Abstract Pediatric high-grade pediatric gliomas (pHGG) and particularly diffuse midline gliomas (DMG), remain among the most lethal pediatric brain tumors. Their intrinsic resistance to radiotherapy and systemic treatments result in dismal outcome, with limited progress over the past two decades. We conducted a nationwide retrospective study across the seven Belgian pediatric oncology centers and collected data for all patients aged 0–18 years diagnosed with radiological and/or histological pHGG between January 2000 and December 2024. A total of 191 patients have been included, with a median follow-up time of 117.9 months (95% CI, 89.5- 204.2). The prevalence of a cancer predisposition syndrome (CPS) is 9%, with constitutional mismatch repair deficiency syndrome (CMMRD) being the most common syndrome, followed by Li and Fraumeni and Neurofibromatosis type 1. The molecular landscape is enriched with TP53 mutations (ten missense, six nonsenses, and three frameshift), H3F3A, PTEN, ATRX, CDKN2A, EGFR, ACVR1, NF1, BRCA2, and PDGFRA. Median overall survival was 11.4 months (10.3–13.1), with significantly worse outcomes for midline tumors compared to non-midline locations. Progression-free survival decreased markedly across subsequent treatment lines. Treatment strategies evolved over time, with a shift from intensive chemotherapy regimens toward targeted therapies, particularly in pontine DMG. Radiotherapy remained the mainstay of treatment, with increasing use of re-irradiation in recent years. Twenty short survivors (10.4%) and twelve long survivors (6.2%) were identified. More than sixteen different treatment lines have been proposed as first-line therapy; however, none of them prolonged survival. Among irradiated midline tumors, surgical treatment of hydrocephalus was associated with improved overall survival (HR 0.53, 95% CI 0.30–0.94, p = 0.031), whereas temozolomide-based chemotherapy and mTOR inhibitors did not retain independent prognostic significance. More than thirty biopsies are currently being analyzed for an in-depth multi-omics analysis, as part of the European GLIOMATCH project.
Calò et al. (Tue,) studied this question.