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Introduction: Treatment and prevention of VTE is crucial, yet anticoagulation is under-prescribed in cancer patients. The recommended treatment for established VTE in cancer patients is low molecular weight heparin (LMWH) once daily for at least 3 months, and termination or continuation of treatment after 3-6 months is still based on individual evaluation of the benefit-risk ratio, tolerability, drug availability, patient preference, and cancer. Despite important concerns about long-term patient tolerance for LMWH treatment (after 10 days) and its side effects, no study has analyzed the overall impact of LMWH on quality-of-life (QoL) in cancer patients. Methods: In this prospective, longitudinal, multicenter study, consecutive eligible adult cancer patients (>18 years), diagnosed with either deep vein thrombosis or a pulmonary embolism (PE), were recruited at participating centers between February 2011 and 2012. Patients were asked to answer three questionnaires administered at time of VTE diagnosis (M0), and 3 (M3) and 6 (M6) months after start of anticoagulant treatment: 1) the Medical Outcome Study 36-item Short-Form Health Survey (MOS SF-36) for generic Health-Related Quality of Life (HRQoL), 2) the European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire, and 3) the Venous Insufficiency Epidemiological and Economic Study (VEINES)-QOL questionnaire. Results (median[iqr], Wilcoxon Signed Rank Test): At M0, 400 cancer patients (51.5% female) were included, 60.4% with metastatic disease and 67.0% on chemotherapy. The choice of anticoagulant was made by the attending physician. 88.75% of patients received LMWH, 5.5% a vitamin K antagonist, 1.5% unfractionated heparin, and 3.75% a direct oral anticoagulant. Throughout the study, 18.9% of patients on LMWH reported at least one side effect with injection (number of reports: pain, 26 (7.3%); ecchymosis, 57(16.1%); pruritis, 2(0.6%); nodules, 28 (7.9%)). Mortality rate was 24.73%, with 79 deaths attributable to cancer progression and 3 to VTE. At M3, patients on LMWH showed a significant increase of 3.9 [5.7-14 ] points in the MOS SF-36 global HRQoL score (p=0.0007) and 8.3 [-8.3;17] points in the EORTC global Health status/QoL survey (p=0.0001). The veinsQoL score decreased by 2 [-5.2-4] points (p=0.022). Logistic regression analysis identified predictive factors common to both MOS SF-36 and EORTC: ECOG scores (MOS SF-36, p=0.050; EORTC, p=0.006) and whether patients were ambulatory as opposed to bedridden (MOS SF-36, p=0.001; EORTC, p=0.019). Cancer surgery (p=0.005), presence of central venous catheter (CVC) (p=0.018) or PE (p=0.029), and absence of chemotherapy (p=0.017), or acute infection (p=0.048) were also positive predictors of cancer-related QoL in the EORTC survey. No predictive factors were identified for veinsQoL. At M6, patients on LMWH showed sustained point increases of 5.5 [-5.6; 22] in the MOS SF-36 global HRQoL score (p There was no change in the MOS SF-36 global HRQoL score between 3 and 6 months, but there was significant improvement in the sub-dimensions of general health (1.9 pts, p=0.057) and vitality (3.7 pts; p=0.016). The improved global health status/QoL score in the EORTC was also maintained between 3 and 6 months, with a significant 4.7 point reduction in the fatigue symptom subscale (p=0.016). No change was observed in the VeinsQoL. Painful side effects of LMWH treatment did not predict diminished QoL in the logistic regression analysis. Cancer progression was a negative predictor of MOS SF-36 global HRQoL in these patients (p=0.051). Conclusion: In cancer patients with established VTE who survive to 3 and 6 month follow-ups under recommended anticoagulant treatment, QoL increases despite long term treatment with LMWH. This analysis is the first to show that LMWH treatment from 3 to 6 months does not diminish QoL in cancer patients diagnosed with VTE. Disclosures No relevant conflicts of interest to declare.

