Selective sparing normal tissue in the gastrointestinal tract in FLASH radiotherapy for both proton and electron beamlines
Introduction
Ultra-high dose rate (FLASH) radiation therapy (RT) spares damage to normal tissue compared to conventional treatment while maintaining tumor cure. However, the reported magnitude of normal tissue sparing induced by FLASH RT varies greatly between studies. The reason for this is unknown but could be due to the physical beam parameters of the beam or on the radiation type itself. In this study, we aim to elucidate the sparing ability of FLASH RT across two separate beam types: electron and proton.
Methods
Eight-week-old female C57BL/6 mice were randomized to receive either electron or proton treatment. Abdominal irradiation was performed for both radiation types using either conventional (CONV, 0.16-0.5 Gy/s) or FLASH (200-300 Gy/s) dose rates to a dose ranging from 11 to 17 Gy. The 9MeV electron beam delivered a whole abdominal irradiation with a 4cm field, while the spread-out Bragg peak proton beam delivered a slightly smaller abdominal field at 2 cm due to machine limitations. After treatment, one cohort of mice from each group were sacrificed at 3.5 days post irradiation to determine the acute toxicity through the crypt assay, and a second cohort was used to determine differences in survival and in long term toxicity for up to 6 months post irradiation. At 6 months post irradiation, a full necropsy was performed to determine the full toxicity profile of all tissues irradiated.
Results
Both proton and electron FLASH demonstrated normal tissue sparing compared to CONV controls. The electron beam had a clear delineation in body weight change across FLASH and CONV, with a greater recovery from weight loss in the FLASH group. The proton body weight loss was seen to be less homogeneous, but again, the FLASH treated mice had a greater weight loss recovery. These changes were evaluated on both beams with little variation even though there were different field sizes between them.
Conclusion
This study distinguished the differences in the effect of beam type on radiation therapy. The magnitude of GI tract sparing was more pronounced following electron compared to proton FLASH irradiation, despite utilizing a larger field than the proton experiments. However, the results with proton FLASH were also less homogeneous between the groups and more data is being taken to fully elucidate any potential difference in the magnitude of the FLASH effect between radiation types. These data provide the first direct comparison of the FLASH effect in the GI tract between protons and electron beams and may serve as a benchmark for future studies.