Rates of symptomatic radiation necrosis appear to be higher for the BRAF inhibitor therapy group. Prospective studies investigating BRAF inhibitor therapy and SRS for melanoma brain metastases should consider incorporating methods to decrease potential radiation necrosis, including fractionating radiosurgery.
Kirtesh Patel, MD, Roshan Prabhu, MD, Mohammad K. Khan, MD; Winship Cancer Institute, Emory University; Levine Cancer Institute, Carolinas Medical Center
INTRODUCTION: Melanoma is an aggressive malignancy with a deplorable penchant for spreading to the brain. BRAF inhibitors, as single agents, have demonstrated intracranial efficacy. The 2015 National Comprehensive Cancer Network (NCCN) guidelines have raised concerns about increased toxicity when BRAF inhibitors are combined with radiotherapy, based on limited case reports. Thus, we investigate the safety and efficacy of stereotactic radiosurgery (SRS) and BRAF inhibitors for melanoma brain metastases patients.
METHODS: We reviewed melanoma patients with newly diagnosed brain metastases from 2005–2012. Radiation necrosis was compared by Fisher’s exact test; local control, intracranial control, and overall survival were estimated by the Kaplan-Meier method.
RESULTS: A total of 72 patients received SRS, with 12 (16.7%) also receiving BRAF inhibitor therapy. BRAF inhibitor patients were similar to SRS-alone patients, except for having a higher percentage of RPA class 3 patients (25.0% vs 0.0%; P = .0030) and lower rates of solitary metastases (25.0% vs 55.0%; P = .034). No significant differences between radiation therapy total dose and dose per fraction, gross tumor volume (GTV), prescription isodose line, or conformality index were identified. Rates of all grades of radiation necrosis were statistically higher in the BRAF cohorts (58.3 vs 26.7%; P = .044); furthermore, symptomatic radiation necrosis was also more frequent in the BRAF inhibitor group (41.7% vs 15.0%; P = .048). One-year local control (83.5% vs 83.5%, P = .835) and intracranial control were similar between cohorts (30.3% vs 26.3%; P = .395). One-year overall survival was higher in the BRAF inhibitor group but not statistically significant (72.7% vs 38.1%; P = .172).
CONCLUSION: Rates of symptomatic radiation necrosis appear to be higher for the BRAF inhibitor therapy group. Prospective studies investigating BRAF inhibitor therapy and SRS for melanoma brain metastases should consider incorporating methods to decrease potential radiation necrosis, including fractionating radiosurgery.
Proceedings of the 97th Annual Meeting of the American Radium Society - americanradiumsociety.org