Volume-Dependent Expression of In-Field and Out-of-Field Effects in the Proton-Irradiated Rat Lung

Robert P. Coppes*, Christina T. Muijs, Hette Faber, Sascha Gross, Jacobus M. Schippers, Sytze Brandenburg, Johannes A. Langendijk, Peter van Luijk

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)262-269
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume81
Issue number1
DOIs
Publication statusPublished - 1-Sep-2011

Keywords

  • Lungs
  • Radiation pneumonitis
  • Predictive models
  • Protons
  • Vascular damage
  • GROWTH-FACTOR-BETA
  • EARLY DNA-DAMAGE
  • RADIATION PNEUMONITIS
  • THORACIC IRRADIATION
  • INFLAMMATORY CYTOKINES
  • REGIONAL DIFFERENCES
  • PULMONARY-FUNCTION
  • CANCER PATIENTS
  • INJURY
  • RADIOTHERAPY

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