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

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.