Analysis of normal tissue complication probability of the lung using a reliability model

Abstract

The volume effect of normal tissues and organs is an important factor for predicting normal tissue complication probability (NTCP) following partial, heterogeneous irradiation of organs at risk, and reducing the late sequela by conformal radiation therapy. We have previously developed a reliability model for calculation of NTCP, assuming a parallel architecture of functional subunits (FSU), where a critical number (k) out of the total number of FSUs (N) must be intact for the organ to maintain its function. Published data on radiation-induced lethal pneumonitis and altered breathing rate following partial volume irradiation of the mouse lung were analysed, and critical fraction and corresponding spatial density distribution of FSUs were estimated using this model. The critical fraction (k/N) seemed to be similar for the two endpoints, and a value of 0.7 was found to provide good fit to the experimental data. The critical fraction did not vary throughout the lung, and variation in volume effect cannot therefore be attributed to heterogeneous tissue architecture. On the other hand, our analysis revealed that the observed variation in volume effect of mouse lung may be attributed to heterogeneous spatial distribution in FSU density or also the spatial variation in inactivation probability of the FSUs.