Purpose: Knowledge regarding prognostic factors and long-term survival for patients with diffuse hemispheric glioma, H3 G34-mutant (DHG, H3 G34) is limited in this poor-outcome tumor.
Experimental design: This retrospective, multi-institutional study investigated prognostic variables for patients with DHG, H3 G34 and their association with progression-free survival (PFS) and overall survival (OS). Univariable and multivariable Cox proportional hazard models were applied with multiple imputed data sets.
Results: One hundred fifty-three patients (142 G34R, 9 G34V, 2 via DNA methylation) were included. Median age at diagnosis was 17 years (range, 2-45). Initial gross/near total resection (GTR/NTR) was achieved in 43% of patients. Radiation was given in 91% (85% focal irradiation) and initial chemotherapy in 87% (70% temozolomide-based (TMZ), 25% TMZ/CCNU, 5% non-TMZ). Median OS was 24 months (interquartile range [IQR], 22-28) with a median PFS of 14.0 months (IQR 12.0-19.0). Twelve patients (8%) were found to be long-term survivors ≥ 5 years. Exploratory multivariable analysis showed adjuvant radiation therapy (HR 0.076, 95% CI 0.033, 0.17) and achieving GTR/NTR compared to < NTR (HR 0.51, 95% CI 0.33, 0.78) were associated with improved PFS. Multivariable analysis showed improved OS with increasing age at diagnosis (HR 0.70, 95% CI 0.57, 0.87), initial radiation therapy (HR 0.38, 95% CI 0.15, 0.96), and initial GTR/NTR compared to < NTR (HR 0.60, 95% CI 0.37, 0.97).
Conclusion: This cohort highlights prognostic factors for patients with DHG, H3 G34, describes relapse patterns, and therapy approaches. Clinical trials and prospective registries are needed to improve outcomes.