A radiation action model based on nanodosimetry is presented. It is motivated by the finding that the biological effects of various types of ionizing radiation lack a consistent relation with absorbed dose. It is postulated that the common fundamental cause of these effects is the production of elementary sublesions (DSB), which are created at a rate that is proportional to the probability to produce more than two ionisations within a volume of 10 base pairs of the DNA. The concepts of nanodosimetry allow for a quantitative characterization of this process in terms of the cumulative probability F2. The induced sublesions can interact in two ways to produce lethal damage. First, if two or more sublesions accumulate in a locally limited spherical volume of 3-10 nm in diameter, clustered DNA damage is produced. Second, consequent interactions or rearrangements of some of the initial damage over larger distances ( µm) can produce additional lethal damage. From the comparison of theoretical predictions deduced from this concept with experimental data on relative biological effectiveness, a cluster volume with a diameter of 7.5 nm could be determined. It is shown that, for electrons, the predictions agree well with experimental data over a wide energy range. The only free parameter needed to model cell survival is the intersection cross-section which includes all relevant cell-specific factors. Using ultra-soft X-rays it could be shown that the energy dependence of cell survival is directly governed by the nanodosimetric characteristics of the radiation track structure. The cell survival model derived in this work exhibits exponential cell survival at a high dose and a finite gradient of cell survival at vanishing dose, as well as the dependence on dose-rate.

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Purpose In view of the potential of treatment plan optimization based on nanodosimetric quantities, fast Monte Carlo methods for obtaining nanodosimetric quantities in macroscopic volumes are important. In this work, a “fast” method for obtaining nanodosimetric parameters from a clinical proton pencil beam in a macroscopic volume is compared with a slow and detailed method. Furthermore, the variations of these parameters, when obtained with the Monte Carlo codes TOPAS and NOREC, are investigated. Methods Monte Carlo track structure simulations of 1 keV–100 MeV protons and 12 eV–1 MeV electrons in a volume of 8 nm 3 liquid water provided us with an atlas of cluster size distributions. Two kinds of ionization cluster size distributions were recorded, counting all ionizations or only ionizations directly produced by the primary particle. The simulations of the proton pencil beam were performed in two different ways. A “fast” method where only the protons were simulated and a “slow and detailed” method where protons and electrons were simulated in order to obtain spectra at different depths. The obtained spectra were then convoluted with cluster size distributions. Results It was shown that the nanodosimetric quantity F2 from the “fast” method is, depending on the location, between 43.6% and 63.6% smaller than the F2 obtained by the “slow and detailed” method. However, it was also shown that variations of nanodosimetric quantities are even larger when the cluster size distributions of the electrons are simulated with the Monte Carlo code NOREC, that is, the cumulative F2 probabilities obtained with NOREC were between 50.8% and 75.5% smaller than the F2 probabilities obtained with TOPAS. Conclusions As long as the uncertainties of different Monte Carlo codes are not improved, it is feasible to only simulate protons in a macroscopic volume. It must be noted, however, that the uncertainty is in the order of 100%.