Optimization of Radiation Therapy Fractionation Schedules in the Presence of Tumor Repopulation

We analyze the effect of tumor repopulation on optimal dose delivery in radiation therapy. We are primarily motivated by accelerated tumor repopulation toward the end of radiation treatment, which is believed to play a role in treatment failure for some tumor sites. A dynamic programming framework i...

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Bibliographic Details
Main Authors: Bortfeld, Thomas, Ramakrishnan, Jagdish, Unkelbach, Jan, Tsitsiklis, John N
Other Authors: Massachusetts Institute of Technology. Laboratory for Information and Decision Systems
Format: Article
Language:en_US
Published: Institute for Operations Research and the Management Sciences (INFORMS) 2017
Online Access:http://hdl.handle.net/1721.1/111066
https://orcid.org/0000-0003-2658-8239
Description
Summary:We analyze the effect of tumor repopulation on optimal dose delivery in radiation therapy. We are primarily motivated by accelerated tumor repopulation toward the end of radiation treatment, which is believed to play a role in treatment failure for some tumor sites. A dynamic programming framework is developed to determine an optimal fractionation scheme based on a model of cell kill from radiation and tumor growth in between treatment days. We find that faster tumor growth suggests shorter overall treatment duration. In addition, the presence of accelerated repopulation suggests larger dose fractions later in the treatment to compensate for the increased tumor proliferation. We prove that the optimal dose fractions are increasing over time. Numerical simulations indicate a potential for improvement in treatment effectiveness.