Comparison of risk prediction scores for venous thromboembolism in cancer patients: a prospective cohort study

Nick van Es, Marcello Di Nisio, Gabriela Cesarman, Ankie Kleinjan, Hans-Martin Otten, Isabelle Mahé, Ineke T Wilts, Desirée C Twint, Ettore Porreca, Oscar Arrieta, Alain Stépanian, Kirsten Smit, Michele De Tursi, Suzanne M Bleker, Patrick M Bossuyt, Rienk Nieuwland, Pieter W Kamphuisen, Harry R Büller, Nick van Es, Marcello Di Nisio, Gabriela Cesarman, Ankie Kleinjan, Hans-Martin Otten, Isabelle Mahé, Ineke T Wilts, Desirée C Twint, Ettore Porreca, Oscar Arrieta, Alain Stépanian, Kirsten Smit, Michele De Tursi, Suzanne M Bleker, Patrick M Bossuyt, Rienk Nieuwland, Pieter W Kamphuisen, Harry R Büller

Abstract

In ambulatory patients with solid cancer, routine thromboprophylaxis to prevent venous thromboembolism is not recommended. Several risk prediction scores to identify cancer patients at high risk of venous thromboembolism have been proposed, but their clinical usefulness remains a matter of debate. We evaluated and directly compared the performance of the Khorana, Vienna, PROTECHT, and CONKO scores in a multinational, prospective cohort study. Patients with advanced cancer were eligible if they were due to undergo chemotherapy or had started chemotherapy in the previous three months. The primary outcome was objectively confirmed symptomatic or incidental deep vein thrombosis or pulmonary embolism during a 6-month follow-up period. A total of 876 patients were enrolled, of whom 260 (30%) had not yet received chemotherapy. Fifty-three patients (6.1%) developed venous thromboembolism. The c-statistics of the scores ranged from 0.50 to 0.57. At the conventional positivity threshold of 3 points, the scores classified 13-34% of patients as high-risk; the 6-month incidence of venous thromboembolism in these patients ranged from 6.5% (95%CI: 2.8-12) for the Khorana score to 9.6% (95%CI: 6.6-13) for the PROTECHT score. High-risk patients had a significantly increased risk of venous thromboembolism when using the Vienna (subhazard ratio 1.7; 95%CI: 1.0-3.1) or PROTECHT (subhazard ratio 2.1; 95%CI: 1.2-3.6) scores. In conclusion, the prediction scores performed poorly in predicting venous thromboembolism in cancer patients. The Vienna CATS and PROTECHT scores appear to discriminate better between low- and high-risk patients, but further improvements are needed before they can be considered for introduction into clinical practice.

Trial registration: ClinicalTrials.gov NCT02095925.

Copyright© 2017 Ferrata Storti Foundation.

Figures

Figure 1.
Figure 1.
Cumulative incidence of venous thromboembolism in low- and high-risk patients. Cumulative incidence of venous thromboembolism in patients enrolled prior to chemotherapy (n=260) who were classified as being at low or high risk of venous thromboembolism by the (A) Khorana score, (B) Vienna CATS score, (C) PROTECHT score, and (D) CONKO score.

