Fractionation dose optimization facilities the implementation of transmission proton FLASH-RT

Area of Science:

• Radiation Oncology
• Medical Physics
• Cancer Treatment

Background:

• Beam switching time and fractional dose are critical factors influencing the biological effects of ultra-high dose rate (FLASH) radiotherapy.
• Current single-beam-per-fraction (SBPF) schemes often use uniform fractional doses (UFD), which may not fully exploit the FLASH effect.
• Optimizing dose fractionation is key to maximizing therapeutic benefits while minimizing normal tissue toxicity in advanced radiotherapy techniques.

Purpose of the Study:

• To develop and evaluate a fractionation dose optimization algorithm for non-uniform fractional dose (non-UFD) plans in FLASH radiotherapy.
• To compare the efficacy of non-UFD plans against UFD plans in terms of target coverage and normal tissue sparing for lung cancer patients.
• To investigate the combined impact of enhanced fractionation and FLASH effects on treatment outcomes.

Main Methods:

• A cohort of 11 lung cancer patients underwent FLASH radiotherapy using both UFD and optimized non-UFD plans with 236 MeV proton beams.
• Fractionation dose optimization algorithm was employed to create non-UFD plans, aiming to maximize fractionation and dose-dependent FLASH effects.
• Equivalent dose to 2 Gy (EQD2) for target and normal tissues was calculated using varying alpha/beta ratios (10 and 3) to assess treatment outcomes.

Main Results:

• Both UFD and non-UFD plans achieved the target EQD2 of 96.3 Gy, with no significant difference in target EQD2$_{2%}$ and EQD2$_{98%}$.
• The non-UFD plans demonstrated a significant 15.1% reduction in the target's D$_{95%}$ and significantly improved normal tissue sparing.
• FLASH-enhanced EQD2$_{mean}$ in normal tissue and ipsilateral lung was reduced by 3.5% and 10.4% respectively with non-UFD plans.

Conclusions:

• Fractionation dose optimization effectively addresses limitations of multiple-beam FLASH-RT by leveraging the relationship between fractional dose and the FLASH effect.
• Non-UFD schemes significantly enhance normal tissue sparing compared to UFD schemes in FLASH radiotherapy.
• The observed improvements are attributed to the synergistic effects of optimized fractionation and enhanced FLASH biological responses.