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Optimization of Dose Fractionation for Radiotherapy of a Solid Tumor with Account of Oxygen Effect and Proliferative Heterogeneity

Author

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  • Maxim Kuznetsov

    (Division of Theoretical Physics, P.N. Lebedev Physical Institute of the Russian Academy of Sciences, 53 Leninskiy Prospekt, 119991 Moscow, Russia
    Nikolsky Mathematical Institute, Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, 117198 Moscow, Russia)

  • Andrey Kolobov

    (Division of Theoretical Physics, P.N. Lebedev Physical Institute of the Russian Academy of Sciences, 53 Leninskiy Prospekt, 119991 Moscow, Russia)

Abstract

A spatially-distributed continuous mathematical model of solid tumor growth and treatment by fractionated radiotherapy is presented. The model explicitly accounts for three time and space-dependent factors that influence the efficiency of radiotherapy fractionation schemes—tumor cell repopulation, reoxygenation and redistribution of proliferative states. A special algorithm is developed, aimed at finding the fractionation schemes that provide increased tumor cure probability under the constraints of maximum normal tissue damage and maximum fractional dose. The optimization procedure is performed for varied radiosensitivity of tumor cells under the values of model parameters, corresponding to different degrees of tumor malignancy. The resulting optimized schemes consist of two stages. The first stages are aimed to increase the radiosensitivity of the tumor cells, remaining after their end, sparing the caused normal tissue damage. This allows to increase the doses during the second stages and thus take advantage of the obtained increased radiosensitivity. Such method leads to significant expansions in the curative ranges of the values of tumor radiosensitivity parameters. Overall, the results of this study represent the theoretical proof of concept that non-uniform radiotherapy fractionation schemes may be considerably more effective that uniform ones, due to the time and space-dependent effects.

Suggested Citation

  • Maxim Kuznetsov & Andrey Kolobov, 2020. "Optimization of Dose Fractionation for Radiotherapy of a Solid Tumor with Account of Oxygen Effect and Proliferative Heterogeneity," Mathematics, MDPI, vol. 8(8), pages 1-20, July.
    • Handle: RePEc:gam:jmathe:v:8:y:2020:i:8:p:1204-:d:387847
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    References listed on IDEAS

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    1. Jalalimanesh, Ammar & Shahabi Haghighi, Hamidreza & Ahmadi, Abbas & Soltani, Madjid, 2017. "Simulation-based optimization of radiotherapy: Agent-based modeling and reinforcement learning," Mathematics and Computers in Simulation (MATCOM), Elsevier, vol. 133(C), pages 235-248.
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