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碳离子治疗中的 LET 三重困境:强大的靶区覆盖、均匀剂量和剂量平均 LET 之间的冲突。

The LET trilemma: Conflicts between robust target coverage, uniform dose, and dose-averaged LET in carbon therapy.

机构信息

RaySearch Laboratories, Stockholm, Sweden.

出版信息

Med Phys. 2023 Dec;50(12):7338-7348. doi: 10.1002/mp.16771. Epub 2023 Oct 11.


DOI:10.1002/mp.16771
PMID:37820319
Abstract

BACKGROUND: Linear energy transfer (LET) is closely related to the biological effect of ionizing radiation. Increasing the dose-averaged LET (LET ) within the target volume has been proposed as a means to improve clinical outcome for hypoxic tumors. However, doing so can lead to reduced robustness to range uncertainty. PURPOSE: To quantify the relationship between robust target coverage, target dose uniformity, and LET , we employ robust optimization using dose-based and LET -based functions and allow varying amounts of target non-uniformity. METHODS AND MATERIALS: Robust carbon therapy optimization is used to create plans for phantom cases with increasing target sizes (radii 1, 3, and 5 cm). First, the influence of respectively range and setup uncertainty on the LET in the target is studied. Second, we employ strategies allowing overdosage in the clinical target volume (CTV) or gross tumor volume (GTV), which enable increased LET in the target. The relationship between robust target coverage and LET in the target is illustrated by tradeoff curves generated by optimization using varying weights for the LET -based functions. RESULTS: As the range uncertainty used in the robust optimization increased from 0% to 5%, the near-minimum nominal LET decreased by 17%-29% (9-21 keV/µm) for the different target sizes. The effect of increasing setup uncertainty was marginal. Allowing 10% overdosage in the CTV enabled 9%-29% (6-12 keV/µm) increased near-minimum worst case LET for the different target sizes, compared to uniform dose plans. When 10% overdosage was allowed in the GTV only, the increase was 1%-20% (1-8 keV/µm). CONCLUSIONS: There is an inherent conflict between range uncertainty robustness and high LET in the target, which is aggravated with increasing target size. For large tumors, it is possible to simultaneously achieve two of the three qualities range robustness, uniform dose, and high LET in the target.

摘要

背景:线性能量传递(LET)与电离辐射的生物效应密切相关。提高靶区的平均剂量LET(LET)已被提议作为改善乏氧肿瘤临床疗效的一种手段。然而,这样做会导致对射程不确定性的稳健性降低。

目的:为了量化稳健的靶区覆盖、靶区剂量均匀性和 LET 之间的关系,我们使用基于剂量和 LET 的函数进行稳健优化,并允许靶区非均匀性的变化。

方法和材料:使用稳健的碳治疗优化为具有不同靶区大小(半径为 1、3 和 5 cm)的体模病例创建计划。首先,研究了分别的射程和设置不确定性对靶区 LET 的影响。其次,我们采用了允许在临床靶区(CTV)或大体肿瘤区(GTV)中过度照射的策略,这使得靶区中的 LET 增加。通过使用不同权重的 LET 基函数进行优化生成的折衷曲线,说明了稳健的靶区覆盖与靶区中 LET 的关系。

结果:随着稳健优化中使用的射程不确定性从 0%增加到 5%,不同靶区大小的近最小名义 LET 降低了 17%-29%(9-21 keV/µm)。增加设置不确定性的影响可以忽略不计。允许 CTV 中 10%的超剂量照射,可以使不同靶区大小的近最小最坏情况 LET 增加 9%-29%(6-12 keV/µm),与均匀剂量计划相比。仅允许 GTV 中 10%的超剂量照射时,增加幅度为 1%-20%(1-8 keV/µm)。

结论:射程不确定性稳健性和靶区中高 LET 之间存在固有冲突,随着靶区大小的增加而加剧。对于大肿瘤,可以同时实现三个目标中的两个,即射程稳健性、均匀剂量和靶区中高 LET。

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