OS02.3 Need for reclassifying treatment strategies for different subgroups of SHH medulloblastoma, paediatric and adult SHH-MB fail deferentially
Authors: A. Dasgupta, E. Sridhar, N. Shirsat, G. Chinnaswamy, H. Menon, A. Moiyadi, R. Krishnatry, J. S. Goda, T. Gupta, R. Jalali
Journal: Neuro-Oncology (2017)

BACKGROUND: SHH pathway driven medulloblastoma (MB) forms the most heterogeneous subtype. We studied the diversities amongst the different groups in terms of demographic, radiological, molecular features and correlated with survival outcomes. METHODS: RT-PCR assay based on expression of miRNA and protein coding genes identified 60 patients with SHH-MB registered at our institute during 2009–2015. The patient details and outcome data were retrieved from patient case record files, electronic database, radiotherapy planning systems. Results: The median age was 14 years (1–48 years). Twenty nine were adults (a-SHH), 31 were paediatric SHH (p-SHH) with age <16 yrs, with 8 having age less than 3 year. In general SHH-MB were having characteristic features like lateralised location, mild to moderate degree of contrast enhancement, cystic changes, oedema; without any differential distribution across two age groups. p-SHH were seen to have higher frequency of p53 mutations (70% vs 45%) and higher Mib-1 index (p-not significant) for those available. At a median follow up of 37 months (range 11 to 91 months) for surviving patients, total 25 failures were seen. The distribution were-isolated tumour bed (TB) in 10, TB and supratentorially in 2, cranium outside TB in 1, craniospinal in 5 (along with TB involvement), extraneuraxial (ENM) in 5, second primary in 2 (lymphomas). The disease free survival (DFS) at 1 year was 74% (p-SHH) vs 96% (a-SHH) while 3 yr DFS was 58% vs 73% respectively (p-0.19). The failures seen in a-SHH were typically late(10 of 11 having failed beyond 22 months) as compared to p-SHH (12 of 14 failing within 24 months). Also the location of recurrences were different, with 7 of a-SHH failing at TB and rest 3 developed ENM. Ten of 13 in the younger cohort had failure beyond the TB, supporting the aggressive biological behaviour. Post recurrence salvage rates were better for a-SHH compared to p-SHH, 1 year survival being 50% vs 19% (p-0.08). Overall survival (OS) was significantly better in adult group (p-0.04), 1 yr and 3 yr being 84% and 55% for p-SHH and 100% and 88% for a-SHH respectively. Of the various factors studied, histology and location of tumour on vertical aspect (central location better than superior/ inferiorly placed tumour-92% vs 60%) were significantly affecting OS. No significant correlation was achieved with doses of cranio-spinal RT or chemotherapy with location of failures. CONCLUSION: Adult and paediatric SHH MB form extreme diverse groups with different patterns of failure reflecting different tumour kinetics. Adults fail primarily over TB after initial 2 years. Increasing RT dose to TB with careful de-escalation of CSI can be potentially explored in future trials. Paediatric SHH follow aggressive course with early disseminated recurrences in 1st year which needs intensification of existing treatment standards in form of targeted therapy or protracted chemotherapy.