HGG-49. Gliomatosis cerebri in children: A collaborative report from the European Society for Pediatric Oncology (SIOPE)
Authors: Nussbaumer Gunther , Benesch Martin , Gielen Gerrit H , Castel David , Grill Jacques , Alonso Roldán Marta M , Antonelli Manila , Bailey Simon , Baugh Joshua N , Biassoni Veronica , Carai Andrea , Colditz Niclas , Colefati Giovanni Stefania , Corbacioglu Selim , Crampsie Shauna , Entz-Werle Natacha , Eyrich Matthias , Frühwald Michael C , Garrè Maria Luisa , Gerber Nicolas U , Giangaspero Felice , Gil-da-Costa Maria João , Grabovska Yura , Graf Norbert , Hargrave Darren , Hauser Peter , Hoffmann Marion , Hulleman Esther , Jacobs Sandra , Karremann Michael , Kattamis Antonis , Kebudi Rejin , Kortmann Rolf-Dieter , Kwiecien Robert , Mackay Alan , Massimino Maura , Miele Evelina , Mastronuzzi Angela , Morana Giovanni , Noack Claudia M , Pentikainen Virve , Perwein Thomas , Pfister Stefan M , Pietsch Torsten , Roka Kleoniki , Rossi Sabrina , Rutkowski Stefan , Schiavello Elisabetta , Štěrba Jaroslav , Sturm Dominik , Sumerauer David , Temelso Sara , van Vuurden Dannis , Varlet Pascale , Veldhuijzen van Zanten Sophie E M , Vinci Maria , von Bueren André O , Warmuth-Metz Monika , Wesseling Pieter , Wiese Maria , Wolff Johannes E A , Zamecnik Josef , Jones David T W , Bison Brigitte , La Madrid Andrés Morales , Jones Chris , Kramm Christof M 
Published: June 2022

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&lt;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.