# Carbon ion FLASH irradiation reduces acute skin toxicity compared with conventional dose rate irradiation

## TL;DR

Carbon-ion FLASH radiotherapy reduces acute skin toxicity in mice compared to conventional dose rates, while maintaining similar tumor control.

## Contribution

This study demonstrates the tissue-sparing potential of carbon-ion FLASH irradiation through dose-response comparisons in mice.

## Key findings

- FLASH group showed consistently lower skin reaction scores across all doses and time points.
- FLASH irradiation required approximately 1.5 times higher dose to produce the same biological effect as conventional irradiation.
- Temporal patterns of skin response were similar between FLASH and conventional groups.

## Abstract

FLASH radiotherapy, defined by ultra-high dose rates exceeding 40 Gy/s, has shown potential for widening the therapeutic window due to its demonstrated normal tissue-sparing effects while maintaining tumor control with electrons, photons, and protons. However, limited biological data are available regarding its effects with heavy ions. This study aimed to investigate the biological effects of carbon-ion FLASH irradiation by assessing acute skin reactions in mice. C3H/He mice received irradiation to the right hind limb with 34–58 Gy of carbon-ion pencil beam scanning at the entrance region (dose-averaged LET: 13 keV/µm), delivered at either conventional dose rate (CONV: 0.047–0.051 Gy/s) or ultra-high dose rate (FLASH: 166.7–190.8 Gy/s). Skin reactions were evaluated every other day for up to 5 weeks to monitor early responses. The temporal patterns of skin response were similar between the CONV and FLASH groups. However, FLASH group consistently resulted in lower reaction scores across all doses and time points. Dose–response curve indicated a tissue-sparing effect with FLASH group, requiring approximately 1.5 times higher dose to produce the same biological effect as CONV group. These findings confirm the normal tissue-sparing potential of carbon-ion FLASH irradiation, with the FLASH effect quantitatively demonstrated through dose–response comparisons.

The online version contains supplementary material available at 10.1038/s41598-025-32014-w.