Microenvironmental remodeling in FLASH radiotherapy.

Area of Science:

• Oncology
• Radiation Oncology
• Biophysics

Background:

• Ultra-high dose rate radiation (FLASH-RT) offers a potential therapeutic advantage by sparing normal tissues.
• Understanding the physical-chemical-biological continuum of FLASH-RT is crucial for its clinical application.

Purpose of the Study:

• To propose a microenvironment-centered framework for interpreting FLASH-RT.
• To integrate evidence on physical aspects, normal tissue responses, tumor control, and biological mechanisms of FLASH-RT.

Main Methods:

• Review of preclinical and early clinical studies on FLASH-RT.
• Analysis of physical prerequisites, organ-specific responses, and tumor control outcomes.
• Integration of data on biological mechanisms and microenvironmental remodeling.

Main Results:

• FLASH-RT can attenuate inflammation, preserve regenerative capacity, reduce DNA damage, and mitigate fibrosis in normal tissues.
• Tumor control with FLASH-RT is comparable to conventional radiotherapy in preclinical models.
• Early clinical studies indicate feasibility and preliminary safety of FLASH-RT.

Conclusions:

• FLASH-RT-induced microenvironmental remodeling involves altered oxygen/radical dynamics, immune modulation, and preserved homeostasis.
• Responses are context-dependent, influenced by radiation parameters and tissue type.
• Standardized dosimetry and paired tumor-normal tissue evaluations are vital for clinical translation.