Mitigating the impact of FLASH-model uncertainties through personalized FLASH optimization functions for delivery...

Area of Science:

• Radiotherapy
• Medical Physics
• Radiation Oncology

Background:

• The FLASH effect in radiotherapy is traditionally triggered at high dose rates (DRs) of ≥40 Gy/s.
• Recent evidence suggests a sigmoid relationship, not a binary threshold, for the FLASH effect across different patient samples.
• Current FLASH models do not account for this variability, potentially limiting treatment efficacy.

Purpose of the Study:

• To develop and evaluate a method for optimizing FLASH-weighted dose (FWD) distributions.
• To maximize the FLASH effect over a broader range of dose rates using dose-rate-dependent FLASH delivery pattern optimization (DPO).
• To maintain the FLASH effect at the established threshold of 40 Gy/s while exploring lower DRs.

Main Methods:

• Optimized and evaluated 1397 FLASH optimization functions for FWD distributions using DPO.
• Assessed FWD distributions across a dose rate range of 10–60 Gy/s.
• Compared optimized FWD distributions against those optimized assuming a binary threshold at 40 Gy/s.

Main Results:

• FLASH optimization functions significantly improved FWD distributions.
• Optimal FLASH optimization functions were patient- and beam-specific.
• Class solutions for FLASH optimization functions also yielded overall FWD distribution improvements.

Conclusions:

• Dose-rate-dependent FLASH optimization functions can substantially improve FWD distributions.
• Exploiting the FLASH effect over a wider dose rate range is feasible and beneficial.
• Personalized optimization strategies are key to maximizing FLASH radiotherapy benefits.