Leary SES, Packer RJ, Li Y, et al. - This randomized clinical trial was undertaken to determine if carboplatin during radiotherapy or isotretinoin during maintenance chemotherapy improve survival in children with high-risk medulloblastoma. Patients aged 3 to 21 years with newly diagnosed high-risk medulloblastoma were included from Children's Oncology Group institutions in the US, Canada, Australia, and New Zealand. Study participants were randomly assigned to either 36-Gy craniospinal radiation therapy and weekly vincristine with or without daily carboplatin followed by 6 cycles of maintenance chemotherapy with cisplatin, cyclophosphamide, and vincristine with or without 12 cycles of isotretinoin during and after maintenance. In this randomized clinical trial including 261 children with medulloblastoma, therapy intensification with carboplatin improved event-free survival by 19% at 5 years for children with high-risk group 3 medulloblastoma. Such findings support the importance of combining clinical and molecular risk stratification for medulloblastoma.