VOLUME-DEPENDENT EXPRESSION OF IN-FIELD AND OUT-OF-FIELD EFFECTS IN THE PROTON-IRRADIATED RAT LUNG

Purpose: To investigate whether occurance of early radiation effects in lung tissue depends on local close only. Methods and Materials: Twenty-five percent. 50%, 66%, 88%, or 100% of the rat lung was irradiated using single fractions of 150-MeV protons. For all volumes, in-field and out-of-field dose-response curves were obtained 8 weeks after irradiation. The pathohistology of parenchymal inflammation, infiltrates, fibrosis, and vascular damage and the relative expression of proinflammatory cytokines interleukin (IL)-1 alpha, transforming growth factor-beta. IL-6, and tumor necrosis factor-alpha were assessed. Results: For all histologic endpoints, irradiated dose- and volume-dependent in-field and out-of-field effects were observed, albeit with different dynamics. Of note, the out-of-field effects for vascular damage were very similar to the in-field effects. Interestingly, only IL-6 showed a clear dose-dependent increase in expression both in-field and out-of-field, whereas the expression levels of IL-1 alpha, transforming growth factor-beta, and tumor necrosis factor-alpha were either very low or without a clear dose-volume relation. As such, none of the radiation effects studied depended only on local dose to the tissue. Conclusion: The effects of radiation to lung tissue do not only depend on local dose to that tissue. Especially at high-volume irradiation, lung damage seems to present globally rather than locally. The accuracy of predictive modeling may be improved by including nonlocal effects. (C) 2011 Elsevier Inc.