Influence of heterogeneous media on Very High Energy Electron (VHEE) dose penetration and a Monte Carlo-based comparison with existing radiotherapy modalities

Lagzda, Agnese; Angal-Kalinin, D.; Jones, James; Aitkenhead, A.; Kirkby, Karen J; Mackay, Ranald I; Herk, Marcel van; Farabolini, Wilfrid; Zeeshan, Sumaira; Jones, R. M.

doi:10.1016/j.nimb.2020.09.008

Cited by 24 publications

(23 citation statements)

References 20 publications

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“…www.nature.com/scientificreports/ dose and the corresponding charge determined. This method has been verified to within a maximum error of 5.26% by Lagzda et al 6,45,46 . For both dry and wet irradiations, EBT-XD film, a radiochromic film commonly used in radiotherapy dosimetry with a dynamic range of 0.1-60 Gy 47 , was placed behind the samples.…”

Section: Methodsmentioning

confidence: 72%

“…The CLEAR user facility was chosen for VHEE plasmid irradiation experiments as it can produce stable highenergy electron beams over an energy range of 60-220 MeV, with readily adaptable beam size, bunch charge and energy-see Table 6 for a full description of beam parameters. CLEAR also has a strong history of VHEE experiments over recent years, including inhomogeneity sensitivity and dosimetry studies from the University of Manchester 6,45,46 .…”

Section: Methodsmentioning

confidence: 99%

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Evaluating very high energy electron RBE from nanodosimetric pBR322 plasmid DNA damage

Small

Henthorn

Angal-Kalinin

et al. 2021

Sci Rep

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This paper presents the first plasmid DNA irradiations carried out with Very High Energy Electrons (VHEE) over 100–200 MeV at the CLEAR user facility at CERN to determine the Relative Biological Effectiveness (RBE) of VHEE. DNA damage yields were measured in dry and aqueous environments to determine that ~ 99% of total DNA breaks were caused by indirect effects, consistent with other published measurements for protons and photons. Double-Strand Break (DSB) yield was used as the biological endpoint for RBE calculation, with values found to be consistent with established radiotherapy modalities. Similarities in physical damage between VHEE and conventional modalities gives confidence that biological effects of VHEE will also be similar—key for clinical implementation. Damage yields were used as a baseline for track structure simulations of VHEE plasmid irradiation using GEANT4-DNA. Current models for DSB yield have shown reasonable agreement with experimental values. The growing interest in FLASH radiotherapy motivated a study into DSB yield variation with dose rate following VHEE irradiation. No significant variations were observed between conventional and FLASH dose rate irradiations, indicating that no FLASH effect is seen under these conditions.

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Section: Methodsmentioning

confidence: 72%

Section: Methodsmentioning

confidence: 99%

Evaluating very high energy electron RBE from nanodosimetric pBR322 plasmid DNA damage

Small

Henthorn

Angal-Kalinin

et al. 2021

Sci Rep

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show abstract

“…Differences in tissue densities would impact the dosimetric properties of these beams, and potentially the microdosimetric quantities on which our theoretical radiobiological calculations are based. Nevertheless, one of the most important dosimetric advantage of VHEEs is their relative insensitivity to tissue heterogeneities as compared to photon and ion beams, making them more robust to potential calculation errors as experimentally demonstrated by Lagzda et al 57 , 58 . Hence, the differences between simulated and realistic materials should not significantly impact our conclusions about VHEEs and their relative comparison with other beams.…”

Section: Discussionmentioning

confidence: 99%

“…RF-based accelerators can provide relatively compact and quasi monoenergetic VHEE beams up to 250 MeV, such as the CLEAR user research platform at CERN 11 . Several dosimetry experiments have already been performed on it which demonstrated the behavior of beam stability 3 , 11 , 58 . Interesting propositions were made to reduce the doses delivered to entrance tissue, an inherent problem of VHEEs, by focusing the beam at a certain depth in tissue, a configuration whose feasibility was demonstrated on CLEAR 16 , 17 .…”

Section: Discussionmentioning

confidence: 99%

First theoretical determination of relative biological effectiveness of very high energy electrons

Delorme

Masilela

Etoh

et al. 2021

Sci Rep

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Very high energy electrons (VHEEs, E > 70 MeV) present promising clinical advantages over conventional beams due to their increased range, improved penumbra and relative insensitivity to tissue heterogeneities. They have recently garnered additional interest in their application to spatially fractionated radiotherapy or ultra-high dose rate (FLASH) therapy. However, the lack of radiobiological data limits their rapid development. This study aims to provide numerical biologically-relevant information by characterizing VHEE beams (100 and 300 MeV) against better-known beams (clinical energy electrons, photons, protons, carbon and neon ions). Their macro- and microdosimetric properties were compared, using the dose-averaged linear energy transfer ($$\overline{{L_{d} }}$$ L d ¯ ) as the macroscopic metric, and the dose-mean lineal energy $$\overline{{y_{d} }}$$ y d ¯ and the dose-weighted lineal energy distribution, yd(y), as microscopic metrics. Finally, the modified microdosimetric kinetic model was used to calculate the respective cell survival curves and the theoretical RBE. From the macrodosimetric point of view, VHEEs presented a potential improved biological efficacy over clinical photon/electron beams due to their increased $$\overline{{L_{d} }}$$ L d ¯ . The microdosimetric data, however, suggests no increased biological efficacy of VHEEs over clinical electron beams, resulting in RBE values of approximately 1, giving confidence to their clinical implementation. This study represents a first step to complement further radiobiological experiments.

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“…These results were later confirmed by experiments conducted at the VESPER test stand of the CLEAR facility (CERN, Switzerland), with a beam of 156 MeV and 1.2 mm standard deviation. The authors showed that the longitudinal dose profiles in water of the VHEE beam were relatively unaffected (less than 5–8% dose variation) when crossing different heterogeneities with densities 0.001–2.2 g/cm 3 [ 48 ].…”

Section: Very High-energy Electrons and Their Potential Application In Radiation Therapymentioning

confidence: 99%

Back to the Future: Very High-Energy Electrons (VHEEs) and Their Potential Application in Radiation Therapy

Ronga

Cavallone

Patriarca

et al. 2021

Cancers

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The development of innovative approaches that would reduce the sensitivity of healthy tissues to irradiation while maintaining the efficacy of the treatment on the tumor is of crucial importance for the progress of the efficacy of radiotherapy. Recent methodological developments and innovations, such as scanned beams, ultra-high dose rates, and very high-energy electrons, which may be simultaneously available on new accelerators, would allow for possible radiobiological advantages of very short pulses of ultra-high dose rate (FLASH) therapy for radiation therapy to be considered. In particular, very high-energy electron (VHEE) radiotherapy, in the energy range of 100 to 250 MeV, first proposed in the 2000s, would be particularly interesting both from a ballistic and biological point of view for the establishment of this new type of irradiation technique. In this review, we examine and summarize the current knowledge on VHEE radiotherapy and provide a synthesis of the studies that have been published on various experimental and simulation works. We will also consider the potential for VHEE therapy to be translated into clinical contexts.

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Influence of heterogeneous media on Very High Energy Electron (VHEE) dose penetration and a Monte Carlo-based comparison with existing radiotherapy modalities

Cited by 24 publications

References 20 publications

Evaluating very high energy electron RBE from nanodosimetric pBR322 plasmid DNA damage

Evaluating very high energy electron RBE from nanodosimetric pBR322 plasmid DNA damage

First theoretical determination of relative biological effectiveness of very high energy electrons

Back to the Future: Very High-Energy Electrons (VHEEs) and Their Potential Application in Radiation Therapy

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