References

    1. Di Nisio M, Porreca E, Candeloro M, De Tursi M, Russi I, Rutjes AW. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2016;12(2):CD008500.
    1. Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med. 2012;9(7):e1001275.
    1. Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007;5(3):632–634.
    1. Lyman GH, Bohlke K, Khorana AA, et al. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update 2014. J Clin Oncol. 2013;31(17):654–656.
    1. Mandala M, Falanga A, Roila F, Mandalà M, Falanga A, Roila F. Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2011;22 Suppl 6:vi85–92.
    1. Farge D, Debourdeau P, Beckers M, et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thromb Haemost. 2013;11(1):56–70.
    1. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111(10):4902–4907.
    1. Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer patients. Blood. 2010;116(24):5377–5382.
    1. Verso M, Agnelli G, Barni S, Gasparini G, LaBianca R. A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the Protecht score. Intern Emerg Med. 2012;7(3):291–292.
    1. Pelzer U, Sinn M, Stieler J, Riess H. [Primary pharmacological prevention of thromboembolic events in ambulatory patients with advanced pancreatic cancer treated with chemotherapy?]. Dtsch Med Wochenschr. 2013;138(41):2084–2088.
    1. Simanek R, Vormittag R, Ay C, et al. High platelet count associated with venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). J Thromb Haemost. 2010;8(1):114–120.
    1. Mansfield AS, Tafur AJ, Wang CE, Kourelis TV, Wysokinska EM, Yang P. Predictors of active cancer thromboembolic outcomes: validation of the Khorana score among patients with lung cancer. J Thromb Haemost. 2016;14(9):1773–1778.
    1. Muñoz Martín AJ, García Alfonso P, Rupérez Blanco AB, Pérez Ramírez S, Blanco Codesido M, Martín Jiménez M. Incidence of venous thromboembolism (VTE) in ambulatory pancreatic cancer patients receiving chemotherapy and analysis of Khorana’s predictive model. Clin Transl Oncol. 2014;16(10):927–930.
    1. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007; 370(9596):1453–1457.
    1. Martín AJM, Ziyatdinov A, Rubio VC, et al. PO-04 - A new genetic risk score for predicting venous thromboembolic events in cancer patients receiving chemotherapy. Thromb Res. 2016;140 Suppl:S177–178.
    1. Putter H, Fiocco M, Geskus RB. Tutorial in biostatistics: competing risks and multi-state models. Stat Med. 2007;26(11):2389–2430.
    1. Choudhury JB. Non-parametric confidence interval estimation for competing risks analysis: application to contraceptive data. Stat Med. 2002;21(8):1129–1144.
    1. Wolbers M, Blanche P, Koller MT, Witteman JCM, Gerds TA. Concordance for prognostic models with competing risks. Biostatistics. 2014;15(3):526–539.
    1. Fine JP, Gray RJ. A Proportional Hazards Model for the Subdistribution of a Competing Risk. J Am Stat Assoc. 1999; 94(446):496.
    1. Donders ART, van der Heijden GJMG, Stijnen T, Moons KGM. Review: a gentle introduction to imputation of missing values. J Clin Epidemiol. 2006;59(10):1087–1091.
    1. Rubin DB. Inference and missing data. Biometrika. 1976;63(3):581–592.
    1. Posch F, Riedl J, Reitter E-M, et al. Hypercoagulabilty, venous thromboembolism, and death in patients with cancer. A Multi-State Model. Thromb Haemost. 2016;115(4):1–10.
    1. van Es N, Franke VF, Middeldorp S, Wilmink JW, Büller HR. The Khorana score for the prediction of venous thromboembolism in patients with pancreatic cancer. Thromb Res. 2017;150:30–32.
    1. Srikanthan A, Tran B, Beausoleil M, et al. Large retroperitoneal lymphadenopathy as a predictor of venous thromboembolism in patients with disseminated germ cell tumors treated with chemotherapy. J Clin Oncol. 2015;33(6):582–587.
    1. Mandala M, Clerici M, Corradino I, et al. Incidence, risk factors and clinical implications of venous thromboembolism in cancer patients treated within the context of phase I studies: the “SENDO experience”. Ann Oncol. 2012;23(6):1416–1421.
    1. Agnelli G, George DJ, Kakkar AK, et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med. 2012;366(7):601–609.
    1. Agnelli G, Gussoni G, Bianchini C, et al. Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol. 2009;10(10):943–949.
    1. Unverzagt S, Prondzinsky R, Peinemann F. Single-center trials tend to provide larger treatment effects than multicenter trials: A systematic review. J Clin Epidemiol. 2013; 66(11):1271–1280.

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