Clinical Outcomes and Prognostic Features of Diffuse Hemispheric Glioma, H3 G34-Mutant: An International Multi-institutional Study.
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PURPOSE: Knowledge of prognostic factors and long-term survival in patients with diffuse hemispheric glioma, H3 G34-mutant (DHG, H3 G34), remains limited in this tumor with a poor prognosis. 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). Uni- and multivariable Cox proportional hazard models were applied with multiple imputed datasets. RESULTS: A total of 153 patients (142 G34R, 9 G34V, 2 via DNA methylation) were included. The 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 was given in 87% [70% temozolomide-based (TMZ), 25% TMZ/lomustine, 5% non-TMZ]. Median OS was 24 months [interquartile range (IQR), 22-28] with a median PFS of 14 months (IQR, 12-19). Twelve patients (8%) were found to be long-term survivors (≥5 years). Exploratory multivariable analysis showed that adjuvant radiotherapy [HR, 0.076; 95% confidence interval (CI), 0.033-0.17] and achieving GTR/NTR compared with < 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 radiotherapy (HR, 0.38; 95% CI, 0.15-0.96), and initial GTR/NTR compared with < NTR (HR, 0.60; 95% CI, 0.37-0.97). CONCLUSIONS: This cohort highlights prognostic factors for patients with DHG, H3 G34, and describes relapse patterns and therapy approaches. Clinical trials and prospective registries are needed to improve outcomes.