Clinical Relevance of BRAF V600E Mutation Status in Brain Tumors with a Focus on a Novel Management Algorithm

The possible application of BRAF-targeted therapy in brain tumors is growing continuously. We have analyzed clinical strategies that address BRAF activation in primary brain tumors and verified current recommendations regarding screening for BRAF mutations. There is preliminary evidence for a range of positive responses in certain brain tumor types harboring the BRAF V600E mutation. National Comprehensive Cancer Network Guidelines for central nervous system cancers recommend screening for the BRAF V600E mutation in pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and ganglioglioma. We suggest additional testing in glioblastomas WHO grade IV below the age of 30 years, especially those with epithelioid features, papillary craniopharyngiomas, and pediatric low-grade astrocytomas. BRAF-targeted therapy should be limited to the setting of a clinical trial. If the patient harboring a V600E mutation does not qualify for a trial, multimodality treatment is recommended. Dual inhibition of both RAF and MEK is expected to provide more potent and durable effects than anti-BRAF monotherapy. First-generation RAF inhibitors should be avoided. Gain-of-function mutations of EGFR and KIAA fusions may compromise BRAF-targeted therapy. BRAF alterations that result in MAPK pathway activation are common events in several types of brain tumors. BRAF V600E mutation emerges as a promising molecular target. The proposed algorithm was designed to help oncologists to provide the best therapeutic options for brain tumor patients.