IMG-24. MAPK-ALTERED PEDIATRIC LOW-GRADE GLIOMA: MRI HINTS TO EXPLAIN THE INTERPLAY BETWEEN GLIOMA AND IMMUNE CELLS

Abstract

Abstract BACKGROUND In MAPK-altered pediatric low-grade glioma (pLGG), immune infiltration may be involved in treatment response. It is debated whether tumor immune cell infiltration is due to expansion of endogenous resident microglia or to the active recruitment of bone marrow-derived microglial progenitors from the bloodstream. This study aimed to investigate the relation between neuroradiological features of MAPK-altered pLGG and treatment response to MAPK-inhibitors (MAPKi). METHODS We conducted a retrospective analysis of all patients with unresectable BRAF-V600E mutated brain pLGG, radiotherapy naïve, treated with MAPKi at our institution since 2015. MRI studies were reviewed by two experienced neuroradiologist and tumor response assessed according to RAPNO criteria. RESULTS 12 patients were enrolled (9 female). Median age at treatment start was 6.2 years (range 2.7–14.3 years). Four were pilocytic astrocytomas, 6 gangliogliomas, and 2 desmoplastic infantile gangliogliomas. Five patients received MAPKi as first line, 7 following other chemotherapy lines. Median follow-up was 4.1 years (range 2.5–8.7 years). Tumor response was associated with contrast enhancement (CE): 9 out of 10 patients with CE at treatment onset had at least partial response and subsequent CE resolution, while both 2 out of 2 patients without CE showed stable disease. A 4-year old contrast enhancing-ganglioglioma who reached partial response and CE resolution with MAPKi, presented disease progression four days after treatment withdrawal; treatment re-start determined tumor and CE reduction after only 7 days. CONCLUSIONS We hypothesize that brain-blood barrier breakage is induced by tumor infiltration of bloodstream immune cells, and that this trafficking is stimulated by tumor cell secreted products and determined by microglial progenitors shift from the bloodstream to the tumor site. MAPKi treatment may incite blood-brain barrier reconstitution as it reduces the trafficking between tumor site and bloodstream. ACKNOWLEDGEMENT This work was supported by grant number NET-2018-12366666 NeuroArtP3 from the Italian Ministry of Health.