Optimal scheduling of radiotherapy and angiogenic inhibitors.
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 a modest 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.
Ergun
Ayla
A
Operations Research Center, MIT, Cambridge, MA 02139, USA.
Camphausen
Kevin
K
Wein
Lawrence M
LM
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D002985:Clinical Protocols; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000532:radiotherapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000532:radiotherapy*; D011881:Radiotherapy, Computer-Assisted / Q000379:methods*; D012062:Relative Biological Effectiveness
D020533:Angiogenesis Inhibitors