Decrease in dose per fraction impairs the FLASH sparing effect in murine intestine model.

Area of Science:

• Radiation Oncology
• Preclinical Research
• Radiobiology

Background:

• Conventional radiotherapy (CONV) poses risks of normal tissue toxicity.
• Ultra-high dose rate FLASH radiotherapy (FLASH) shows promise in sparing normal tissues.
• The efficacy of FLASH in clinically relevant fractionation schedules requires further investigation.

Purpose of the Study:

• To investigate the normal tissue sparing effect of FLASH radiotherapy across different fractionation protocols.
• To evaluate FLASH's benefit in a murine model of acute gastrointestinal toxicity.
• To determine the dose modifying factor (DMF) for FLASH under various fractionation schemes.

Main Methods:

• C57BL/6 mice underwent abdominal irradiation using either CONV or FLASH (9 MeV electron beam).
• Three protocols were tested: single fraction, two equal fractions over two days, and ten daily fractions over two weeks.
• Dose escalation was performed, and overall survival monitored normal tissue sparing; DMF was calculated from NTCP curves.

Main Results:

• Single-fraction FLASH demonstrated significant sparing (mean DMF = 1.14).
• The two-fraction regimen showed diminished sparing (mean DMF = 1.03).
• No significant sparing was observed with the ten-fraction regimen (mean DMF = 1.00).

Conclusions:

• FLASH radiotherapy's normal tissue sparing effect is reduced in fractionated protocols, particularly with higher fraction numbers.
• The benefit of FLASH may be dose-per-fraction dependent, with limited efficacy in hypofractionated or conventionally fractionated schedules.
• Further research is needed in diverse models to define FLASH's therapeutic applicability in clinical settings.