Determination of fast neutron RBE using a fully mechanistic computational model

Zabihi, Azam; Tello, John; Incerti, S.; Francis, Z.; Forozani, Ghasem; Semsarha, Farid; Moslehi, Amir; Bernal, Mario A.

doi:10.1016/j.apradiso.2019.108952

Cited by 4 publications

(5 citation statements)

References 62 publications

(90 reference statements)

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“…Step 2: Track-structure simulations 2.3.1. Nuclear DNA model Despite an abundance of nuclear DNA models that are described in the literature (Friedland et al 2011, Lampe et al 2018, Tang et al 2019, Zhu et al 2020a, Sakata et al 2020, Zabihi et al 2020, there were no complete open-source models available at the time of this study. Thus, we constructed a custom nuclear DNA model using the TOPAS extensions framework.…”

Section: 3mentioning

confidence: 99%

“…For each scoring volume k and initial neutron or x-ray energy E, particles were simulated until 1 Gy of dose was delivered to the nucleus. A target dose D 0 of 1 Gy was chosen for consistency with recent literature (Baiocco et al 2016, Tang et al 2019, Zhu et al 2020a, Zabihi et al 2020. Additional simulations were performed with alternative D 0 values to assess dose dependence, as described in section 2.6.…”

Section: Irradiation Setupmentioning

confidence: 99%

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Towards the characterization of neutron carcinogenesis through direct action simulations of clustered DNA damage

et al. 2021

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Neutron exposure poses a unique radiation protection concern because neutrons have a large, energy-dependent relative biological effectiveness (RBE) for stochastic effects. Recent computational studies on the microdosimetric properties of neutron dose deposition have implicated clustered DNA damage as a likely contributor to this marked energy dependence. So far, publications have focused solely on neutron RBE for inducing clusters of DNA damage containing two or more DNA double strand breaks (DSBs). In this study, we have conducted a novel assessment of neutron RBE for inducing all types of clustered DNA damage that contain two or more lesions, stratified by whether the clusters contain DSBs (complex DSB clusters) or not (non-DSB clusters). This assessment was conducted for eighteen initial neutron energies between 1 eV and 10 MeV as well as a reference radiation of 250 keV x-rays. We also examined the energy dependence of cluster length and cluster complexity because these factors are believed to impact the DNA repair process. To carry out our investigation, we developed a user-friendly TOPAS-nBio application that includes a custom nuclear DNA model and a novel algorithm for recording clustered DNA damage. We found that neutron RBE for inducing complex DSB clusters exhibited similar energy dependence to the canonical neutron RBE for stochastic radiobiological effects, at multiple depths in human tissue. Qualitatively similar results were obtained for non-DSB clusters, although the quantitative agreement was lower. Additionally we identified a significant neutron energy dependence in the average length and complexity of clustered lesions. These results support the idea that many types of clustered DNA damage contribute to the energy dependence of neutron RBE for stochastic radiobiological effects and imply that the size and constituent lesions of individual clusters should be taken into account when modeling DNA repair. Our results were qualitatively consistent for (i) multiple radiation doses (including a low-dose 0.1 Gy irradiation), (ii) variations in the maximal lesion separation distance used to define a cluster, and (iii) two distinct collections of physics models used to govern particle transport. Our complete TOPAS-nBio application has been released under an open-source license to enable others to independently validate our work and to expand upon it.

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Section: 3mentioning

confidence: 99%

Section: Irradiation Setupmentioning

confidence: 99%

Towards the characterization of neutron carcinogenesis through direct action simulations of clustered DNA damage

et al. 2021

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“…Other authors have published descriptions of far more complex models, for example using GEANT 4 and other simulations, with multiple assumptions regarding biophysical events such as DNA double strand break (DSB) production density etc, and over much more limited energy ranges than the present study (Chen et al 2017, Zabihi et al 2020. The DSB end point, although better than single strand breaks, may not adequately reflect cell killing for RBE determination, since DSB are normally repaired efficiently.…”

