Although patients with solid-tumor cancers and implanted ports have a high risk for venous thromboembolism (VTE), guidelines advise against routine thromboprophylaxis, given the wide variation in thrombotic risks in this setting. In results from a prospective cohort study published in Blood, researchers determined risk factors associated with thromboembolic events in this patient population that could help identify patients who would benefit from thromboprophylaxis. Specifically, the use of the cephalic vein for catheter insertion was a substantial risk factor for catheter-related thrombosis, but not for non– catheter-related thrombosis.
"That risk factors for catheter-related thrombosis differ from those for VTE unrelated to the catheter was an unexpected finding and may have clinical implications," the authors, led by HervÃ© Decousus, MD, of the Centre d'Investigation Clinique, in Saint- Etienne, France, wrote. Data from this real-world study may help risk-stratify patients and guide decisions about catheter insertion site and antiplatelet or anticoagulant therapy.
To identify risk factors for catheter-related thrombosis and non– catheter-related VTE in patients with an implanted port, the ONCOCIP (ONCOlogie et Chambres ImPlantables) study included 3,032 adult patients (median age = 63 years; range not reported) from 29 French medical centers. The most common cancer sites were breast (33.7%), lung (18.5%), and colon (15.6%), and 43.2 percent of patients had metastatic cancer. Nearly all patients (97.1%) received chemotherapy.
Follow-up consisted of in-person, face-to-face visits every month for up to six months, then every three months for up to 12 months (or until death or port removal). Participants were directed to report to the study center immediately if any signs or symptoms occurred, including any thromboembolic event, infection, or local port-related complication.
At 12-month follow-up, 656 patients (21.6%) had died, and 48 (1.6%) were lost to follow-up. Another 479 patients (15.8%) discontinued the study prematurely due to definitive port removal.
Overall, thrombosis occurred in 397 patients (13.8%), including:
- catheter-related thrombosis: 111 patients (3.8%)
- non–catheter-related VTE: 276 patients (9.6%)
Catheter-related thrombosis included 106 patients (3.8%) who developed an upper-extremity deep vein thrombosis and five patients (0.2%) who developed a pulmonary embolism associated with upper-extremity deep vein thrombosis.
The median time to any symptomatic catheter-related thrombosis was 45 days (range = 23-99 days). In addition, of the 397 patients who experienced a thromboembolic event, 329 (82.9%) received anticoagulation at therapeutic dose.
In multivariate analyses, use of the cephalic vein for catheter insertion was the only risk factor significantly and independently associated with 12-month catheter-related thrombosis (hazard ratio [HR] = 2.51; 95% CI 1.68-3.75; p<0.0001). Conversely, ongoing use of antiplatelet therapy at baseline had a protective effect and was independently associated with a reduced risk of catheter-related thrombosis at 12 months (HR=0.44; 95% CI 0.21-0.90; p=0.024).
However, neither of these risk factors were associated with rates of non–catheter-related VTE at 12 months. The researchers instead found that the following factors predicted the development of non– catheter-related thrombosis, although p values were not reported:
- age â‰¥60 years (HR=1.54; 95% CI 1.13-2.11)
- previous VTE (HR=2.68; 95% CI 1.85-3.89)
- hemoglobin levels <10 g/dL (HR=2.07; 95% CI 1.37-3.12)
- leukocyte counts >11×109 cells/L prior to chemotherapy initiation (HR=1.57; 95% CI 1.12-2.20)
"We did not find that previous VTE was a risk factor for catheter-related thrombosis, even though 14.8 percent of our patients had such a medical history," the authors noted. "The reason for this may be that mechanical factors are more important than medical background in determining the risk of specific events such as catheter-related thrombosis."
The disparity between the risk factors for catheter-related and non–catheter-related thrombosis suggests the need for different prevention strategies. "Catheter-related thrombosis may affect primarily catheter function/permeability … thus, prevention of catheter-related thrombosis may focus mainly on mechanical factors, with the objective of protecting catheter function," the researchers explained. However, the prevention of VTE unrelated to the catheter may "rely on anticoagulant drugs to improve patient prognosis."
The study did not include any patients with a multilumen port, so the researchers were unable to assess its thrombotic effects, they noted. The study's implications also may be limited by the use of prophylactic anticoagulation among patients perceived to have a higher risk of VTE, which may have affected the observed VTE rate.
These authors report no conflicts of interest.
Decousus H, Bourmaud A, Fournel P, et al; for the ONCOCIP Investigators. Cancer-associated thrombosis in patients with implanted ports: a prospective multicenter French cohort study (ONCOCIP). Blood. 2018;132:707-16.
"These findings confirm associations between non–catheter-related VTE and cancer type, low hemoglobin, and increased leukocyte count. These factors are already used in risk-scoring algorithms like the Khorana Risk Score for VTE, but the researchers also observed increased VTE risk with advanced age and previous VTE history – factors that are associated with VTE in patients without cancer. Incorporation of these risk factors into algorithms may increase the ability to identify â€˜at-risk' patients with cancer for increased surveillance or prophylactic anticoagulation. Because this study was not designed to identify VTE mechanisms, future work should aim to understand how a patient's risk factors interact with prothrombotic signals from the tumor and the central venous access device to increase thrombotic risk at different locations."
Alisa Wolberg, PhD
Department of Pathology and Laboratory Medicine
University of North Carolina School of Medicine
Chapel Hill, NC