Prediction of biological radiation effects based on ionization clusters (nanodosimetry)

Abstract

This article reviews approaches that link the formation of ionization clusters in nanometric volumes to radiobiological effectiveness. The corresponding models were developed as the field of nanodosimetry developed. Some address early biological radiation effects, such as DNA damage, while most aim to predict cell survival or inactivation. The models also differ in the nanodosimetric quantities considered, with many based on the probability distribution of ionization cluster formation in a single target. Some models account for the synergistic effects of pairs of ionization clusters formed in different targets. Several models feature macroscopic aggregation frameworks based on particle fluence, which are proposed for use in radiotherapy treatment planning, particularly in ion-beam radiotherapy. The models are presented here using harmonized terminology and notation for nanodosimetric quantities. An extension of the conceptual framework of nanodosimetry is also discussed. This extension transitions from a target-centered description to a track-centered description. It also introduces nanodosimetry-based analogs of dosimetric concepts, such as dose and linear energy transfer. This paper traces and summarizes the historical development of nanodosimetry-based biological effect models and discusses conceptual aspects of the models to reveal their underlying assumptions and the extent to which they are mechanistic or merely elucidate correlations. Eventually, an attempt is made to identify the key open questions in this field that still need to be addressed.

arXiv commentPaper has been restructured & section on nanodosimetry extended by dependencies of IC distributions & elaborationg on the transition to yields of clusters vs. probability of cluster formation. Several Figs./Tables & Supplementary Figs./Tables have been added (e.g. historical development of nanodosimetry & biological models, comparison of notations, summary of key model features)