CNSC-70. Response to Selumetinib in a Neurofibromatosis 1 Patient With High-Grade Astrocytoma With Piloid Features Complicated by Leptomeningeal Dissemination

High-grade astrocytoma with piloid features (HGAP) is a recently recognized central nervous system (CNS) tumor characterized by a distinct methylation profile. HGAP is incorporated in the 2021 World Health Organization (WHO) classification of CNS tumors as a circumscribed astrocytic tumor, but it frequently harbors genetic alterations in the mitogen-activated protein kinase (MAPK) pathway and cyclin-dependent kinase (CDKN) 2A/B homozygous deletion mutations seen in diffuse astrocytomas. A strong association with neurofibromatosis type 1 (NF1) has also been identified. While there is no formal histopathologic grading assigned to HGAPs, the estimated five-year survival rate is approximately 50%, intermediate between that of glioblastomas and IDH-mutant gliomas. Currently, there is no HGAP-specific treatment protocol. Management typically follows glioblastoma treatment guidelines, including maximal safe surgical resection followed by concurrent chemoradiotherapy with temozolomide. Notably, NF1-associated HGAPs may exhibit sensitivity to targeted therapies such as mammalian target of rapamycin (mTOR) and MAPK pathway inhibitors, including MEK inhibitors. HGAPs have the potential for leptomeningeal dissemination, which portends a poorer prognosis and is often managed palliatively. A phase II trial of the oral MEK1/2 inhibitor selumetinib (25mg/m2 twice daily) demonstrated a 40% partial response rate in pediatric patients with recurrent, refractory, or progressive NF1-associated gliomas. We present the case of a 31-year-old patient with NF1 and a left thalamic HGAP who underwent standard chemoradiation and subsequently developed out-of-field leptomeningeal disease involving the cauda equina. Following re-irradiation to the lumbosacral spine, selumetinib 25mg/m2 twice daily was initiated. Four months later, follow-up magnetic resonance imaging showed interval stability or slight reduction in disease burden. This case highlights the potential therapeutic relevance of MAPK pathway inhibition in NF-1-associated HGAP with leptomeningeal dissemination and supports further exploration of MEK inhibition in this setting.