Importance of the Study
glioblastoma, tumor
DISEASE, GLIOBLASTOMA, TUMOR
Radiation therapy administration schedules fail to account for the dynamic cellular heterogeneity and plasticity of glioblastoma. We previously developed a mathematical model to quantitatively characterize this heterogeneity and plasticity, which we employed to optimize a radiation therapy schedule that substantially improved survival over a conventional schedule, in a mouse model of glioblastoma. In this study we adapted the schedule from mice to recurrent glioblastoma patients, using mathematical modeling, and performed a phase I trial to test the feasibility of administering our novel schedule. We successfully demonstrated that our novel schedule is indeed feasible and safe to administer, providing a route to a future efficacy trial. Hypothesis-generating analyses, comparing our trial with an external control dataset, are suggestive of a potential effect of the schedule on tumor response. We will investigate this finding in a future preclinical study.Progress in developing new therapies for glioblastoma (GBM) has been slow.We hypothesized that these advances in the understanding of disease biology, together with improvements in mouse modeling,To investigate the clinical potential of a model-informed optimized schedule, we used mathematical modeling to adapt the approach from mice to humans, and conducted a phase I trial, assessing the feasibility and safety of administering the schedule.