Effects of ultra-high dose rate radiotherapy with different fractions and dose rate on acute and chronic lung injury in mice

Ultra-high dose rate radiotherapy (FLASH radiation) can naturally render normal tissues around the tumor tissue resistant to radiotherapy. In contrast, the tumor tissue remains sensitive to radiation under the same conditions. However, the effects of different fractions and dose rates on FLASH radiation remain unclear. This study aimed to determine the optimal dose rate and fraction of FLASH radiation for thoracic radiotherapy. Female Balb/c mice aged 6-8 weeks were irradiated with different dose rates (100 Gy/s or 250 Gy/s) and fractions (1, 2, or 4). Survival was observed in mice receiving 30Gy, with lung tissue examined for acute radiation damage 48 h post-radiation. Late radiation pneumonia and survival rates were monitored in mice irradiated with 20 Gy. The median overall survival (OS) was not reached on the 95th day for mice irradiated with 250 Gy/s FLASH radiation, while it was 89.5 days for those irradiated with 100 Gy/s (P = 0.0436). Mice irradiated with 30 Gy/2 Fr and 250 Gy/s FLASH had shorter median OS than those with 30 Gy/1F (P = 0.0132). However, there was no significant difference in OS between mice irradiated with 30 Gy/2 F and 30 Gy/4 F. Survival curves for mice receiving 20 Gy showed no significant difference in toxicity between different dose rates and fractions. FLASH radiation at 250 Gy/s reduced the incidence of acute radiation pneumonitis in mice compared to 100 Gy/s. Different fractions of irradiation influenced survival in mice, but they were only observed in acute radiation reactions and not chronic radiation reactions. Among the tested fraction methods, fraction 2 had the worst impact on the survival of mice, while fractions 1 and 4 showed similar effects and improved survival compared to fraction 2.