Dynamic assessment of venous thromboembolism risk in patients with cancer by longitudinal D-Dimer analysis: A prospective study.

BACKGROUND:Venous thromboembolism (VTE) is a frequent complication of cancer. Elevated D-Dimer is associated with an increased risk of cancer-associated VTE. Whether changes in D-Dimer over time harbor additional prognostic information that may be exploited clinically for dynamic prediction of VTE is unclear. OBJECTIVES:To explore the potential role of longitudinal D-Dimer trajectories for personalized prediction of cancer-associated VTE. PATIENTS/METHODS:167 patients with active malignancy were prospectively enrolled (gastrointestinal: n=59 (35%), lung: n=56 (34%), brain: n=50 (30%), others: n=2 (1%); metastatic disease: n=74 (44%)). D-Dimer (median=0.8µg/mL [25th -75th percentile: 0.4-2.0]) was measured at baseline and during 602 monthly follow-up visits. Joint models of longitudinal and time-to-event data were implemented to quantify the association between D-Dimer trajectories and prospective risk of VTE. RESULTS:VTE occurred in 20 patients (250-day VTE risk=12.1%, 95%CI: 7.8-18.5). D-Dimer increased by 34%/month (0.47µg/mL/month, 95%CI: 0.22-0.72, p<0.0001) in patients who developed VTE, but remained constant in patients who did not develop VTE (change/month=-0.06µg/mL/month, 95%CI: -0.15-0.02, p=0.121). In joint modeling, a doubling of the D-Dimer trajectory was associated with a 2.8-fold increase in the risk of VTE (Hazard ratio=2.78, 95%CI: 1.69-4.58, p<0.0001). This finding was independent of established VTE risk factors. Highly personalized, dynamic predictions of VTE conditional on individual patients' D-Dimer trajectories could be obtained. CONCLUSIONS:D-Dimer increases before the onset of cancer-associated VTE, but remains constant over time in patients without VTE. This study represents proof-of-concept that longitudinal trajectories of D-Dimer may advance the personalized assessment of VTE risk in the oncologic setting.