LGG-16. BRAFV600K LOW-GRADE GLIOMA EMERGENCE DURING THERAPY FOR BRAFV600E HIGH-GRADE GLIOMA

Abstract

Abstract BACKGROUND BRAFV600E mutations are prevalent in pediatric brain tumors, constituting 20% of low-grade and 5% of high-grade gliomas. Other single-nucleotide substitutions in BRAF are described in adult cancers but rarely in pediatric brain tumors. Our case sheds light on a unique scenario—a patient with a BRAF-mutated high-grade spinal glioma who later developed slowly progressive intracranial low-grade glioma, subsequently undergoing rapid high-grade transformation. METHODS Case Report RESULTS Our patient initially presented as a thirteen-year-old male with a two-month history of progressive bilateral hand weakness/paresthesias. Spine MRI revealed a fusiform expansile intramedullary neoplasm from C3-T2, brain MRI was negative. Biopsy showed an anaplastic astrocytoma with BRAFV600E mutation and MYC-N amplification. Initial treatment included proton radiation and a 2-year course of Dabrafenib/Trametinib, maintaining disease stability. After four months off therapy, he developed local progression, and re-staging brain MRI showed new cerebellar/supratentorial lesions. Dabrafenib/Trametinib was re-started until progression two years later. He developed hydrocephalus and underwent ETV and brain tumor biopsy, which revealed a low-grade glioma with BRAFV600K mutation. At this point, Dabrafenib/Trametinib continued for another 1.5 years; he exhibited slow progression of the brain tumors before a cerebellar lesion developed rapid progression. He had GTR of the rapid-growing lesion, and pathology reported a Grade 4 invasive astrocytoma harboring BRAFV600E, two VUS MTOR mutations, and MGMT promoter methylation. Current treatment involves radiation therapy concurrent with temozolomide. CONCLUSIONS While combinatorial Dabrafenib/Trametinib is effective in glioma therapy, resistance and progression challenges persist. Our case presents a unique manifestation—a patient with a spinal high-grade glioma with BRAFV600E who developed a secondary low-grade glioma with BRAFV600K in the brain, which, after several years, transformed into a high-grade glioma. Future research is crucial for comprehending the intricate role of BRAF mutations in pediatric gliomas, paving the way for improved patient outcomes.