Abstract

Background: Patients with cancer commonly require a central venous catheter (CVC) for delivery of cancer therapies and/or supportive care. The presence of a CVC is associated with an increased risk of venous thromboembolism (VTE). Despite the frequent occurrence, the optimal anticoagulation management and outcomes for patients with cancer and catheter-related upper extremity deep vein thrombosis (DVT) are unclear. Objective: We performed a systematic review and meta-analysis to evaluate the rates of recurrent VTE and bleeding complications in patients with cancer and catheter-related upper extremity DVT. Methods: We searched MEDLINE, Embase, Scopus, and CENTRAL (Cochrane) from inception to June 2, 2023. We aimed to include randomized controlled trials (RCTs) (if any), prospective and retrospective cohort studies, and case-control studies (including ≥ 10 patients) evaluating adult patients with cancer and catheter-related upper extremity DVT. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding as defined by individual studies. Secondary outcomes included clinically relevant non-major bleeding, total bleeding events, and all-cause mortality. By using R software (version 4.0.3), the incidence rates (with 95% confidence interval [CI]) of recurrent VTE and bleeding outcomes at different time points were pooled using random effects model. Results: After screening 4,264 records, we included 29 studies (N=2,848 patients) in the systematic review. There were no RCTs, 5 prospective cohort studies (including 260 patients), and 24 retrospective cohort studies. Most studies had modest sample size (N<100). Overall from 24 studies with reported tumor types, the most common malignancy was hematological malignancy (50.4%), followed by gastrointestinal (13.6%), breast (10.2%), and lung (5.5%) cancers. The median or mean follow-up duration varied widely from 1 to 20 months. Duration of anticoagulation also varied considerably with median or mean duration of 20 days to 6 months. The main long-term anticoagulant used was low-molecular-weight heparin (58.1%), followed by direct oral anticoagulants (24.3%). Only two studies (N=87 patients) specifically reported the management and associated outcomes after catheter removal. Thirteen studies (N=1105 patients) reported a 3-month recurrent VTE rate, with the pooled rate of 1% (95% CI 0-3%, I 2 = 0%) (Figure 1). Nine studies (N=811 patients) reported a 3-month major bleeding rate, with the pooled rate of 2% (95% CI 1-5%, I 2 = 0%) (Figure 2). We were unable to pool event rates beyond 3 months given high degree of heterogeneity in the follow-up duration, bleeding definition, and duration of anticoagulation. Conclusions: Our systematic review and meta-analysis demonstrated relatively low rates of recurrent VTE and major bleeding events within the first 3 months in patients with cancer and catheter-related upper extremity DVT. However, there was significant heterogeneity in the management and reporting after 3 months, and available data are poor to guide treatment strategies and duration of anticoagulation. The optimal management after catheter removal was also unclear. Future large prospective studies are needed.

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