Clinical and Molecular Divergences in Diffuse Midline Glioma, H3 K27-Altered: A Comparative Study of Survival Outcomes in 1498 Adults and Children

Abstract Introduction Diffuse midline glioma, H3 K27-altered (DMG), is a highly lethal brain tumour that predominantly affects children but is increasingly diagnosed in adults. This study aims to compare the clinical features, molecular profiles, and survival outcomes between these groups. Method PubMed and EMBASE searches (June 2021) identified 82 studies with 1,498 patients (34.7% adults). Individual patient data were reconstructed from Kaplan–Meier curves where necessary. Cox regression analyses were used to compare the overall survival (OS) and progression-free survival (PFS) between adults and children, with subgroup analyses for age effects on OS. Result Adults demonstrated longer median OS than children (16.2 vs 11.4 months, p < 0.05) and longer PFS (9.17 vs 7.2 months, p < 0.05). Brainstem involvement was significantly less common in adults than in children (22.6% vs 78.7%). Among patients with brainstem tumours, adults had longer OS, whereas survival was similar between age groups in non-brainstem tumours. Molecular data were limited, available in only 14.2–37.1% of cases. Adults had higher rates of PPM1D (37.0% vs 12.6%), FGFR1 (17.1% vs 5.6%), and NF1 (35.1% vs 12.3%) mutations, and lower rates of ACVR1 mutations (5.0% vs 24.1%). FGFR1, NF1, and TP53 mutations were prognostic in both age groups. Conclusion Adults with DMG have longer OS compared to children, with the survival advantage confined to brainstem tumours and not observed in non-brainstem tumours. Whether this reflects intrinsic biological differences or tumour location remains uncertain. Prospective studies with comprehensive molecular profiling are needed to better define differences in DMG biology across the age groups.