循环肿瘤 DNA 可预测癌症患者的静脉血栓栓塞。

IF 5.5 2区 医学 Q1 HEMATOLOGY Journal of Thrombosis and Haemostasis Pub Date : 2024-09-26 DOI:10.1016/j.jtha.2024.09.009
Shengling Ma, Jun Y Jiang, Rock Bum Kim, Elizabeth Chiang, Joyce Wan Theng Tiong, Justine Ryu, Danielle Guffey, Raka Bandyo, Heidi Dowst, Kaitlin N Swinnerton, Nathanael R Fillmore, Jennifer La, Ang Li
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引用次数: 0

摘要

导言:尽管循环肿瘤 DNA(ctDNA)的液体活检技术发展迅速,但其对癌症患者静脉血栓栓塞症(VTE)的预后价值尚未得到充分探索,尤其是在服务不足和少数群体中:我们分析了在美国一家大型安全网医院系统接受ctDNA检测的1038名肿瘤患者的数据。在使用 Fine-Gray 模型对癌症类型、分期、治疗和初始诊断时间进行调整后,我们研究了 ctDNA 与 VTE 之间的关联。我们使用时间依赖性接收器操作特征曲线下面积(AUC)进一步评估了基因模型、纯临床模型和组合模型的区分度:结果:在对临床变量进行调整后,致病性ctDNA的存在与VTE独立相关。与肿瘤类型无关,致病性ctDNA突变的数量可预测未来的VTE风险(与无致病性突变相比,≥3、2和1个致病性突变的调整亚分布危险比分别为2.75、1.94和1.38;p结论:CtDNA检测可作为癌症患者临床风险评估模型的辅助工具,以改善个性化的VTE风险评估和管理。
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Circulating tumor DNA predicts venous thromboembolism in patients with cancers.

Introduction: Despite rapid advances in liquid biopsy for circulating tumor DNA (ctDNA), its prognostic value for venous thromboembolism (VTE) in patients with cancer is underexplored, particularly in underserved and minoritized populations.

Methods: We analyzed data from 1,038 cancer patients who underwent ctDNA measurement for oncologic care at a large safety-net hospital system in the US. We investigated the association between ctDNA and VTE after adjusting for cancer type, stage, treatment, and time from initial diagnosis using Fine-Gray models. We further assessed the discrimination of the genetic, clinical-only, and combined models using the area under the time-dependent receiver operating characteristic curve (AUC).

Results: The presence of pathogenic ctDNA was independently associated with VTE after adjusting for clinical variables. Independent of tumor type, the number of pathogenic ctDNA mutations was predictive of future VTE risk (adjusted subdistribution hazard ratio 2.75, 1.94, and 1.38 for ≥3, 2, and 1 pathogenic mutation, respectively, compared to none; p<0.0001). The association was primarily driven by mutations in KRAS, PTEN, CDKN2A, NF1, and EGFR genes. Compared to the clinical-only model (AUC 0.71, 95% CI 0.64-0.76), the combined clinical and ctDNA model had a numerically higher time-dependent AUC (AUC 0.74, 95% CI 0.67-0.80).

Conclusions: CtDNA testing may serve as an adjunctive tool to clinical risk assessment models in cancer patients to improve personalized VTE risk assessment and management.

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来源期刊
Journal of Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis 医学-外周血管病
CiteScore
24.30
自引率
3.80%
发文量
321
审稿时长
1 months
期刊介绍: The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.
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