Optimal scheduling of radiotherapy and angiogenic inhibitors

Bull Math Biol. 2003 May;65(3):407-24. doi: 10.1016/S0092-8240(03)00006-5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Clinical Protocols
  • Combined Modality Therapy
  • Dose Fractionation, Radiation
  • Drug Administration Schedule
  • Humans
  • Models, Biological*
  • Neoplasms / blood supply
  • Neoplasms / drug therapy*
  • Neoplasms / radiotherapy*
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / radiotherapy*
  • Radiotherapy, Computer-Assisted / methods*
  • Relative Biological Effectiveness

Substances

  • Angiogenesis Inhibitors