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

IF 3.2 2区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING Medical physics Pub Date : 2025-02-18 DOI:10.1002/mp.17697

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 (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).

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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基于生物剂量的Bragg峰值FLASH-RT治疗肺癌的分数剂量优化。

背景：目的：本研究探讨了分次剂量优化在增强布拉格峰FLASH放射治疗（FLASH-RT）对正常组织的保护方面的性能。方法：对15例肺癌患者进行了回顾性分析，其中8例患者的肿瘤位于外周，7例患者的肿瘤位于中央。采用的统一分次处方为 50 Gy，分五次进行，对应的生物等效剂量 (BED) 为 100 Gy，α/β 值为 10 Gy。为每位患者设计了均匀（UFD）和非均匀分数剂量（non-UFD）计划。在UFD FLASH计划中，使用单场优化法优化了五束多能量布拉格峰光束，每束光束可向靶点输出10 Gy。在非 UFD FLASH 计划中，对部分剂量进行了优化，以增强疏通效果，同时确保靶点获得与 UFD 计划相当的 BED。与剂量相关的 FLASH 增强比（FER）与 BED 相结合，形成 FER-BED 指标，用于比较 UFD 和非 UFD 计划。计算中，正常组织的α/β值为3 Gy：结果：布拉格峰FLASH计划对周围和中心肿瘤均显示出较高的剂量符合性，所有计划的符合性指数（接受规定剂量的体积与CTV体积之比）均低于1.2。在非超导计划中，分次剂量从 5.0 Gy 到 20.0 Gy 不等。与 UFD 计划相比，非 UFD 计划实现了相似的 BED 覆盖率（BED98%：96.6 Gy vs. 97.1 Gy，p = 0.256），同时提供了更好的风险器官疏通。具体来说，心脏的 FER-BED15cc 降低了 10.5%（9.4 Gy 对 10.5 Gy，p = 0.017），同侧肺的 V6.7GyFER-BED 降低了 4.3%（29.1% 对 30.4%，p = 0.008）。脊髓的FER-BED0.25cc（UFD：7.1 Gy，非UFD：6.9 Gy，p = 0.626）和食道的FER-BED5cc（UFD：0.4 Gy，非UFD：0.4 Gy，p = 0.831）无明显差异：结论：布拉格峰FLASH-RT对周边和中心肿瘤都能达到较高的剂量一致性。分次剂量优化采用单束分次投放模式，通过利用分次和FLASH效应，增强了对正常组织的保护。

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来源期刊

Medical physics 医学-核医学

CiteScore

6.80

自引率

15.80%

发文量

660

审稿时长

1.7 months

期刊介绍： Medical Physics publishes original, high impact physics, imaging science, and engineering research that advances patient diagnosis and therapy through contributions in 1) Basic science developments with high potential for clinical translation 2) Clinical applications of cutting edge engineering and physics innovations 3) Broadly applicable and innovative clinical physics developments Medical Physics is a journal of global scope and reach. By publishing in Medical Physics your research will reach an international, multidisciplinary audience including practicing medical physicists as well as physics- and engineering based translational scientists. We work closely with authors of promising articles to improve their quality.