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Applications of Nonlinear Programming to the Optimization of Fractionated Protocols in Cancer Radiotherapy

Institute for Systems Analysis and Computer Science—National Research Council of Italy, Via dei Taurini 19, 00185 Rome, Italy
Authors to whom correspondence should be addressed.
Information 2020, 11(6), 313;
Received: 30 April 2020 / Revised: 31 May 2020 / Accepted: 8 June 2020 / Published: 10 June 2020
(This article belongs to the Special Issue New Frontiers for Optimal Control Applications)
The present work of review collects and evidences the main results of our previous papers on the optimization of fractionated radiotherapy protocols. The problem under investigation is presented here in a unitary framework as a nonlinear programming application that aims to determine the optimal schemes of dose fractionation commonly used in external beam radiotherapy. The radiation responses of tumor and normal tissues are described by means of the linear quadratic model. We formulate a nonlinear, non-convex optimization problem including two quadratic constraints to limit the collateral normal tissue damages and linear box constraints on the fractional dose sizes. The general problem is decomposed into two subproblems: (1) analytical determination of the optimal fraction dose sizes as a function of the model parameters for arbitrarily fixed treatment lengths; and (2) numerical determination of the optimal fraction number, and of the optimal treatment time, in different parameter settings. After establishing the boundedness of the optimal number of fractions, we investigate by numerical simulation the optimal solution behavior for experimentally meaningful parameter ranges, recognizing the crucial role of some parameters, such as the radiosensitivity ratio, in determining the optimality of hypo- or equi-fractionated treatments. Our results agree with findings of the theoretical and clinical literature. View Full-Text
Keywords: cancer radiotherapy optimization; linear-quadratic model; nonlinear programming cancer radiotherapy optimization; linear-quadratic model; nonlinear programming
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Bertuzzi, A.; Conte, F.; Papa, F.; Sinisgalli, C. Applications of Nonlinear Programming to the Optimization of Fractionated Protocols in Cancer Radiotherapy. Information 2020, 11, 313.

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