First-passage times and normal tissue complication probabilities in the limit of large populations

The time of a stochastic process rst passing through a boundary is important to many diverse applications. However, we can rarely compute the analytical distribution of these rst-passage
times. We develop an approximation to the rst and second moments of a general rst-passage time problem in the limit of large, but nite, populations using Kramers–Moyal expansion techniques. We demonstrate these results by application to a stochastic birth-death model for a population of cells
in order to develop several approximations to the normal tissue complication probability (NTCP): a problem arising in the radiation treatment of cancers. We speci cally allow for interaction between cells, via a nonlinear logistic growth model, and our approximations capture the e ects of intrinsic noise on NTCP. We consider examples of NTCP in both a simple model of normal cells and in a model of normal and damaged cells. Our analytical approximation of NTCP could help optimise radiotherapy planning, for example by estimating the probability of complication-free tumour under di erent treatment protocols.