Sublethal damage repair times for a late-responding tissue relevant to brachytherapy (and external-beam radiotherapy): implications for new brachytherapy protocols

Abstract

Purpose: Data were analyzed from recent experiments with the end point of late rectal obstruction in rats, involving acute and various protracted radiation exposures. Because the end point is of direct relevance both for brachytherapy as well as external beam radiotherapy, the goal was to estimate the linear-quadratic (LQ) parameters alpha/beta and T1/2, which are of importance for designing improved protraction/fractionation schemes.

Methods and materials: The data were fit to the LQ model, both in its standard form and in a form in which two different components of sublethal damage repair-fast and slow-are assumed. The design of the experiments was such that both slow and reasonably fast sublethal damage repair components should be separately estimated, if they were contributing to a significant degree.

Results: LQ parameter estimates were alpha/beta = 4.6 Gy [4.0, 5.5] and T1/2 = 70.2 min [59.1, 91.4]. Despite the experimental design facilitating detection of a rapid component of repair, no statistically robust evidence for a very fast repair component was found.

Conclusions: The long estimated repair time for a late-responding normal-tissue end point with direct relevance to brachytherapy suggests a variety of possible brachytherapy protocols that may be more efficacious than continuous low dose rate irradiation. Just as a difference in alpha/beta ratios between early- and late-responding tissues are a central tenet in radiotherapy, so corresponding differences in T1/2 values have the potential to be exploited, particularly for brachytherapy.