Ionization Detail Parameters for DNA Damage Evaluation in Charged Particle Radiotherapy: Simulation Study Based on Cell Survival Database.

Details of excitation and ionization acts hide a description of the biological effects of charged particle traversal through living tissue. Nanodosimetry enables the introduction of novel quantities that characterize and quantify the particle track structure while also serving as a foundation for assessing biological effects based on this quantification. This presents an opportunity to enhance the planning of charged particle radiotherapy by taking into account the ionization detail. This work uses Monte Carlo simulations with Geant4-DNA code for a wide variety of charged particles and their radiation qualities to analyze the distribution of ionization cluster sizes within nanometer-scale volumes, similar to DNA diameter. By correlating these results with biological parameters extracted from the PIDE database for the V79 cell line, a novel parameter R2 based on ionization details is proposed for the evaluation of radiation quality in terms of biological consequences, i.e., radiobiological cross section for inactivation. By incorporating the probability p of sub-lethal damage caused by a single ionization, we address limitations associated with the usually proposed nanodosimetric parameter Fk for characterizing the biological effects of radiation. We show that the new parameter R2 correlates well with radiobiological data and can be used to predict biological outcomes.

Intercomparison of nanodosimetric distributions in nitrogen simulated with Geant4 and PTra track structure codes.

To facilitate the use of Geant4-DNA for radiation transport simulations in micro- and nanodosimeters, which are physically operated with tissue-equivalent gases such as nitrogen (and propane), this work aims to extend the cross section data available in Geant4-DNA to include those of nitrogen for electron energies ranging from 1 MeV down to the ionisation threshold. To achieve this, interaction cross section data for nitrogen that have been used with the in-house PTB PTra track structure code have been implemented in the current state-of-the-art Geant4-DNA simulation toolkit. An intercomparison has been performed between the two codes to validate this implementation. To quantify the agreement between the cross section models for nitrogen adopted in PTra and those implemented in Geant4-DNA, the simulation results of both codes were analysed using three physical parameters describing the ionisation cluster size distribution (ICSD): mean ionisation cluster size, variance of the cluster size and the probability to obtain a single ionisation within the target. Statistical analysis of the results indicates that the interaction cross section models for nitrogen used in PTra (elastic scattering, impact ionisations and electronic excitations) have been successfully implemented in Geant4-DNA. In addition, simulated ICSDs were compared to those measured with the Jet Counter nanodosimeter for energies between 100 and 2000 eV. For greater energies, the ICRP data for LET and particle range were used as a reference. The modified Geant4-DNA code and data successfully passed all these benchmarks fulfilling the requirement for their public release in the next version of the Geant4 toolkit.

Geant4-DNA modeling of nanodosimetric quantities in the Jet Counter for alpha particles.

The purpose of this work was to validate the calculation accuracy of nanodosimetric quantities in Geant4-DNA track structure simulation code. We implemented the Jet Counter (JC) nanodosimeter geometry in the simulation platform and quantified the impact of the Geant4-DNA physics models and JC detector performance on the ionization cluster size distributions (ICSD). ICSD parameters characterize the quality of radiation field and are supposed to be correlated to the complexity of the initial DNA damage in nanoscale and eventually the response of biological systems to radiation. We compared Monte Carlo simulations of ICSD in JC geometry performed using Geant4-DNA and PTra codes with experimental data collected for alpha particles at 3.8 MeV. We investigated the impact of simulation and experimental settings, i.e., three Geant4-DNA physics models, three sizes of a nanometer sensitive volume, gas to water density scaling procedure, JC ion extraction efficiency and the presence of passive components of the detector on the ICSD and their parameters. We found that ICSD in JC geometry obtained from Geant4-DNA simulations in water correspond well to ICSD measurements in nitrogen gas for all investigated settings, while the best agreement is for Geant4-DNA physics option 4. This work also discusses the accuracy and robustness of ICSD parameters in the context of the application of track structure simulation methods for treatment planning in particle therapy.