Radiation Oncology/Melanoma/Metastatic

Metastatic Melanoma Overview Prognostic factors: Balch et al, 1983 - 6668496 — "A multifactorial analysis of melanoma. IV. Prognostic factors in 200 melanoma patients with distant metastases (stage III)." Balch CM et al. J Clin Oncol. 1983 Feb;1(2):126-34. Systemic therapy Dacarbazine - standard of care Metastatic to brain Epidemiology Brain metastases are common in melanoma, with brain involvement found on autopsy in 49-73% of those who die from melanoma 665907 - Patel et al. Metastatic pattern of malignant melanoma. A study of 216 autopsy cases.,6850649 - de la Monte et al. Patterned distribution of metastases from malignant melanoma in humans.. 10% of pts with melanoma ultimately develop brain mets9420067 - Sampson et al. Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma.. Melanoma is the third most common cause of brain mets (after lung and breast). Brain mets present in 6.7% of pts with melanoma at the time of diagnosis15051777. Brain mets more common in males (2/3 of cases are in men). Those with brain mets were more likely to be male; have a primary lesion on the trunk, head and neck, or mucosa; or have a thick or ulcerated primary lesion. Limb primaries have a low chance of metastasizing to the brain. Median time from diagnosis of primary lesion to development of brain mets was 3.7 years. Radiotherapy Doses: 30 Gy in 10, or 20 Gy in 5. May be better outcomes for patients treated more aggressively, but that may also be due in part to selection bias. Outcome Katz, 1981 - 6171554 — "The relative effectiveness of radiation therapy, corticosteroids, and surgery in the management of melanoma metastatic to the central nervous system." Katz HR. Int J Radiat Oncol Biol Phys. 1981 Jul;7(7):897-906. Ziegler (New York University), 1986 - 3759534 — "Brain metastases from malignant melanoma: conventional vs. high-dose-per-fraction radiotherapy." Ziegler J et al. Int J Radiat Oncol Biol Phys. 1986 Oct;12(10):1839-42. Retrospective, 72 pts. No difference in outcome for standard fractionation (300 cGy/fx) and high dose per fraction (500-600 cGy/fx) to total dose of 30 Gy. U.Penn 1988 - see discussion below (All sites) Fraction size and total dose have no effect on survival Finland, 1996 (1980-1994) - 8966226 - "Radiation therapy of intracranial malignant melanoma." Isokangas OP et al. Radiother Oncol. 1996 Feb;38(2):139-44. Retrospective. 64 pts. Improved survival for those with total dose normalized to 3 Gy per fraction (NTD-3Gy) > 30 Gy versus those with <= 30 Gy. Duke University, 1998 - 9420067 — "Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma." Sampson JH et al. J Neurosurg. 1998 Jan;88(1):11-20. Netherlands, 1998 - 10098435 — "Identification of prognostic factors in patients with brain metastases: a review of 1292 patients." Lagerwaard FJ et al. Int J Radiat Oncol Biol Phys. 1999 Mar 1;43(4):795-803. University of Sydney, 2004 (1952-2000) - 15051777 — "Determinants of outcome in melanoma patients with cerebral metastases." Fife KM et al. J Clin Oncol. 2004 Apr 1;22(7):1293-300. Purpose is to determine prognostic factors. Used the database of the Sydney Melanoma Unit, which contains more than 21,000 pts treated since 1952. 1137 pts with brain mets from 1952-2000. Restricted this study to the subgroup of 686 pts with brain mets diagnosed between 1985 (when CT scanning became available) and 2000. Median survival surgery+XRT, 8.9 months; surgery alone, 8.7 mo.; XRT alone, 3.4 mo.; supportive care only, 2.1 mo. By multivariate analysis, the type of treatment and the presence of other metastases were the most important predictors of survival. Germany, 2010 - 19733017 — "Dose Escalation of WBRT for Brain Metastases from Melanoma." Rades D et al. Int. J. Radiat Oncol Biol Phys. 2010 Jun 1;77(2):537-41. Retrospective analysis of pts receiving 30/10 vs 40/20 or 45/15. Higher doses associated with better intracranial control and overall survival. All sites Germany, 1999 (1977-95) - 10348291 — "Palliative radiotherapy for recurrent and metastatic malignant melanoma: prognostic factors for tumor response and long-term outcome: a 20-year experience." Seegenschmiedt MH et al. Int J Radiat Oncol Biol Phys. 1999 Jun 1;44(3):607-18. 121 pts. Retrospective. Received RT for palliation, mostly Stage III-IV. Median RT dose 48 Gy / 21 days. 77 pts treated with conventionally fractionated RT (2-3 Gy/fx), 44 with hypofractionated (>3 - 6 Gy/fx). Very heterogeneous population. EBRT can provide local control and palliation. Total RT dose > 40 Gy associated with improved response. U.Penn, 1988 - 2460420 — "Palliative radiotherapy for metastatic malignant melanoma: brain metastases, bone metastases, and spinal cord compression." Rate WR et al. Int J Radiat Oncol Biol Phys. 1988 Oct;15(4):859-64. Retrospective. Dose and fraction size had no effect on survival for brain mets or palliation from bone mets and spinal cord compression. Tufts University; 1981 (1971-1979) 6164470 -- "Radiation therapy of malignant melanomas: an evaluation of clinically used fractionation schemes." (Strauss A, Cancer. 1981 Mar 15;47(6):1262-6.) Retrospective. 48 patients, 83 sites. Metastatic disease, local recurrence, or gross residual disease. RT fractionation evolved from standard to large dose. Endpoint palliation Outcome: Fractions 6-8 Gy response 80%. Rapid fractionation 8-4-4 Gy on successful days response 58%, may be useful for palliation Denmark; 1980 6767663 -- "Radiation treatment of malignant melanoma." (Overgaard J, Int J Radiat Oncol Biol Phys. 1980 Jan;6(1):41-4.) No abstract Yale; 1976 (1958-1974) 1000466 -- "Radiation therapy of malignant melanoma: experience with high individual treatment doses." (Habermalz HJ, Cancer. 1976 Dec;38(6):2258-62.) Retrospective. 44 metastatic lesions, 13 patients. RT various, from 2 Gy/fx to 23 Gy/fx Outcome: skin CR 31%, PR 22%. If dose >=6 Gy/fx, 88% CR/PR rate, if dose 2-3 Gy/fx, no responses Conclusion: Results are preliminary, but RT may play a useful role in management of melanoma Review MD Anderson; 1996 8977557 -- "Radiation therapy for malignant melanoma." (Geara FB, Surg Clin North Am. 1996 Dec;76(6):1383-98.) General review Unresectable local disease: most loco-regional sites 36/6 BIW; large axillary or inguinal mets 50/20 to reduce risk of limb edema and neuropathy Brain mets: 30/10, consider SRS Other sites: 20/5 or 30/10 Footnotes