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Predictors of Venous Thromboembolic Events Associated with Central Venous Port Insertion in Cancer Patients

Predictors of Venous Thromboembolic Events Associated with Central Venous Port Insertion in... Hindawi Publishing Corporation Journal of Oncology Volume 2014, Article ID 743181, 6 pages http://dx.doi.org/10.1155/2014/743181 Clinical Study Predictors of Venous Thromboembolic Events Associated with Central Venous Port Insertion in Cancer Patients 1 2 1 2 Christine Hohl Moinat, Daniel Périard, Adrienne Grueber, Daniel Hayoz, 3 4 1 1 Jean-Luc Magnin, Pascal André, Marc Kung, and Daniel C. Betticher Department of Medical Oncology, Hoˆpital Cantonal de Fribourg, Chemin des Pensionnats 2, 1700 Fribourg, Switzerland Department of Angiology, Hoˆpital Cantonal de Fribourg, Chemin des Pensionnats 2, 1700 Fribourg, Switzerland Central Laboratory, Hoˆpital Cantonal de Fribourg, Chemin des Pensionnats 2, 1700 Fribourg, Switzerland Pharmacy Unit, Hoˆpital Cantonal de Fribourg, Chemin des Pensionnats 2, 1700 Fribourg, Switzerland Correspondence should be addressed to Daniel Per ´ iard; daniel.periard@h-fr.ch Received 29 August 2013; Revised 2 December 2013; Accepted 16 December 2013; Published 9 February 2014 Academic Editor: Bruno Vincenzi Copyright © 2014 Christine Hohl Moinat et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Insertion of central venous port (CVP) catheter in the cancer population is associated with increased incidence of venous thromboembolic events (VTE). However, trials have shown limited benefit of antithrombotic treatment to prevent catheter-related venous thrombosis. This prospective observational cohort study was designed to assess the incidence of VTE closely related to CVP implantation in patients with cancer and undergoing chemotherapy, and to identify a high risk subgroup of patients. Between February 2006 and December 2011, 1097 consecutive cancer patients with first CVP implantation were included. Catheter-related VTE were defined as deep venous thrombosis in the arm, with or without pulmonary embolism (PE), or isolated PE. The incidence of CVP-associated VTE was 5.9% (IC95 4.4–7.3%) at 3 months, and 11.3% (IC95 9.4–13.2%) at 12 months. eTh incidence of any VTE was 7.6% (IC95 6.0–9.3%) at 3 months, and 15.3% (IC95 13.1–17.6%) at 12 months. High Khorana risk score and lung cancer were significant predictors of 3 month VTE. In conclusion, this large cohort study of patients with first CVP catheter implantation confirms the high incidence of VTE associated with the CVP implantation and allow identifying high risk patients who may benefit from thromboprophylaxis. 1. Introduction lead to significant clinical burden with upper limb post- thrombotic syndrome reported in 5 to 28% [6, 7]and res- The majority of patients with cancer undergoing chemother- piratory failure in case of pulmonary embolism. Moreover, apy require an efficient venous access for several weeks or catheter thrombosis can also lead to catheter occlusion in 14 months. Central venous port (CVP) catheter is widely used to 36% and delay chemotherapy [8]. in this setting. The incidence of deep venous thrombosis At least eight randomized controlled trials have evaluated (DVT) and pulmonary embolism (PE) associated with cen- antithrombotic therapy versus placebo in the prevention tral venous catheter has been reported between 2% and 67% of central venous catheter-associated thrombosis [9–16]. A [1]. The cancer population combines nonspecific throm- smallstudy foundthatfixeddoseofwarfarin1mg once daily boembolic risk factors (age, malignancy, hypercoagulability, reduced the incidence of upper extremity DVT at the 90th chemotherapy, infections, and bed rest) [2]and specicfi day of venography [9]. However, two subsequent trials failed to confirm any benefit with this regimen [ 10, 11]. In two risk factors such as catheter material, multiple placement attempts, catheter size and length, number of lumens, and large studies, the administration of a prophylactic dose of catheter tip localization [3–5]. Catheter-related VTE may be low molecular weight heparin (LMWH) during at least 6 limited to asymptomatic radiological nd fi ings but may also weeks aeft r the catheter insertion did not reduce significantly 2 Journal of Oncology the incidence of upper limb DVT compared to placebo [14, swelling at the CVP side. Any other symptom suggesting 15]. A systematic thromboprophylaxis is therefore not rec- upper or lower limb DVT or any thoracic symptom sug- ommended at the time of CVP implantation, and should be gesting a PE was further investigated by compression venous considered only for patients with solid tumor and additional sonography of the limbs or thoracic CT scan. During follow- risk factors for VTE and low bleeding risk [17]. During the up, patient with symptomatic anaemia received blood trans- last years, Khorana and colleagues developed and validated fusion. Erythropoietin agent was not used in our institution. a predictive model for chemotherapy-associated thrombosis Granulocyte-colony stimulation factor administration was [18, 19]. This model allows identification of patients at high allowedtoreducethe length of neutropenia. risk who may benetfi from antithrombotic treatment during chemotherapy. To the best of our knowledge, there is no risk 2.4. Den fi ition and Assessment of Outcome. The main out- score available to evaluate the risk of VTE following CVP come was the 3-month incidence of catheter-related VTE, insertion and the Khorana score has not been validated in defined as occlusive DVT in the arm along the catheter, with this setting. eTh purpose of this study was to evaluate the inci- dence of VTE closely associated with the insertion and use of or without PE, or isolated PE of unknown origin. eTh sec- CVP catheters and to identify high-risk patients amenable to ondary outcomes were the 12-month incidence of catheter- benetfi from a short course of thromboprophylaxis aeft r CVP related VTE and the 3- and 12-month incidence of any VTE implantation. related or not to the catheter, including DVT of the leg, DVT of the other arm and visceral DVT. Asymptomatic DVT or PE observed on CT scan performed for tumoral staging 2. Patients and Method was classified as asymptomatic event. Catheter dysfunctions 2.1. Patient Inclusion. From February 2006 to December 2011, were investigated by US-Doppler or phlebography. Catheter all consecutive adult patients suffering from cancer and who dysfunction and small, nonoccluding thrombosis along the were implanted with a CVP in the Surgery Department of the catheter were not considered as event. Complete occlusion of Cantonal Hospital, Fribourg, Switzerland (Tertiary Care Cen- the vein along the catheter was considered as asymptomatic ter) were screened for inclusion in this prospective cohort. eventifitwas notassociatedwithlocal symptoms. We included only patients older than 18 years with rfi st CVP implantation. All included patients were then followed up 2.5. Khorana Score. The Khorana score is a validated tool for by the department of medical oncology. eTh study received estimation of VTE during chemotherapy [18]. The Khorana approval