Anatomic Staging of H3 G34-Mutant Diffuse Hemispheric Glioma.

Abstract

H3 G34-mutant diffuse hemispheric gliomas are rare, aggressive primary brain tumors predominantly affecting young patients. We investigated the prognostic value of anatomic staging (AS)-a system previously validated in adult-type diffuse gliomas-in this molecularly distinct tumor type. Patients from an international cohort with H3 G34-mutant gliomas underwent AS based on pretreatment imaging, performed independently by 2 raters blinded to clinical outcomes. Inter-rater reliability was evaluated using Cohen kappa. Kaplan-Meier curves and Cox proportional hazards models-unadjusted and adjusted for sex, extent of resection, and O6-methylguanine DNA-methyltransferase (<i>MGMT</i>) status-were used to analyze overall survival across stages. Thirty-seven patients were included (median age 22 years; 54% female). Inter-rater reliability was high (weighted κ = 0.93, 95% CI 0.85-1.0). Median overall survival was 36 months for stage 1 (95% CI 16-67 months), 25 months for stage 2 (95% CI 8-41), and 9 months for stage 3 (95% CI 3-26). After adjustment for sex, extent of resection, and <i>MGMT</i> status, survival differences persisted (hazard ratio [HR]_{Stage 2 adjusted} 2.25, 95% CI 0.67-7.5, <i>p</i> = 0.19; HR_{Stage 3 adjusted} 4.37, 95% CI 1.39-13.7, <i>p</i> = 0.01). AS is reproducible and prognostically relevant for H3 G34-mutant gliomas, providing insights into tumor spread. It may inform treatment decisions, but larger studies are needed to confirm its clinical utility.