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Photon FLASH spares radiation-induced changes in cardiac function, remodelling and arrythmia in a preclinical model

Ghita-Pettigrew, Mihaela ; Brown, Kathryn H. ; Kerr, Brianna N. ; Walls, Gerard M. ; Verginadis, Ioannis I. ; Adrian, Gabriel LU orcid ; Petersson, Kristoffer LU ; McMahon, Stephen J. and Butterworth, Karl T. (2026) In Radiotherapy and Oncology 216.
Abstract

Introduction: Preclinical studies have demonstrated the ability of FLASH irradiation to expand the therapeutic window by sparing normal tissues. The heart is a critical organ at risk in patients receiving radiotherapy for thoracic cancers. This study aimed to quantify the cardiac sparing effects of photon FLASH delivered as single (FLASH) or FLASH split dose (FSD) exposures. Methods: Female C57BL/6 mice were irradiated with 18.5 ± 0.6 Gy delivered to the whole heart using a FLASH-SARRP (Xstrahl Life Sciences, UK) at a dose rate of 85.6 ± 1.6 Gy/s (isocentre dose rate 75.9 ± 1.5 Gy/s). Comparative studies were undertaken using 18.6 ± 0.4 Gy delivered using two consecutive pulses (FSD) at an average dose rate of 2.8 ± 0.9 Gy/s, and with... (More)

Introduction: Preclinical studies have demonstrated the ability of FLASH irradiation to expand the therapeutic window by sparing normal tissues. The heart is a critical organ at risk in patients receiving radiotherapy for thoracic cancers. This study aimed to quantify the cardiac sparing effects of photon FLASH delivered as single (FLASH) or FLASH split dose (FSD) exposures. Methods: Female C57BL/6 mice were irradiated with 18.5 ± 0.6 Gy delivered to the whole heart using a FLASH-SARRP (Xstrahl Life Sciences, UK) at a dose rate of 85.6 ± 1.6 Gy/s (isocentre dose rate 75.9 ± 1.5 Gy/s). Comparative studies were undertaken using 18.6 ± 0.4 Gy delivered using two consecutive pulses (FSD) at an average dose rate of 2.8 ± 0.9 Gy/s, and with 20.1 ± 0.5 Gy using a conventional SARRP at a dose rate of 3.4 ± 0.2 Gy/min (CONV). Transthoracic echocardiography was performed at 10 and 30 weeks with supporting histology and analysis of serum biomarkers 30 weeks post irradiation. Results: In comparison to CONV and FSD exposures, FLASH significantly reduced radiation-induced loss of cardiac function, cardiac remodelling and arrythmia 30 weeks after irradiation. These observations were supported by reduced myocardial fibrosis, cardiac injury biomarkers and inflammatory cytokines. Conclusions: This study highlights the ability of photon FLASH to preserve cardiac function and structure from radiation damage with the level of sparing dependent on average dose rate and beam structure.

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type
Contribution to journal
publication status
published
subject
in
Radiotherapy and Oncology
volume
216
article number
111369
publisher
Elsevier
external identifiers
  • pmid:41500467
  • scopus:105028863460
ISSN
0167-8140
DOI
10.1016/j.radonc.2026.111369
language
English
LU publication?
yes
id
6f84767b-9c1e-4ea4-becf-c9732febbb48
date added to LUP
2026-02-18 12:27:31
date last changed
2026-02-18 12:28:44
@article{6f84767b-9c1e-4ea4-becf-c9732febbb48,
  abstract     = {{<p>Introduction: Preclinical studies have demonstrated the ability of FLASH irradiation to expand the therapeutic window by sparing normal tissues. The heart is a critical organ at risk in patients receiving radiotherapy for thoracic cancers. This study aimed to quantify the cardiac sparing effects of photon FLASH delivered as single (FLASH) or FLASH split dose (FSD) exposures. Methods: Female C57BL/6 mice were irradiated with 18.5 ± 0.6 Gy delivered to the whole heart using a FLASH-SARRP (Xstrahl Life Sciences, UK) at a dose rate of 85.6 ± 1.6 Gy/s (isocentre dose rate 75.9 ± 1.5 Gy/s). Comparative studies were undertaken using 18.6 ± 0.4 Gy delivered using two consecutive pulses (FSD) at an average dose rate of 2.8 ± 0.9 Gy/s, and with 20.1 ± 0.5 Gy using a conventional SARRP at a dose rate of 3.4 ± 0.2 Gy/min (CONV). Transthoracic echocardiography was performed at 10 and 30 weeks with supporting histology and analysis of serum biomarkers 30 weeks post irradiation. Results: In comparison to CONV and FSD exposures, FLASH significantly reduced radiation-induced loss of cardiac function, cardiac remodelling and arrythmia 30 weeks after irradiation. These observations were supported by reduced myocardial fibrosis, cardiac injury biomarkers and inflammatory cytokines. Conclusions: This study highlights the ability of photon FLASH to preserve cardiac function and structure from radiation damage with the level of sparing dependent on average dose rate and beam structure.</p>}},
  author       = {{Ghita-Pettigrew, Mihaela and Brown, Kathryn H. and Kerr, Brianna N. and Walls, Gerard M. and Verginadis, Ioannis I. and Adrian, Gabriel and Petersson, Kristoffer and McMahon, Stephen J. and Butterworth, Karl T.}},
  issn         = {{0167-8140}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Radiotherapy and Oncology}},
  title        = {{Photon FLASH spares radiation-induced changes in cardiac function, remodelling and arrythmia in a preclinical model}},
  url          = {{http://dx.doi.org/10.1016/j.radonc.2026.111369}},
  doi          = {{10.1016/j.radonc.2026.111369}},
  volume       = {{216}},
  year         = {{2026}},
}