AI Article Synopsis

  • - The study investigates the effects of ultrahigh dose-rate FLASH proton therapy on gastrointestinal injury, highlighting that while FLASH therapy aims to reduce normal tissue toxicity, it showed significantly reduced survival rates in mice compared to conventional therapy.
  • - Whole abdominal irradiation was conducted on mice, using both FLASH and conventional proton therapy, and survival rates were assessed, along with intestinal histology analysis through a new AI-based technique.
  • - Results indicated that despite enhanced dose rates with FLASH therapy, there was no significant improvement in gut cell regeneration or histology at 4 days post-irradiation, raising questions about FLASH's efficacy for gastrointestinal sparing.

Article Abstract

Purpose: Ultrahigh dose-rate FLASH radiation therapy has emerged as a modality that promises to reduce normal tissue toxicity while maintaining tumor control. Previous studies of gastrointestinal toxicity using passively scattered FLASH proton therapy (PRT) have, however, yielded mixed results, suggesting that the requirements for gastrointestinal sparing by FLASH are an open question. Furthermore, the more clinically relevant pencil beam scanned (PBS) FLASH PRT has not yet been assessed in this context, despite differences in the spatiotemporal dose-rate distributions compared with passively scattered PRT. Here, to our knowledge, we provide the first report on the effects of PBS FLASH PRT on acute gastrointestinal injury in mice after whole abdominal irradiation.

Methods And Materials: Whole abdominal irradiation was performed on C57BL/6J mice using the entrance channel of the Bragg curve of a 250 MeV PBS proton beam at field-averaged dose rates of 0.6 Gy/s for conventional (CONV) and 80 to 100 Gy/s for FLASH PRT. A 2D strip ionization chamber array was used to measure the dose and dose rate for each mouse. Survival was assessed at 14 Gy. Intestines were harvested and processed as Swiss rolls for analysis using a novel artificial intelligence-based crypt assay to quantify crypt regeneration 4 days after irradiation.

Results: Survival was significantly reduced after 14 Gy FLASH PRT compared with CONV (P < .001). Our artificial intelligence-based crypt assays demonstrated no significant difference in intestinal crypts/cm or crypt depth between groups 4 days after irradiation. Furthermore, we found no significant difference in 5-ethynyl-2'-deoxyuridine cells/crypt or Olfactomedin4 intestinal stem cells with FLASH relative to CONV PRT.

Conclusions: Overall, our data demonstrate significantly impaired survival after abdominal PBS FLASH PRT without apparent differences in intestinal histology 4 days after irradiation.

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Source
http://dx.doi.org/10.1016/j.ijrobp.2024.09.006DOI Listing

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