Investigation into the foundations of the track-event theory of cell survival and the radiation action model based on nanodosimetry

Abstract

This work aims at elaborating the basic assumptions behind the “track-event theory” (TET) and its derivate “radiation action model based on nanodosimetry” (RAMN) by clearly distinguishing between effects of tracks at the cellular level and the induction of lesions in subcellular targets. It is demonstrated that the model assumptions of Poisson distribution and statistical independence of the frequency of single and clustered DNA lesions are dispensable for multi-event distributions because they follow from the Poisson distribution of the number of tracks affecting the considered target volume. It is also shown that making these assumptions for the single-event distributions of the number of lethal and sublethal lesions within a cell would lead to an essentially exponential dose dependence of survival for practically relevant values of the absorbed dose. Furthermore, it is elucidated that the model equation used for consideration of repair within the TET is based on the assumption that DNA lesions induced by different tracks are repaired independently. Consequently, the model equation is presumably inconsistent with the model assumptions and requires an additional model parameter. Furthermore, the methodology for deriving model parameters from nanodosimetric properties of particle track structure is critically assessed. Based on data from proton track simulations it is shown that the assumption of statistically independent targets leads to the prediction of negligible frequency of clustered DNA damage. An approach is outlined how track structure could be considered in determining the model parameters, and the implications for TET and RAMN are discussed.

ICRU Report 98, Stochastic Nature of Radiation Interactions: Microdosimetry

“…In a model of cell inactivation proposed by Schneider et al (2020), the assumption is made that sublesions (which they describe as DSB) are produced in irradiated cells in proportion to the frequency ( F 2 ) of clusters of two or more ionizations in about 10 base pairs of DNA (approximated as spherical volume of 2 nm diameter), and that a lethal lesion can result from two or more sublesions within about 7.5 nm of each other or from interaction of sublesions over longer distances up to about a micrometer. Some shortcomings of the model are discussed by Ngcezu and Rabus (2021).…”

Applications of nanodosimetry in particle therapy planning and beyond

“…With the development of experimental nanodosimetry and Monte Carlo track structure simulations (section 3), a correlation of nanodosimetric parameters with cell survival data has been reported (Nettelbeck and Rabus 2011, Conte et al 2017. This has opened possibilities to use nanodosimetry and track structure simulations as a future approach for particle therapy treatment planning and optimization (Selva et al 2018, Burigo et al 2019, Ngcezu and Rabus 2021. In the following we describe in more detail recent work in this field distinguishing nanodosimetric RBE and non-RBE approaches.…”