Changes in Expression of Injury After Irradiation of Increasing Volumes in Rat Lung

Abstract

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