Average Dose Rate is the Major Temporal Beam Structure Parameter for Preserving Murine Intestines With Pulsed...

Area of Science:

• Radiation Oncology
• Medical Physics

Background:

• The FLASH effect, a phenomenon in radiotherapy, demonstrates differential biological responses between normal tissues and tumors when irradiated at ultra-high dose rates.
• The specific physical parameters of pulsed electron beams that elicit the FLASH effect are not well understood, particularly concerning average dose rate (DRav) and dose per pulse (DPP).

Purpose of the Study:

• To systematically investigate the beam requirements for pulsed-electron FLASH radiotherapy (FLASH-RT).
• To determine the relationship between physical beam parameters (DRav, DPP) and the FLASH effect in vivo.

Main Methods:

• Irradiation of tumor-free C57BL/6 mice abdominal cavities with a pulsed electron beam at 17 Gy.
• Systematic variation of pulse repetition frequency and dose per pulse (DPP) to alter the time structure of the beams.
• Assessment of overall survival and evaluation of jejunum crypt regeneration to quantify toxicity and sparing effects.

Main Results:

• Reduced average dose rates (DRav) and doses per pulse (DPP) correlated with increased side effects and decreased survival.
• Increasing DRav while maintaining DPP maximized the FLASH sparing effect, with a minimum DRav of 100 Gy/s identified.
• High DPP (> 1 Gy/pulse) with low DRav exacerbated side effects and reduced survival.

Conclusions:

• Average dose rate (DRav) is the primary temporal parameter for achieving normal tissue sparing in pulsed FLASH radiotherapy.
• A minimum DRav of 100 Gy/s is essential for maximizing the protective FLASH effect in the intestines at a 17 Gy dose.