from the institutional ethic committee. predictive score assigns 2 points to very high-risk cancer sites (pancreatic, gastric, brain) and 1 point to high risk cancer 2.2. Surgical Implantation Procedure. Implantation was per- sites (lung, ovarian, renal, or bladder). In addition, 1 point formed under local anaesthesia in the operating room by ded- is assigned for each of the following: platelet count≥ 350 icated surgeons. eTh operator always attempted to n fi d the × 10 /L, hemoglobin < 10 g/dL, or use of erythropoietin- cephalic-subclavian junction at the right upper limb and to stimulating agents, leukocyte count≥ 11× 10 /L, and body place a J-curved 0.035 inch guide wire in the superior cava vein. eTh catheter tip was then placed at the level of the tho- mass index≥ 35 kg/m . Patients with Khorana score≥ 3are racic rib, under u fl oroscopy guidance. eTh chamber was then considered at high risk for VTE. placed in the pectoral region by tunelisation from the same skin incision. When the cephalic vein was not accessible, 2.6. Statistical Analysis. Incidences of event were expressed the catheter was implanted in the subclavian vein by direct as proportions with 95% confidence intervals, calculated by punction. er Th e was no routine sonography or phlebography binomial Wilson test. Proportions of event were compared of the subclavian vein prior to the intervention except in using Chi test, and continuous variables were compared by case of known previous DVT, previous central line use or the Mann-Whitney rank sum test according to the normality failure to pass the guide wire in a previous attempt. During of their distribution. Statistical significance was considered the study period, the same senior vascular surgeon was in for 𝛼 < 0.05 . eTh contribution of clinical characteristics charge of the dedicated CVP surgery team. eTh re was no (age, sex, weight, body mass index, previous VTE, respira- ultrasound guidance during implantation. eTh rfi st chemo- tory failure, renal failure, antithrombotic treatment, cancer therapy infusion was allowed at the same day of the CVP location, metastatic stage, low performance status, class of implantation. er Th e was no systematic antithrombotic ther- apy administration at the time of CVP insertion. chemotherapy agent, major surgery close to CVP implanta- tion or during follow-up, side of CVP implantation, baseline laboratory values, and Khorana score) to asymptomatic and 2.3. Patient Follow-Up. Patients were regularly followed up symptomatic VTE was analysed using multivariable logistic clinically during chemotherapy treatment and then every regression analysis. Factors were rfi st analyzed individually 6 months aeft r chemotherapy completion until complete in univariate analysis and then selected for multivariable remission, death of any cause, or loss of follow-up. Patients analysis based on a𝑃 value< 0.2 or known confounding whose CVP catheter has been removed for lack of use were effect. The statistical analysis was performed using Stata 9.0 followed up until 6 weeks aeft r removal. At each visit, the subjects were questioned about any local pain or upper limb (Statacorp, College Station, Texas, USA). Journal of Oncology 3 Table 1: Clinical characteristics of the cohort including 1097 consecutive patients receiving their first implantable central venous catheter (catheter port) for antitumoral chemotherapy.𝑃 values are for patients with VTE (𝑛=122 ) versus patients without event (𝑛=933 ). Patients with All patients Patients without Patients with any Clinical characteristics catheter-related VTE 𝑃 value (𝑛=1097 ) VTE (𝑛=933 ) VTE (𝑛=164 ) (𝑛=122 ) Age (median, range) 62 (18 to 89) 63 (18 to 89) 62 (29 to 84) 63 (31 to 84) NS Age> 70 y 299 (27.3%) 261 (28%) 38 (23.2%) 26 (21.5%) NS Male 617 (56.2%) 527 (56.5%) 90 (54.9%) 65 (53.3%) NS BMI (median, range) 25.0 (14.9 to 57.8) 24.4 (14.9 to 51.4) 24.3 (16.1 to 38.1) 24.2 (16.1 to 38.1) NS BMI> 35 51 (4.6%) 41 (4.4%) 11 (6.7%) 10 (8.3%) 0.05 Major comorbidities Coronary heart disease 117 (10.7%) 108 (11.6%) 9 (5.4%) 7 (5.8%) 0.06 Diabetes 138 (12.6%) 122 (13.1%) 16 (9.8%) 15 (12.3%) NS Respiratory failure 306 (27.9%) 252 (27%) 54 (32.9%) 48 (39.7%) 0.002 Renal failure 63 (5.7%) 58 (6.2%) 5 (3%) 3 (2.5%) NS Previous VTE 118 (10.8%) 99 (10.6%) 19 (11.6%) 16 (13.2%) NS Cancer Lung 260 (23.7%) 207 (22.2%) 53 (32.3%) 47 (38.5%) <0.001 Colorectal 206 (18.8%) 176 (18.9%) 30 (18.3%) 17 (13.9%) 0.09 Oesogastic 146 (13.3%) 128 (13.8%) 18 (11%) 14 (11.5%) NS Breast 120 (10.9%) 106 (11.3%) 14 (8.5%) 10 (8.2%) NS ORL 84 (7.7%) 76 (8.1%) 8 (4.9%) 7 (5.7%) NS Hepatocholangiopancreas 76 (6.9%) 64 (6.9%) 12 (7.3%) 5 (4.1%) NS Lymphomas 75 (6.8%) 69 (7.4%) 6 (3.7%) 5 (4.1%) NS Other 130 (11.8%) 107 (11.5%) 23 (14%) 17 (13.9%) NS Stage IV 396 (36.1%) 327 (35%) 69 (42.1%) 49 (40.2%) NS Performance status 2–4 629 (57.3%) 527 (56.5%) 111 (67.6%) 83 (67.7%) 0.01 CVP placed on left side 86 (7.8%) 64 (6.9%) 21 (12.8%) 17 (14.1%) 0.01 Surgery during 30 days before 146 (13.3%) 125 (13.4%) 22 (13.3%) 15 (12.4%) NS CVC placement Major surgery during follow-up 217 (19.8%) 180 (19.3%) 37 (22.6%) 27 (22.3%) NS Therapeutic antithrombotic treatment at time of CVP 90 (8.2%) 78 (8.3%) 12 (7.3%) 10 (8.3%) NS placement Chemotherapy, first cycle Platin based 510 (46.5%) 425 (45.5%) 85 (51.8%) 69 (56.6%) 0.08 Bevacizumab 34 (3.1%) 23 (3.2%) 11 (17.2%) 9 (7.3%) 0.01 Mean follow-up duration 14 (13–15) 14 (13–15) 16 (13–18) 16 (13–18) NS (months) VTE: venous thromboembolic event. 3. Results characteristics of the 1097 patients included are shown in Table 1. eTh most frequent cancers were lung (21.1%), colo- 3.1. Patients. Throughout the 6-year study period, 1243 con- rectal (18.6%), and oesogastric (13.3%). secutive patients were candidates for a CVP implantation in our institution and were screened for inclusion. We included 3.2. Venous rTh omboembolic Events. Table 2 shows the inci- 1074 patients with CVP placement at first attempt and 23 dence of VTE at 3 and 12 months. The incidence of CVP- patients with failure at rfi st attempt but success at second associated VTE was 5.9% of patients (IC95 4.4–7.3%) at attempt. We excluded 146 patients (15 patients for previous 3 months and 11.3% (IC95 9.4–13.2%) at 12 months. The CVP placement, 129 patients for choice for another intra- incidence of VTE at any location was 7.6% of patients (IC95 venous access aer ft CVP placement failure, and 2 patients for 6.0–9.3%) at 3 months and 15.3% (IC95 13.1–17.6%) at 12 failure to place CVP at rfi st and second attempt). eTh clinical months. 4 Journal of Oncology Table 2: Incidence of thrombotic events at 3 months and 12 months (proportion and CI95). 