Introduction Few data are available on the long-term LMWH prescription and treatment follow-up in clinical practice in patients with cancer-associated VTE. Study objectives were to document the prescription and use of treatment doses of LMWH in cancer patients and to assess adherence to established recommendations. Methods Adult cancer patients receiving antineoplastic treatment or palliative care, age ≥18 years, with recent symptomatic VTE in whom treatment with LMWH had been initiated within 7 days prior to inclusion, were eligible to participate in this prospective observational French multicenter study. Patients with a contra-indication to LMWH were not eligible for participation. Main study outcome was the description of LMWH use and prescription in usual medical care. Adherence to recommendations was measured as the proportion of patients receiving a prescription of a LMWH at treatment doses according to the approved dosing schedule and treated for at least 3 months in the absence of severe renal insufficiency (CrCl Results A total of 409 patients aged 65±12.1 years of whom 49.9% female were consecutively included from November 2012 to August 2013. A history of previous VTE was found in 54 (13.2%), surgery or trauma in 100 (24.4%), central venous catheter (CVC) in 303 (74.1%) and immobilization >1 month in 47 (11.5%) patients, respectively. Four (1.03%) patients had severe renal insufficiency. VTE diagnosis at inclusion included lower-limb deep-vein thrombosis (DVT) in 193 (47.2%), pulmonary embolism in 145 (35.5%), CVC-associated thrombosis in 66 (16.1%), upper-limb DVT in 45 (11.0%) and visceral thrombosis in 16 (3.9%) patients, respectively. Most cancers were solid tumors gastro-intestinal (24.4%), lung (17.4%) or breast (15.9%); 81% of patients received chemotherapy and 61.4% were metastatic cancers. LMWH prescriptions included dalteparin in 42 (10.3%), enoxaparin in 61 (14.9%), nadroparin in 5 (1.2%) and tinzaparin in 301 (73.6%) patients. Only 4 (1%) patients received LMWH despite severe renal insufficiency. Table 1 –Prescription adherence to recommendations at inclusion [n (%)]Adherence criteriaTinzaparin (N=301)Other LMWH (N=108)All (N=409)Treatment duration > 3 months293 (97.3)108 (100)401 (98.0)Adequate dosing regimen*231 (76.7)14 (13.0)245 (59.9)Adequate dosing schedule296 (98.3)45 (41.7)341 (83.4)Overall adherence219 (72.8)7 (6.5)226 (55.3) *includes adequate treatment dose and dose adjustment according to recommendations A total of 274 (67.0%) patients received the recommended treatment dose, while 87 (21.3%) patients received doses exceeding this by more than 10% and 39 (9.5%) patients received doses more than 10% below the recommended doses. Based on the pre-defined adherence criteria, 226 (55.3%) [95% CI 50.4-60.1] patients had a LMWH prescription consistent with recommendations. Tinzaparin prescriptions were associated with higher adherence scores compared to other LMWH. During follow-up, actual mean treatment duration was 5.28 ± 2.07 months and 85.7% of patients were treated for 3 months or more Table 2 - Adherence to recommendations at inclusion according to cancer characteristics (N=409) [n (%)] Cancer characteristics Proportion of study population Proportion of adherence to recommendations Gastro-intestinal Lung Breast Hemato lymphopoietic Other Metastatic Chemotherapy (n=405)* 100 (24.4) 71 (17.4) 65 (15.9) 54 (13.2) 119 (29.1) 251 (61.4) 328 (81.0) 53 (53.0) 37 (52.1) 46 (70.8) 28 (51.9) 62 (52.1) 133 (53.0) 186 (56.7) *405 patients documented with chemotherapy At inclusion, the rate of prescriptions consistent with recommendations was low (55.3%) while the highest rate of adherence (70.8%) was observed in patients with breast cancer known to be at rather lower risk of VTE recurrence. Conclusion Adherence to treatment duration was adequate whereas dosing regimen was insufficiently compliant with recommendations. Overall adherence with tinzaparin seemed higher compared to other LMWH Management of patients with cancer-associated VTE requires further education and information of health care professionals. Farge D, J Thromb Haemost. 2013 Jan; 11(1):56-70. Disclosures Farge: Pfizer: Research Funding; LEO Pharma: Research Funding. Debourdeau:Pfizer: Research Funding; LEO Pharma: Research Funding. Cajfinger:Pfizer: Research Funding; LEO Pharma: Research Funding.

