prognosis patients with single brain metastasis (less than 3 to 4 cm in maximum dimension and amenable to gross total resection), either surgery or radiosurgery may be considered. Surgery may be favored in patients with unknown primary, or In patients with single brain metastasis causing significant mass effect. In good prognosis patients with single brain metastasis less than 3 to 4 cm in maximum dimension (in eloquent brain areas not amenable to safe total resection or in patients who are unfit for surgery), radiosurgery may be considered There is no proper trial showing any evidence for decision regarding modality. Most of studies are underpowered or closed due to slow accrual. Ecog (A phase II trial of radiosurgery for 1 to 3 newly diagnosed brain metastases (4 cm or less in maximum dimension) from histologies (renal cell carcinoma, melanoma, and sarcoma) that have been deemed radioresistant to fractioned external beam radiotherapy) has done a trial of radiosurgery on 33 patients but Three-month intracranial failure with radiosurgery alone was 25.8%; in-field failure rate at 3 months was 19.3%. Distant intracranial failure rate at 3 months was 32.2%.Whether surgery has better local control or survival as comparedwith radiosurgery for “radioresistant” single brain metastasis could not be answered by this study due to lack of direct comparisons with a surgical group.
- 17. At present, there are insufficient high-quality data on whether certain histologies benefit from the use of radiosurgery to treat more than 4 intracranial metastases. WBRT ± Radiosurgery BOOST RTOG 9508 TRIAL51included selected patients with 1 to 3 newly diagnosed brain metastases with a maximum diameter of 4 cm (for the largest lesion) and additional lesions not exceeding 3 cm in diameter WBRT+RADIOSURG. BOOST(n=167) MEDIAN SURVIVAL 6.5 MONTHS(SINGLE LESION) WBRT(n=164) SINGLE LESION MEDIAN SURVIVAL(4.9 MONTHS) There was no survival benefit with the use of radiosurgery boost as compared with WBRT alone in patients with multiple brain metastases Higher response rates at 3 months and better control of treated lesions at 1 year were observed in the WBRT and radiosurgery group versus WBRT alone (82% vs 71%,P= .01) There is improvement in KPS and decreased steroid use at 6 months with the use of radiosurgery boost added to WBRT. P< .04
- 18. None of the trials have examined validated quality of life outcomes with patients managed with WBRT alone versus WBRT and radiosurgery boost. Given no expected survival benefit, either option of WBRT alone with possible salvage treatment or upfront WBRT and radiosurgery boost may be offered for selected patients with multiple brain metastases. It is unclear from these published trials whether there is benefit with radiosurgery boost to more than 4 lesions. However, there are level 3 data on patients undergoing radiosurgery for 4 or more intracranial metastases suggesting a survival benefit, and that total intracranial volume rather than number of brain metastases may be the more important predictor of survival
- 19. 199 radiosurgery 100 observation 99 wbrt 160 surgery 89 observation 71 wbrt Radiosurgery or surgery alone versus WBRT and radiosurgery or surgery EORTC 22952-26001 trial- includes brain metastases (1 to3). Patients eligible for radiosurgery had 1 to 3 metastases of solid tumors (small cell lung cancer, lymphoma, leukemia, myeloma, and germ cell tumors were excluded) and brain metastasis size≤3.5 cm in diameter for a single lesion (≤2.5 cm for 2 to 3 lesions). Overall survival (10.9 months vs 10.7 months) was similar in both arms (P= .89). WBRT reduced the 2-year relapse rate both at initial sites (surgery: 59% to 27%,; radiosurgery: 31% to 19%,P= .040) and at new sites (surgery: 42% to 23%, P= .008; radiosurgery: 48% to 33%,P= .023). In well-performing patients with stable systemic disease and 1 to 3 brain metastases, treated with initial radiosurgery or surgery, WBRT can be withheld if serial imaging for follow-up is performed. For patients undergoing surgery for a single brain metastasis, postoperative local irradiation is an option that should be investigated as adjuvant irradiation substantially reduces the risk of tumor bed recurrence
- 20. For selected patients with poor life expectancy (less than 3 months), the use of whole brain radiotherapy may or may not significantly improve symptoms from brain metastases. Comfort measures only, or short course (20 Gy in 5 daily fractions) whole brain radiotherapy, are reasonable option There is 1 on-going Medical Research Council trial (Quartz) that randomizes patients to optimal supportive care using dexamethasone versus optimal supportive care using dexamethasone and whole brain radiotherapy for patients with inoperable brain metastases from non-small cell lung cancer. Outcomes of interest include quality of life, overall survival, and side effects. Supportive care
- 21. Optimum Dosage Some common dose fractionation: • 30 Gy in 10 daily fractions • 20 Gy in 5 daily fractions. • 37.5 Gy in 15 daily fractions a • 40 Gy in 20 daily (or twice daily) fractions • There is no difference in overall survival or symptom control. No altered dose fractionation scheme has shown improvement in either survival or symptom control (neurologic functional status, neurologic symptom relief, palliative index, or performance status) as compared with 20 Gy in 5 fractions or 30 Gy in 10 fractions of daily WBRT. Graham PH, Bucci J, Browne L. Randomized comparison of whole brain radiotherapy, 20 Gy in 4 daily fractions versus 40 Gy in 20 twice-daily fractions for brain metastases reveals primary endpoint of brain progression favored patients treated with 40 Gy in 20 twice daily fractions (44% vs 64%, P= .03).
- 22. different dose fractionation schedules in the setting of single brain metastasis treated with surgery, dose fractionation schedules of WBRT in the setting of upfront WBRT with radiosurgery or in the setting of WBRT at the time of salvage after radiosurgery alone,neurocognitive outcomes were not considered in any trial. WBRT and radiosensitizers More trials are needed to make a decision to use of radiosensatizers. RSR-13 in breast cancer and motexafin gadolinium in preventing the neurologic progression in nsclc are ceported but US-FDA has not approved it. The chemotherapy agents used were chloroethylnitrosoureas, teniposide, fotemustine, temozolomide, thalidomide, and topotecan used in almost 8 trials, No survival difference was seen between early versus delayed WBRT with chemotherapy Chemotherapy and WBRT
- 25. The most important endpoint should be the deciding factor for which treatment is most appropriate. For selected patients with single brain metastasis, the use of surgery or radiosurgery has been shown to improve survival and this should be the primary consideration. Treatment options which have been shown to improve whole brain control (such as the use of WBRT) or local brain control (such as the use of radiosurgery) without survival benefit for selected multiple brain metastases patients are more difficult in terms of best treatment choice. The most important outcome likely is quality of life (taking into account the morbidity of symptomatic brain recurrence and the morbidity of treatment such as neurocognitive decline, which may be associated with the use of WBRT or the side effects associated with the prolonged use of dexamethasone). Quality of life has inconsistently been measured in these trials and drop-outs are a problem with assessing this endpoint conclusion