3 months 12 months All events Symptomatic events All events Symptomatic events Subclavian DVT 3.0% (1.9–4.0) 2.1% (1.2–3.1) 5.9% (4.5–7.8) 4.1% (2.7–5.4) PE 3.0% (1.9–4.0) 1.4% (0.7–2.1) 5.5% (4.1–6.9) 2.7% (1.6–3.7) Catheter-related event (subclavian DVT or PE) 5.9% (4.4–7.3) 3.6% (2.4–4.7) 11.3% (9.4–13.2) 6.7% (5.1–8.4) Lower extremity or visceral DVT 2.2% (1.3–3.1) 1.3% (0.6–2.1) 4.6% (3.3–5.9) 2.8% (1.7–3.9) All thrombotic events 7.6% (6.0–9.3) 4.7% (3.4–6.0) 15.3% (13.1–17.6) 9.3% (7.3–11.2) Cumulative incidence of VTE aer fir ft st port catheter implantation 3.3. Predictors of Catheter-Associated VTE at 3 Months. The multivariate logistic regression analysis identified 2 signif- icantpredictorsofcatheter-relatedVTE at 3months: a Khorana score≥ 3 (odd ratio (OR) 3.50, CI95 1.00 to 12.3, and𝑃 = 0.05 ) and lung cancer (OR 5.45, CI95 1.87 to 15.87, and 𝑃 = 0.002 ). Low performance status was borderline significant (OR 4.68, CI95 0.97 to 22.4, and 𝑃 = 0.054 ) (Table 3). Advanced stage with distant metastases was only borderline significant in the univariate analysis but fell in 0 180 360 540 720 900 themultivariable regression.PreviousVTE,highBMI,age> Days aer im ft plantation 70, and platinum-based regimen were not associated with Catheter-related VTE VTEat3months in this cohort.Thedelay betweenCVP Any VTE implantation and chemotherapy infusion was analysed. Most patients had chemotherapy close to the CVP implantation Figure 1 (31% of patients had chemotherapy before CVP implantation, 14.7% of patients had chemotherapy 0 to 3 days aer ft CVP implantation, 20.6% of patients had chemotherapy 4 to 8 days 4. Discussion after implantation, and 33.7% of patients >8dayslater).Com- pared to the 3 other groups, the group of patients receiving This large cohort study, designed to evaluate the incidence of chemotherapy within days 0 to 8 aer ft CVP implantation had VTE closely related to central venous Port catheter implan- no additional risk of CVP-related VTE at 3 months (OR 1.00, tation, shows that 7.6% of the patients will develop DVT 0.67 to 1.57, and𝑃=0.98 ). or PE during the rfi st 3 months aer ft catheter implantation. This n fi ding conrfi ms the important burden linked to the IV management of chemotherapy and the importance to develop 3.4. Incidence of VTE in High-Risk Subgroups. The incidence efficient preventive antithrombotic strategies. This study also of VTE was particularly high in the 3 subpopulations identi- validates high Khorana score and lung cancer as significant efi d. Among the 102 patients (9.3%) with a baseline Khorana predictors of VTE during the whole study period. Despite score≥ 3, 18.6% (CI95 10.9 to 26.4) had a VTE during the several trials, evaluating different drug regimens to prevent first 3 months of follow-up. This incidence was 10.8% (CI95 chemotherapy-associated VTE, no clear benefit emerged 6.8 to 14.8) among the 232 patients (21.1%) with lung cancer from any specific regimen up to now [ 20]. One limitation of and 10.9% (CI95 7.7 to 14.1) among the 367 patients (33.5%) thromboprophylaxis trials is due to the fact that the benetfi with metastatic cancer at the time of CVP insertion. from antithrombotic treatment can be overwhelmed by the bleeding risk occuring during chemotherapy. The other diffi- 3.5. Predictors of VTE at 12 Months. The cumulative inci- culty is to identify patients at risk as well as the period at risk. dence of VTE is shown in Figure 1. eTh steeper part of the Efforts have been made to identify those patients who will slope is observed during the first 3 months after catheter benefit most from thromboprophylaxis. eTh current practice implantation. However, additional events continue to be now is to consider prophylactic antithrombotic treatment for observed up to the end of follow-up. Multivariable regression patients with solid tumor and an additional risk factor for analysis identiefi d the same predictors of VTE at 12 months VTE, such as previous VTE, immobilization, and specific than at 3 months. Khorana score≥ 3(OR 2.67,CI951.49to anticancer therapy (thalidomide or lenalidomide in associa- 4.78, and𝑃 = 0.001 ) and lung cancer (OR 1.93, CI95 1.15 to tion with dexamethasone) [17, 21]. 3.25,𝑃=0.01 ) were significantly associated with VTE (from Limiting thromboprophylaxis on a high-risk period any origin) during the 12-month study period. Bevacizumab could increase efficiency and reduce the bleeding risk inher- and platinol based regimen were both borderline significant ent to prolonged antithrombotic treatment. eTh period of predictors of 12-month VTE events (Table 3). CVP implantation concentrates major risk factors for VTE Cumulative incidence (%) Journal of Oncology 5 Table 3: Predictors of VTE events during the first 3 months and 12 months following CVP catheter placement, identified by univariate and multivariate regression analysis. Univariate analysis or (95% CI)𝑃 value Multivariate analysis or (95% CI)𝑃 value 3 Months catheter-related VTE event Lung cancer 5.3 (1.98 to 14.1)𝑃=0.0001 5.45 (1.87 to 15.87)𝑃=0.002 Khorana score≥ 3 2.65 (0.88 to 8.0)𝑃=0.08 3.50 (1.00 to 12.30)𝑃=0.05 Low performance status 4.82 (1.08 to 21.4)𝑃=0.03 4.68 (0.97 to 22.4)𝑃=0.054 Metastatic stage 2.33 (0.86 to 6.37)𝑃=0.09 1.21 (0.41 to 3.61)𝑃=0.73 Previous VTE event 1.76 (0.54 to 5.86)𝑃=0.34 Age> 70 0.69 (0.24 to 2.00)𝑃=0.50 Platinum based chemotherapy 1.72 (0.66 to 4.45)𝑃=0.26 Chemotherapy within 0 to 8 days aer ft CVP placement 1.00 (0.62 to 1.57) 𝑃=0.98 3 months VTE event at any location Khorana score≥ 3 2.59 (0.99 to 6.77)𝑃=0.05 3.56 (1.26 to 10.74)𝑃=0.01 Lung cancer 3.07 (1.37 to 6.87)𝑃=0.006 2.56 (1.06 to 6.17)𝑃=0.03 CVP inserted left 3.04 (0.89 to 10.3) 𝑃=0.07 2.39 (0.64 to 8.89)𝑃=0.19 Platinum based chemotherapy 2.01 (0.90 to 4.5)𝑃=0.09 1.84 (0.74 to 4.54)𝑃=0.18 Respiratory failure 2.47 (1.11 to 5.49)𝑃=0.02 Metastatic stage 1.96 (0.86 to 4.46)𝑃=0.11 Low performance status 1.64 (0.67 to 4.04)𝑃=0.28 Previous VTE event 1.42 (0.50 to 4.06)𝑃=0.50 12 months VTE event at any location Khorana score≥ 3 2.66 (1.50 to 4.70)𝑃=0.001 2.67 (1.49 to 4.78)𝑃=0.001 Lung cancer 2.16 (1.34 to 3.49)𝑃=0.002 1.93 (1.15 to 3.25)𝑃=0.01 Bevacizumab based chemotherapy 2.51 (0.89 to 7.11)𝑃=0.08 3.04 (0.98 to 9.44)𝑃=0.054 Platinum based chemotherapy 1.49 (0.93 to 2.37)𝑃=0.09 1.51 (0.89 to 3.25)𝑃=0.12 Respiratory failure 1.75 (1.09 to 2.82)𝑃=0.02 Metastatic stage 1.49 (0.93 to 2.37)𝑃=0.17 Low performance status 2.24 (1.33 to 3.78)𝑃=0.002 Previous VTE event 1.35 (0.71 to 2.56)𝑃=0.35 CVP inserted left 2.20 (1.13 to 4.26) 𝑃=0.02 (surgery, intravenous foreign material, upper limb immo- One limitation of our study is that the definition of the bilization, untreated cancer, and repeated chemotherapy primary outcome did not include death due to probable or infusions). Our study investigated specifically this period possible VTE. At thetimeofthe studydesign, we were and confirmed the high incidence of VTE close to the CVP concerned about being unable to exclude formally PE as the insertion and its key role in the pathogenesis of cancer-related causeofdeath,especiallyinthe settingofpalliativecare. VTE. Our study also identified 2-patient categories prone to However, we consider that the conclusions of our study are develop VTE in 10 to 20% at 3 months and who will certainly rather conservative since adding deaths for VTE origin could benefit from thromboprophylaxis, at the time of CVP implan- increase the incidence of VTE related to CVP insertion. tation. Interestingly, identification of these patients based on Another limitation of our study is the lack of ultrasound guid- simple clinical data (lung cancer) or a widely used score based ance during CVP placement. Ultrasound guidance has shown on the type of tumor, BMI, and prechemotherapy