Venous Thromboembolism (VTE) Recurrence in Patients with Recurrent/Metastatic Solid Cancer Receiving Anticoagulation Therapy After Index VTE; Findings From Korean VTE Registry,

Cancer patients (pts) with venous thromboembolism (VTE) have an increased risk of VTE recurrence. However, few data are available regarding the incidence, impact of malignancy characteristics on VTE recurrence in pts with recurrent/metastatic solid cancer. Reliable information on the factors determining the risk of VTE recurrence may facilitate tailored anticoagulation therapy by discriminating cancer-associated VTE pts according to the risk of recurrence. Therefore, the aims of this study are to investigate the incidence of VTE recurrence, its association with malignancy characteristics, and prognostic factors for VTE recurrence in pts with recurrent/metastatic solid cancer receiving anticoagulation therapy after prior index VTE.

The data source in this study is a web-based registry of Korean VTE Working Party (http://kdvt.chamc.co.kr), which is an ongoing, multicenter database system recruiting consecutive patients with VTE confirmed by objective tests. The pts were eligible to enter the study cohort if they had received a diagnosis of recurrent/metastatic solid cancer between May 2005 and Dec 2010 and initiated anticoagulation therapy after the diagnosis of index VTE. Pts were excluded from the study cohort if they had received a diagnosis of hematologic malignancies, if solid cancers were not recurrent or metastatic disease, if index VTE was intra-abdominal venous thrombosis (IVT) or vascular access-induced thrombosis, or if anticoagulation therapy was not instituted. The period of follow-up considered for the analysis was the duration of anticoagulation therapy with a maximum of 6 months and pts in whom anticoagulation therapy was stopped within 6 months were censored at the time of treatment cessation.

The data of 363 recurrent/metastatic solid cancer pts with anticoagulation therapy following the diagnosis of index VTE were analyzed. The median age was 65 (range, 27–91) years and 201 pts (55%) were male. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0 or 1 in 164 pts (55%). The primary sites of cancer were breast in 17 pts, genito-urinary tract in 36, stomach-esophagus in 74, colo-rectum in 81, hepato-biliary tract in 28, pancreas in 34, and lung in 93. Two hundred sixty (72%) pts received active systemic chemotherapy. The location of index VTE was isolated pulmonary embolism (PE) in 151 (42%), isolated deep venous thrombosis (DVT) in 136 (37%), and combined PE and DVT in 76 (21%). The type of anticoagulation therapy for initial therapy was low molecular weight heparin in 282 pts (78%), and for long-term therapy was warfarin in 272 (75%). Eighteen (5%) pts received systemic or catheter-directed thrombolytic therapy for their index VTE at the time of initial diagnosis. Median duration of anticoagulation therapy was 2.4 months (range, 0.1–6.0). Fifty four (15%) pts presented with VTE recurrence within the first 6 months of index VTE. The distribution of site at VTE recurrence was 32 (57%) isolated PE, 10 (18%) isolated extremity DVT, 1 (2%) isolated IVT, 10 (18%) combined PE and DVT, 2 (4%) combined DVT and IVT, and 1 (2%) combined PE/DVT and IVT.

The 6-month cumulative incidence of VTE recurrence after index VTE was 26.6% (95% CI, 19.7–33.5). In the univariate analysis for cumulative incidence of VTE recurrence, male gender (P=0.022), 2 to 4 of ECOG PS (P=0.002), lung or pancreas of primary site of cancer (P<0.001), presence of diabetes (P=0.028), and PE as an index VTE (P=0.016) were associated with higher incidence of VTE recurrence. In the multivariate analysis of risk factors for the development of VTE recurrence, lung (HR, 4.26; 95% CI, 1.48–12.34) or pancreas (HR, 10.63; 3.48–32.41) of primary site of cancer, 2 to 4 of ECOG PS (HR, 2.17; 1.23–3.84), and male gender (HR, 1.86; 1.01–3.44) were independent factors for increasing risk of VTE recurrence.

This study demonstrated that the risk of VTE recurrence in Asian patients with recurrent/metastatic solid cancer receiving anticoagulation therapy after prior VTE was substantially high. Pancreas or lung as a cancer site, poor PS, and male gender were strong predictors of VTE recurrence. These may provide basic information to optimize treatment strategies for tailored thromboprophylaxis in recurrent or metastatic solid cancer pts. Further larger studies are needed to confirm our results and to compare with different ethnicities.

No relevant conflicts of interest to declare.