Abstract
Medulloblastoma (MB) is the most common malignant brain tumor in children. WHO 2016 classify MB into four distinct molecular subgroups. The aim of this study is to characterize the molecular MB subgroups and correlate it with defined clinical outcomes in Middle Eastern children. A retrospective study of newly diagnosed MB in 55 children (>3 year and < 16 year) was collected. All treated at KFMC between 2009–2016. Molecular analysis was done using next generation targeted sequencing (NGS) for 560 cancer-relevant genes. 38(69.1%) are male and 17 (30.9%) are females, median age at diagnosis 83 months. Classic MB 39(70.9%), Desmoplastic/nodular MB 10 (18.2%), MB- extensive nodularity 2(3.6%) and LC/Anaplastic MB 4(7.3%), 21 patients (71%) had metastatic disease M2/3. 28 (50.4%) patients treated as average-risk and 27 (48.6%) treated as high-risk. Molecular analysis was done for 31 patients: 3 WNT group (9.7%), 5 SHH (16, 1%), 3 group 3 (9.7%), and 12 group 4 (38.7%), 8(25.8%) non-WNT/non-SHH. A median follow-up of 36 months: PFS for the entire study patients was 81.8% and 3-year OS was 83.6. 3-year PFS across the 5 subgroups was statistically significant difference in a pooled analysis. Three-year PFS for the WNT subgroup was 100%, for the SHH subgroup 80% for Group Three 33.3%, for Group Four 83.3% and for the Non WNT/Non SHH group 75% (p<0.001 across all 5 subgroups). This is the first study in Middle East which highlights the prognostic implications of MB genomic subgroups. Our result was excellent compared to international studies although most of our patients had unfavorable molecular subgrouping. Our group 4 patients had better survival than previously reported. NGS classification has potential for future reduction of standard therapy for children with favorable molecular subgroup and real implication for precision medicine in our oncology practice.