Models of acute mucosal tolerance to radiotherapy alone applied to synchronous chemoradiation schedules in head and neck cancer

Abstract

Three models defining mucosal tolerance when radiotherapy alone is delivered have been published. Modelling studies have converted the contribution of synchronous chemotherapy to the rate of grade 3 mucositis to biologically effective dose (BED). The purpose of this study was to apply radiotherapy mucosal tolerance models to studies of synchronous chemoradiation. Trials of synchronous cisplatin and radiotherapy were identified. The BED for cell kill for each regime was calculated. Initially, this was done using the protocol parameters and a global value for the contribution of chemotherapy of 5.1 Gy10. These values were then compared with the BED cell kill ceiling values from each of the models calculated using the intended overall treatment time. These steps were then repeated using the delivered radiotherapy parameters and a value for the contribution from chemotherapy calculated to take into account dose intensity. Eight eligible treatment arms were identified. When using the intended radiotherapy parameters, six of these appeared to be tolerable when compared with the ceiling values for two of the models. All were found intolerable by one model. When using the actual delivered radiotherapy doses and overall treatment times and correcting for chemotherapy dose intensity, one treatment arm remained intolerable by all three models, a further treatment arm by two models and four treatment arms by one model. Two current models of mucosal tolerance derived from radiotherapy data predict a majority of previously reported chemoradiation study arms to be tolerable particularly when the delivered parameters are used for calculation.