laboratory to reduce the risk of infectious and thrombotic complications values allows easy identification of patients who could benefit in all percutaneous venous procedures. Its role in the identi- from thromboprophylaxis. fication of the vein during open surgery is less clear. We think In their observational study of 815 CVP implantations, that this was probably compensated by the high experience of Narducci et al. found that the factor most strongly predictive our surgeons. Our institution has a surgical team dedicated to of complications was a delay shorter than 8 days between CVP placement and during the study period (2006 to 2011) CVP implantation and first use [ 22]. These complications thesameseniorvascularsurgeon wasinchargeofthe team. were mostly nonthrombotic (local of systemic infection, port They always tried to identify the cephalic vein for puncture. expulsion, catheter dysfunction, or migration). We analyzed The subclavian vein was punctured only when cephalic vein the delay between implantation and use in our study and was not found. In these cases, the subclavian vein was directly found that a delay> 8 days did not reduce the 3-month VTE incidence. observed and ultrasound would not bring further security. 6 Journal of Oncology In conclusion, this large cohort study of consecutive [11] S. Couban, M. Goodyear, M. Burnell et al., “Randomized placebo-controlled study of low-dose warfarin for the pre- patients with rfi st CVP catheter implantation conrfi ms the vention of central venous catheter-associated thrombosis in high incidence of thrombotic events closely associated with patients with cancer,” Journal of Clinical Oncology,vol.23, no. the CVP intervention. It conrfi ms Khorana score and lung 18, pp. 4063–4069, 2005. cancer as strong predictors of catheter related VTE and VTE [12] A. Abdelkefi, T. B. Othman, L. Kammoun et al., “Prevention of of any origin at 3 and 12 months. eTh se n fi dings will allow the central venous line-related thrombosis by continuous infusion definition of a risk population in order to assess the best of low-dose unfractionated heparin, in patients with haemato- thromboprophylaxis in a randomised trial. Otherwise, we oncological disease: a randomized controlled trial,” Thrombosis may question whether it is still reasonable to delay efficient and Haemostasis,vol.92, no.3,pp. 654–661, 2004. thromboprophylaxis for these patient populations. [13] M. Monreal, A. Alastrue, M. Rull et al., “Upper extremity deep venous thrombosis in cancer patients with venous access devices—prophylaxis with a low molecular weight heparin Conflict of Interests (Fragmin),” rTh ombosis and Haemostasis ,vol.75, no.2,pp. 251– 253, 1996. eTh authors declare that there is no conflict of interests regarding the publication of this paper. [14] M. Verso, G. Agnelli, S. Bertoglio et al., “Enoxaparin for the pre- vention of venous thromboembolism associated with central vein catheter: a double-blind, placebo-controlled, randomized References study in cancer patients,” Journal of Clinical Oncology,vol.23, no.18, pp.4057–4062,2005. [1] C. J. vanRooden,M.E.T.Tesselaar,S.Osanto, F. R. Rosendaal, [15] M. Karthaus, A. Kretzschmar, H. Kronin ¨ g et al., “Dalteparin for and M. V. Huisman, “Deep vein thrombosis associated with prevention of catheter-related complications in cancer patients central venous catheters—a review,” Journal of rTh ombosis and with central venous catheters: final results of a double-blind, Haemostasis,vol.3,no. 11, pp.2409–2419,2005. placebo-controlled phase III trial,” Annals of Oncology,vol.17, [2] M.Mandala,M.Clerici,I.Corradinoetal.,“risk factorsand no. 2, pp. 289–296, 2006. clinical implications of venous thromboembolism in cancer [16] P. Mismetti, D. Mille, S. Laporte et al., “Low-dose molecular- patients treated within the context of phase I studies: the weight heparin (nadroparin) and very low doses of warfarin ’SENDO experience’,” Annals of Oncology,vol.23, pp.1416–1421, in the prevention of upper extremity thrombosis in cancer patients with indwelling long-term central venous catheters: a [3] A.Y.Y.Lee,M.N.Levine, G. Butler et al., “Incidence, risk pilot randomized trial,” Haematologica,vol.88, no.1,pp. 67–73, factors, and outcomes of catheter-related thrombosis in adult patients with cancer,” JournalofClinicalOncology,vol.24, no.9, [17] S. R. Kahn, W. Lim, A. S. Dunn et al., “Prevention of VTE in pp. 1404–1408, 2006. nonsurgical patients: antithrombotic therapy and prevention [4] D. Periard, P. Monney, G. Waeber et al., “Randomized con- of thrombosis, 9th ed: American College of Chest Physicians trolled trial of peripherally inserted central catheters vs. periph- evidence-based clinical practice guidelines,” Chest,vol.141,no. eral catheters for middle duration in-hospital intravenous ther- 2, pp. e195–e226, 2012. apy,” JournalofThrombosis andHaemostasis ,vol.6,no. 8, pp. [18] A.A.Khorana,N.M.Kuderer,E.Culakova,G.H.Lyman,andC. 1281–1288, 2008. W. Francis, “Development and validation of a predictive model for chemotherapy-associated thrombosis,” Blood, vol. 111, no. 10, [5] D. Periard, “Peripherally inserted central catheter in leukemia: pp. 4902–4907, 2008. insertion site determines clotting risk,” Leukemia and Lym- phoma,vol.51, no.8,pp. 1391–1392, 2010. [19] A. A. Khorana and G. C. Connolly, “Assessing risk of venous thromboembolism in the patient with cancer,” Journal of Clini- [6] T. Arnhjort, L. M. Persson, S. Rosfors, U. Ludwigs, and G. cal Oncology,vol.27, no.29, pp.4839–4847,2009. Lar ¨ fars, “Primary deep vein thrombosis in the upper limb: a [20] E. A. Akl, S. R. Vasireddi, S. Gunukula et al., “Anticoagulation retrospective study with emphasis on pathogenesis and late sequelae,” European Journal of Internal Medicine,vol.18, no.4, for patients with cancer and central venous catheters,” Cochrane Database of Systematic Reviews,vol.13, no.4,Article ID pp.304–308,2007. CD006468, 2011. [7] E. E. Elman and S. R. Kahn, “eTh post-thrombotic syndrome [21] M. Mandala, ` A. Falanga, and F. Roila, “Management of venous aer ft upper extremity deep venous thrombosis in adults: a thromboembolism (VTE) in cancer patients: ESMO clinical systematic review,” Thrombosis Research ,vol.117,no. 6, pp.609– practice guidelines,” Annals of Oncology,vol.22, no.6,pp. vi85– 614, 2006. vi92, 2011. [8] J. L. Baskin, C.-H. Pui, U. Reiss et al., “Management of occlusion [22] F. Narducci, M. Jean-Laurent, L. Boulanger et al., “Totally and thrombosis associated with long-term indwelling central implantable venous access port systems and risk factors for venous catheters,” The Lancet ,vol.374,no. 9684,pp. 159–169, complications: a one-year prospective study in a cancer centre,” European Journal of Surgical Oncology,vol.37, no.10, pp.913– [9] M.M.Bern, J. J. Lokich,S.R.Wallach et al., “Verylow dosesof 918, 2011. warfarin can prevent thrombosis in central venous catheters: a randomized prospective trial,” Annals of Internal Medicine,vol. 112, no. 6, pp. 423–428, 1990. [10] D. C. Heaton, D. Y. Han, and A. Inder, “Minidose (1 mg) war- farin as prophylaxis for central vein catheter thrombosis,” Inter- nal Medicine Journal,vol.32, no.3,pp. 84–88, 2002. 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Predictors of Venous Thromboembolic Events Associated with Central Venous Port Insertion in Cancer Patients

