Impact of the Timing of Brain Radiation in Melanoma Patients with BRAF Mutations Who Developed Brain Metastases

Abstract

With the known intracranial activity of BRAFi, it is unclear in BRAF-mutated melanoma patients with brain metastases whether brain radiation should be given upfront at the time of brain metastasis diagnosis or at the time of progression on BRAFi alone. A total of 102 patients at a single institution with BRAF-mutant melanoma who developed brain metastases were included in this retrospective study. Exclusion criteria included prior BRAFi use, or insufficient follow-up. All patients received BRAFi and brain radiation (WBRT or SRS), and they were separated into 2 groups by chronology of treatment: Group A (n=83) received upfront intracranial radiation (prior to initiation of BRAFi or within <30 days of initiation of BRAFi); and Group B (n=19) received brain radiation for salvage (>30 days after initiation of BRAFi treatment). Kaplan-Meier analysis was used to estimate OS (overall survival) and intracranial PFS (progression free survival, defined as no development of a new or growth of a pre-existing lesion), whereas log-rank testing was used to assess for differences. The median OS of Group A and Group B was 15.5 and 12.4 months, respectively (p = 0.52). There was no difference in the OS between the two groups at 6, 12, 18, or 24 months. There was a trend for better median intracranial PFS for Group A, but this did not reach statistical significance (6.2 vs. 4.4 months, p=0.067). At 6 months the intracranial PFS was significantly better for Group A (60.2% vs 31.6%, p=0.04), but not at 12 months (34.9% vs 10.5%, p=0.051), or 24-month intracranial PFS (31.3% vs 10.5%, p=0.088) This single-institution small retrospective analysis showed that the timing of brain radiation delivered either upfront at the time of BM diagnosis or at the time of salvage for progression in BRAFi, did not impact patient’s OS. Although upfront brain radiation did improve 6-month intracranial PFS compared to delayed radiation, such benefit from upfront brain radiation was lost at later time points. A larger, multi-institutional retrospective review or a prospective study is needed to further tease out the significance of the timing of brain radiation in this patient population.