Comparative analysis of clinical characteristics and prognostic factors in adult and pediatric patients with H3K27M-mutant diffuse midline glioma

H3K27M-mutant diffuse midline glioma (H3K27M-DMG) is a lethal brain tumor predominantly affecting children but increasingly recognized in adults. Emerging evidence suggests potential differences in clinical behavior and survival outcomes between pediatric and adult patients. However, comparative studies remain scarce, and the impact of age on disease progression and treatment response is poorly understood. We conducted a retrospective analysis of 105 patients (51 adults, 54 children) diagnosed with H3K27M-DMG at West China Hospital between January 2016 and August 2021. Clinical data, including demographics, tumor characteristics, treatment modalities, and survival outcomes, were collected. Our analysis revealed that pediatric patients exhibited a shorter median overall survival (OS) than adults (pediatric median OS: 3.65 months [95% CI, 2.73-4.40] vs. adults' median OS: 7.37 months [95%CI, 4.27-13.90]; p = 0.0012). Lower KPS scores and omission of radiotherapy/chemotherapy independently predicting poorer outcomes in both cohorts (all p < 0.01). While elevated Ki67 expression correlated with adverse prognosis in adults (p = 0.011), no molecular markers showed significance in pediatric patients. Best median OS was achieved with trimodality therapy (surgery, radiation, and chemotherapy) across all age groups. This study provides a comprehensive comparative analysis of clinicopathological characteristics and survival outcomes between pediatric and adult H3K27M-DMG patients. Through multivariate analysis, we identified key independent prognostic factors. Low preoperative Karnofsky Performance Scale (KPS) score was an independent risk factor in the pediatric cohort, whereas both low preoperative KPS score and omission of radiotherapy were independent risk factors in the adult cohort. This study highlights distinct age-specific risk profiles in H3K27M-DMG, emphasizing that prognostic stratification and treatment strategies should be tailored accordingly for pediatric versus adult patients.