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Copyright © 2014 Christine Hohl Moinat et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Hindawi Publishing Corporation Journal of Oncology Volume 2014, Article ID 743181, 6 pages http://dx.doi.org/10.1155/2014/743181 Clinical Study Predictors of Venous Thromboembolic Events Associated with Central Venous Port Insertion in Cancer Patients 1 2 1 2 Christine Hohl Moinat, Daniel Périard, Adrienne Grueber, Daniel Hayoz, 3 4 1 1 Jean-Luc Magnin, Pascal André, Marc Kung, and Daniel C. Betticher Department of Medical Oncology, Hoˆpital Cantonal de Fribourg, Chemin des Pensionnats 2, 1700 Fribourg, Switzerland Department of Angiology, Hoˆpital Cantonal de Fribourg, Chemin des Pensionnats 2, 1700 Fribourg, Switzerland Central Laboratory, Hoˆpital Cantonal de Fribourg, Chemin des Pensionnats 2, 1700 Fribourg, Switzerland Pharmacy Unit, Hoˆpital Cantonal de Fribourg, Chemin des Pensionnats 2, 1700 Fribourg, Switzerland Correspondence should be addressed to Daniel Per ´ iard; daniel.periard@h-fr.ch Received 29 August 2013; Revised 2 December 2013; Accepted 16 December 2013; Published 9 February 2014 Academic Editor: Bruno Vincenzi Copyright © 2014 Christine Hohl Moinat et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Insertion of central venous port (CVP) catheter in the cancer population is associated with increased incidence of venous thromboembolic events (VTE). However, trials have shown limited benefit of antithrombotic treatment to prevent catheter-related venous thrombosis. This prospective observational cohort study was designed to assess the incidence of VTE closely related to CVP implantation in patients with cancer and undergoing chemotherapy, and to identify a high risk subgroup of patients. Between February 2006 and December 2011, 1097 consecutive cancer patients with first CVP implantation were included. Catheter-related VTE were defined as deep venous thrombosis in the arm, with or without pulmonary embolism (PE), or isolated PE. The incidence of CVP-associated VTE was 5.9% (IC95 4.4–7.3%) at 3 months, and 11.3% (IC95 9.4–13.2%) at 12 months. eTh incidence of any VTE was 7.6% (IC95 6.0–9.3%) at 3 months, and 15.3% (IC95 13.1–17.6%) at 12 months. High Khorana risk score and lung cancer were significant predictors of 3 month VTE. In conclusion, this large cohort study of patients with first CVP catheter implantation confirms the high incidence of VTE associated with the CVP implantation and allow identifying high risk patients who may benefit from thromboprophylaxis. 1. Introduction lead to significant clinical burden with upper limb post- thrombotic syndrome reported in 5 to 28% [6, 7]and res- The majority of patients with cancer undergoing chemother- piratory failure in case of pulmonary embolism. Moreover, apy require an efficient venous access for several weeks or catheter thrombosis can also lead to catheter occlusion in 14 months. Central venous port (CVP) catheter is widely used to 36% and delay chemotherapy [8]. in this setting. The incidence of deep venous thrombosis At least eight randomized controlled trials have evaluated (DVT) and pulmonary embolism (PE) associated with cen- antithrombotic therapy versus placebo in the prevention tral venous catheter has been reported between 2% and 67% of central venous catheter-associated thrombosis [9–16]. A [1]. The cancer population combines nonspecific throm- smallstudy foundthatfixeddoseofwarfarin1mg once daily boembolic risk factors (age, malignancy, hypercoagulability, reduced the incidence of upper extremity DVT at the 90th chemotherapy, infections, and bed rest) [2]and specicfi day of venography [9]. However, two subsequent trials failed to confirm any benefit with this regimen [ 10, 11]. In two risk factors such as catheter material, multiple placement attempts, catheter size and length, number of lumens, and large studies, the administration of a prophylactic dose of catheter tip localization [3–5]. Catheter-related VTE may be low molecular weight heparin (LMWH) during at least 6 limited to asymptomatic radiological nd fi ings but may also weeks aeft r the catheter insertion did not reduce significantly 2 Journal of Oncology the incidence of upper limb DVT compared to placebo [14, swelling at the CVP side. Any other symptom suggesting 15]. A systematic thromboprophylaxis is therefore not rec- upper or lower limb DVT or any thoracic symptom sug- ommended at the time of CVP implantation, and should be gesting a PE was further investigated by compression venous considered only for patients with solid tumor and additional sonography of the limbs or thoracic CT scan. During follow- risk factors for VTE and low bleeding risk [17]. During the up, patient with symptomatic anaemia received blood trans- last years, Khorana and colleagues developed and validated fusion. Erythropoietin agent was not used in our institution. a predictive model for chemotherapy-associated thrombosis Granulocyte-colony stimulation factor administration was [18, 19]. This model allows identification of patients at high allowedtoreducethe length of neutropenia. risk who may benetfi from antithrombotic treatment during chemotherapy. To the best of our knowledge, there is no risk 2.4. Den fi ition and Assessment of Outcome. The main out- score available to evaluate the risk of VTE following CVP come was the 3-month incidence of catheter-related VTE, insertion and the Khorana score has not been validated in defined as occlusive DVT in the arm along the catheter, with this setting. eTh purpose of this study was to evaluate the inci- dence of VTE closely associated with the insertion and use of or without PE, or isolated PE of unknown origin. eTh sec- CVP catheters and to identify high-risk patients amenable to ondary outcomes were the 12-month incidence of catheter- benetfi from a short course of thromboprophylaxis aeft r CVP related VTE and the 3- and 12-month incidence of any VTE implantation. related or not to the catheter, including DVT of the leg, DVT of the other arm and visceral DVT. Asymptomatic DVT or PE observed on CT scan performed for tumoral staging 2. Patients and Method was classified as asymptomatic event. Catheter dysfunctions 2.1. Patient Inclusion. From February 2006 to December 2011, were investigated by US-Doppler or phlebography. Catheter all consecutive adult patients suffering from cancer and who dysfunction and small, nonoccluding thrombosis along the were implanted with a CVP in the Surgery Department of the catheter were not considered as event. Complete occlusion of Cantonal Hospital, Fribourg, Switzerland (Tertiary Care Cen- the vein along the catheter was considered as asymptomatic ter) were screened for inclusion in this prospective cohort. eventifitwas notassociatedwithlocal symptoms. We included only patients older than 18 years with rfi st CVP implantation. All included patients were then followed up 2.5. Khorana Score. The Khorana score is a validated tool for by the department of medical oncology. eTh study received estimation of VTE during chemotherapy [18]. The Khorana approval