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

Noori A.M. Guman, Roos J. van Geffen, Frits I. Mulder, Thijs F. van Haaps, Vahram Hovsepjan, Mariette Labots, Geert A. Cirkel, Filip Y. F. L. de Vos, Albert J. ten Tije, Laurens V. Beerepoot, Vivianne C.G. Tjan-Heijnen, Hanneke W.M. van Laarhoven, Paul Hamberg, Annelie J.E. Vulink, Maartje Los, Aeilko H. Zwinderman, Bart Ferwerda, Martijn P.J.K. Lolkema, Neeltje Steeghs, Harry R. BüllerPieter W. Kamphuisen, Nick van Es

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17 Citations (Scopus)


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 date2021
Publication statusPublished - Dec 2021


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

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