PATH-29. CLINICAL OUTCOMES FOR YOUNG ADULTS WITH H3 G34-MUTANT GLIOMAS

Abstract

Abstract Diffuse hemispheric gliomas are rare brain tumors with mutations in H3F3A codon 34 which have recently been molecularly classified as their own entity. They are primarily diagnosed in adolescents and young adults and are generally associated with a poor prognosis. Given the limited published clinical data on young adults with H3 G34-mutant diffuse hemispheric glioma, we reviewed our institutional experience to evaluate clinical outcomes. We reviewed pathology reports and targeted sequencing results from patients at our institution for alterations in G34. All cases of patients 18 years or older were reviewed for baseline characteristics and clinical outcomes. Eleven patients were identified that followed at our institution since 2013. Median age at diagnosis was 24 (range 19-32) and nine were male. Three had multifocal intracranial disease at diagnosis, while 8 had localized disease. All but one underwent surgery, and all were treated with radiotherapy and temozolomide. Four received an additional investigative systemic agent for initial treatment. At time of review, 9 patients had recurred and median time to first recurrence was 6.4 months. Site of first failure was intracranial in all patients, of which three developed multifocal intracranial recurrence. Overall, 6 patients eventually developed multifocal intracranial disease and 1 patient developed leptomeningeal disease involving the spinal cord. Four patients received subsequent radiation to the brain and one received radiation to the spine. After progression, one patient received one subsequent line of systemic therapy, 7 patients received two lines, and one received three lines before they died of disease. Median overall survival from diagnosis was 20 months, and median survival from first failure was 11 months. For H3 G34-mutant glioma, survival is comparable to IDH WT Glioblastoma patients. These findings augment the existing literature on histone altered gliomas. Further investigation of patterns of failure is needed to guide optimal therapy.