Medulloblastoma Molecular Subgrouping and Outcomes Data of a Single Center From a Low- and Middle-Income Country

Introduction: Medulloblastoma (MB) is the most common malignant childhood brain tumor. Molecular subgrouping of MB has become a major determinant of management in high-income countries. Subgrouping is still very limited in low- and middle-income countries (LMICs), and its relevance to management with the incorporation of risk stratification (low risk, standard risk, high risk, and very high risk) has yet to be evaluated in this setting. We describe molecular findings from a tertiary care center in Pakistan and their implications for outcome.

Methods: Children aged between 3 and 18 years diagnosed with MB from April 2014 to December 2020 at Aga Khan University Hospital (AKUH) were included. Subgrouping was performed by NanoString through a collaboration with The Hospital for Sick Children, Toronto.

Results: Thirty-seven patients (30 males) were included in this study; median age was 9 years. Twenty patients (54.1%) were high-risk, including 12 with metastatic disease. In 30 children, there was a clear molecular subgroup: 4 wingless (WNT) (10.8%), 6 sonic hedgehog (SHH) (16.2%), 3 Group 3 (8.1%), and 17 Group 4 (45.9%) MBs. Molecular subgrouping was inconclusive for three patients (8.1%) and not done in four patients (10.8%). All patients underwent surgery; 26 patients received radiation therapy at AKUH, and 9 were referred outside for radiotherapy; 24 patients received chemotherapy at AKUH (10 outside AKUH). Overall survival (OS) at 5 years was 100%, 66.7%, 66.7%, and 88.2% for WNT, SHH, Group 3, and Group 4 patients, respectively (p = 0.668). Low- and standard-risk patients had a 5-year OS of 100%, whereas very high-risk patients exhibited a significantly lower OS of 0% (p < 0.001).

Conclusion: WNT and Group 4 patients had excellent results despite one WNT patient having metastatic disease and eight Group 4 patients being high risk. Our study depicts that molecular subgrouping aids in accurately predicting survival, suggesting the potential benefit of tailored testing and treatment in the LMIC setting.