21 Integrated Clinical and Molecular Landscape of Disseminated Pediatric Low-Grade Glioma

Pediatric-type low-grade gliomas (PLGG) are the most common central nervous system (CNS) tumor in children. Many are indolent and have excellent outcomes, however some inexplicably spread throughout the CNS leading to increased morbidity and mortality. To better understand this rare and difficult-to-treat entity, as well as the underlying processes driving dissemination in CNS tumors, we assembled a large international cohort (n=269) of patients with disseminated PLGG with detailed clinical and molecular characterization. We identified three subgroups of patients based on the temporal and spatial distribution of dissemination. Tumors with diffuse leptomeningeal spread without a primary tumor mass and those occurring in infants had the worst clinical outcomes. The genetics overlapped substantially with that of non-disseminated PLGG, suggesting that non-genetic mechanisms are an important contributor to dissemination. Therapeutically, targeted MAPK-pathway inhibition was more effective than conventional chemotherapy as first or second-line treatment. In sum, this cohort increases our clinical and biological understanding of this rare disease, provides insights for improving patient care, and directs future clinical trials and basic science research.