Outcomes From a Contemporary Mono-Institutional Cohort of Histone-Mutant Diffuse Hemispheric Glioma: A Rare and Aggressive Pediatric-Type High-Grade Primary Brain Tumor.

Background: The discovery of histone alterations has changed fundamental understanding of pediatric-type diffuse high-grade gliomas (HGG). The glycine-to-arginine (or valine) substitution at position 34 of histone H3.3 (H3 G34) is found exclusively in diffuse hemispheric glioma (DHG). This report summarizes clinical outcomes of a contemporary mono-institutional cohort of H3 G34-mutant DHG treated in low- and middle-income country setting.

Methods: Patients with biopsy-proven, molecularly-confirmed H3 G34-mutant DHG registered at a tertiary-care comprehensive cancer center between 2015 and 2023 were identified from a neuro-oncology database. Clinico-demographic characteristics, histo-molecular features, treatment details, and outcomes were retrospectively extracted from electronic medical records. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier methods and expressed as point estimates with 95% confidence intervals (CI).

Results: Twenty-five patients with H3 G34-mutant DHG, with a median age of 19 years (interquartile range [IQR] of 14-24 years), constituted the study cohort. Sixteen patients received postoperative radiotherapy (RT) while 13 patients also received temozolomide chemotherapy. At a median follow-up of 14 months, the 1-year Kaplan-Meier estimates of PFS and OS were 47% (95% CI: 30%-75%) and 63% (95% CI: 45%-87%) yielding median PFS and OS of 12 months (IQR: 6-22 months) and 15 months (IQR: 9-31 months), respectively. Older age at diagnosis (≥18 years) and administration of RT emerged as significant prognostic factors for survival.

Conclusion: H3 G34-mutant DHG is a rare, aggressive pediatric-type HGG with notable differences from adult counterparts. Recent biological insights implicating key signaling pathways provide unique opportunities to target therapeutic vulnerabilities in this enigmatic disease with universally poor prognosis.