癌症患者血栓性静脉血栓栓塞复发风险：个体患者数据Meta分析及预测模型开发
Risk of Recurrent Venous Thromboembolism in Patients with Cancer: An Individual Patient Data Meta-analysis and Development of a Prediction Model
影响因子:4.30000
分区:医学2区 Top / 血液学2区 外周血管病2区
发表日期:2025 Jun
作者:
Vincent R Lanting, Toshihiko Takada, Floris T M Bosch, Andrea Marshall, Michael A Grosso, Annie M Young, Agnes Y Y Lee, Marcello Di Nisio, Gary E Raskob, Pieter W Kamphuisen, Harry R Büller, Nick van Es
摘要
约7%的癌症相关静脉血栓栓塞（CAT）患者在抗凝治疗期间会发生复发。识别高危患者有助于指导治疗决策。本研究旨在通过个体患者数据Meta分析，识别临床预测因素并建立抗凝治疗期间复发CAT的预测模型。我们利用来自4项随机对照试验（评估低分子量肝素或直接口服抗凝药物（DOACs）治疗CAT）数据（Hokusai VTE Cancer、SELECT-D、CLOT和CATCH）。主要结局为6个月随访期间的经裁定的复发性血栓栓塞。采用多变量逻辑回归分析和向后变量选择，建立预测模型，并进行内部-外部交叉验证。模型性能由c统计量和校准图评估。排除使用维生素K拮抗剂的患者后，合并数据集包括2245名癌症伴急性血栓栓塞患者（其中23%用依度沙班，9%用利伐沙班，47%用达肝素，20%用廷扎肝素）。在6个月随访中，150例（6.7%）发生复发性血栓栓塞。最终模型预测因子包括：年龄（限制立方样条）、乳腺癌（比值比[OR]：0.42；95%置信区间[CI]：0.20-0.87）、转移性疾病（OR：1.44；95%CI：1.01-2.05）、使用DOAC（OR：0.66；95%CI：0.44-0.98）以及仅有深静脉血栓作为起始事件（OR：1.72；95%CI：1.31-2.27）。模型的c统计量为0.63（95%CI：0.54-0.72），经过内部-外部交叉验证。校准情况在不同研究中存在差异。该预测模型包含五个临床预测因子，其判别能力有限，预估抗凝治疗开始时复发性血栓栓塞仍具挑战性。
Abstract
About 7% of patients with cancer-associated venous thromboembolism (CAT) develop a recurrence during anticoagulant treatment. Identification of high-risk patients may help guide treatment decisions.To identify clinical predictors and develop a prediction model for on-treatment recurrent CAT.For this individual patient data meta-analysis, we used data from four randomized controlled trials evaluating low-molecular-weight heparin or direct oral anticoagulants (DOACs) for CAT (Hokusai VTE Cancer, SELECT-D, CLOT, and CATCH). The primary outcome was adjudicated on-treatment recurrent CAT during a 6-month follow-up. A clinical prediction model was developed using multivariable logistic regression analysis with backward selection. This model was validated using internal-external cross-validation. Performance was assessed by the c-statistic and a calibration plot.After excluding patients using vitamin K antagonists, the combined dataset comprised 2,245 patients with cancer and acute CAT who were treated with edoxaban (23%), rivaroxaban (9%), dalteparin (47%), or tinzaparin (20%). Recurrent on-treatment CAT during the 6-month follow-up occurred in 150 (6.7%) patients. Predictors included in the final model were age (restricted cubic spline), breast cancer (odds ratio [OR]: 0.42; 95% confidence interval [CI]: 0.20-0.87), metastatic disease (OR: 1.44; 95% CI: 1.01-2.05), treatment with DOAC (OR: 0.66; 95% CI: 0.44-0.98), and deep vein thrombosis only as an index event (OR: 1.72; 95% CI: 1.31-2.27). The c-statistic of the model was 0.63 (95% CI: 0.54-0.72) after internal-external cross-validation. Calibration varied across studies.The prediction model for recurrent CAT included five clinical predictors and has only modest discrimination. Prediction of recurrent CAT at the initiation of anticoagulation remains challenging.The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).