我们在此报道了一项前瞻性研究的结果，该研究探讨了循环肿瘤DNA（ctDNA）检测在经过虹膜黑色素瘤（UM）肝转移切除手术的患者中的应用（NCT02849145）。在UM患者中，肝脏是最常见且通常是唯一的转移部位。肝转移的局部治疗，如手术切除在选择的患者中可能有益。在招募期间，符合手术治疗条件的转移性UM患者在手术前后收集了血浆样本。通过水滴数字PCR鉴定存档的肿瘤组织中的GNAQ / GNA11突变，并用于定量ctDNA，然后与患者的手术结果相关联。共纳入了47名患者。肝手术与游离循环DNA水平的迅速增加有关，手术后两天达到峰值（约增加20倍）。在40名可评估的患者中，14名（35％）在手术前检测到有可检测的ctDNA，其等位基因频率中位数为1.1％。这些患者的无复发生存期（RFS）明显较短（中位数RFS：5.5 vs. 12.2 mo；危害比= 2.23，95％置信区间 [1.06-4.69]，P = 0.04），且总体生存期（OS）也略短（中位数OS：27.0 vs. 42.3 mo）。术后时点的ctDNA阳性也与RFS和OS相关。这项研究首次报道了ctDNA检出率和在符合手术治疗条件的UM患者中的预后影响。如果在此环境中进一步证实，这种非侵入性生物标志物可能会在UM患者的肝转移治疗决策中发挥作用。版权所有©2023作者。由Wolters Kluwer Health，Inc. 发布。

We report here the results of a prospective study of circulating tumor DNA (ctDNA) detection in patients undergoing uveal melanoma (UM) liver metastases resection (NCT02849145).In UM patients, the liver is the most common and often only site of metastases. Local treatments of liver metastases, such as surgical resection, have a likely benefit in selected patients.Upon enrollment, metastatic UM patients eligible for curative liver surgery had plasma samples collected before and after surgery. GNAQ/GNA11 mutations were identified in archived tumor tissue and used to quantify ctDNA by droplet digital PCR which was then associated with the patient's surgical outcomes.Forty-seven patients were included. Liver surgery was associated with a major increase of cell-free circulating DNA levels, with a peak two days after surgery (~20-fold). Among 40 evaluable patients, 14 (35%) had detectable ctDNA before surgery, with a median allelic frequency of 1.1%. These patients experienced statistically shorter relapse-free survival (RFS) versus patients with no detectable ctDNA before surgery (median RFS: 5.5 vs. 12.2 mo; Hazard Ratio=2.23, 95% confidence interval [1.06-4.69], P=0.04), and had a numerically shorter overall survival (OS) (median OS: 27.0 vs. 42.3 mo). ctDNA positivity at post-surgery time points was also associated with RFS and OS.This study is the first to report ctDNA detection rate and prognostic impact in UM patients eligible for surgical resection of their liver metastases. If confirmed by further studies in this setting, this non-invasive biomarker could inform treatment decisions in UM patients with liver metastases.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.