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Purpose: The use of Monte Carlo (MC) simulations capable of reproducing radiobiological effects of ionising radiation on human cell lines is of great importance, especially for cases involving protons and heavier ion beams. In the latter, huge uncertainties can arise mainly related to the effects of the secondary particles produced in the beam-tissue interaction. This paper reports on a detailed MC study performed using Geant4-based approach on three cancer cell lines, the HTB-177, CRL-5876 and MCF-7, that were previously irradiated with therapeutic proton and carbon ion beams. Methods: A Geant4-based approach used jointly with analytical calculations has been developed to provide a more realistic estimation of the radiobiological damage produced by proton and carbon beams in tissues, reproducing available data obtained from in vitro cell irradiations. The MC “Hadrontherapy” Geant4 application and the Local Effect Model: LEM I, LEM II and LEM III coupled with the different numerical approaches: RapidRusso (RR) and RapidScholz (RS) were used in the study. Results: Experimental survival curves are compared with those evaluated using the highlighted Geant4 MC-based approach via chi-square statistical analysis, for the combinations of radiobiological models and numerical approaches, as outlined above. Conclusion: This study has presented a comparison of the survival data from MC simulations to experimental survival data for three cancer cell lines. An overall best level of agreement was obtained for the HTB-177 cells.

Purpose:ThescientificcommunityshowsgreatinterestinthestudyofDNAdamageinduction,DNAdamagerepair,andthebiologicaleffectsoncellsandcellularsystemsafterexposuretoionizingradiation.Severalin silicomethodshavebeenproposedsofar to study these mechanisms using Monte Carlo simulations. This study outlinesaGeant4-DNAexampleapplication,named“molecularDNA”,publiclyreleasedinthe11.1versionofGeant4(December2022).Methods:ItwasdevelopedfornoviceGeant4usersandrequiresonlyabasicunder-standing of scripting languages to get started. The example includes two differentDNA-scalegeometriesofbiologicaltargets,namely“cylinders”and“humancell”.Thispublicversionisbasedonapreviousprototypeandincludesnewfeatures,suchas:theadoptionofanewapproachforthemodelingofthechemicalstage,theuseofthestan-dardDNAdamageformattodescriberadiation-inducedDNAdamage,andupgradedcomputationaltoolstoestimateDNAdamageresponse.Results:Simulationdataintermsofsingle-strandbreakanddouble-strandbreakyieldswereproducedusingeachoftheavailablegeometries.Theresultswerecomparedwiththeliterature,tovalidatetheexample,producinglessthan5%differenceinallcases.Conclusion:“molecularDNA”isaprototypetoolthatcanbeappliedinawidevarietyofradiobiologystudies,providingthescientificcommunitywithanopen-accessbasefor DNA damage quantification calculations. New DNA and cell geometries for the“molecularDNA”examplewillbeincludedinfutureversionsofGeant4-DNA.

The scientific community has a large interest in the studies of DNA damage and response after exposure to ionizing radiation. Several in-silico methods have been proposed so far to model and study the mechanisms of DNA damage using Monte Carlo simulations. The “molecularDNA” example is one of the most recent applications to simulate the irradiation of human cancer cells and bacteria using Geant4-DNA. This example enables the simulation of the physical, physico-chemical and chemical stages of liquid water irradiation, including radiolytic processes following the particle irradiation of the pre-defined human cell geometries and it can be used to calculate the early direct and non-direct DNA damage such as single (SSB) and double strand breaks (DSB) as well as DNA fragment distribution. The application is user friendly and can be used following simple macro commands. The results of the Monte Carlo simulation are compared to experimental data of DSB yields, as well as with previously published simulation data.

In the present hadrontherapy scenario, there is a growing interest in exploring the capabilities of different ion species other than protons and carbons. The possibility of using different ions paves the way for new radiotherapy approaches, such as the multi-ions treatment, where radiation could vary according to target volume, shape, depth and histologic characteristics of the tumor. For these reasons, in this paper, the study and understanding of biological-relevant quantities was extended for the case of 4He ion. Approach. Geant4 Monte Carlo based algorithms for dose- and track-averaged LET (Linear Energy Transfer) calculations, were validated for 4He ions and for the case of a mixed field characterised by the presence of secondary ions from both target and projectile fragmentation. The simulated dose and track averaged LETs were compared with the corresponding dose and frequency mean values of the lineal energy, and , derived from experimental microdosimetric spectra. Two microdosimetric experimental campaigns were carried out at the Italian eye proton therapy facility of the Laboratori Nazionali del Sud of Istituto Nazionale di Fisica Nucleare (INFN-LNS, Catania, I) using two different microdosimeters: the MicroPlus probe and the nano-TEPC (Tissue Equivalent Proportional Counter). Main results. A good agreement of and with and experimentally measured with both microdosimetric detectors MicroPlus and nano-TEPC in two configurations: full energy and modulated 4He ion beam, was found. Significance. The results of this study certify the use of a very effective tool for the precise calculation of LET, given by a Monte Carlo approach which has the advantage of allowing detailed simulation and tracking of nuclear interactions, even in complex clinical scenarios.