Survival for children with recurrent malignant brain tumors remains dismal and there continues to be a desperate need for new ways of thinking about treatment, and better use of currently available therapies. This first-in-kind clinical trial seeks to do both by targeting brain tumor metabolism in a manner that captures the cell-intrinsic sex differences in metabolism that are present from the time of fertilization. Cancerous growth requires adaptations in cellular metabolism. The large increase in glucose utilization in particular, is the basis for diagnostic FDG PET imaging, and is likely to constitute an Achilles heel for cancer cells. We recently published that tumor glycolysis and its correlation with survival differs for male and female brain tumor patients. This trial will determine whether sex differences in pediatric brain tumor metabolic phenotypes confer differential responses to combined ketogenic diet and chemotherapy, using Washington University’s cutting-edge PET/MRI imaging facilities, world-renowned genomic capabilities, and leading metabolomics research platforms in combination with the highly successful ketogenic diet program at St. Louis Children’s Hospital.