Software-based versus visual assessment of the minimal ablative margin in patients with liver tumours undergoing percutaneous thermal ablation (COVER-ALL): a randomised phase 2 trial.

The minimal ablative margin has traditionally been assessed through visual inspection of co-registered CT images.

最小消融边缘传统上是通过注册CT图像的视觉检查来评估的。

However, rates of local tumour control after thermal ablation are highly variable with visual assessment.

然而，通过热消融后肿瘤局部控制率的变异性很高，主要依靠视觉评估。

We aimed to assess the use of a novel software-based method for minimal ablative margin assessment that incorporates biomechanical deformable image registration and artificial intelligence (AI)-based autosegmentation.

我们旨在评估一种新颖的基于软件的方法，用于最小消融边缘评估，该方法结合了生物力学变形图像配准和基于人工智能（AI）的自动分割。

Methods

The COVER-ALL randomised, phase 2, superiority trial was conducted at The University of Texas MD Anderson Cancer Center (Houston, TX, USA).

COVER-ALL 随机、二期、优效试验在德克萨斯州休斯顿的德克萨斯大学 MD 安德森癌症中心进行。

Patients aged 18 years or older with up to three histology-agnostic liver tumours measuring 1-5 cm and undergoing CT-guided thermal ablation were enrolled.

年龄在18岁或以上的患者，最多有三个组织学不明确的肝脏肿瘤，大小在1-5厘米之间，并接受CT引导的热消融治疗，被纳入研究。

Thermal ablation was performed with the aim of achieving a minimal ablative margin of 5 mm or greater.

热消融术的目的是实现至少5毫米或更大的最小消融边缘。

Patients were randomly assigned (1:1) to the experimental group (software-based assessment) or the control group (visual assessment) by use of dynamic minimisation to balance covariates.

患者被随机分配（1:1）到实验组（基于软件的评估）或对照组（视觉评估），使用动态最小化法来平衡协变量。

Randomisation was performed intraprocedurally after placement of the ablation applicator.

随机化是在放置消融装置后在手术过程中进行的。

Assessment of oncological outcomes and adverse events were masked to treatment allocation.

对肿瘤学结果和不良事件的评估对治疗分配进行了盲法处理。

All analyses were conducted on an intention-to-treatbasis.

所有分析均基于意向治疗原则进行。

The primary endpoint was the minimal ablative margin on post-ablation intraprocedural CT.

主要终点是术后消融术中CT上的最小消融边界。

A preplanned interim analysis for superiority was done at 50% patient enrolment.

在患者入组率达到50%时，进行了预先计划的优效性中期分析。

Adverse events were recorded with the Common Terminology Criteria for Adverse Events.

不良事件使用通用不良事件术语标准进行记录。

This trial is registered with ClinicalTrials.gov (NCT04083378), and recruitment is complete.

该试验已在ClinicalTrials.gov注册（NCT04083378），招募工作已完成。

Results

Patients were enrolled and treated with thermal ablation between June 15, 2020, and Oct 5, 2023. 26 patients were randomly assigned to the control group (mean age 58·1 [SD 14·8] years; 18 [69%] male and eight [31%] female; 11 [42%] colorectal cancer liver metastasis; median tumour diameter 1·7 cm [IQR 1·3-2·3]) and 24 to the experimental group (mean age 60·5 [14·4] years; 16 [67%] male and eight [33%] female; ten [42%] colorectal cancer liver metastasis; median tumour diameter 1·8 cm [1·5-2·5]).

患者在2020年6月15日至2023年10月5日期间接受热消融治疗并入组。26名患者被随机分配到对照组（平均年龄58.1岁[标准差14.8]；18名[69%]男性和8名[31%]女性；11名[42%]结直肠癌肝转移；肿瘤中位直径1.7厘米[四分位数间距1.3-2.3]），24名患者被分配到实验组（平均年龄60.5岁[标准差14.4]；16名[67%]男性和8名[33%]女性；10名[42%]结直肠癌肝转移；肿瘤中位直径1.8厘米[四分位数间距1.5-2.5]）。

The interim analysis showed a mean minimal ablative margin of 2·2 mm (SD 2·8) in the control group and 5·9 mm (2·7) in the experimental group (p<0·0001), prompting halting of enrolment in the control group.

中期分析显示对照组的平均最小消融边缘为2.2毫米（标准差2.8），实验组为5.9毫米（标准差2.7）（p<0.0001），导致对照组停止招募。

A further 50 patients were enrolled to a non-randomised experimental group (mean age 56·5 [SD 11·7] years; 27 [54%] male and 23 [46%] female; 30 [60%] colorectal cancer liver metastasis; median tumour diameter 1·5 cm [IQR 1·3-2·2]); among these patients, the mean minimal ablative margin was 7·2 mm (SD 2·8).

另外有50名患者被纳入非随机实验组（平均年龄56.5岁[标准差11.7]；27名[54%]为男性，23名[46%]为女性；30名[60%]为结直肠癌肝转移；肿瘤中位直径为1.5厘米[IQR 1.3-2.2]）；在这些患者中，平均最小消融边缘为7.2毫米（标准差2.8）。

Grade 1-3 adverse events were reported in five (5%) of 100 patients: three (12%) of 26 in the control group and two (3%) of 74 in the experimental groups.

在100名患者中报告了5例（5%）1-3级不良事件：对照组26人中有3例（12%），实验组74人中有2例（3%）。

No grade 4-5 adverse events or treatment-related deaths were reported.

未报告4-5级不良事件或与治疗相关的死亡事件。

interpretation

Software-based assessment during CT-guided thermal ablation of liver tumours is safe and significantly improves the minimal ablative margin compared to visual assessment.

在CT引导下的肝脏肿瘤热消融过程中，基于软件的评估是安全的，并且与视觉评估相比，显著提高了最小消融边界。

Adoption of software-based assessment as a standard component of thermal ablation should be considered to achieve the intended minimal ablative margin.

应考虑将基于软件的评估作为热消融的标准组成部分，以实现预期的最小消融边界。

funding

US National Institutes of Health and US National Cancer Institute.

美国国家卫生研究院和美国国家癌症研究所。