Quantitative clinical radiobiology of early and late lung reactions

Purpose: To quantify the response of human lung to a course of fractionated radiotherapy based on a literature review of published clinical data. Materials and methods: Quantitative clinical radiobiology is concerned with the estimation of parameters that describe the clinical outcome of radioth erapy as a function of patient and treatment characteristics. Here, paramet ers describing the steepness of the dose-response curve, the response to a change in dose per fraction and to a change in overall treatment time for e arly and late lung injury are compiled based on published clinical studies. Results: Two phases of lung injury are seen, radiation pneumonitis and lung fibrosis. The first signs of early lung changes are seen almost immediatel y after irradiation. This reaction peaks after 5 to 6 months, and settles p artially before 9-10 months. Around that time, the late changes become mani fest and these are stable in most cases. There is an important distinction between lung injury and radiotherapy-related morbidity, as even severe chan ges in a small volume may not give rise to any clinical symptoms. Many assa ys have been developed for lung damage, and these highlight various clinica l and biological aspects of lung damage. Here, the literature on steepness of dose-response curves and fractionation sensitivity is reviewed and quant ified by the alpha/beta ratio of the linear-quadratic model for both radiat ion pneumonitis and lung fibrosis. For the early phase a significant time F actor exists. Current best estimates for these radiobiological parameters a re derived. Other external factors affecting these estimates are briefly di scussed. Conclusions: Quantitative estimates of radiobiological characteristics of h uman lung are available for the pneumonitis phase where the fractionation s ensitivity is in the same range as for most late-responding normal tissues. Short intensive schedules may also bear an added risk for pneumonitis as t he dose recovered per day is around 0.5 Gy. For the later phase of lung fib rosis, the estimates are fewer and generally less precise. It is clear thou gh, that the alpha/beta ratio is low, possibly 2-3 Gy. No time factor has b een demonstrated for the late reaction. Due to the considerable physiologic al reserve capacity in the normal human lung, the relationship between dama ge and morbidity depends strongly on the lung volume affected. It therefore seems likely that for small volumes irradiated to high doses, the dose-lim iting complications may not be due to restriction of lung function, but rat her to haemorrhage and formation of fistulae.