Ma Shengling, Jiang Jun Yang, Kim Rock Bum, Chiang Elizabeth, Theng Tiong Joyce Wan, Ryu Justine, Guffey Danielle, Bandyo Raka, Dowst Heidi, Swinnerton Kaitlin N, Fillmore Nathanael R, La Jennifer, Li Ang
Section of Hematology & Oncology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
School of Medicine, Baylor College of Medicine, Houston, Texas, USA.
J Thromb Haemost. 2025 Jan;23(1):139-148. doi: 10.1016/j.jtha.2024.09.009. Epub 2024 Sep 26.
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.
To evaluate the role of ctDNA in risk stratification for cancer-associated VTE.
We analyzed data from 1038 cancer patients who underwent ctDNA measurement for oncologic care at a large safety-net hospital system in the United States. 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).
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 ratios of 2.75, 1.94, and 1.38 for ≥3, 2, and 1 pathogenic mutation, respectively, compared with none; P < .0001). The association was primarily driven by mutations in KRAS, PTEN, CDKN2A, NF1, and EGFR genes. Compared with 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).
ctDNA testing may serve as an adjunctive tool to clinical risk assessment models in cancer patients to improve personalized VTE risk assessment and management.
尽管循环肿瘤DNA（ctDNA）的液体活检技术取得了快速进展，但其对癌症患者静脉血栓栓塞（VTE）的预后价值尚未得到充分探索，尤其是在医疗服务不足和少数族裔人群中。
评估ctDNA在癌症相关VTE风险分层中的作用。
我们分析了美国一家大型安全网医院系统中1038例因肿瘤治疗而接受ctDNA检测的癌症患者的数据。我们使用Fine-Gray模型，在调整癌症类型、分期、治疗以及从初始诊断开始的时间后，研究ctDNA与VTE之间的关联。我们还使用时间依赖性受试者操作特征曲线（AUC）下的面积，进一步评估了基因模型、仅临床因素模型和联合模型的判别能力。
在调整临床变量后，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VTE风险（与无致病性突变相比，≥3个、2个和1个致病性突变的调整后亚分布风险比分别为2.75、1.94和1.38；P <.000）。这种关联主要由KRAS、PTEN、CDKN2A、NF1和EGFR基因的突变驱动。与仅临床因素模型（AUC，0.71；95% CI，0.64 - 0.76）相比，临床因素与ctDNA联合模型的时间依赖性AUC在数值上更高（AUC，0.74；95% CI，0.67 - 0.80）。
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VTE风险评估和管理。
