Spread-out Bragg peak FLASH: quantifying normal tissue toxicity in a murine model.

Area of Science:

• Radiation Oncology
• Preclinical Research
• Medical Physics

Background:

• Ultra-high dose rate (FLASH) radiation shows promise for sparing normal tissues while maintaining tumor control in preclinical studies.
• Most FLASH research focuses on the beam entrance, but clinical proton therapy utilizes Spread-out Bragg Peaks (SOBP) for targeted dose delivery.
• Investigating FLASH effects within an SOBP is crucial for clinical relevance.

Purpose of the Study:

• To quantify the normal tissue-sparing effect of FLASH radiation on acute and late toxicity within a Spread-out Bragg Peak (SOBP).
• To compare FLASH irradiation to conventional dose rate (CONV) irradiation within an SOBP in a murine model.

Main Methods:

• Murine hindlegs were irradiated with single-fraction doses using either FLASH (60 Gy/s) or CONV (0.34 Gy/s) dose rates within a 5 cm SOBP.
• Acute skin toxicity (hair loss, moist desquamation, toe separation) was monitored daily for 29 days.
• Late toxicity (fibrotic development via leg extendibility) was monitored biweekly for 30 weeks.

Main Results:

• FLASH irradiation demonstrated significant tissue sparing for acute skin toxicity, with a mean protection ratio of 1.40.
• Late fibrotic development also showed normal tissue sparing with a protection ratio of 1.18.
• The observed tissue sparing within the SOBP was comparable to previous findings using entrance-beam irradiations.

Conclusions:

• FLASH radiation retains its normal tissue-sparing properties when delivered within a Spread-out Bragg Peak (SOBP).
• A dose-modifying factor of 40% for acute skin damage and 18% for fibrotic development was observed.
• These findings support the clinical potential of FLASH radiation therapy within SOBPs.