Yiling Zeng, Qi Zhang, Wei Wang, Xu Liu, Bin Qin, Bo Pang, Muyu Liu, Shuoyan Chen, Hong Quan, Yu Chang, Zhiyong Yang
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Abstract
Background: The FLASH effect is dose-dependent, and fractional dose optimization may enhance it, improving normal tissue sparing.
Purpose: This study investigates the performance of fractional dose optimization in enhancing normal tissue sparing for Bragg peak FLASH radiotherapy (FLASH-RT).
Methods: 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.
Results: 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 (BED98%: 96.6 Gy vs. 97.1 Gy, p = 0.256), while offering improved organ-at-risk sparing. Specifically, the FER-BED15cc for the heart reduced by 10.5% (9.4 Gy vs. 10.5 Gy, p = 0.017) and the V6.7GyFER-BED for the ipsilateral lung decreased by 4.3% (29 .1% vs. 30.4%, p = 0.008). No significant difference was observed in FER-BED0.25cc of spinal cord (UFD: 7.1 Gy, non-UFD: 6.9 Gy, p = 0.626) and FER-BED5cc in esophagus (UFD: 0.4 Gy, non-UFD: 0.4 Gy, p = 0.831).
Conclusions: 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.
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