from the institutional ethic committee. predictive score assigns 2 points to very high-risk cancer sites (pancreatic, gastric, brain) and 1 point to high risk cancer 2.2. Surgical Implantation Procedure. Implantation was per- sites (lung, ovarian, renal, or bladder). In addition, 1 point formed under local anaesthesia in the operating room by ded- is assigned for each of the following: platelet count≥ 350 icated surgeons. eTh operator always attempted to n fi d the × 10 /L, hemoglobin < 10 g/dL, or use of erythropoietin- cephalic-subclavian junction at the right upper limb and to stimulating agents, leukocyte count≥ 11× 10 /L, and body place a J-curved 0.035 inch guide wire in the superior cava vein. eTh catheter tip was then placed at the level of the tho- mass index≥ 35 kg/m . Patients with Khorana score≥ 3are racic rib, under u fl oroscopy guidance. eTh chamber was then considered at high risk for VTE. placed in the pectoral region by tunelisation from the same skin incision. When the cephalic vein was not accessible, 2.6. Statistical Analysis. Incidences of event were expressed the catheter was implanted in the subclavian vein by direct as proportions with 95% confidence intervals, calculated by punction. er Th e was no routine sonography or phlebography binomial Wilson test. Proportions of event were compared of the subclavian vein prior to the intervention except in using Chi test, and continuous variables were compared by case of known previous DVT, previous central line use or the Mann-Whitney rank sum test according to the normality failure to pass the guide wire in a previous attempt. During of their distribution. Statistical significance was considered the study period, the same senior vascular surgeon was in for 𝛼 < 0.05 . eTh contribution of clinical characteristics charge of the dedicated CVP surgery team. eTh re was no (age, sex, weight, body mass index, previous VTE, respira- ultrasound guidance during implantation. eTh rfi st chemo- tory failure, renal failure, antithrombotic treatment, cancer therapy infusion was allowed at the same day of the CVP location, metastatic stage, low performance status, class of implantation. er Th e was no systematic antithrombotic ther- apy administration at the time of CVP insertion. chemotherapy agent, major surgery close to CVP implanta- tion or during follow-up, side of CVP implantation, baseline laboratory values, and Khorana score) to asymptomatic and 2.3. Patient Follow-Up. Patients were regularly followed up symptomatic VTE was analysed using multivariable logistic clinically during chemotherapy treatment and then every regression analysis. Factors were rfi st analyzed individually 6 months aeft r chemotherapy completion until complete in univariate analysis and then selected for multivariable remission, death of any cause, or loss of follow-up. Patients analysis based on a𝑃 value< 0.2 or known confounding whose CVP catheter has been removed for lack of use were effect. The statistical analysis was performed using Stata 9.0 followed up until 6 weeks aeft r removal. At each visit, the subjects were questioned about any local pain or upper limb (Statacorp, College Station, Texas, USA). Journal of Oncology 3 Table 1: Clinical characteristics of the cohort including 1097 consecutive patients receiving their first implantable central venous catheter (catheter port) for antitumoral chemotherapy.𝑃 values are for patients with VTE (𝑛=122 ) versus patients without event (𝑛=933 ). Patients with All patients Patients without Patients with any Clinical characteristics catheter-related VTE 𝑃 value (𝑛=1097 ) VTE (𝑛=933 ) VTE (𝑛=164 ) (𝑛=122 ) Age (median, range) 62 (18 to 89) 63 (18 to 89) 62 (29 to 84) 63 (31 to 84) NS Age> 70 y 299 (27.3%) 261 (28%) 38 (23.2%) 26 (21.5%) NS Male 617 (56.2%) 527 (56.5%) 90 (54.9%) 65 (53.3%) NS BMI (median, range) 25.0 (14.9 to 57.8) 24.4 (14.9 to 51.4) 24.3 (16.1 to 38.1) 24.2 (16.1 to 38.1) NS BMI> 35 51 (4.6%) 41 (4.4%) 11 (6.7%) 10 (8.3%) 0.05 Major comorbidities Coronary heart disease 117 (10.7%) 108 (11.6%) 9 (5.4%) 7 (5.8%) 0.06 Diabetes 138 (12.6%) 122 (13.1%) 16 (9.8%) 15 (12.3%) NS Respiratory failure 306 (27.9%) 252 (27%) 54 (32.9%) 48 (39.7%) 0.002 Renal failure 63 (5.7%) 58 (6.2%) 5 (3%) 3 (2.5%) NS Previous VTE 118 (10.8%) 99 (10.6%) 19 (11.6%) 16 (13.2%) NS Cancer Lung 260 (23.7%) 207 (22.2%) 53 (32.3%) 47 (38.5%) <0.001 Colorectal 206 (18.8%) 176 (18.9%) 30 (18.3%) 17 (13.9%) 0.09 Oesogastic 146 (13.3%) 128 (13.8%) 18 (11%) 14 (11.5%) NS Breast 120 (10.9%) 106 (11.3%) 14 (8.5%) 10 (8.2%) NS ORL 84 (7.7%) 76 (8.1%) 8 (4.9%) 7 (5.7%) NS Hepatocholangiopancreas 76 (6.9%) 64 (6.9%) 12 (7.3%) 5 (4.1%) NS Lymphomas 75 (6.8%) 69 (7.4%) 6 (3.7%) 5 (4.1%) NS Other 130 (11.8%) 107 (11.5%) 23 (14%) 17 (13.9%) NS Stage IV 396 (36.1%) 327 (35%) 69 (42.1%) 49 (40.2%) NS Performance status 2–4 629 (57.3%) 527 (56.5%) 111 (67.6%) 83 (67.7%) 0.01 CVP placed on left side 86 (7.8%) 64 (6.9%) 21 (12.8%) 17 (14.1%) 0.01 Surgery during 30 days before 146 (13.3%) 125 (13.4%) 22 (13.3%) 15 (12.4%) NS CVC placement Major surgery during follow-up 217 (19.8%) 180 (19.3%) 37 (22.6%) 27 (22.3%) NS Therapeutic antithrombotic treatment at time of CVP 90 (8.2%) 78 (8.3%) 12 (7.3%) 10 (8.3%) NS placement Chemotherapy, first cycle Platin based 510 (46.5%) 425 (45.5%) 85 (51.8%) 69 (56.6%) 0.08 Bevacizumab 34 (3.1%) 23 (3.2%) 11 (17.2%) 9 (7.3%) 0.01 Mean follow-up duration 14 (13–15) 14 (13–15) 16 (13–18) 16 (13–18) NS (months) VTE: venous thromboembolic event. 3. Results characteristics of the 1097 patients included are shown in Table 1. eTh most frequent cancers were lung (21.1%), colo- 3.1. Patients. Throughout the 6-year study period, 1243 con- rectal (18.6%), and oesogastric (13.3%). secutive patients were candidates for a CVP implantation in our institution and were screened for inclusion. We included 3.2. Venous rTh omboembolic Events. Table 2 shows the inci- 1074 patients with CVP placement at first attempt and 23 dence of VTE at 3 and 12 months. The incidence of CVP- patients with failure at rfi st attempt but success at second associated VTE was 5.9% of patients (IC95 4.4–7.3%) at attempt. We excluded 146 patients (15 patients for previous 3 months and 11.3% (IC95 9.4–13.2%) at 12 months. The CVP placement, 129 patients for choice for another intra- incidence of VTE at any location was 7.6% of patients (IC95 venous access aer ft CVP placement failure, and 2 patients for 6.0–9.3%) at 3 months and 15.3% (IC95 13.1–17.6%) at 12 failure to place CVP at rfi st and second attempt). eTh clinical months. 4 Journal of Oncology Table 2: Incidence of thrombotic events at 3 months and 12 months (proportion and CI95). 