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CC BY 4.0 · Thromb Haemost
DOI: 10.1055/a-2418-3960
Stroke, Systemic or Venous Thromboembolism

Risk of Recurrent Venous Thromboembolism in Patients with Cancer: An Individual Patient Data Meta-analysis and Development of a Prediction Model

Vincent R. Lanting 
1   Amsterdam UMC, University of Amsterdam, Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
2   Department of Internal Medicine, Tergooi Hospital, Hilversum, The Netherlands
,
Toshihiko Takada
3   Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
4   Department of General Medicine, Shirakawa Satellite for Teaching and Research (STAR), Fukushima Medical University, Fukushima, Japan
,
Floris T. M. Bosch
1   Amsterdam UMC, University of Amsterdam, Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
2   Department of Internal Medicine, Tergooi Hospital, Hilversum, The Netherlands
,
Andrea Marshall
5   Warwick Clinical Trials Unit, University of Warwick, Coventry, United Kingdom
,
Michael A. Grosso
6   Clinical Development, Daiichi Sankyo, Basking Ridge, New Jersey, United States
,
Annie M. Young
5   Warwick Clinical Trials Unit, University of Warwick, Coventry, United Kingdom
7   Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, United Kingdom
,
Agnes Y. Y. Lee
8   Division of Hematology, University of British Columbia, British Columbia Cancer Agency, Vancouver BC, Canada
,
Marcello Di Nisio 
9   Department of Medicine and Ageing Sciences, Gabriele D′Annunzio University, Chieti, Italy
,
Gary E. Raskob
10   University of Oklahoma Health Sciences Center and OU Health, Oklahoma City, Oklahoma, United States
,
Pieter W. Kamphuisen
1   Amsterdam UMC, University of Amsterdam, Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
2   Department of Internal Medicine, Tergooi Hospital, Hilversum, The Netherlands
,
Harry R. Büller
1   Amsterdam UMC, University of Amsterdam, Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
,
Nick van Es
1   Amsterdam UMC, University of Amsterdam, Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
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Abstract

Background 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.

Aim To identify clinical predictors and develop a prediction model for on-treatment recurrent CAT.

Methods 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.

Results 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.

Conclusion 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.

Keywords

recurrent VTE - cancer - prediction

Authors' Contribution

All authors contributed to the interpretation of the results and writing the manuscript. V.R.L. performed data management, analysis, and led writing of the manuscript. T.T. and N.v.E. performed analysis. F.T.M.B. has written the study protocol and obtained the datasets.


Supplementary Material



Publication History

Received: 17 July 2024

Accepted: 09 September 2024

Accepted Manuscript online:
19 September 2024

Article published online:
16 October 2024

© 2024. 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/)

Georg Thieme Verlag KG
Stuttgart · New York

 

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