Mathematical Modeling Enables the Derivation of a Novel Radiation Therapy Schedule Predicted to Increase Survival of Recurrent GBM Patients
tumor
REGRESSION, TUMOR
Before translating our novel radiation schedule from mice to humans, we first predicted its benefit to GBM patients by developing linear regression models to predict the magnitude of GBM patient survival benefits afforded by interventions based on their benefit in the mouse model employed in our prior study (Standard-of-care therapy for newly diagnosed GBM is surgery followed by radiation therapy with concurrent and adjuvant temozolomide.To design a clinical study, we used our previously developed mathematical modelThe details of our mathematical model used to design the schedule have been previously described.Before using this model to design a human schedule, we used available data to explore whether the 3.25 h interval between fractions associated with improved survival in the mouse model was likely to be consistent between species (While our preclinical study suggested that employing a 3.25 h interfraction interval prolongs survival,Mathematical modeling identifies a radiation therapy administration schedule predicted to improve survival of recurrent GBM patients. (A) Predicted tumor volume dynamics resulting from a radiation schedule of 51.6 Gy in 30 fractions with three times daily dosing with 3.25 h interfraction intervals compared to those from a schedule of 35 Gy in 10 fractions. (B) Predicted stem-like cell dynamics resulting from the administration schedules in (A). (C) Predicted effect of different two-phase radiation administration schedules on tumor volume dynamics. (D) Predicted stem-like cell dynamics resulting from the administration schedules in (C). QD—once daily dosing; TID—three times daily dosing.As TID administrations are less convenient than QD administrations, we tested whether schedules with fewer TID administrations could achieve close to the predicted benefit achieved by the optimal schedule. Our simulations revealed that a schedule of 7 fractions of 3.96 Gy (QD) followed by 9 fractions of 1.0 Gy (TID; 3.25 h interfraction interval) is predicted to be minimally inferior to the optimal schedule (