3 months 12 months All events Symptomatic events All events Symptomatic events Subclavian DVT 3.0% (1.9–4.0) 2.1% (1.2–3.1) 5.9% (4.5–7.8) 4.1% (2.7–5.4) PE 3.0% (1.9–4.0) 1.4% (0.7–2.1) 5.5% (4.1–6.9) 2.7% (1.6–3.7) Catheter-related event (subclavian DVT or PE) 5.9% (4.4–7.3) 3.6% (2.4–4.7) 11.3% (9.4–13.2) 6.7% (5.1–8.4) Lower extremity or visceral DVT 2.2% (1.3–3.1) 1.3% (0.6–2.1) 4.6% (3.3–5.9) 2.8% (1.7–3.9) All thrombotic events 7.6% (6.0–9.3) 4.7% (3.4–6.0) 15.3% (13.1–17.6) 9.3% (7.3–11.2) Cumulative incidence of VTE aer fir ft st port catheter implantation 3.3. Predictors of Catheter-Associated VTE at 3 Months. The multivariate logistic regression analysis identified 2 signif- icantpredictorsofcatheter-relatedVTE at 3months: a Khorana score≥ 3 (odd ratio (OR) 3.50, CI95 1.00 to 12.3, and𝑃 = 0.05 ) and lung cancer (OR 5.45, CI95 1.87 to 15.87, and 𝑃 = 0.002 ). Low performance status was borderline significant (OR 4.68, CI95 0.97 to 22.4, and 𝑃 = 0.054 ) (Table 3). Advanced stage with distant metastases was only borderline significant in the univariate analysis but fell in 0 180 360 540 720 900 themultivariable regression.PreviousVTE,highBMI,age> Days aer im ft plantation 70, and platinum-based regimen were not associated with Catheter-related VTE VTEat3months in this cohort.Thedelay betweenCVP Any VTE implantation and chemotherapy infusion was analysed. Most patients had chemotherapy close to the CVP implantation Figure 1 (31% of patients had chemotherapy before CVP implantation, 14.7% of patients had chemotherapy 0 to 3 days aer ft CVP implantation, 20.6% of patients had chemotherapy 4 to 8 days 4. Discussion after implantation, and 33.7% of patients >8dayslater).Com- pared to the 3 other groups, the group of patients receiving This large cohort study, designed to evaluate the incidence of chemotherapy within days 0 to 8 aer ft CVP implantation had VTE closely related to central venous Port catheter implan- no additional risk of CVP-related VTE at 3 months (OR 1.00, tation, shows that 7.6% of the patients will develop DVT 0.67 to 1.57, and𝑃=0.98 ). or PE during the rfi st 3 months aer ft catheter implantation. This n fi ding conrfi ms the important burden linked to the IV management of chemotherapy and the importance to develop 3.4. Incidence of VTE in High-Risk Subgroups. The incidence efficient preventive antithrombotic strategies. This study also of VTE was particularly high in the 3 subpopulations identi- validates high Khorana score and lung cancer as significant efi d. Among the 102 patients (9.3%) with a baseline Khorana predictors of VTE during the whole study period. Despite score≥ 3, 18.6% (CI95 10.9 to 26.4) had a VTE during the several trials, evaluating different drug regimens to prevent first 3 months of follow-up. This incidence was 10.8% (CI95 chemotherapy-associated VTE, no clear benefit emerged 6.8 to 14.8) among the 232 patients (21.1%) with lung cancer from any specific regimen up to now [ 20]. One limitation of and 10.9% (CI95 7.7 to 14.1) among the 367 patients (33.5%) thromboprophylaxis trials is due to the fact that the benetfi with metastatic cancer at the time of CVP insertion. from antithrombotic treatment can be overwhelmed by the bleeding risk occuring during chemotherapy. The other diffi- 3.5. Predictors of VTE at 12 Months. The cumulative inci- culty is to identify patients at risk as well as the period at risk. dence of VTE is shown in Figure 1. eTh steeper part of the Efforts have been made to identify those patients who will slope is observed during the first 3 months after catheter benefit most from thromboprophylaxis. eTh current practice implantation. However, additional events continue to be now is to consider prophylactic antithrombotic treatment for observed up to the end of follow-up. Multivariable regression patients with solid tumor and an additional risk factor for analysis identiefi d the same predictors of VTE at 12 months VTE, such as previous VTE, immobilization, and specific than at 3 months. Khorana score≥ 3(OR 2.67,CI951.49to anticancer therapy (thalidomide or lenalidomide in associa- 4.78, and𝑃 = 0.001 ) and lung cancer (OR 1.93, CI95 1.15 to tion with dexamethasone) [17, 21]. 3.25,𝑃=0.01 ) were significantly associated with VTE (from Limiting thromboprophylaxis on a high-risk period any origin) during the 12-month study period. Bevacizumab could increase efficiency and reduce the bleeding risk inher- and platinol based regimen were both borderline significant ent to prolonged antithrombotic treatment. eTh period of predictors of 12-month VTE events (Table 3). CVP implantation concentrates major risk factors for VTE Cumulative incidence (%) Journal of Oncology 5 Table 3: Predictors of VTE events during the first 3 months and 12 months following CVP catheter placement, identified by univariate and multivariate regression analysis. Univariate analysis or (95% CI)𝑃 value Multivariate analysis or (95% CI)𝑃 value 3 Months catheter-related VTE event Lung cancer 5.3 (1.98 to 14.1)𝑃=0.0001 5.45 (1.87 to 15.87)𝑃=0.002 Khorana score≥ 3 2.65 (0.88 to 8.0)𝑃=0.08 3.50 (1.00 to 12.30)𝑃=0.05 Low performance status 4.82 (1.08 to 21.4)𝑃=0.03 4.68 (0.97 to 22.4)𝑃=0.054 Metastatic stage 2.33 (0.86 to 6.37)𝑃=0.09 1.21 (0.41 to 3.61)𝑃=0.73 Previous VTE event 1.76 (0.54 to 5.86)𝑃=0.34 Age> 70 0.69 (0.24 to 2.00)𝑃=0.50 Platinum based chemotherapy 1.72 (0.66 to 4.45)𝑃=0.26 Chemotherapy within 0 to 8 days aer ft CVP placement 1.00 (0.62 to 1.57) 𝑃=0.98 3 months VTE event at any location Khorana score≥ 3 2.59 (0.99 to 6.77)𝑃=0.05 3.56 (1.26 to 10.74)𝑃=0.01 Lung cancer 3.07 (1.37 to 6.87)𝑃=0.006 2.56 (1.06 to 6.17)𝑃=0.03 CVP inserted left 3.04 (0.89 to 10.3) 𝑃=0.07 2.39 (0.64 to 8.89)𝑃=0.19 Platinum based chemotherapy 2.01 (0.90 to 4.5)𝑃=0.09 1.84 (0.74 to 4.54)𝑃=0.18 Respiratory failure 2.47 (1.11 to 5.49)𝑃=0.02 Metastatic stage 1.96 (0.86 to 4.46)𝑃=0.11 Low performance status 1.64 (0.67 to 4.04)𝑃=0.28 Previous VTE event 1.42 (0.50 to 4.06)𝑃=0.50 12 months VTE event at any location Khorana score≥ 3 2.66 (1.50 to 4.70)𝑃=0.001 2.67 (1.49 to 4.78)𝑃=0.001 Lung cancer 2.16 (1.34 to 3.49)𝑃=0.002 1.93 (1.15 to 3.25)𝑃=0.01 Bevacizumab based chemotherapy 2.51 (0.89 to 7.11)𝑃=0.08 3.04 (0.98 to 9.44)𝑃=0.054 Platinum based chemotherapy 1.49 (0.93 to 2.37)𝑃=0.09 1.51 (0.89 to 3.25)𝑃=0.12 Respiratory failure 1.75 (1.09 to 2.82)𝑃=0.02 Metastatic stage 1.49 (0.93 to 2.37)𝑃=0.17 Low performance status 2.24 (1.33 to 3.78)𝑃=0.002 Previous VTE event 1.35 (0.71 to 2.56)𝑃=0.35 CVP inserted left 2.20 (1.13 to 4.26) 𝑃=0.02 (surgery, intravenous foreign material, upper limb immo- One limitation of our study is that the definition of the bilization, untreated cancer, and repeated chemotherapy primary outcome did not include death due to probable or infusions). Our study investigated specifically this period possible VTE. At thetimeofthe studydesign, we were and confirmed the high incidence of VTE close to the CVP concerned about being unable to exclude formally PE as the insertion and its key role in the pathogenesis of cancer-related causeofdeath,especiallyinthe settingofpalliativecare. VTE. Our study also identified 2-patient categories prone to However, we consider that the conclusions of our study are develop VTE in 10 to 20% at 3 months and who will certainly rather conservative since adding deaths for VTE origin could benefit from thromboprophylaxis, at the time of CVP implan- increase the incidence of VTE related to CVP insertion. tation. Interestingly, identification of these patients based on Another limitation of our study is the lack of ultrasound guid- simple clinical data (lung cancer) or a widely used score based ance during CVP placement. Ultrasound guidance has shown on the type of tumor, BMI, and prechemotherapy