A Monte Carlo approach to the microdosimetric kinetic model to account for dose rate time structure effects in ion beam therapy with application in treatment planning simulations

Manganaro, L.; Russo, G.; Cirio, R.; Dalmasso, F; Giordanengo, S.; Monaco, V.; Muraro, S.; Sacchi, R.; Vignati, A.; Attili, A.

doi:10.1002/mp.12133

Cited by 32 publications

(66 citation statements)

References 44 publications

(79 reference statements)

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“…Many previous studies, for example, Friedland et al (2011), Friedrich et al (2012), Ballarini et al (2013), and Manganaro et al (2017) have investigated the connection between energy depositions in an SV and cell survival using various approaches. These studies are similar in that they model the microscopic patterns of energy deposition and molecular-level processes leading to cell inactivation.…”

Section: Methodsmentioning

confidence: 99%

A new formalism for modelling parametersαandβof the linear–quadratic model of cell survival for hadron therapy

2017

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We propose a new formalism for calculating parameters α and β of the linear quadratic model of cell survival. This formalism, primarily intended for calculating relative biological effectiveness (RBE) for treatment planning in hadron therapy, is based on a recently proposed microdosimetric revision of the single-target multi-hit model. The main advantage of our formalism is that it reliably produces α and β that have correct general properties with respect to their dependence on physical properties of the beam, including the asymptotic behavior for very low and high linear energy transfer (LET) beams. For example, in the case of monoenergetic beams, our formalism predicts that, as a function of LET, (a) α has a maximum and (b) the α/β ratio increases monotonically with increasing LET. No prior models reviewed in this study predict both properties (a) and (b) correctly, and therefore, these prior models are valid only within a limited LET range. We first present our formalism in a general form, for polyenergetic beams. A significant new result in this general case is that parameter β is represented as an average over the joint distribution of energies E1 and E2 of two particles in the beam. This result is consistent with the role of the quadratic term in the linear quadratic model. It accounts for the two-track mechanism of cell kill, in which two particles, one after another, damage the same site in the cell nucleus. We then present simplified versions of the formalism and discuss predicted properties of α and β Finally, to demonstrate consistency of our formalism with experimental data, we apply it to fit two sets of experimental data: (1) α for heavy ions, covering a broad range of LETs, and (2) β for protons. In both cases, good agreement was achieved.

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Section: Methodsmentioning

confidence: 99%

A new formalism for modelling parametersαandβof the linear–quadratic model of cell survival for hadron therapy

2017

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“…The aim of this paper is to present a new software, developed by the Istituto Nazionale di Fisica Nucleare (INFN) in collaboration with the University of Torino (UniTO), which provides different implementations of some radiobiological models, namely LEM I (Scholz & Kraft 1996, Scholz et al 1997, LEM II (Elsässer & Scholz 2006, Elsässer & Scholz 2007, LEM III (Elsässer et al 2008), MKM (Hawkins 1994, Hawkins 1996, Hawkins 1998, Hawkins 2003 and MCt-MKM (Manganaro et al 2017). The code is written in C ++ and it is open source for the benefit of the scientific community (published under the GNU general public licence (GPL), version 2); it is available at https://github.com/batuff/Survival.…”

Section: Introductionmentioning

confidence: 99%

‘Survival’: a simulation toolkit introducing a modular approach for radiobiological evaluations in ion beam therapy

et al. 2018

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One major rationale for the application of heavy ion beams in tumour therapy is their increased relative biological effectiveness (RBE). The complex dependencies of the RBE on dose, biological endpoint, position in the field etc require the use of biophysical models in treatment planning and clinical analysis. This study aims to introduce a new software, named 'Survival', to facilitate the radiobiological computations needed in ion therapy. The simulation toolkit was written in C++ and it was developed with a modular architecture in order to easily incorporate different radiobiological models. The following models were successfully implemented: the local effect model (LEM, version I, II and III) and variants of the microdosimetric-kinetic model (MKM). Different numerical evaluation approaches were also implemented: Monte Carlo (MC) numerical methods and a set of faster analytical approximations. Among the possible applications, the toolkit was used to reproduce the RBE versus LET for different ions (proton, He, C, O, Ne) and different cell lines (CHO, HSG). Intercomparison between different models (LEM and MKM) and computational approaches (MC and fast approximations) were performed. The developed software could represent an important tool for the evaluation of the biological effectiveness of charged particles in ion beam therapy, in particular when coupled with treatment simulations. Its modular architecture facilitates benchmarking and inter-comparison between different models and evaluation approaches. The code is open source (GPL2 license) and available at https://github.com/batuff/Survival.

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“…However, our aim in this research is to explore the difference in the biological effectiveness of the protons between acute and prolonged irradiation; hence, we took G = 1 for survival of reference radiation. 14,15,17 Using RBE r defined above, the biological dose, denoted as D bio , can be obtained by multiplying the physical dose and RBE r :…”

Section: A Biophysical Modelmentioning

confidence: 99%

The impact of dose delivery time on biological effectiveness in proton irradiation with various biological parameters

et al. 2020

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The purpose of this study is to evaluate the sublethal damage (SLD) repair effect in prolonged proton irradiation using the biophysical model with various cell-specific parameters of (α/β) x and T 1/2 (repair half time). At present, most of the model-based studies on protons have focused on acute radiation, neglecting the reduction in biological effectiveness due to SLD repair during the delivery of radiation. Nevertheless, the dose-rate dependency of biological effectiveness may become more important as advanced treatment techniques, such as hypofractionation and respiratory gating, come into clinical practice, as these techniques sometimes require long treatment times. Also, while previous research using the biophysical model revealed a large repair effect with a high physical dose, the dependence of the repair effect on cell-specific parameters has not been evaluated systematically. Methods: Biological dose [relative biological effectiveness (RBE) × physical dose] calculation with repair included was carried out using the linear energy transfer (LET)-dependent linear-quadratic (LQ) model combined with the theory of dual radiation action (TDRA). First, we extended the dose protraction factor in the LQ model for the arbitrary number of different LET proton irradiations delivered sequentially with arbitrary time lags, referring to the TDRA. Using the LQ model, the decrease in biological dose due to SLD repair was systematically evaluated for spread-out Bragg peak (SOBP) irradiation in a water phantom with the possible ranges of both (α/β) x and repair parameters ((α/β) x = 1-15 Gy, T 1/2 = 0-90 min). Then, to consider more realistic irradiation conditions, clinical cases of prostate, liver, and lung tumors were examined with the cell-specific parameters for each tumor obtained from the literature. Biological D 99% and biological dose homogeneity coefficient (HC) were calculated for the clinical target volumes (CTVs), assuming dose-rate structures with a total irradiation time of 0-60 min.

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A Monte Carlo approach to the microdosimetric kinetic model to account for dose rate time structure effects in ion beam therapy with application in treatment planning simulations

Cited by 32 publications

References 44 publications

A new formalism for modelling parametersαandβof the linear–quadratic model of cell survival for hadron therapy

A new formalism for modelling parametersαandβof the linear–quadratic model of cell survival for hadron therapy

‘Survival’: a simulation toolkit introducing a modular approach for radiobiological evaluations in ion beam therapy

The impact of dose delivery time on biological effectiveness in proton irradiation with various biological parameters

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