Evaluation of the Khorana, PROTECHT, and 5-SNP scores for prediction of venous thromboembolism in patients with cancer

N.A.M. Guman*, R.J. van Geffen, F.I. Mulder, T.F. van Haaps, V. Hovsepjan, M. Labots, G.A. Cirkel, F.Y.F.L. de Vos, A.J. ten Tije, L.V. Beerepoot, V.C.G. Tjan-Heijnen, H.W.M. van Laarhoven, P. Hamberg, A.J.E. Vulink, M. Los, A.H. Zwinderman, B. Ferwerda, M.P.J.K. Lolkema, N. Steeghs, H.R. BullerP.W. Kamphuisen, N. van Es

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background The Khorana score is a validated tool to identify cancer patients at higher risk of venous thromboembolism (VTE). Objective We compared its predictive performance to that of the clinical PROTECHT and the polygenic 5-SNP scores in patients who participated in the Dutch CPCT-02 study. Patients/methods Data on VTE and its risk factors were retrospectively collected for 2729 patients with advanced stage solid tumors planned for systemic cancer treatment. Patients were followed for 6 months. Overall discriminatory performance of the scores was evaluated by time-dependent c-indices. The scores were additionally evaluated dichotomously in competing risk models. Results A total of 160 (5.9%) patients developed VTE during follow-up. Time-dependent c-indices at 6 months for the Khorana, PROTECHT, and 5-SNP scores were 0.57 (95% confidence interval [CI]: 0.55-0.60), 0.60 (95% CI: 0.57-0.62), and 0.54 (95% CI: 0.51-0.57), respectively. The dichotomous scores classified 9.6%, 16.8%, and 9.5% as high-risk, respectively. VTE risk was about 2-fold higher among high-risk patients than low-risk patients for the Khorana (subdistribution hazard ratio [SHR] 1.9, 95% CI: 1.3-3.0), PROTECHT (SHR 2.1, 95% CI: 1.5-3.0), and 5-SNP scores (SHR 1.7, 95% CI: 1.03-2.8). The sensitivity at 6 months was 16.6% (95% CI: 10.5-22.7), 28.9% (95% CI: 21.5-36.3), and 14.9% (95% CI: 8.5-21.2), respectively. Conclusions Performance of the PROTECHT or 5-SNP score was not superior to that of the Khorana score. The majority of cancer patients who developed VTE during 6-month follow-up were not identified by these scores. Future directions for studies on cancer-associated VTE prediction may include combined clinical-genetic scores.
Original languageEnglish
Pages (from-to)2974-2983
Number of pages10
JournalJournal of Thrombosis and Haemostasis
Issue number12
Early online date6 Sept 2021
Publication statusPublished - Dec 2021


  • neoplasms
  • polymorphism
  • risk assessment
  • single nucleotide
  • thrombosis
  • venous thromboembolism


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