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DOI: 10.1055/a-1792-7720
Growth Differentiation Factor-15, High-Sensitivity Cardiac Troponin T, and N-Terminal pro-B-type Natriuretic Peptide for Predicting Risk of Venous Thromboembolism in Ambulatory Cancer Patients Receiving Chemotherapy
Funding This study was supported by funding from Canadian Institute of Health Research (CIHR) and Bristol Myers Squibb/Pfizer (to P.W.).

Abstract
Growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin T (hs-TnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with increased risk of venous thromboembolism (VTE) in noncancer patients. However, the performance of these biomarkers in cancer patients is unknown. Our objective was to assess performance of these biomarkers in predicting VTE in cancer patients at intermediate to high risk for VTE (Khorana Score ≥ 2). We used 1-month plasma samples from AVERT trial patients to determine if GDF-15, NT-proBNP, and hs-TnT levels are associated with VTE incidence between 1 and 7 months from the start of chemotherapy. The minimal Euclidean distance of the receiver operating characteristic curve was used to derive optimal cut-offs for GDF-15 and NT-proBNP given there was no evidence of a commonly used cut-off. Logistic and Fine and Gray competing risk regression analyses were used to calculate odds ratios (ORs) and subdistribution hazard ratios, respectively, while adjusting for age, sex, anticoagulation, and antiplatelet therapy. We tested in two groups: all patients (n = 476, Model 1) and all patients with nonprimary brain cancers (n = 454, Model 2). In models 1 and 2, GDF-15 ≥2,290.9 pg/mL had adjusted ORs for VTE of 1.65 (95% confidence interval [CI]: 0.89–3.08), and 2.28 (95% CI: 1.28–4.09), respectively. hs-TnT ≥14.0 pg/mL was associated with higher odds of VTE in models 1 and 2 (adjusted ORs: 2.26 [95% CI: 1.40–3.65] and 2.03 [95% CI: 1.07–3.84], respectively). For NT-proBNP, levels ≥183.5 pg/mL were not associated with VTE. Similar results were observed in the Fine and Gray analysis. Our results indicate that increased GDF-15 and hs-TnT levels predicted increased VTE risk.
Ethical Approval
No ethics approval was sought for this study. The AVERT trial did receive ethical approval for plasma and DNA blood banking for future thrombosis research, on the condition of patient consent.
Author Contributions
D.C.R. designed the research, performed statistical analysis, analyzed results, made the tables, and wrote the manuscript. L.Z. and P.L. designed the research, contributed laboratory tools, performed experiments, and proofread the manuscript. T-.F.W., M.C., and P.W. designed the research, collected the data, interpreted the data, and proofread the manuscript. R.M. designed the research, assisted with performing the statistical analysis, analyzing the results, and proofreading the manuscript. E.M. analyzed and interpreted the data and proofread the manuscript. S.H. aided with statistical analysis, analyzed results, and proofread the manuscript.
Publication History
Received: 03 November 2021
Accepted: 07 March 2022
Accepted Manuscript online:
09 March 2022
Article published online:
31 May 2022
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