International Clinical Practice Guidelines for the Treatment and Prophylaxis of Thrombosis Associated with Central Venous Catheters in Patients with Cancer

Use of long term indwelling central venous catheter (CVC) is associated with symptomatic (Σ) events in up to 30% of cancer patients (pts), which may lead to pulmonary embolism (PE) and loss of the CVC. Lack of consensus on management of CVC related thrombosis (CVCT) and heterogeneity in clinical practices worldwide led us to establish international Good Clinical Practices Guidelines (GCPG) for the management of CRT in cancer pts.

The international working group (WG) met 4 times and worked 2 years with the methodological support and quality control of the French institute of Cancer (INCa). All studies on cancer, venous thromboembolism (VTE, including pulmonary embolism PE), and anticoagulant drugs (AC) published from 1996 to 2011 weree searched using MEDLINE^®database. Meta-analyses, systematic reviews, randomized or non-randomized prospective or retrospective studies in the absence of randomized clinical trials, and abstracts only if a full paper had been accepted in a peer-reviewed medical journal were included in the analysis. The included studies concerned the prophylaxis and treatment of CVC in cancer pts. Studies in non-cancer pts, pts with a peripheral or dialysis catheter, or with a history of cancer in remission for more than 5 years were not considered. The main study outcomes were rates of proven catheter related thrombosis (CRT), extension of CRT, PE associated with CRT, major and minor bleeding, thrombocytopenia, and death. Quality of the studies was evaluated in a double-blind manner by the methodologists using the GRADE appraisal grids. Extracted data were entered in evidence tables, subsequently validated by all the WG. The level of evidence (High A, Moderate B, Low C, Very low D) depended on study design, limitations, inconsistency, indirectness, imprecision and publication bias. For each question, results analysis were summarized and discussed by the WG. Overall conclusions and recommendations were classified as Strong (Grade 1 Guideline) or Weak (Grade 2 Guideline) based on evidence levels, the balance between desirable/undesirable effects, values and preferencesand costs. In the absence of scientific evidence, judgment based on consensus within the WG was defined as Best Clinical Practice (BCP). The GCP were reviewed and evaluated using a specific grid in February 2012 by 45 independent experts in managing cancer pts worldwide and 3 pt representatives.

1. For the treatment of established CVC in cancer pts, we found no prospective randomized study, only 2 non-randomized prospective studies and 1 retrospective study examining the efficacy and safety of LMWH+VKA. One retrospective study evaluated the benefit of CVC removal and 2 retrospective studies, with few patients assessing the thrombolytic drugs values. We recommend A) For the treatment of Σ CRT in cancer pts, AC is recommended for a minimum of months; in this setting, LMWH are suggested. Oral VKA can be used [BCP]. B) The CVC can be kept in place if it is functional, well-positioned, non-infected and shows good evolution under close surveillance; whether the CVC is kept or removed, no standard approach in term of duration of anticoagulation is established [BCP].

2. For the prophylaxis of CVCRT in cancer pts, 6 randomized studies investigated the efficacy and safety of VKA vs. placebo or no treatment, 1 the efficacy and safety of UFH, 6 the value of LMWH and one double-blind randomized study the thrombolytic drugs in the prevention of CVC-RT. Six meta-analyses of AC and CVC thromboprophylaxis have been performed. The type of catheter (open-ended, such as the Hickman^® catheter, versus closed-ended catheter with a valve, such as the Groshong^®catheter), its position (above, below or at the junction of the superior vena cava and the right atrium), and the method of placement may influence the onset of CVCT on the basis of 6 retrospective, 4 prospective non-randomized trials, 3 randomized trials and 1 meta-analysis. In light of these data,

   • Use of AC for routine prophylaxis of CRT is not recommended [1A];

   • CVC should be inserted on the right side, in the jugular vein, and distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium [1A].

Dissemination and implementation of these international GCPG on the prevention and treatment of CRT in cancer ptsat each national level is a major public health priority, necssitating world wide collaboration.

No relevant conflicts of interest to declare.