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

Abstract Background Brain metastases are a common problem in patients with melanoma but little is known about the effect of gene mutations on survival in these patients Methods We 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). Results BRAF 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