RADIATION-INDUCED LUNG DAMAGE IN RATS - THE INFLUENCE OF FRACTION SPACING ON EFFECT PER FRACTION

Purpose: When the linear-quadratic model is used to predict fractionat ed treatments which are isoeffective, it is usually assumed that each (equal size) treatment fraction has an equal effect, independent of th e time at which it was delivered during a course of treatment. Previou s work by our group has indicated that this assumption may not be vali d in the context of radiation-induced lung damage in rats. Consequentl y we tested directly the validity of the assumption that each fraction has an equal effect, independent of the time it is delivered. Methods and Materials: An experiment was completed in which fractionated irra diation was given to whole thoraces of Sprague-Dawley rats. All treatm ent schedules consisted of eleven equal dose fractions in 36 days give n as a split course, with some groups receiving the bulk of the doses early in the treatment schedule, before a 27-day gap, and others recei ving most of the dose toward the end of the treatment schedule, after the time gap. To monitor the incidence of radiation-induced damage, br eathing rate and lethality assays were used. Results: The maximum diff erences in the LD(50)s and breathing rate ED(50)s for the different fr actionation schedules were 4.0% and 7.7% respectively. The lethality d ata and breathing rate data were consistent with results expected from modelling using the linear-quadratic model with the inclusion of an o verall time factor, but not the generalized linear-quadratic model whi ch accounted for fraction spacing. Conclusion: For conventional daily fractionation, and within the range of experimental uncertainties, the results indicate that the effect of a treatment fraction does not dep end on the time at which it is given (its position) in the treatment. The results indicate no need to extend isoeffect formulae to consider the effect of each fraction separately for radiation-induced lung dama ge.