Tumor radioresponsiveness versus fractionation sensitivity.

Since the introduction of mammalian cell survival curves, the parameters D0 and N have been used as quantitative measures of inherent radiation sensitivity, as was the shoulder width Dq. These parameters are more generally applicable at high doses. We propose to introduce a measure of tumor radioresponsitivity that is more applicable to the clinical treatment schedules that employ small fractional doses (1-2 Gy), the ratio alpha/E, derived from the linear quadratic model for cell inactivation as the intercept on the reciprocal-dose plot. For tumor-control experiments this ratio is the reciprocal of the TCD50 when radiation is given in very small fractions or at low dose rates (assuming negligible clonogen proliferation). The rationales for this choice are: alpha is a measure of the steepness of the initial linear segment of the dose-survival curve. Accordingly, at doses per fraction of 1-2 Gy the observed effect increases with alpha. E is by definition a positive measure of the clonogen kill required for a specified tumor response, e.g., E = -log (surviving fraction of clonogens at the 50% control level). Therefore it is also a measure of the number of clonogens present at the time of inception of treatment, which for a given dose is a prime determinant of the probability of tumor control. This measure of radioresponsitivity is to be distinguished from the ratio alpha/beta, which is a measure of fractionation sensitivity. A survey of the literature indicates that these do not correlate, except in highly hypoxic tumors (e.g., clamped); such tumors are characterized by low radioresponsitivity as well as low fractionation sensitivity (high alpha/beta ratio). There are at present only limited data for determination of this ratio, however, since reciprocal-dose analysis requires tumor control doses for several different sizes of dose per fraction.