Direct analysis of quantal radiation response data

A direct analysis is proposed for quantal (all-or-nothing) responses to fractionated radiation and endpoint-dilution assays of cell survival. As opposed to two-step methods such as the reciprocal-dose technique, in which ED50 values are first estimated for different fractionation schemes and then fit (as reciprocals) against dose per fraction, all raw data are included in a single maximum-likelihood treatment. The method accommodates variations such as short-interval fractionation regimens designed to determine tissue repair kinetics, tissue response to continuous exposures, and data obtained using endpoint-dilution assays of cell survival after fractionated doses. Monte-Carlo techniques were used to compare the direct and reciprocal-dose methods for analysis of small-scale and large-scale studies of response to fractionated doses. Both methods tended toward biased estimates in the analysis of small-scale (3 fraction numbers) studies. The α/β ratios showed less scatter when estimated by the direct method. The 95% confidence intervals determined by the direct method were more appropriate than those determined by reciprocal-dose analysis, for which 18% (small-scale study) or 8% (large-scale study) of the confidence intervals did not include the 'true' value of α/β. (author)