Radiation Oncology/Melanoma/Metastatic

Metastatic Melanoma

Overview

Prognostic factors:

• Balch et al, 1983 - PMID 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 ^,. 10% of pts with melanoma ultimately develop brain mets. 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 diagnosis. 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 - PMID 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 - PMID 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) - PMID 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 - PMID 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 - PMID 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) - PMID 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 - PMID 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) - PMID 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 - PMID 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) PMID 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 PMID 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) PMID 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 PMID 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