LGG-59. DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR; MOLECULAR IMPLICATIONS ON PROGNOSIS

Abstract

Abstract BACKGROUND Diffuse leptomeningeal glioneuronal tumors (DLGNTs) are extremely rare tumors that were first described in the WHO Classification in 2016. While usually considered low-grade tumors, DLGNTs currently lack a standard of care as well as literature on molecular profiling and treatment responses. METHODS Retrospective review of pediatric DLGNTs seen at MD Anderson Cancer Center with Institutional Board Review approval. RESULTS Twelve patients with a histopathological and neuroradiological diagnosis of DLGNT were identified with a median age at diagnosis of 7.5 years (range 4 months – 21 years). Histologically, 10/12 (83%) tumors were low-grade while 2 were reported as high-grade. BRAF gene alterations were reported in 50% (6/12; 4 fusions and 2 mutations). Other reported genetic alterations were mutations [PTPN11 (n=2), PIK3CA (n=1), FGFR1 (n=1), ALK (n=1)], amplifications [NOTCH1 (n=1) and STK11(n=1)], and fusion [NTRK (n=1)]. Upfront, 9 patients received chemotherapy including temozolomide (n=5), carboplatin (n=4), and vincristine (n=4) or vinblastine (n=1). Nine patients (88%) received proton radiation, including 5 upfront and 4 upon progression. Targeted therapy [NTRK (n=1), BRAF (n=1) or MEK inhibitors (n=6)] was initiated upon progression in 8 patients, and at diagnosis in one. The median progression-free survival (PFS) in the group receiving upfront chemoradiation (n=3) is 57 months versus chemotherapy alone (n=6) of 30.5 months, and 26.7 months for radiotherapy alone (n=3). The PFS at 2 years and 5 years were 58.3% and 17% respectively; OS was 100% at both time intervals. BRAF genetic alterations and younger age trended toward a worse outcome, hence upfront targeted therapy may be warranted when radiation needs to be avoided. CONCLUSION In our experience, DLGNTs are more commonly low-grade with frequent BRAF gene alterations; upfront chemoradiation provided the longest PFS compared to chemotherapy or radiation alone. In the absence of established standard of care, our case series emphasizes the potential role of targeted therapy upfront for younger patients and progressive disease post-chemoradiation. Larger prospective, collaborative studies are greatly needed for DLGNTs.