Introduction Long-term treatment with LMWH is the recommended standard for patients with cancer-associated VTE [1, 2]. Data on the long-term prescription of LMWH and treatment follow-up in clinical practice, and particularly the patient’s view on the treatment, are scarce. The main objective of TROPIQUE was to document the prescription and use of LMWH in these patients. A sub-study aimed to assess patients’ perception of long-term anticoagulant treatment with LMWH based on the validated Perception AntiCoagulant Treatment Questionnaire (PACT-Q) [2]. Methods Adult cancer patients with recent symptomatic VTE from the TROPIQUE study were asked to fill-in a PACT-Q at inclusion and at 6 months or study end. PACT-Q1 administered at study start included “Treatment Expectations” (7 items) measured by separate scores expressed on a 5-point Likert scale. PACT-Q2 performed at 6 months or at the end of the study included “Convenience” and “Anticoagulant Treatment Satisfaction” (13 and 7 items, respectively) measured by global scores on a 0-to-100 scale. Results A total of 409 patients (49.9% female), aged 65±12.1 years, were consecutively included from November 2012 to August 2013. Most of cancers were solid tumors; 81% of patients received chemotherapy and 60.9% of cancers were metastatic. Mean treatment duration was 5.28 ± 2.07 months and 98.0% of patients were treated for 3 months or more. PACT-Q1 and PACT-Q2 were collected on a voluntarily basis from 269 (67.8%) and 139 (34.0%) patients, respectively. At study start patients’ treatment expectations were high, particularly regarding the confidence in the treatment to prevent blood clots (mean 3.94 ± 0.75), the expectations of symptom relief (mean 3.98 ± 1.04) and the importance of ease of use (mean 4.22 ± 0.9) while 54.3% of patients had low or no expectations of treatment-related side effects (bruise, bleeding) (mean 2.45±1.1). The treatment was considered convenient (global score 79.7 ± 17.1), with the majority of patients reporting small or no difficulties with taking the treatment (subcutaneous injections) and with regards to impact on daily life. The impact of treatment-related side effects on activities was reported as low. A proportion of 69.1% of patients were overall satisfied or very satisfied with their anticoagulant treatment whereas the experience with treatment-related side effects was worse or much worse than expected for only 12.9% of patients. The “Anticoagulant Treatment Satisfaction” global score was 62.9 ± 16.7. Abstract 4272. Table 1: Cancer patient’s perception of long-term anticoagulant treatment with LMWH [n (%)] Selected perception items* Not at all or to a small extent Moderately Very much or extremely Mean score on Likert scale ± SD PACT-Q1 Treatment expectations (n=269) Confident in preventing clots Symptom relief Side effects (n=267) Importance of ease to use - 10 (3.7) 22 (8.2) 145 (54.3) 17 (6.3) - 45 (16.7) 38 (14.1) 76 (28.5) 14 (5.2) - 214 (79.6) 209 (77.7) 46 (17.2) 238 (88.5) - 3.94 ± 0.75 3.98 ± 1.04 2.45 ± 1.1 4.22 ± 0.9 PACT-Q2 Convenience (n=138) Difficulty in taking treatment (n=137) Difficulties regarding daily life Bother in follow-up required Difficulties on regular intake Side effects impact on activities - 92 (67.2) 101 (73.2) 101 (73.2) 114 (82.6) 116 (84.1) - 37 (27) 26 (18.8) 16 (11.6) 17 (12.3) 14 (10.1) - 8 (5.8) 11 (8.0) 7 (5.1) 7 (5.1) 8 (5.8) 79.7 ± 17.1 Treatment satisfaction (n=137) Experience with side effects (n=132) Worse or much worse 17 (12.9) As expected 55 (41.7) Better or much better 60 (45.5) 62.9 ± 16.7 Overall satisfaction (n=136) Unsatisfied or very unsatisfied 10 (7.4) Neutral 32 (23.5) Satisfied or very satisfied 94 (69.1) *Only some items selected