MEDB-27. Clinico-Radiological Outcomes in WNT-pathway Medulloblastoma: Retrospective Single Institutional Audit

BACKGROUND: Medulloblastoma (MB) is a heterogeneous disease comprising 4 molecular subgroups - wingless (WNT), sonic hedgehog, Group 3, and Group 4 tumors - with distinct developmental origins, diverse clinico-demographic characteristics, unique transcriptional profiles, and widely varying outcomes. WNT-MB is associated with the best outcomes (5-year survival >90%) prompting attempts at treatment de-escalation to reduce late toxicity. We undertook a clinical audit of WNT-MB patients treated at our tertiary-care comprehensive cancer centre. METHODS: Patients with molecularly confirmed WNT-MB treated with maximal safe resection followed by post-operative standard-of-care risk-stratified adjuvant radio(chemo)therapy were identified retrospectively via electronic search of the neuro-oncology database. Data regarding clinico-demographic characteristics, histo-molecular features, treatment details, patterns of failure, and survival outcomes was retrieved from electronic medical records and/or hospital case files. Time-to-event outcomes were analyzed using Kaplan-Meier methods and compared with the log-rank test. RESULTS: Between 2004 to 2018, a total of 65 patients of WNT-MB were registered at our institute. Five patients treated on a prospective clinical trial of therapy de-intensification were excluded leaving 60 patients that constitute the present study cohort. Median age at presentation was 12 years (inter-quartile range 9-18 years) with male preponderance (2:1). Six patients (1 post-operative mortality and 5 without adequate details of treatment or outcomes) were excluded from the survival analysis which was restricted to 54 patients. At a median follow-up of 66 months, Kaplan-Meier estimates of 5-year progression-free survival and overall survival were 87.9% and 92.8% respectively. Traditional high-risk features such as age, residual tumor (>1.5cm(2)) and leptomeningeal metastases (M+) did not emerge as significant prognostic factors for survival in this molecularly-characterized WNT-MB cohort. CONCLUSION: WNT-MB patients have excellent survival outcomes irrespective of traditional high-risk features suggesting the need for more tailored and refined risk-stratification with potential de-intensification of therapy. ACKNOWLEDGEMENTS: Brain Tumor Foundation (BTF) of India