Clinical radiobiology of head and neck cancer: the hypothesis of stem cell activation

To estimate and reduce uncertainties of a self-consistent set of radiobiological parameters based on the outcome of head and neck cancer (HNC) patients treated with radiotherapy (RT). Published studies comparing at least two RT schedules for HNC patients were selected. The method used to estimate the radiobiological parameters consists of three sequential steps that allow a significant reduction of uncertainties: the first, in which the intrinsic (alpha) and the repair (beta) radio-sensitivities were estimated together with the doubling time (T (d)) by an analytical/graphical method; the second, in which the kick-off time for accelerated proliferation (T (k)) was estimated applying the hypothesis of activation for sub-populations of stem cells during the RT; the third, in which the number of clonogens (N) was obtained by the Tumor Control Probability (TCP) model. Independent clinical data were used to validate results. The best estimate and the 95 % confidence intervals (95 % CIs) were: alpha = 0.24 Gy(-1) (0.23-0.26), beta = 0.023 Gy(-2) (0.021-0.025), alpha/beta = 10.6 Gy (8.4-12.6), T (d) = 3.5 days (3.1-3.9), T (k) = 19.2 days (15.1-23.3), N = 7 x 10(7) (4 x 10(7)-1 x 10(8)). From these data, the dose required to offset repopulation occurring in 1 day (D (prolif)) and starting after T (k) was also estimated as 0.69 Gy/day (0.52-0.86). The estimation of all the radiobiological parameters of HNC was obtained based on the hypothesis of activation for specifically tumorigenic sub-populations of stem cells. The similarity of results to those from other studies strengthens such a hypothesis that could be very useful for the predictivity of the TCP model and to design new treatment strategies for HNC.