Volume-dependent expression of in-field and out-of-field effects in the proton-irradiated rat lung.

摘要

PURPOSE: To investigate whether occurrence of early radiation effects in lung tissue depends on local dose 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)-1alpha, 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-1alpha, 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.