FLASH Effect Is Not Always Induced by Ultra-high Dose-rate Proton Irradiation Under Hypoxic Conditions

Area of Science:

• Radiation Oncology
• Cell Biology
• Medical Physics

Background:

• Pre-clinical electron irradiation studies suggest ultra-high dose-rate (FLASH) spares normal tissue.
• Previous proton FLASH studies were limited to non-clinical systems and normoxic conditions.
• The biological impact of proton FLASH therapy under varying oxygen levels requires further investigation.

Purpose of the Study:

• To evaluate the biological response of non-tumor and tumor cells to ultra-high dose-rate proton irradiation.
• To compare proton FLASH irradiation with conventional dose rate (CONV) under normoxic and hypoxic conditions.
• To assess the efficacy of proton FLASH therapy using a clinical irradiation system.

Main Methods:

• Non-tumor (V79) and tumor (U-251, A549) cells were irradiated with 230 MeV protons.
• Irradiation was performed at ultra-high dose rate (>50 Gy/s) and conventional dose rate (0.1 Gy/s).
• Cell survival was analyzed using clonogenic assays under normoxic and hypoxic conditions.

Main Results:

• No significant difference in cell survival was observed between FLASH and CONV irradiation for either cell type.
• The oxygen concentration (normoxia vs. hypoxia) did not alter the observed survival rates.
• FLASH proton irradiation did not demonstrate a sparing effect on normal or tumor cells in this study.

Conclusions:

• Proton irradiation at FLASH dose rates (>40 Gy/s) did not induce a sparing effect on non-tumor or tumor cells under the tested conditions.
• The findings suggest that factors beyond dose rate and oxygen concentration may influence FLASH therapy outcomes.
• Further research is necessary to elucidate the mechanisms and optimal conditions for proton FLASH therapy.