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. 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). 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. 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.
Jeeva et al. (Wed,) studied this question.