Does Incomplete Repair Explain the Apparent Failure of the Basic LQ Model to Predict Spinal Cord and Kidney Responses to Low Doses Per Fraction?

Summary

Recent evidence indicates that isoeffect doses for spinal cord and kidney may be overestimated for fraction sizes as small as 1 or 2 Gy when calculated from a linear-quadratic (LQ) model fitted to data obtained for fraction sizes larger than 2 Gy. Reasons for this are unknown, but possible interpretations include exhaustion of repair capacity and incomplete repair in experiments designed to study the response to these small doses. The latter interpretation is motivated by the relatively short intervals between multiple daily doses given to the spinal cord (4 h) and kidney (5 h) when fraction sizes were small. The possibility that overestimation of isoeffect dose could be explained by incomplete repair during short intervals between doses was assessed by fitting experimental data to the incomplete-repair model. For the spinal cord the data could be interpreted by assuming that a repair process with a half-time of 1·7 h was incomplete; this half-time is negligibly different from the estimate obtained from repair-kinetics experiments with larger doses per fraction. The deviation from the (complete-repair) LQ model could be interpreted for the kidney in terms of a half-time of repair of 2·8 h (a negligibly different fit was obtained with the value 1·5 h). The clinical implication could be that multiple-fractions-per-day treatment would benefit from use of the longest feasible interfraction interval when late reactions are dose limiting.