Electron vs proton FLASH radiation on murine skin toxicity

Line Kristensen; Sky Rohrer; Lone Hoffmann; Lars H Præstegaard; Christina Ankjærgaard; Claus E Andersen; Eleni Kanouta; Jacob Graversgaard Johansen; Morten Sahlertz; Jasper Nijkamp; Per Rugaard Poulsen; Brita Singers Sørensen

doi:10.1016/j.radonc.2025.110796

Electron vs proton FLASH radiation on murine skin toxicity

Line Kristensen, Sky Rohrer, Lone Hoffmann, Lars H Præstegaard, Christina Ankjærgaard, Claus E Andersen, Eleni Kanouta, Jacob Graversgaard Johansen, Morten Sahlertz, Jasper Nijkamp, Per Rugaard Poulsen, Brita Singers Sørensen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

1 Citation (Scopus)

Abstract

BACKGROUND AND PURPOSE: Dose-response modification of FLASH has previously been established for acute skin toxicity in protons. This study used a similar experimental setup to quantify the dose-response modification of electron FLASH irradiation for acute skin- and late fibrotic toxicity in mice. The setup similarity enabled quantitative comparison of the acute skin response for electrons to protons.

METHOD: Female unanaesthetised C3D2F1 mice were restrained with the right hindleg fixated and submerged in a water bath for horizontal electron irradiation at 16 MeV. Mice were randomised in groups of varying single doses (19.4-57.6 Gy) and irradiated with either 0.162 Gy/s conventional (CONV) or 233 Gy/s FLASH dose rate using 8-10 mice per group. Acute skin toxicity was assessed daily from the 8th to the 28th day post-irradiation. The same mice were kept for a fibrotic assay of leg extension assessment done biweekly until 52 weeks post-irradiation. The dose-modifying factor (DMF) of FLASH was quantified from dose-response curves.

RESULTS AND DISCUSSION: Electron FLASH irradiated mice showed a considerable skin-sparing effect with a DMF of 1.45-1.54 and a smaller fibrotic-sparing effect with a DMF of 1.15. The development of acute skin toxicity was similar between CONV and FLASH groups with biological equivalent doses based on the DMF. The acute response of the electron irradiations was similar to previous reports on protons.

CONCLUSION: Despite apparent differences, e.g. average and instantaneous dose rates, the acute skin toxicity of electron beams and previously published proton beams were remarkably similar regarding both biological response and quantified acute skin DMFs.

Original language	English
Article number	110796
Journal	Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
Volume	206
Pages (from-to)	110796
ISSN	0167-8140
DOIs	https://doi.org/10.1016/j.radonc.2025.110796
Publication status	Published - May 2025

Keywords

Acute damage
Electron irradiation
FLASH
In vivo
Late damage

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Kristensen, L., Rohrer, S., Hoffmann, L., Præstegaard, L. H., Ankjærgaard, C., Andersen, C. E., Kanouta, E., Johansen, J. G., Sahlertz, M., Nijkamp, J., Poulsen, P. R., & Sørensen, B. S. (2025). Electron vs proton FLASH radiation on murine skin toxicity. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 206, 110796. Article 110796. https://doi.org/10.1016/j.radonc.2025.110796

@article{952ace0a6fb841abb0bc5662d92ad46a,

title = "Electron vs proton FLASH radiation on murine skin toxicity",

abstract = "BACKGROUND AND PURPOSE: Dose-response modification of FLASH has previously been established for acute skin toxicity in protons. This study used a similar experimental setup to quantify the dose-response modification of electron FLASH irradiation for acute skin- and late fibrotic toxicity in mice. The setup similarity enabled quantitative comparison of the acute skin response for electrons to protons.METHOD: Female unanaesthetised C3D2F1 mice were restrained with the right hindleg fixated and submerged in a water bath for horizontal electron irradiation at 16 MeV. Mice were randomised in groups of varying single doses (19.4-57.6 Gy) and irradiated with either 0.162 Gy/s conventional (CONV) or 233 Gy/s FLASH dose rate using 8-10 mice per group. Acute skin toxicity was assessed daily from the 8th to the 28th day post-irradiation. The same mice were kept for a fibrotic assay of leg extension assessment done biweekly until 52 weeks post-irradiation. The dose-modifying factor (DMF) of FLASH was quantified from dose-response curves.RESULTS AND DISCUSSION: Electron FLASH irradiated mice showed a considerable skin-sparing effect with a DMF of 1.45-1.54 and a smaller fibrotic-sparing effect with a DMF of 1.15. The development of acute skin toxicity was similar between CONV and FLASH groups with biological equivalent doses based on the DMF. The acute response of the electron irradiations was similar to previous reports on protons.CONCLUSION: Despite apparent differences, e.g. average and instantaneous dose rates, the acute skin toxicity of electron beams and previously published proton beams were remarkably similar regarding both biological response and quantified acute skin DMFs.",

keywords = "Acute damage, Electron irradiation, FLASH, In vivo, Late damage",

author = "Line Kristensen and Sky Rohrer and Lone Hoffmann and Pr{\ae}stegaard, \{Lars H\} and Christina Ankj{\ae}rgaard and Andersen, \{Claus E\} and Eleni Kanouta and Johansen, \{Jacob Graversgaard\} and Morten Sahlertz and Jasper Nijkamp and Poulsen, \{Per Rugaard\} and S{\o}rensen, \{Brita Singers\}",

