Biphasic Repair and Prediction of Late Effects Following Lung Irradiation

Abstract

Late effects are essential concomitants in clinical radiotherapy of malignant diseases. Generally these are typical for normal tissues and organs with flexible nonhierarchical structure and a relatively low proliferative activity and consequently consist preferentially of functional cells. In terms of the widely used linear-quadratic (LQ) model, late effects correspond to low α/β ratios, and the incidence and latency times of these effects show a strong dependence on possible changes in the fractionation regime. The α/β ratio of the lung (humans and experimental animals) with respect to the radiation-induced pneumonitis reaction is low and has been determined to be 3–4 Gy. Thus, the lung is a typical late-reacting organ. Indeed, the pneumonitis reaction as one of the most severe side effects of irradiations of the thoracic region appears some months after the end of treatment. Therefore it is highly desirable to have reliable mathematical and statistical methods to analyze clinical and experimental data and to predict the complication rate and mean latency time of the side effects in cases of new schedules. This is an essential precondition for the determination of optimal fractionation schedules in tumor treatment having the lung as dose-limiting organ.