KEY POINTS
- This experimental preclinical study randomized 36 female BALB/c mice bearing syngeneic 4T1 breast tumors to sham irradiation, conventional radiotherapy, or FLASH radiotherapy, with 12 mice per group.
- Tumors received a nominal single fraction of 20 Gy using 6 MeV electrons, delivered at approximately 625 Gy/swith FLASH or 0.54 Gy/s conventionally; measured doses were 23.64 ± 0.79 Gy and 21.33 ± 0.67 Gy, respectively.
- FLASH and conventional irradiation produced comparable tumor growth inhibition over 14 days, despite the approximately 10.8% higher measured physical dose in the FLASH group.
- Compared with conventional irradiation, FLASH was associated with lower alanine aminotransferase and alkaline phosphatase levels, reduced oxidative stress and apoptosis, less macrophage and CD8-positive T-cell infiltration, and lower early pro-fibrotic signaling.
- Exploratory liver metabolomics identified 81 differentially abundant metabolites using the primary criteria; FLASH preserved lipid- and membrane-associated metabolic patterns disrupted by conventional irradiation.
CLINICAL TAKEAWAY
These findings support a potential normal-tissue-sparing effect of ultra-high dose-rate irradiation while maintaining short-term tumor control. However, this is an early murine study with a 14-day endpoint, unequal measured doses, exploratory metabolomics, and a liver positioned outside the primary irradiation field, so it does not provide evidence for changing clinical breast radiotherapy practice.