Changes in expression of injury after irradiation of increasing volumes in rat lung

Alena Novakova-Jiresova, Peter van Luijk, Harry van Goor, Harm H. Kampinga, Robert P. Coppes*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

43 Citations (Scopus)

Abstract

Purpose: To improve the cure rates of thoracic malignancies by radiation dose escalation, very accurate insight is required in the dose delivery parameters that maximally spare normal lung function. Radiation-induced lung complications are classically divided into an early pneumonitic and a late fibrotic phase. This study investigated the relative dose-volume sensitivity, underlying pathologic findings, and consequentiality of early to late pathologic features.

Methods and Materials: We used high-precision, graded dose-volume lung irradiations and followed the time dependency of the morphologic sequelae in relation to overall respiratory function.

Results: Two distinct pathologic lesions were identified in the early postirradiation period (6-12 weeks): vascular inflammation and parenchymal inflammation. Vascular inflammation occurred at single doses as low as 9 Gy. This translated into early respiratory dysfunction only when a large lung volume had been irradiated and was reversible with time. Parenchymal inflammation was seen after higher doses only (onset at 16 Gy), progressed into later fibrotic remodeling but did not translate into dysfunction at a 25% lung volume even after single doses up to 36 Gy.

Conclusion: Our data imply that a low dose scattered over a large lung volume causes more early toxicity than an extreme dose confined to a small volume. Such findings are crucial for clinical treatment planning of dose escalations and choices for modern radiotherapy techniques. (c) 2007 Elsevier Inc.

Original languageEnglish
Pages (from-to)1510-1518
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume67
Issue number5
DOIs
Publication statusPublished - 1-Apr-2007

Keywords

  • radiation-induced lung injury
  • irradiated volume
  • parenchymal inflammation
  • vascular damage
  • fibrosis
  • RADIATION PNEUMONITIS
  • X-RAYS
  • MOUSE LUNG
  • THORACIC IRRADIATION
  • REGIONAL DIFFERENCES
  • PULMONARY-FUNCTION
  • HISTOGRAM ANALYSIS
  • BREAST-CANCER
  • TARGET-CELLS
  • PHASE-I

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