Section: Discussionmentioning

confidence: 92%

“…Cell death is better correlated with lethal chromosome breaks (Cornforth and Bedford 1987). For example, the advanced models of Boccacio and colleagues (Zabihi et al 2020) consider the relative proportions of other ion species produced within a neutron beam using fundamental and phenomenological approaches, but there is no validation with extant biological data sets. This group did predict a second peak of RBE between 20 and 40 MeV, as appeared to be the case for the experimental data of Hall et al (1975) as shown in figure 6, but when the NEeff correction is applied for Hall's 35 and 50 MeV beams effective neutron energy this peak at 35 MeV cannot be found, since (Hall et al 1975), H=Hammersmith (Berry 1973, Berry andBewley 1976), followed by the fission sources at P=Petten (Hall et al 1975), B(A)=Brookhaven (full spectrum) (Hall et al 1975), B(B)=Brookhaven (using plate converter assumed to have max energy of 6 MeV) (Hall et al 1975).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, there are fewer models of the LET and RBE relationship for fast neutron beams of different energies, probably because of the inherent complexity of the neutron interactions resulting in many different ionising products. Consequently, there are a large number of resulting variables, which can be studied by use of Geant4 Monte Carlo and other simulation programmes (Baiocco et al 2016, Zabihi et al 2020.…”

Section: Introductionmentioning

confidence: 99%

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Fast neutron energy based modelling of biological effectiveness with implications for proton and ion beams

Jones

2021

Phys. Med. Biol.

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A practical neutron energy dependent RBE model has been developed, based on the relationship between a mono-energetic neutron energy and its likely recoil proton energy. Essentially, the linear energy transfer (LET) values of the most appropriate recoil proton energies are then used to modify the linear quadratic model radiosensitivities (α and β) from their reference LET radiation values to provide the RBE estimates. Experimental neutron studies published by Hall (including some mono-energetic beams ranging from 0.2 to 15 MeV), Broerse, Berry, and data from the Clatterbridge and Detroit clinical neutron beams, which all contain some data from a spectrum of neutron energies, are used to derive single effective neutron energies (NEeff) for each spectral beam. These energies yield a recoil proton spectrum, but with an effective mean proton energy (being around 50% of NEeff). The fractional increase in LET is given by the recoil proton LET divided by the proton (LETU) value which provides the highest RBE. This ratio is then used to determine the change in the linear-quadratic model α and β parameters, from those of the reference radiation, to estimate the RBE. The predicted proton recoil RBE is then reasonably close to the experimental neutron RBE values found when taking into account the variation inherent in biological experiments. The work has some important consequences. The data of Hall et al (1975 Radiat. Res. 64 245–55) shows that the highest RBE values are found with neutron energies around 0.3–0.4 MeV, but this energy cannot possibly generate recoil proton energies which are higher, as necessary for a 0.68 MeV proton with a 30.5 keV μm−1 LETU (the LET value which provides the maximum obtainable RBE for a specified ion). For 0.4 MeV neutrons with proton recoil energies of around 0.2 MeV, the latter have a LET of around 62.88 keV μm−1. This could have an impact on proton beam RBE modelling. However, this is compensated by finding that the maximum radiosensitivity for mono-energetic neutrons was around 1.7 times larger than previously suggested from experimental ion beam studies, probably due to the necessary spreading out of Bragg peaks for ion beam experimental purposes, sampling errors and particle range considerations. This semi-empirical model can be used with minimal computer support and could have applications in ionic beams and in radioprotection.

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The associated killing of hepatoma cells using multilayer drug-loaded mats combined with fast neutron therapy

Jing

et al. 2020

Nano Res.

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Determination of fast neutron RBE using a fully mechanistic computational model

Cited by 4 publications

References 62 publications

Towards the characterization of neutron carcinogenesis through direct action simulations of clustered DNA damage

Towards the characterization of neutron carcinogenesis through direct action simulations of clustered DNA damage

Fast neutron energy based modelling of biological effectiveness with implications for proton and ion beams

The associated killing of hepatoma cells using multilayer drug-loaded mats combined with fast neutron therapy

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