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

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 non-cancer 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 one- 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 analysis were used to calculate odds ratios (OR) and subdistribution hazard ratios (SHR), 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 non-primary brain cancers (n=454, Model 2). In Model 1 and 2, GDF-15 ≥2290.9pg/mL had adjusted ORs for VTE of 1.65 (95%CI: 0.89-3.08), and 2.28 (95%CI: 1.28-4.09), respectively. hs-TnT ≥14.0pg/mL was associated with higher odds of VTE in Model 1 and 2 [adjusted ORs: 2.26 (95%CI: 1.40-3.65), 2.03 (95%CI: 1.07-3.84), respectively]. For NT-proBNP, levels ≥183.5pg/mL was 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.

Circulating Blood Biomarkers and Risk of Venous Thromboembolism in Cancer Patients: A Systematic Review and Meta-Analysis

“…Key study characteristics and individual biomarker estimates of all studies are shown in Table 1 and Supplementary Tables S1 to S6 (available in the online version). From the 113 studies included, 18 19 21 22 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 1...…”

In Search of the Perfect Thrombosis and Bleeding-Associated Cancer Scale

“…Roy et al 33 showed an association between growth differentiation factor-15 (GDF-15) and high-sensitivity cardiac troponin T (hs-TnT) levels and the risk of VTE. The cohort included 454 patients with nonprimary brain cancers with intermediate to high risk of CT during chemotherapy (Khorana score ≥ 2).…”

Open Issues in the Choice and Management of Direct Oral Anticoagulants in Patients with Cancer-Related Venous Thromboembolism

“…10 In addition, risk factors and biomarkers for cancer-related VTE and bleeding have some heterogeneity between different cohorts, although common risk factors do feature. [11][12][13] Interestingly, the cancer site does not seem to influence the choice of DOAC. In 2019, the European Society of Cardiology guidelines suggested not to use edoxaban and rivaroxaban in patients with gastrointestinal cancer.…”