Differences in Biological Responses to Ultra-high Dose Rate Proton Irradiation Between Entrance and SOBP Regions In Vitro

Background/Aim: Ultra-high dose rate (FLASH) radiotherapy has been reported to reduce normal tissue toxicity while maintaining tumor control. However, whether proton FLASH induces different biological responses in the entrance versus spread-out Bragg peak (SOBP) regions under controlled irradiation conditions remains unclear. This study compared biological responses to ultra-high dose rate proton irradiation in the entrance and SOBP regions at matched dose and time-averaged dose rate conditions. Materials and Methods: Non-tumor V79 Chinese hamster lung fibroblasts cells were irradiated with 230 MeV protons using pencil beam scanning under hypoxic (1% O2) conditions. Dose-rate conditions of 1, 40, and 100 Gy/s were applied for entrance irradiation, and 1 and 100 Gy/s for SOBP irradiation. The surviving fraction was analyzed using a clonogenic cell survival assay. Results: Clonogenic survival decreased dose-dependently at all dose rates. In the entrance region, no consistent dose-rate differences were observed up to 21 Gy; at 24 Gy, 100 Gy/s yielded a significantly higher surviving fraction than 1 Gy/s. In the SOBP region, the surviving fraction did not differ significantly between 1 and 100 Gy/s at 24 Gy. Conclusion: Under controlled conditions, a significant dose-rate-associated difference in clonogenic survival was observed in the entrance region at 24 Gy but not in the SOBP region. Further studies are required to determine whether the dose rate effect differs according to irradiation depth.