PATH-20. CLINICAL FINDINGS AND PROGNOSIS OF ADULT GLIOBLASTOMA HARBORING A<i>BRAF V600E</i> MUTATION

Abstract BACKGROUND AND AIM Although the BRAF V600E mutation is commonly associated with pediatric low-grade gliomas, glioblastomas (GB) with this mutation (BRAF-GB) have also been reported. The recent emergence of RAF and MEK inhibitors for BRAF V600E-positive tumors highlights the potential for targeted therapy in a subset of GB patients. This study aimed to characterize the clinical features and prognosis of BRAF-mutant glioblastomas. MATERIALS AND METHODS A retrospective analysis was conducted on a cohort of patients diagnosed with GB (confirmed by 2021 WHO criteria) above 16 years of age. Targeted genetic analysis for mutations in BRAF V600E, TERT promoter, and CDKN2A/B was performed on the GB samples. Clinical features of BRAF-GB were analyzed, and patients were further categorized into three groups: BRAF-GB, typical GB, and molecular GB. Subsequent analysis compared the prognosis among these groups. RESULTS Our study identified 11 cases (5.1%) harboring the BRAF V600E mutation among 215 adult GB patients. Patients with BRAF-GB exhibited a significantly younger median age of onset (38-year-old) compared to the typical GB (N = 167, 64-year-old) and molecular GB (N = 37, 61-year-old) groups. Further analysis of the BRAF-GB cohort (n=11) revealed a high prevalence (82%) of homozygous CDKN2A/B deletions, and only one case (9%) harbored a TERT promoter mutation. Interestingly, three BRAF-GB patients presented with hemorrhagic onset. Four cases showed evidence of prior lesions, with one case diagnosed histologically as a low-grade glioma 14 years earlier. The BRAF-GB group exhibited significantly longer median progression-free survival (32.8 months) and overall survival (84.2 months) compared to both the typical GB group (9.6 months and 18.9 months, respectively) and the molecular GB group (14.1 months and 32.1 months, respectively). CONCLUSIONS Early-age onset, with hemorrhagic onset or presence of prior lesions are factors that could lead to recommendation of BRAF analysis for adult GB patients.