Biological-equivalent-dose-based integrated optimization framework for fast-energy-switching Bragg peak FLASH-RT...

When comparing the delivery of all beams per fraction (ABPF) to single beam per fraction (SBPF), it is observed that SBPF not only helps meet the FLASH dose threshold but also mitigates the uncertainty with beam switching in the FLASH effect. However, SBPF might lead to a higher biological equivalent dose in 2 Gy (EQD2) for normal tissues.

This study aims to develop an EQD2-based integrated optimization framework (EQD2-IOF), encompassing robust dose, delivery efficiency, and beam orientation optimization (BOO) for Bragg peak FLASH plans using the SBPF treatment schedule. The EQD2-IOF aims to enhance both dose sparing and the FLASH effect.

A superconducting gantry was employed for fast energy switching within 27 ms, while universal range shifters were utilized to improve beam current in the implementation of FLASH plans with five Bragg peak beams. To enhance dose delivery efficiency while maintaining plan quality, a simultaneous dose and spot map optimization (SDSMO) algorithm for single field optimization was incorporated into a Bayesian optimization-based auto-planning algorithm. Subsequently, a BOO algorithm based on Tabu search was developed to select beam angle combinations (BACs) for 10 lung cases. To simultaneously consider dose sparing and FLASH effect, a quantitative model based on dose-dependent dose modification factor (DMF) was used to calculate FLASH-enhanced dose distribution. The EQD2-IOF plan was compared to the plan optimized without SDSMO using BAC selected by a medical physicist (Manual plan) in the SBPF treatment schedule. Meanwhile, the mean EQD2 in the normal tissue was evaluated for the EQD2-IOF plan in both SBPF and ABPF treatment schedules.

No significant difference was found in D_2% and D_98% of the target between EQD2-IOF plans and Manual Plans. When using a minimum DMF of 0.67 and a dose threshold of 4 Gy, EQD2-IOF plans showed a significant reduction in FLASH-enhanced EQD2_mean of the ipsilateral lung and normal tissue by 10.5% and 11.5%, respectively, compared to Manual plans. For normal tissues that received a dose greater than 70% of the prescription dose, using a minimum DMF of 0.7 for FLASH sparing compensated for the increase in EQD2_mean resulting from replacing ABPF with SBPF schedules.

The EQD2-IOF can automatically optimize SBPF FLASH-RT plans to achieve optimal sparing of normal tissues. With an energy switching time of 27 ms, the loss of fractionate repairing using SBPF schedules in high-dose regions can be compensated for by the FLASH effect. However, when an energy switching time of 500 ms is utilized, the SBPF schedule needs careful consideration, as the FLASH effect diminishes with longer irradiation time.