Response of the canine lung to fractionated irradiation: pathologic changes and isoeffect curves

Canine lungs were irradiated with a range of total doses given in 2, 3, or 4 Gy per fraction. Sequential histopathologic evaluations were done at 1, 3, 6, and 12 months. Pathologic changes in canine lungs were found to be similar to those found in other species demonstrating a clinically latent period, a pneumonitis phase, and late fibrosis and vascular damage. The relative impact of endothelial cell and pneumocyte injury on either early or late radiation injury of the lung is difficult to resolve. Therefore, it is not possible to define a target cell for lung injury at this time. The alpha/beta ratios determined in this study indicate that the target cell or cells associated with lung consolidation are slowly proliferating and represent late responding tissues. Lungs were evaluated histomorphometrically for alveolar air space and radiographically for alveolar consolidation at 6 months after irradiation. Alpha/beta ratios of 3 Gy and 4 Gy were calculated respectively. Both assays demonstrated an increasing effect on lung damage with increasing fraction size from 2 to 4 Gy. Application of the LQ model and use of alpha/beta ratios for calculation of dose adjustments remains theoretical. Clinical data are insufficient to define specific alpha/beta ratios for the various normal tissues at risk in radiation therapy. The data are sufficient to demonstrate the sparing effects of decreasing size of dose per fraction for late responding tissue. Results of this study suggest caution against the use of large doses per fraction for radiation therapy fields which include large lung volumes.