FLASH or flare: variable intestinal toxicity results in a mouse model following proton pencil beam scanning irradiation on a clinical superconducting synchrocyclotron

  1. Eva Bogaerts
  2. Ellina Macaeva
  3. Sima Qamhiyeh
  4. Laurence Delombaerde
  5. Brigitte Reniers
  6. Marco Caprioli
  7. Nicolas Gerard
  8. Jarrick Nys
  9. Valentin Hamaide
  10. Alexis Warnier
  11. Rudi Labarbe
  12. Swati Girdhani
  13. Richard Coos
  14. Stéphane Lucas
  15. Sofie Isebaert
  16. Rüveyda Dok
  17. Evelien Dierick
  18. Karin Haustermans
  19. Edmond Sterpin
Read the full article See related articles

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

This article is not in any list yet, why not save it to one of your lists.
Log in to save this article

Abstract

Background and aims

Ultra-high dose rate (FLASH) irradiation is a promising technique to reduce radiation-induced normal tissue toxicities while preserving antitumor efficacy. We evaluated the feasibility and intestinal sparing potential of FLASH irradiation using a clinical synchrocyclotron-based proton therapy system generating a pulsed beam.

Material and methods

C57BL/6J mice received abdominal irradiation (2×2 cm) in transmission mode at FLASH (>60 Gy/s) or conventional (CONV, 0.5 Gy/s) dose rates using a 230 MeV superconducting synchrocyclotron proton pencil beam scanning (PBS) system. Two independent irradiation rounds were performed. Endpoints included 75-day survival, regenerating crypt counts, whole blood counts at day 4, and intestinal wall thickness, cyst-like structures, and cytokine levels at day 75.

Results

In the first irradiation round, survival after 14.5 Gy FLASH was markedly improved (5/8 survivors) compared to CONV (0/8), whereas in the second round, survival rates were identical (2/7 per group). Overall, pooled data indicated improved survival with 14.5 Gy FLASH. The LD50 was 13.74 Gy in CONV and 14.48 Gy in FLASH mode, corresponding to a FLASH modifying factor of 0.95. FLASH at 14.5 Gy increased regenerating crypt numbers compared to CONV, but only in the first round, supporting survival outcomes. No significant differences were observed in whole blood counts, cytokine profiles, or long-term intestinal structural changes between groups.

Conclusion

FLASH proton therapy delivered with a clinical synchrocyclotron PBS system can reduce short-term gastrointestinal toxicity in mice. However, inconsistent results across irradiation rounds highlight limitations of this model for reliable FLASH studies.

Article activity feed

  1. Version published to 10.1101/2025.09.17.676536 on bioRxiv