Revising the radiobiological model of synchronous chemotherapy in head-and-neck cancer : a new analysis examining reduced weighting of accelerated repopulation

Purpose Previous studies of synchronous chemoradiation therapy have modeled the additional effect of chemotherapy as additional radiation therapy biologically effective dose (BED). Recent trials of accelerated versus conventional fractionation chemoradiation have cast doubt on such modeling. The purpose of this study was to identify alternative models. Methods and Materials Nine trials of platinum-based chemoradiation were identified. In radiation therapy-alone arms, the radiation therapy BED for tumor was calculated using standard parameters. In chemoradiation arms, 3 methods were used to calculate tumor BED (tBED): additional BED, addition of 9.3 Gy BED for tumor to the radiation therapy BED; zero repopulation, BED with no correction for repopulation; variable tp (the average doubling time during accelerated repopulation), values of tp 3-10 were used to examine a partial suppression of repopulation. The correlations between the calculated percentage change in tBED for each method and observed percentage change in local control were assessed using the Pearson product moment correlation. Results Significant correlations were obtained for all 3 methods but were stronger with zero repopulation (P=.0002) and variable tp (tp = 10) (P=.0005) than additional BED (P=.02). Conclusions Radiobiological models using modified parameters for accelerated repopulation seem to correlate strongly with outcome in chemoradiation studies. The variable tp method shows strong correlation for outcome in local control and is potentially a more suitable model in the chemoradiation setting. However, a lack of trials with an overall treatment time of more than 46 days inhibits further differentiation of the optimal model