Radiobiology of the FLASH effect

Area of Science:

• Radiation Oncology
• Radiobiology
• Medical Physics

Background:

• Ultrahigh dose rate (UHDR) radiation elicits differential radiobiological responses compared to conventional (CONV) dose rates.
• FLASH radiotherapy (FLASH-RT) has demonstrated reduced normal tissue toxicity with equivalent tumor control, sparking significant research interest since 2014.

Purpose of the Study:

• To summarize current evidence and review preclinical studies of the FLASH effect in normal tissue response.
• To critically examine the underlying molecular and cellular mechanisms of UHDR radiation exposures in normal and tumor cells.
• To identify key research questions for advancing FLASH-RT clinical implementation.

Main Methods:

• Review of existing literature on FLASH-RT and UHDR radiation effects.
• Evaluation of in vitro studies on normal and tumor cells exposed to UHDR versus CONV irradiation.
• Analysis of preclinical models investigating normal tissue response to FLASH-RT.

Main Results:

• Differential responses to UHDR versus CONV irradiation often involve reduced inflammation and altered gene expression.
• UHDR irradiation frequently results in reduced DNA damage or misrepair products.
• Potential mechanisms involve reactive species, altered metabolic pathways, and differential DNA repair capacities between normal and tumor cells.

Conclusions:

• The precise signaling mechanisms eliciting the FLASH effect require further elucidation.
• Understanding differential susceptibility between normal and tumor cells is crucial for therapeutic advantage.
• Further mechanistic research is essential for the successful clinical translation of FLASH-RT.