We incorporate a previously validated mathematical model of a vascularized tumor into an optimal control problem to determine the temporal scheduling of radiotherapy and angiogenic inhibitors that maximizes the control of a primary tumor. Our results reveal that optimal antiangiogenic monotherapy gives a large initial injection to attain a 20: 1 ratio of tumor cell volume to supporting vasculature volume. It thereafter maintains this 20: 1 ratio via a continuous dose rate that is intensified over time. The optimal radiation monotherapy schedule is characterized by amodest dose intensification over time. The best performance is achieved by our optimal combination regimen, where the antiangiogenic treatment again maintains a constant tumor-to-vasculature ratio, but is administered in a dose-intensified manner only during the latter portion of the radiation fractionation schedule.
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Ergun, A., Camphausen, K. & Wein, L.M. Optimal scheduling of radiotherapy and angiogenic inhibitors. Bull. Math. Biol. 65, 407–424 (2003). https://doi.org/10.1016/S0092-8240(03)00006-5
- Dose Rate
- Optimal Schedule
- Antiangiogenic Therapy
- Early Tissue
- Target Ratio