H3K27M-altered diffuse midline glioma: experience and outcomes from a low-Middle income country (LMIC) setting in the contemporary era

Purpose H3K27M-altered diffuse midline glioma (DMG) is an aggressive pediatric-type high-grade glioma (HGG) arising from midline structures in the central nervous system. This report summarizes the experience with this disease entity at a tertiary-care comprehensive cancer center in a low-middle income country. Methods Patients with biopsy-proven H3K27M-altered DMG were identified from prospective database with retrospective data extraction and analysis. Following biopsy/debulking surgery, patients were treated with radiotherapy (RT) with or without temozolomide (TMZ). Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier methods and expressed as point estimates with 95% confidence intervals (CI). Results A total of 225 patients with biopsy-proven H3K27M-altered DMG were identified; survival analysis was restricted to 194 patients with outcome data. Median age at diagnosis was 20 years with 70% patients being ≥12 years of age. At a median follow-up of 12 months, 1-year PFS and OS were 30.8% (95%CI: 24.8–38%) and 46.8% (95%CI: 40–54.5%) respectively yielding median PFS and OS of 7 months (95%CI: 6–10 months) and 12 months (95%CI: 10–14 months) respectively. Leptomeningeal dissemination at initial diagnosis (10.9%) and on follow-up (24.5%) was documented in a substantial proportion of evaluable patients. Female gender, supratentorial location, debulking surgery, administration of RT, and addition of TMZ emerged as prognostic factors for survival. Conclusion Despite contemporary standard-of-care chemoradiotherapy paradigm, prognosis of H3K27M-altered DMG—an aggressive pediatric-type HGG—remains universally poor with virtually no long-term survivors. Deeper molecular insights and better elucidation of biological underpinnings are required to guide discovery of novel targeted therapeutics.