A review of alpha/beta ratios for experimental tumors: implications for clinical studies of altered fractionation.

Clinical interest in the use of more and smaller dose fractions in radical radiotherapy has been stimulated by recent reviews of experimental results with normal tissues. It has been found that if the dose per fraction is reduced (i.e., in hyperfractionation) there is sparing of late responding normal tissues relative to those which respond early. This phenomenon can be understood in terms of the shapes of the underlying dose effect relationships, which can be described using the linear quadratic equation. The ratio (alpha/beta) of the linear (alpha) and quadratic (beta) terms is a useful measure of the curviness of such dose effect curves. Low alpha/beta values (1.5 to 5 Gy) have been observed for late responding normal tissues and indicate that radiation damage should be greatly spared by the use of dose fractions smaller than the 2 Gy used in conventional radiotherapy. By contrast the high alpha/beta values (6-14 Gy) observed for acutely responding normal tissues indicate that the response is relatively linear over the dose range of clinical interest. Hence less extra sparing effect is to be expected if lower doses per fraction are administered. If tumors respond in the same way as acutely responding normal tissues then hyperfractionation might confer a therapeutic gain relative to late responding normal tissues. We have reviewed published results for experimental tumors irradiated in situ and either assayed in situ or after excision. The alpha/beta ratios were usually at least as high as those for acutely responding normal tissues, and 36/48 tumors gave values greater than 8 Gy. Low values of less than 5 Gy were obtained for only 4/48 tumors. There are considerable technical problems in interpreting these experiments, but the results do suggest that hyperfractionation might confer therapeutic gain relative to late responding normal tissues on the basis of differences in repair capability. In clinical practice more efficient reoxygenation, cell cycle redistribution and decreased overall treatment time might also confer therapeutic gain.