ID #1087 Clinical Characteristics and Outcomes of Pediatric Diffuse High-Grade Gliomas in the WHO 2021 Era: A Nationwide Multicenter Cohort Study in Japan

Abstract Background Pediatric diffuse high-grade gliomas (DHGGs) are rare but highly lethal tumors. Following the 2021 WHO classification, real-world data describing molecular subtypes, clinical characteristics, and outcomes remain limited. We conducted a nationwide multicenter cohort study to characterize pediatric DHGGs in Japan and to identify key prognostic factors. Methods Clinical, pathological, and molecular data were retrospectively analyzed from the Japan Children’s Cancer Group registry, including patients aged 0–19 years diagnosed with DHGGs between 2009 and 2024 across 104 institutions. Tumors were classified according to the 2021 WHO criteria when molecular data were available. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan–Meier analysis. Results Among 900 pediatric patients with gliomas, glioneuronal, or neuronal tumors, 226 were diagnosed with DHGGs (median age 8.8 years). Tumors were hemispheric in 53.5% and midline in 46.5%. Major subtypes included diffuse midline glioma, H3K27-altered (DMG-H3K27; n = 54), pediatric-type diffuse high-grade glioma, H3/IDH-wildtype (pHGG H3/IDH WT; n = 75), diffuse hemispheric glioma, H3 G34-mutant (n = 9), infant-type hemispheric glioma (n = 12), and high-grade astrocytoma, IDH-mutant (n = 4). Median OS and PFS for the entire cohort were 24.0 and 17.0 months, respectively. Midline tumors had significantly worse OS than hemispheric tumors (14.9 vs. 31.7 months; P 0.001). Gross total resection was associated with improved OS (P = 0.011). Radiation-induced high-grade gliomas (RIGs) were more frequent in DHGGs than in other tumor types (4.9% vs. 0.3%) and showed significantly poorer OS (11.9 vs. 24.7 months; P = 0.012). Cancer predisposition syndromes were identified in 2.7% of DHGGs. Conclusions In this nationwide cohort, prognosis of pediatric DHGGs was strongly influenced by tumor location, extent of resection, and prior radiotherapy. RIGs represent a rare but extremely high-risk subgroup, highlighting the need for improved surveillance and therapeutic strategies.