Heterogeneous spectrum of childhood and adult SHH medulloblastoma: Clinical, radiogenomic features, patterns of failure and survival.

Abstract

2063 Background: To present SHH pathway driven medulloblastoma (MB) diversities in pediatric and adult patient populations. Methods: 60 patients with SHH-MB seen at our institute during 2009-2015. We assigned 22 predefined radiological features for all MB subgroups including SHH. Outcome data was retrieved from a prospectively maintained database. Results: Median age of entire cohort was 14 years (1-48 years). 29 were adults (a-SHH) and 31 were pediatric SHH (p-SHH). Radiological data available for 39 patients showed a-SHH having lateralised location in 72% cases. Distinct MRI features to predict SHH include mild/moderate contrast enhancement (90%), cystic changes (82%), edema (92%); identical in two age groups. We could predict SHH accurately 95% times. p-SHH were seen to have higher frequency of p53 mutations (70% vs 45%). At median follow-up of 37 months, 25 patients failed [isolated tumor bed (TB) in 10, TB and supratentorially in 2, cranium outside TB in 1, craniospinal in 5 (along with TB), extraneuraxial (ENM) in 5, second primary in 2 (lymphomas)]. 1 and 3 year DFS was 74% (p-SHH) vs 96% (a-SHH) and 58% vs 73% respectively (p-0.19). The failures seen in a-SHH were typically late (10/11 failed > 22 months) as compared to p-SHH (12/14 failing < 24 months). Also location of recurrences was different, with 7 of a-SHH failing at TB and rest 3 developed ENM. Ten of 13 in p-SHH failed beyond TB. Post- recurrence salvage was better in a-SHH compared to p-SHH, 1-year survival of 50% vs 19% (p-0.08). Overall survival at 1 and 3 year 84% and 55% for p-SHH and 100% and 88% for a-SHH respectively (p = 0.04). Histology and tumor location significantly correlated with OS. No significant correlation was seen with CSI dose or chemotherapy. Conclusions: SHH medulloblastoma have unique MRI features and can be predicted up to 95% times pre-operatively. Adult and pediatric SHH MB form extreme diverse groups with different patterns of failure reflecting different tumor kinetics. Adults fail primarily over TB after initial 2 years. Paediatric SHH follow aggressive course with early disseminated recurrences in 1st year. Different treatment modalities may be needed for pediatric and adult SHH MB.