note = "Copyright {\textcopyright} 2025. Published by Elsevier B.V.",

year = "2025",

month = may,

doi = "10.1016/j.radonc.2025.110796",

language = "English",

volume = "206",

pages = "110796",

journal = "Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

}

Kristensen, L, Rohrer, S , Hoffmann, L, Præstegaard, LH, Ankjærgaard, C, Andersen, CE, Kanouta, E, Johansen, JG , Sahlertz, M , Nijkamp, J , Poulsen, PR & Sørensen, BS 2025, 'Electron vs proton FLASH radiation on murine skin toxicity', Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, vol. 206, 110796, pp. 110796. https://doi.org/10.1016/j.radonc.2025.110796

Electron vs proton FLASH radiation on murine skin toxicity. / Kristensen, Line; Rohrer, Sky ; Hoffmann, Lone et al.
In: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, Vol. 206, 110796, 05.2025, p. 110796.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Electron vs proton FLASH radiation on murine skin toxicity

AU - Kristensen, Line

AU - Rohrer, Sky

AU - Hoffmann, Lone

AU - Præstegaard, Lars H

AU - Ankjærgaard, Christina

AU - Andersen, Claus E

AU - Kanouta, Eleni

AU - Johansen, Jacob Graversgaard

AU - Sahlertz, Morten

AU - Nijkamp, Jasper

AU - Poulsen, Per Rugaard

AU - Sørensen, Brita Singers

PY - 2025/5

Y1 - 2025/5

N2 - BACKGROUND AND PURPOSE: Dose-response modification of FLASH has previously been established for acute skin toxicity in protons. This study used a similar experimental setup to quantify the dose-response modification of electron FLASH irradiation for acute skin- and late fibrotic toxicity in mice. The setup similarity enabled quantitative comparison of the acute skin response for electrons to protons.METHOD: Female unanaesthetised C3D2F1 mice were restrained with the right hindleg fixated and submerged in a water bath for horizontal electron irradiation at 16 MeV. Mice were randomised in groups of varying single doses (19.4-57.6 Gy) and irradiated with either 0.162 Gy/s conventional (CONV) or 233 Gy/s FLASH dose rate using 8-10 mice per group. Acute skin toxicity was assessed daily from the 8th to the 28th day post-irradiation. The same mice were kept for a fibrotic assay of leg extension assessment done biweekly until 52 weeks post-irradiation. The dose-modifying factor (DMF) of FLASH was quantified from dose-response curves.RESULTS AND DISCUSSION: Electron FLASH irradiated mice showed a considerable skin-sparing effect with a DMF of 1.45-1.54 and a smaller fibrotic-sparing effect with a DMF of 1.15. The development of acute skin toxicity was similar between CONV and FLASH groups with biological equivalent doses based on the DMF. The acute response of the electron irradiations was similar to previous reports on protons.CONCLUSION: Despite apparent differences, e.g. average and instantaneous dose rates, the acute skin toxicity of electron beams and previously published proton beams were remarkably similar regarding both biological response and quantified acute skin DMFs.

AB - BACKGROUND AND PURPOSE: Dose-response modification of FLASH has previously been established for acute skin toxicity in protons. This study used a similar experimental setup to quantify the dose-response modification of electron FLASH irradiation for acute skin- and late fibrotic toxicity in mice. The setup similarity enabled quantitative comparison of the acute skin response for electrons to protons.METHOD: Female unanaesthetised C3D2F1 mice were restrained with the right hindleg fixated and submerged in a water bath for horizontal electron irradiation at 16 MeV. Mice were randomised in groups of varying single doses (19.4-57.6 Gy) and irradiated with either 0.162 Gy/s conventional (CONV) or 233 Gy/s FLASH dose rate using 8-10 mice per group. Acute skin toxicity was assessed daily from the 8th to the 28th day post-irradiation. The same mice were kept for a fibrotic assay of leg extension assessment done biweekly until 52 weeks post-irradiation. The dose-modifying factor (DMF) of FLASH was quantified from dose-response curves.RESULTS AND DISCUSSION: Electron FLASH irradiated mice showed a considerable skin-sparing effect with a DMF of 1.45-1.54 and a smaller fibrotic-sparing effect with a DMF of 1.15. The development of acute skin toxicity was similar between CONV and FLASH groups with biological equivalent doses based on the DMF. The acute response of the electron irradiations was similar to previous reports on protons.CONCLUSION: Despite apparent differences, e.g. average and instantaneous dose rates, the acute skin toxicity of electron beams and previously published proton beams were remarkably similar regarding both biological response and quantified acute skin DMFs.

KW - Acute damage

KW - Electron irradiation

KW - FLASH

KW - In vivo

KW - Late damage

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U2 - 10.1016/j.radonc.2025.110796

DO - 10.1016/j.radonc.2025.110796

M3 - Journal article

C2 - 39983873

SN - 0167-8140

VL - 206

SP - 110796

JO - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

JF - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

M1 - 110796

ER -

Electron vs proton FLASH radiation on murine skin toxicity

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