DIPG-57. INITIAL AND EARLY METASTATIC SPREAD IN DIPG AND DIFFUSE MIDLINE GLIOMA, H3 K27-ALTERED - REPORT FROM THE EUROPEAN SOCIETY FOR PEDIATRIC ONCOLOGY (SIOPE) AND INTERNATIONAL DIPG/DMG REGISTRIES

Abstract

Abstract BACKGROUND We aimed to assess frequency, patterns and potential prognostic impact of initial and early dissemination in pediatric patients with diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma, H3K27-altered (DMG). METHODS 199 patients (age, 0-18 years) with DIPG/DMG and positive CSF cytology and/or metastases on MRI at diagnosis (Types 1-3) were identified within the SIOPE and International DIPG/DMG Registries. Data on metastatic first progression (PD) in DIPG/DMG (Type 4) were analyzed from the HIT-HGG-2007/2013 trials. RESULTS Dissemination at diagnosis was present in 5% of patients with DIPG/DMG (16.9% in non-pontine DMG). For all 199 patients with initially disseminated pontine (n=166) and non-pontine DMG (n=33), median overall survival (OS) was 10±0.5 months and progression-free survival (PFS) was 6.6±0.2 months. Tumor cells in the CSF without metastases on initial MRI (Type 1) were detected in 12 patients. Four patients had no primary tumor but primary extensive leptomeningeal dissemination resembling diffuse leptomeningeal glioneuronal tumor, molecularly confirmed as DMG, with aggressive course (Type 2). 183 DIPG/DMG patients were identified with primary tumor and metastases on MRI at diagnosis (Type 3). OS and PFS was superior in patients receiving additional treatment to radiotherapy (n=124), without significant differences between focal and craniospinal irradiation. Metastatic spread at first progression (Type 4) occurred in 32.1% (65.3% in non-pontine DMG) of 224 HIT-HGG patients with DMG and recorded PD. OS of patients with metastatic PD was inferior to local PD (median, 10.8±0.9 vs. 13.3±0.9 months, p=0.005), as was post-progression survival (median, 3.1±0.4 vs. 5.2±0.5 months, p=0.003). CONCLUSIONS We observed a propensity for early dissemination in (especially non-pontine) DMG. While additional treatment beyond radiotherapy seems beneficial, preventing dissemination at progression (e.g., by upfront CSI) may help to prolong survival of patients with DMG and possibly provide options for further therapy.