Classification of tolerable/intolerable mucosal toxicity of head-and-neck radiotherapy schedules with a biomathematical model of cell dynamics

Purpose: The purpose of this study is to present a biomathematical model based on the dynamics of cell populations to predict the tolerability/intolerability of mucosal toxicity in head-and-neck radiotherapy. Methods and Materials: Our model is based on the dynamics of proliferative and functional cell populations in irradiated mucosa, and incorporates the three As: Accelerated proliferation, loss of Asymmetric proliferation, and Abortive divisions. The model consists of a set of delay differential equations, and tolerability is based on the depletion of functional cells during treatment. We calculate the sensitivity (sen) and specificity (spe) of the model in a dataset of 108 radiotherapy schedules, and compare the results with those obtained with three phenomenological classification models, two based on a biologically effective dose (BED) function describing the tolerability boundary (Fowler and Fenwick) and one based on an equivalent dose in 2 Gy fractions (EQD(2)) boundary (Strigari). We also perform a machine learning-like cross-validation of all the models, splitting the database in two, one for training and one for validation. Results: When fitting our model to the whole dataset, we obtain predictive values (sen + spe) up to 1.824. The predictive value of our model is very similar to that of the phenomenological models of Fowler (1.785), Fenwick (1.806), and Strigari (1.774). When performing a k = 2 cross-validation, the specificity and sensitivity in the validation dataset decrease for all models, from similar to 1.82 to similar to 1.55-1.63. For Fowler, the worsening is higher, down to 1.49. Conclusions: Our model has proved useful to predict the tolerability/intolerability of a dataset of 108 schedules. As the model is more mechanistic than other available models, it could prove helpful when designing unconventional dose fractionations, schedules not covered by datasets to which phenomenological models of toxicity have been fitted. (C) 2021 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine

Automated summary

The purpose of this study is to develop a biomathematical model for predicting the tolerability/intolerability of mucosal toxicity in head-and-neck radiotherapy based on cell population dynamics. The model incorporates three As: Accelerated proliferation, loss of Asymmetric proliferation, and Abortive divisions. The predictive values of the model are comparable to phenomenological models when fitted to a dataset of radiotherapy schedules.