The Prognostic Value of BRAF, cKIT and NRAS Mutations in Melanoma Patients with Brain Metastases

Publication date: Available online 29 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Paul W. Sperduto, Wen Jiang, Paul D. Brown, Steve Braunstein, Penny Sneed, Daniel A. Wattson, Helen A. Shih, Ananta Bangdiwala, Ryan Shanley, Natalie A. Lockney, Kathryn Beal, Emil Lou, Thomas Amatruda, William A. Sperduto, John P. Kirkpatrick, Norman Yeh, Laurie E. Gaspar, Jason K. Molitoris, Laura Masucci, David Roberge, James Yu, Veronica Chiang, Minesh Mehta
BackgroundBrain metastases are a common problem in patients with melanoma but little is known about the effect of gene mutations on survival in these patientsMethodsWe created a retrospective multi-institutional database of 823 patients with melanoma and brain metastases, diagnosed between 2006-2015. Clinical parameters, gene mutation status (BRAF, C-KIT, NRAS) and treatment were correlated with survival.. Treatment patterns and outcomes were compared to a prior era (1985-2005).ResultsBRAF status was known in 584/823 (71%) of patients. BRAF, NRAS and C-KIT mutations were present in 51, 22 and 11% of tested patients, respectively. Median time from primary diagnosis to brain metastasis (TPDBM) was 32 months and overall median survival (MS) from the time of initial treatment for brain metastases was 10 months. MS for BRAF-positive and BRAF-negative patients was 13 and 9 months (p=0.02), respectively. There was no significant difference in MS in patients with or without NRAS or C-KIT mutations. TPDBM did not vary by mutation and was not associated with survival after the diagnosis of brain metastases. MS for the 1985-2005 and 2006-2015 cohorts were 6.7 and 10.0 months (p<0.01). Reflecting treatment-trend changes, use of whole brain radiation therapy dropped from 48 to 26% during this period. Among BRAF-positive patients, 71% received targeted BRAF/MEK inhibitors and 57% received some combination of targeted therapy, chemotherapy or immunotherapy.ConclusionFor melanoma patients with brain metastases, BRAF-positive patients survive longer than BRAF-negative patients and overall survival has improved from 1985-2005 to 2006-2015.

Teaser

This retrospective study of gene mutations in 823 melanoma patients with brain metastases shows BRAF-positive patients survive longer than BRAF-negative patients after the diagnosis of brain metastases and that overall survival for these patients diagnosed from 2006-2015 is improved compared to 1985-2005.


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