MDB-05. Personalized, Risk Adapted Therapy for Pediatric Patients With Medulloblastoma – A Single Center 8-Year Retrospective Review

Abstract BACKGROUND Clinically relevant risk stratification and optimal therapies for pediatric medulloblastoma molecular subgroups are still being investigated. METHODS We reviewed host/disease characteristics, patient/tumor specific risk adapted therapy and outcomes of patients treated for medulloblastoma at UC Davis since 2016. RESULTS Fifteen patients (age 1-19 years, 12 male, 3 with Li Fraumeni Syndrome (LFS), 2 with spinal cord disease) were included in our review. Tumor histologies included: Classic (n=8), Desmoplastic-Nodular (n=6), Anaplastic (n=1). Tumor genomic profiles were SHHP53WT(n=5), SHHP53 mutated (n=4), Group4 (n=3), NWNSHH (n=2), WNT (n=1). Gross total resection was achieved in 9 patients. Patients with post resection residual tumor, high risk genomic features or disseminated disease were stratified as high risk. We treated all radiation eligible patients (n=13) per COG ACNS0332 maintenance chemotherapy regardless of risk group with 12/13 receiving radiosensitization (Vincristine/Carboplatin) and either 23.4 Gy/36 Gy CSI (two patients treated per Headstart3D2 and ACNS0334 respectively). 2 patients with spinal cord disease were treated with intrathecal topotecan and liposomal cytarabine respectively. During ACNS0332 maintenance bacteremia, weight loss and hypomagnesemia were frequent complications. 5 patients required chemotherapy dose reductions (4 Vincristine/1 Cisplatin). Two patients with LFS developed glioblastoma/undifferentiated pleomorphic sarcoma following ACNS0332 therapy. Two patients (with WNT and NWNSHH subgroup tumors) experienced medulloblastoma relapse. These patients were treated using LITT/Intrathecal chemotherapy and ACNS0821 chemotherapy. Both are alive and one patient is NED off therapy. All patients who have not developed secondary malignancies (n=13) are alive. (follow up 7-72 months). All attend school with support, 10 have hearing impairment and 5 receive endocrine supplements. CONCLUSIONS Utilizing patient specific risk adapted therapy we have achieved favorable clinical outcomes in our patient cohort. Therapy deintensification for patients with WNT medulloblastomas should be approached with caution. Patients with LFS might require radiation sparing therapeutic protocols for longer term benefit.