MODELING THE OPTIMAL RADIOTHERAPY REGIME FOR THE CONTROL OF T-2 LARYNGEAL CARCINOMA USING PARAMETERS DERIVED FROM SEVERAL DATASETS

Purpose: A number of previous studies have used direct maximum-likelih ood methods to derive the values of radiobiological parameters of the linear-quadratic model for head and neck tumors from large clinical da tasets, Time factors for accelerated repopulation were included, along with a lag period before the start of this repopulation, This study w as performed to attempt to utilise these results from clinical dataset s to compare treatment regimes in common clinical use in the UK, along with other schedules used historically in a number of clinical series in North America and elsewhere, and to determine if an optimal treatm ent regime could be derived based on these clinical data. Methods: The biologically-based linear-quadratic model, applied to local tumor con trol and late morbidity, has been used to derive theoretical optimum ( maximising tumor control whilst not exceeding tolerance for late react ions) radiotherapy schedules based on daily fractions. The specific ca se of T-2 laryngeal carcinoma was considered as this is treated primar ily by radiotherapy in many centers, Parameter values for local contro l were taken from previous analyses of several large single-center and national datasets, A time factor and a lag period were included in th e modelling, Values for the alpha/beta ratio for late morbidity were u sed in the range 1-4Gy, which is compatible with the limited range of values reported in the literature for particular complications followi ng radiotherapy for head and neck cancer, Early reactions and their co nsequential late morbidity were not modelled in this study, but assume d to be within tolerance. Results: For treatments using daily fraction s there was a broad optimum treatment time of between 3-6 weeks. The t heoretical optimum depended to some extent on the value of the alpha/b eta ratio for late morbidity, but in many cases was at or just beyond the end of the purported lag period of 3-4 weeks, although small value s of alpha/beta between 1-2 Gy favour longer treatment times, Similar results were obtained using a range of parameter values derived from f our independent clinical datasets. Conclusion: The mathematical modell ing of this broad range of once-daily treatments for most of which dif ferences in local control and late morbidity are essentially undetecta ble (< 5%) has shown how this clinically-recognised phenomenon is inte rpreted in terms of the combination of dose-response slopes, fractiona tion sensitivities and time factors for both tumor control and normal tissue morbidity, Although the conclusions are inevitably tempered by a number of caveats concerning confounding factors in different center s; for example, the use of different treatment volumes, the present an alysis provides a framework with which to explore the potential value of modifications to conventional treatment schedules, such as the use of multiple fractions per day. (C) 1997 Elsevier Science Inc.