Do We Preserve Tumor Control Probability (TCP) in FLASH Radiotherapy? A Model-Based Analysis.

Area of Science:

• Oncology
• Radiation Oncology
• Medical Physics

Background:

• FLASH radiotherapy utilizes ultra-high dose-rates (uHDR) for potential normal tissue sparing.
• Iso-effectiveness in tumors is often inferred from growth kinetics, but clinical relevance requires further investigation.

Purpose of the Study:

• To investigate the clinical treatment outcome implications of tumor iso-effectiveness indications in FLASH radiotherapy.
• To assess the tumor control probability (TCP) of FLASH radiotherapy under various treatment parameters.

Main Methods:

• A model-based analysis combining the UNIVERSE model for uHDR sparing with tumor volume kinetics and TCP models.
• Comparison of model predictions with experimental data.
• Investigation of TCP by varying dose-rate, fractionation, and oxygen concentration.

Main Results:

• The developed framework accurately describes reported tumor growth kinetics.
• Sparing effects in tumors might be present but too small to be detected in current experimental setups.
• TCP predictions indicate a potential substantial loss of treatment efficacy in FLASH radiotherapy.

Conclusions:

• The clinical viability of FLASH radiotherapy requires careful consideration of potential TCP loss.
• Fractionation scheme, oxygen levels, and DNA repair kinetics are critical variables influencing FLASH radiotherapy efficacy.