laboratory to reduce the risk of infectious and thrombotic complications values allows easy identification of patients who could benefit in all percutaneous venous procedures. Its role in the identi- from thromboprophylaxis. fication of the vein during open surgery is less clear. We think In their observational study of 815 CVP implantations, that this was probably compensated by the high experience of Narducci et al. found that the factor most strongly predictive our surgeons. Our institution has a surgical team dedicated to of complications was a delay shorter than 8 days between CVP placement and during the study period (2006 to 2011) CVP implantation and first use [ 22]. These complications thesameseniorvascularsurgeon wasinchargeofthe team. were mostly nonthrombotic (local of systemic infection, port They always tried to identify the cephalic vein for puncture. expulsion, catheter dysfunction, or migration). We analyzed The subclavian vein was punctured only when cephalic vein the delay between implantation and use in our study and was not found. In these cases, the subclavian vein was directly found that a delay> 8 days did not reduce the 3-month VTE incidence. observed and ultrasound would not bring further security. 6 Journal of Oncology In conclusion, this large cohort study of consecutive [11] S. Couban, M. Goodyear, M. Burnell et al., “Randomized placebo-controlled study of low-dose warfarin for the pre- patients with rfi st CVP catheter implantation conrfi ms the vention of central venous catheter-associated thrombosis in high incidence of thrombotic events closely associated with patients with cancer,” Journal of Clinical Oncology,vol.23, no. the CVP intervention. It conrfi ms Khorana score and lung 18, pp. 4063–4069, 2005. cancer as strong predictors of catheter related VTE and VTE [12] A. Abdelkefi, T. B. Othman, L. Kammoun et al., “Prevention of of any origin at 3 and 12 months. eTh se n fi dings will allow the central venous line-related thrombosis by continuous infusion definition of a risk population in order to assess the best of low-dose unfractionated heparin, in patients with haemato- thromboprophylaxis in a randomised trial. Otherwise, we oncological disease: a randomized controlled trial,” Thrombosis may question whether it is still reasonable to delay efficient and Haemostasis,vol.92, no.3,pp. 654–661, 2004. thromboprophylaxis for these patient populations. [13] M. Monreal, A. Alastrue, M. Rull et al., “Upper extremity deep venous thrombosis in cancer patients with venous access devices—prophylaxis with a low molecular weight heparin Conflict of Interests (Fragmin),” rTh ombosis and Haemostasis ,vol.75, no.2,pp. 251– 253, 1996. eTh authors declare that there is no conflict of interests regarding the publication of this paper. [14] M. Verso, G. Agnelli, S. Bertoglio et al., “Enoxaparin for the pre- vention of venous thromboembolism associated with central vein catheter: a double-blind, placebo-controlled, randomized References study in cancer patients,” Journal of Clinical Oncology,vol.23, no.18, pp.4057–4062,2005. [1] C. J. vanRooden,M.E.T.Tesselaar,S.Osanto, F. R. Rosendaal, [15] M. Karthaus, A. Kretzschmar, H. Kronin ¨ g et al., “Dalteparin for and M. V. Huisman, “Deep vein thrombosis associated with prevention of catheter-related complications in cancer patients central venous catheters—a review,” Journal of rTh ombosis and with central venous catheters: final results of a double-blind, Haemostasis,vol.3,no. 11, pp.2409–2419,2005. placebo-controlled phase III trial,” Annals of Oncology,vol.17, [2] M.Mandala,M.Clerici,I.Corradinoetal.,“risk factorsand no. 2, pp. 289–296, 2006. clinical implications of venous thromboembolism in cancer [16] P. Mismetti, D. Mille, S. Laporte et al., “Low-dose molecular- patients treated within the context of phase I studies: the weight heparin (nadroparin) and very low doses of warfarin ’SENDO experience’,” Annals of Oncology,vol.23, pp.1416–1421, in the prevention of upper extremity thrombosis in cancer patients with indwelling long-term central venous catheters: a [3] A.Y.Y.Lee,M.N.Levine, G. Butler et al., “Incidence, risk pilot randomized trial,” Haematologica,vol.88, no.1,pp. 67–73, factors, and outcomes of catheter-related thrombosis in adult patients with cancer,” JournalofClinicalOncology,vol.24, no.9, [17] S. R. Kahn, W. Lim, A. S. Dunn et al., “Prevention of VTE in pp. 1404–1408, 2006. nonsurgical patients: antithrombotic therapy and prevention [4] D. Periard, P. Monney, G. Waeber et al., “Randomized con- of thrombosis, 9th ed: American College of Chest Physicians trolled trial of peripherally inserted central catheters vs. periph- evidence-based clinical practice guidelines,” Chest,vol.141,no. eral catheters for middle duration in-hospital intravenous ther- 2, pp. e195–e226, 2012. apy,” JournalofThrombosis andHaemostasis ,vol.6,no. 8, pp. [18] A.A.Khorana,N.M.Kuderer,E.Culakova,G.H.Lyman,andC. 1281–1288, 2008. W. Francis, “Development and validation of a predictive model for chemotherapy-associated thrombosis,” Blood, vol. 111, no. 10, [5] D. Periard, “Peripherally inserted central catheter in leukemia: pp. 4902–4907, 2008. insertion site determines clotting risk,” Leukemia and Lym- phoma,vol.51, no.8,pp. 1391–1392, 2010. [19] A. A. Khorana and G. C. Connolly, “Assessing risk of venous thromboembolism in the patient with cancer,” Journal of Clini- [6] T. Arnhjort, L. M. Persson, S. Rosfors, U. Ludwigs, and G. cal Oncology,vol.27, no.29, pp.4839–4847,2009. Lar ¨ fars, “Primary deep vein thrombosis in the upper limb: a [20] E. A. Akl, S. R. Vasireddi, S. Gunukula et al., “Anticoagulation retrospective study with emphasis on pathogenesis and late sequelae,” European Journal of Internal Medicine,vol.18, no.4, for patients with cancer and central venous catheters,” Cochrane Database of Systematic Reviews,vol.13, no.4,Article ID pp.304–308,2007. CD006468, 2011. [7] E. E. Elman and S. R. Kahn, “eTh post-thrombotic syndrome [21] M. Mandala, ` A. Falanga, and F. Roila, “Management of venous aer ft upper extremity deep venous thrombosis in adults: a thromboembolism (VTE) in cancer patients: ESMO clinical systematic review,” Thrombosis Research ,vol.117,no. 6, pp.609– practice guidelines,” Annals of Oncology,vol.22, no.6,pp. vi85– 614, 2006. vi92, 2011. [8] J. L. Baskin, C.-H. Pui, U. Reiss et al., “Management of occlusion [22] F. Narducci, M. Jean-Laurent, L. Boulanger et al., “Totally and thrombosis associated with long-term indwelling central implantable venous access port systems and risk factors for venous catheters,” The Lancet ,vol.374,no. 9684,pp. 159–169, complications: a one-year prospective study in a cancer centre,” European Journal of Surgical Oncology,vol.37, no.10, pp.913– [9] M.M.Bern, J. J. Lokich,S.R.Wallach et al., “Verylow dosesof 918, 2011. warfarin can prevent thrombosis in central venous catheters: a randomized prospective trial,” Annals of Internal Medicine,vol. 112, no. 6, pp. 423–428, 1990. [10] D. C. Heaton, D. Y. Han, and A. Inder, “Minidose (1 mg) war- farin as prophylaxis for central vein catheter thrombosis,” Inter- nal Medicine Journal,vol.32, no.3,pp. 84–88, 2002. 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