Biological dose-based fractional dose optimization of Bragg peak FLASH-RT for lung cancer treatment

The FLASH effect is dose-dependent, and fractional dose optimization may enhance it, improving normal tissue sparing.

This study investigates the performance of fractional dose optimization in enhancing normal tissue sparing for Bragg peak FLASH radiotherapy (FLASH-RT).

15 lung cancer patients, including eight with peripherally located tumors and seven with centrally located tumors, were retrospectively analyzed. A uniform fractionation prescription of 50 Gy in five fractions was utilized, corresponding to a biological equivalent dose (BED) of 100 Gy, calculated using an α/β value of 10 Gy. For each patient, uniform (UFD) and nonuniform fractional dose (non-UFD) plans were designed. In UFD FLASH plans, five multi-energy Bragg peak beams were optimized using single-field optimization, each delivering 10 Gy to the target. In non-UFD FLASH plans, fractional doses were optimized to enhance sparing effects while ensuring the target received a BED comparable to UFD plans. A dose-dependent FLASH enhancement ratio (FER) was integrated with the BED to form the FER-BED metric to compare the UFD and non-UFD plans. An α/β value of 3 Gy was applied for normal tissues in the calculations.

Bragg peak FLASH plans showed high dose conformality for both peripheral and central tumors, with all plans achieving a conformality index (the ratio of the volume receiving the prescribed dose to the CTV volume) below 1.2. In non-UFD plans, fractional doses ranged from 5.0 Gy to 20.0 Gy. Compared to UFD plans, non-UFD plans achieved similar BED coverage (BED_98%: 96.6 Gy vs. 97.1 Gy, p = 0.256), while offering improved organ-at-risk sparing. Specifically, the FER-BED_15cc for the heart reduced by 10.5% (9.4 Gy vs. 10.5 Gy, p = 0.017) and the V_6.7GyFER-BED for the ipsilateral lung decreased by 4.3% (29 .1% vs. 30.4%, p = 0.008). No significant difference was observed in FER-BED_0.25cc of spinal cord (UFD: 7.1 Gy, non-UFD: 6.9 Gy, p = 0.626) and FER-BED_5cc in esophagus (UFD: 0.4 Gy, non-UFD: 0.4 Gy, p = 0.831).

Bragg peak FLASH-RT achieved high dose conformality for both peripheral and central tumors. Fractional dose optimization, using a single beam per fraction delivery mode, enhanced normal tissue sparing by leveraging both fractionation and FLASH effects.