Alok A. Khorana, The Cleveland Clinic, Cleveland, OH; Pieter W. Kamphuisen, Tergooi, Hilversum; Pieter W. Kamphuisen, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Guy Meyer, Georges Pompidou European Hospital, Université Paris Descartes Sorbonne Paris Cité, Institut National de la Santé et de la Recherche Médicale, Unité mixte de recherche 970, Centres d'Investigation Clinique 1418, Paris, France; Rupert Bauersachs, Darmstadt Hospital, Darmstadt; Rupert Bauersachs, University Medical Center Mainz, Mainz, Germany; Mette S. Janas and Mikala F. Jarner, LEO Pharma, Ballerup, Denmark; Agnes Y.Y. Lee, University of British Columbia; and Agnes Y.Y. Lee, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
J Clin Oncol. 2017 Apr 1;35(10):1078-1085. doi: 10.1200/JCO.2016.67.4564. Epub 2016 Dec 28.
Purpose Circulating tissue factor (TF) has been studied as a biomarker for predicting initial, but not recurrent, venous thromboembolism (VTE) in cancer, a setting in which predictors are incompletely understood. We evaluated the association of TF, clinical risk factors, and other biomarkers measured at the time of initial VTE with recurrent VTE in a prespecified analysis of the CATCH (Comparison of Acute Treatments in Cancer Hemostasis) trial. Methods CATCH was a randomized, multicenter trial that investigated tinzaparin 175 IU/kg once daily or dose-adjusted warfarin for 6 months in patients with cancer and acute, symptomatic VTE. TF ELISA, soluble P-selectin, d-dimer, FVIII, and C-reactive protein were assayed. Fisher's exact test was used to screen for association with VTE; competing risk regression analysis of time to recurrent VTE was conducted, accounting for multiple variables. Results The study population comprised 900 patients (recurrent VTE, n = 76; 8.4%). Of these patients, 805 had samples available for TF assay. Mean and median TF levels were 72.5 pg/mL and 50.3 pg/mL, respectively (range, 15.6 pg/mL to 4,798 pg/mL). Patients in the highest quartile of TF experienced the greatest VTE recurrence (> 64.6 pg/mL; 38 [19%] of 203 patients v 34 [6%] of 602 patients; relative risk, 3.3; 95% CI, 2.1 to 5.1; P < .001). In competing risk regression analysis of time to recurrent VTE, TF remained strongly associated with recurrent VTE (subdistribution hazard ratio [SHR], 3.3; 95% CI, 1.7 to 6.4). Other significant variables included venous compression from mass (SHR, 3.1; 95% CI, 1.4 to 6.5) and hepatobiliary cancer (SHR, 5.5; 95% CI, 2.3 to 13.6). Conclusion This is the first report, to our knowledge, to describe TF as a potential biomarker of recurrent VTE in patients with cancer who are on anticoagulation treatment. A risk-adapted strategy could help identify high-risk patients who may benefit from more intensive anticoagulation approaches.
目的 循环组织因子 (TF) 已被研究作为预测癌症患者首发而非复发性静脉血栓栓塞症 (VTE) 的生物标志物，而在这种情况下，预测因子尚不完全明确。我们在 CATCH（癌症止血中的急性治疗比较）试验的预设分析中，评估了首发 VTE 时 TF、临床危险因素和其他生物标志物与复发性 VTE 的相关性。
方法 CATCH 是一项随机、多中心试验，该试验比较了每日一次给予 175 IU/kg 达肝素或调整剂量的华法林用于治疗伴有急性有症状 VTE 的癌症患者 6 个月。测定 TF ELISA、可溶性 P 选择素、D-二聚体、FVIII 和 C 反应蛋白。采用 Fisher 确切检验筛选与 VTE 的关联；采用竞争风险回归分析，考虑多个变量，分析复发性 VTE 的时间。
结果 研究人群包括 900 例患者（复发性 VTE，n=76；8.4%）。其中 805 例患者有 TF 检测样本。TF 水平的均值和中位数分别为 72.5 pg/mL 和 50.3 pg/mL（范围，15.6 pg/mL 至 4798 pg/mL）。TF 四分位最高组的患者 VTE 复发率最高（>64.6 pg/mL；203 例患者中有 38 例[19%]，602 例患者中有 34 例[6%]；相对风险，3.3；95%CI，2.1 至 5.1；P<.001）。在复发性 VTE 的竞争风险回归分析中，TF 与复发性 VTE 仍密切相关（亚分布风险比 [SHR]，3.3；95%CI，1.7 至 6.4）。其他重要变量包括肿块引起的静脉压迫（SHR，3.1；95%CI，1.4 至 6.5）和肝胆癌（SHR，5.5；95%CI，2.3 至 13.6）。
结论 这是我们所知的首个描述 TF 作为癌症患者抗凝治疗时复发性 VTE 潜在生物标志物的报告。风险适应策略可能有助于识别高危患者，这些患者可能受益于更强化的抗凝方法。
