KEY POINTS
- The investigators compared conventional-dose-rate irradiation with ultra-high-dose-rate irradiation above 40 Gy per second using pancreatic cancer and non-tumorigenic cell lines, tissue samples and mouse models.
- Pancreatic cancer cells showed similar reductions in mitochondrial function and similar mitochondrial stress after conventional and FLASH irradiation.
- In non-tumorigenic pancreatic cells, conventional irradiation caused mitochondrial DNA damage, altered respiration and increased cellular stress, while these effects were generally reduced after FLASH.
- Ex vivo and in vivo analyses similarly showed less mitochondrial structural damage in normal pancreatic tissue after FLASH.
- Tumour-growth delay was comparable between modalities, but mice lived longer after FLASH because conventional irradiation caused greater skin toxicity and ulceration, not because FLASH produced superior tumour control.
CLINICAL TAKEAWAY
Preservation of normal-cell mitochondrial integrity is a credible candidate mechanism for the FLASH normal-tissue effect. However, the work remains preclinical, and several experiments used immortalized rather than genuinely normal cells, so it does not establish a therapeutic advantage in patients.
SOURCE
International Journal of Radiation Oncology, Biology, Physics