Key result
PROTECHT and 5-SNP scores fail to outperform the Khorana score in predicting 6-month cancer-associated VTE.
Why the study?
The predictive performance of the validated Khorana score for cancer-associated venous thromboembolism needed to be compared against the clinical PROTECHT and polygenic 5-SNP scores.
Do the PROTECHT and 5-SNP scores improve the prediction of venous thromboembolism compared to the Khorana score in patients with advanced stage solid tumors?
Cohort (n=2,729)
Yes
Do the PROTECHT and 5-SNP scores improve the prediction of venous thromboembolism compared to the Khorana score in patients with advanced stage solid tumors?
The PROTECHT and 5-SNP scores did not demonstrate superior predictive performance compared to the Khorana score for identifying VTE risk in cancer patients, and all scores failed to identify the majority of patients who developed VTE.
Answers are grounded in this paper and cite their sources.
Does not support replacing Khorana with PROTECHT or 5-SNP for VTE risk stratification in advanced cancer; leaves open the need for superior prediction models.
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.
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Guman et al. (2021) conducted a cohort in Venous thromboembolism in advanced stage solid tumors (n=2,729). PROTECHT score (high-risk ≥3 points) and 5-SNP score vs. Low-risk score (<3 points) and Khorana score was evaluated on Venous thromboembolism (VTE) at 6 months (SHR 2.1, 95% CI 1.5-3.0). The PROTECHT (c-index 0.60) and 5-SNP (0.54) scores did not outperform the Khorana score (0.57) in predicting 6-month venous thromboembolism in patients with advanced solid cancer.
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