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
{"title":"循环肿瘤 DNA 可预测癌症患者的静脉血栓栓塞。","authors":"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","doi":"10.1016/j.jtha.2024.09.009","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>CtDNA testing may serve as an adjunctive tool to clinical risk assessment models in cancer patients to improve personalized VTE risk assessment and management.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5000,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Circulating tumor DNA predicts venous thromboembolism in patients with cancers.\",\"authors\":\"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\",\"doi\":\"10.1016/j.jtha.2024.09.009\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>CtDNA testing may serve as an adjunctive tool to clinical risk assessment models in cancer patients to improve personalized VTE risk assessment and management.</p>\",\"PeriodicalId\":17326,\"journal\":{\"name\":\"Journal of Thrombosis and Haemostasis\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2024-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Thrombosis and Haemostasis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jtha.2024.09.009\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Thrombosis and Haemostasis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jtha.2024.09.009","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
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.
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.