Is the track-event theory of cell survival internally consistent?

TL;DR

This paper critically examines the internal consistency of the track event theory (TET) for cell survival under ionizing radiation, revealing assumptions, inconsistencies, and implications for nanodosimetric parameter derivation.

Contribution

It clarifies the basic assumptions of TET, identifies inconsistencies in its equations, and discusses how nanodosimetric properties influence model parameters.

Findings

Poisson distribution underpins the model assumptions.

Modified TET equation for repair is inconsistent with initial assumptions.

Nanodosimetric properties lead to exponential dose dependence.

Abstract

The "track event theory" (TET) has been developed in recent years as an alternative to the phenomenological linear-quadratic model for cell survival under exposure to ionizing radiation, particularly for heavy charged particles. The TET is based on a few simple model assumptions including the possibility to derive some of the model parameters from nanodosimetry. This work intends to carve out more clearly the basic assumptions behind the TET and to critically review the resulting mathematical model equations. It is demonstrated that the model assumptions of Poisson distribution and statistical independence of the frequency distributions of so-called one-track and two-track events follow from the Poisson distribution of the number of tracks affecting the considered target volume. It is also shown that the modified TET model equation used in the literature for consideration of repair is inconsistent with the model assumptions and requires an additional model parameter. Furthermore, the derivation of the model parameters from nanodosimetric properties of particle track structure is revealed to lead to a pure exponential dose dependence when the potentially large number of relevant nanometric target volumes inside a cell nucleus is accounted for.