Braf Mutation is Associated with an Improvement in Local Control for Melanoma Brain Metastases Treated with Stereotactic Radiosurgery (Srs)

Local control (LC) for brain metastases treated with stereotactic radiosurgery (SRS) depends on several factors. Besides histology, tumor size and marginal dose, evidence has also implicated a possible role of tumor mutation status on LC. BRAF is a proto-oncogene that is mutated in approximately 50% of patients with melanoma. We hypothesized that BRAF status may influence LC and retrospectively examined the outcome of melanoma brain metastases treated with GK at our institution. We identified 19 patients with 69 evaluable brain metastases from melanoma that were treated with SRS at our institution between 06/2010 and 11/2014. Patients were included only if their BRAF mutation status was known and follow-up imaging was available. Whole brain radiation was allowed, however, tumors previously treated with GK or surgery were excluded. LC of individual metastases was defined using modified RECIST criteria and compared based on BRAF mutation status using a Frailty-Cox model accounting for within-patient correlation. CNS progression was defined as either local failure or development of new lesions. Of the 19 patients, BRAF was mutated in 11 (with a total of 30 treated metastases) and wild-type in 8 (with a total of 39 treated metastases). Characteristics of these two groups of patients were similar with respect to age, gender, presence of extracranial metastases, GPA, number of metastases, mean tumor size, median marginal dose, use of whole brain radiation and follow-up duration. Among the BRAF-mutated metastases, 16/30 (53%) were exposed to a BRAF inhibitor during or prior to SRS. With a median follow-up of 17.7 months, 1-year tumor LC was significantly better among metastases with mutated BRAF (69% vs. 34%, RR = 0.3, 95% CI = 0.1-0.7, p = 0.01). Within the BRAF-mutated subgroup, there was no difference in tumor LC based on exposure to a BRAF inhibitor. There was also a trend towards improved CNS progression free survival (PFS) at 1 year (26% vs. 0%, p=0.06), favoring BRAF-mutated patients. There was no difference in overall survival between the groups. In this retrospective study we found that BRAF mutation was associated with an improvement in local control for melanoma brain metastases treated with SRS compared to those without the mutation. There was also a trend for improved CNS PFS. Our data suggest that BRAF mutation may sensitize tumors to radiosurgery, and that BRAF wild-type tumors may be more radioresistant. Additional studies will be required to fully characterize the role of BRAF mutation in LC of brain metastases treated with SRS.