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Whole Abdominal Pencil Beam Scanned Proton FLASH Increases Acute Lethality
Brett I Bell1, Christian Velten2, Michael Pennock2
1Departments of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York; Departments of Radiation Oncology and Pathology, Albert Einstein College of Medicine, Bronx, New York.
International Journal of Radiation Oncology, Biology, Physics
|September 19, 2024
Summary
Pencil beam scanned FLASH proton therapy (PRT) impaired survival in mice after abdominal irradiation. However, this ultrahigh dose-rate radiation therapy did not show significant differences in intestinal crypt regeneration compared to conventional PRT.
Area of Science:
- Radiation Oncology
- Gastrointestinal Oncology
- Translational Cancer Research
Background:
- Ultrahigh dose-rate FLASH radiation therapy shows promise for reducing normal tissue toxicity.
- Previous studies on gastrointestinal toxicity with FLASH proton therapy (PRT) have yielded mixed results.
- Pencil beam scanned (PBS) FLASH PRT, a clinically relevant technique, has not been evaluated for gastrointestinal effects.
Purpose of the Study:
- To investigate the effects of PBS FLASH PRT on acute gastrointestinal injury in mice following whole abdominal irradiation.
- To compare gastrointestinal toxicity and survival outcomes between PBS FLASH PRT and conventional (CONV) PRT.
Main Methods:
- Whole abdominal irradiation in C57BL/6J mice using a 250 MeV PBS proton beam.
- Dose rates: 0.6 Gy/s for CONV and 80-100 Gy/s for FLASH PRT.
- Assessment of survival at 14 Gy and intestinal crypt regeneration using an AI-based crypt assay 4 days post-irradiation.
Main Results:
- Survival was significantly reduced in the FLASH PRT group compared to the CONV group (P < .001).
- No significant differences were observed in intestinal crypts/cm or crypt depth between FLASH PRT and CONV PRT groups.
- No significant differences in 5-ethynyl-2'-deoxyuridine+ cells/crypt or Olfactomedin4+ intestinal stem cells were found.
Conclusions:
- Abdominal PBS FLASH PRT resulted in significantly impaired survival in mice.
- Despite survival differences, PBS FLASH PRT did not show apparent differences in intestinal histology or stem cell markers at 4 days post-irradiation.
- Further research is needed to understand the mechanisms behind survival reduction and optimize FLASH PRT for gastrointestinal sparing.
