HGG-49. Gliomatosis cerebri in children: A collaborative report from the European Society for Pediatric Oncology (SIOPE)

Abstract

Abstract BACKGROUND: Gliomatosis cerebri (GC), a radiologically defined diffusely infiltrating glioma, is no longer considered a distinct entity since the 2016 WHO classification for tumors of the CNS. Due to its rarity and dismal prognosis treatment recommendations in children remain ambiguous. Using central neuroradiological review, we performed a multi-institutional, retrospective study of GC providing comprehensive radiological, clinical, and (epi)genetic characterization. RESULTS: We included 104 patients between 1-19 years. Within a median follow-up of 15.5 months (range, 2.3-138.8), 93 patients (89.4 %) had died, 4 (3.8 %) were lost to follow-up and 7 (6.8 %) were alive with stable/progressive disease. Median progression-free- (PFS) and overall survival (OS) were 8.6 months (interquartile range, 4.3-14.0) and 15.5 months (10.9-27.7), respectively. Former WHO grading correlated significantly with median OS: WHO °II: 47.8 months (25.2-55.7); WHO °III: 15.9 months (11.4-26.3); WHO °IV: 10.4 months (8.8-14.4) (p<0.001). In high-grade gliomas (HGG), radiochemotherapy showed best PFS (p=0.002). Compared to hemispheric pediatric non-GC HGG, GC phenotype was associated with decreased OS (p=0.001). Methylation-based classification and exome sequencing were possible for 49 and 45 patients, respectively. According to the 2021 WHO classification, most cases were considered as IDH-/H3-wildtype gliomas (n=37/49, 75.5 %), mostly with a pedRTK2 subtype (n=15, 30.6%), followed by pedMYCN (n=5, 10.2 %). Within the IDH-/H3-wildtype gliomas, EGFR-altered tumors (n=10) seemed overrepresented. Survival analyses revealed a better OS for IDH1-mutant tumors (n=6; 54.6 vs. 15.2 months in IDH-wildtype; p=0.015) and a worse OS for TP53-mutant tumors (n=6; p=0.001). Despite the potential overrepresentation of EGFR-altered tumors, no other specific molecular markers for GC could be identified so far. Further analyses are ongoing. CONCLUSIONS: GC in children is confirmed as a poor prognostic phenotype include various epigenetic pediatric glioma subtypes, without a proven (epi)genetic mark of its own. The relevance of overrepresented EGFR alterations has to be determined yet.