Braf-V600 Mutational Status Is A Significant Associate Of Brain Metastases Recurrence In Patients With Melanoma: A Retrospective Study

Brain metastases (BM) are common in melanoma patients and carry a poor prognosis. Melanoma patients frequently harbor somatic BRAF-V600 mutations, which have been associated with the uncontrolled proliferation, radioresistance, and immune evasion of melanoma cells. The objective of this study was to investigate the prognostic value of BRAF-V600 mutational status in the progression to melanoma BM. We merged radiation oncology, neurosurgical, and cancer registry databases with molecular pathology records from a single institution to identify a retrospective cohort of 225 melanoma patients whose BRAF mutational status (BRAF-WT or BRAF-V600) had been classified. Demographic, clinicopathologic, clinical management, and outcomes data were collected from the cancer registry and electronic medical records. The primary outcome measures were the presence of BM and BM-free survival, which was defined as the time from the initial melanoma diagnosis to radiographic diagnosis of BM. A secondary outcome was survival from BM diagnosis. Eighty-three of the 225 patients (36.9%) were found to have a BRAF-V600 mutation. At primary melanoma diagnosis, BRAF-V600 mutational status was associated with a younger age (P ≤ .001), female sex (P = .0037), a more advanced AJCC pathological stage (P = .030), lymph node involvement (P = .047), and a family history of cancer (P = .044). Compared to BRAF-WT patients and other sites of metastasis, BRAF-V600 patients had a higher frequency of BM (36.1% vs 24.7%), but this result did not reach statistical significance (P = .070). American Joint Committee on Cancer pathological stage at primary diagnosis was the only factor found to be associated with BM (P = .0097). BRAF-WT and BRAF-V600 patients had median BM-free survivals of 2.49 years versus 2.80 years, respectively. After adjusting for AJCC pathological stage, BRAF-V600 mutational status was found to be an independent predictive factor for BM-free survival (HR = 0.57; P = .037). BRAF-WT and BRAF-V600 patients had median survivals from BM diagnosis of 8.7 months versus 12.7 months, respectively (P = .58). In this single center retrospective cohort, BRAF-V600 mutational status was associated with a higher frequency of melanoma BM. This study provides evidence on the prognostic importance of BRAF-V600 mutational status in the progression to melanoma BM.