The dose–response characteristics of four NTCP models: using a novel CT-based radiomic method to quantify radiation-induced lung density changes

Multiple competing normal tissue complication probability (NTCP) models have been proposed for predicting symptomatic radiation-induced lung injury in human. In this paper we tested the efficacy of four common NTCP models applied quantitatively to sub-clinical X-ray computed tomography (CT)-density changes in the lung following radiotherapy. Radiotherapy planning datasets and follow-up chest CTs were obtained in eight patients treated for targets within the lung or hilar region. Image pixel-wise radiation dose exposure versus change in observable CT Hounsfield units was recorded for early (2–5 months) and late (6–9 months) time-points. Four NTCP models, Lyman, Logistic, Weibull and Poisson, were fit to the population data. The quality of fits was assessed by five statistical criteria. All four models fit the data significantly (p < 0.05) well at early, late and cumulative time points. The Lyman model fitted best for early effects while the Weibull Model fitted best for late effects. No significant difference was found between the fits of the models and with respect to parameters D(50) and γ(50). The D(50) estimates were more robust than γ(50) to image registration error. For analyzing population-based sub-clinical CT pixel intensity-based dose response, all four models performed well.