from the PACT questionnaire are shown Conclusion Patients with cancer-associated VTE had high expectations regarding anticoagulant treatment and long-term treatment with LMWH is perceived as convenient with a high degree of patient satisfaction. These results suggest that cancer patient’s capability to accept long-term injectable anticoagulant treatment is probably underestimated. These encouraging observations of patient perception of the anticoagulant therapy are essential in view of improving health professional’s adherence to established treatment recommendations on cancer-associated VTE [3]. 1- Farge D, J Thromb Haemost. 2013 Jan;11(1):56-70. 2- Prins MH, Health Qual Life Outcomes, 2009. 7: p. 9. 3- Debourdeau P, Support Care Cancer. 2008 Dec;16(12):1333-41 Disclosures Farge: Pfizer: Research Funding; LEO Pharma: Research Funding. Debourdeau:Pfizer: Research Funding; LEO Pharma: Research Funding. Cajfinger:Pfizer: Research Funding; LEO Pharma: Research Funding.

Introduction Long-term treatment with LMWH is the standard therapy for patients with cancer-associated VTE. Recommended treatment regimen include the prescription of LMWH at treatment doses according to approved administration schedule for at least 3 months in the absence of severe renal insufficiency (CrCl Methods Adult patients with cancer-associated VTE receiving antineoplastic treatment or palliative care were eligible to participate. Efficacy outcomes measures were VTE recurrence including deep-vein thrombosis (DVT) and pulmonary embolism (PE), visceral thrombosis and central venous catheter (CVC)-associated thrombosis. Safety outcomes included all and major bleeding according to ISTH definition [3], thrombocytopenia and deaths. Incidences of 7% of VTE recurrence and 6% of major bleeding were expected. With a sample of 384 patients, the rate of VTE recurrence and major bleeding would be detected with a precision of ±2.6% and ±2.4%, respectively, with a 95% confidence interval. A total of 400 patients were therefore planned to be included in the study. Results A total of 409 patients with symptomatic cancer-associated VTE (Table 1) aged 65±12.1 years of whom 49.9% female were consecutively included from November 2012 to August 2013. A history of previous VTE was found in 54 (13.2%), surgery or trauma in 100 (24.4%), CVC in 303 (74.1%) and an immobilization over 1 month in 47 (11.5%) patients, respectively. At study inclusion, 30 (7.3%) patients had platelet count ≤ 100 x109/L, and 129 (31.5%) had reported anemia while 16 (3.9%) patients had a history of bleeding in the last month. At baseline, more than 80% of patients presented with at least a PE or a lower-limb DVT of s. Table 1 VTE diagnosis at baseline (patients at least with one of the following) VTE diagnosis (at least one of the following) n (%) PE 145 (35.5) DVT lower limb 193 (47.2) Proximal 107 (56.0) Distal 72 (37.7) DVT upper limb 45 (11.0) Visceral thrombosis 16 (3.9) CVC-associated thrombosis 66 (16.1) Mean treatment duration was 5.28 ± 2.07 months. As the majority of patients were treated with tinzaparin (73.6%), clinical outcomes are therefore presented for tinzaparin, other LMWH and all LMWH (Table 2). A total of 21 events of VTE recurrence occurred in 19 patients during the overall study period, with a Kaplan-Meir estimate of the probability of VTE recurrence at 6 months of 6.1%. Table 2 Outcomes in patients with cancer-associated VTE treated with long-term LMWH [n (%)]. Patients treated Tinzaparin n=301 Other LMWH n=108 All LMWH n=409 Patients documented n=292 n=100 n=392 Patients with at least 14 (4.8) 5 (5) 19 (4.8) one VTE recurrence - - - Events (2 patients had 3 4 7 more than one event) 5 1 6 DVT 0 1 1 PE 6 1 7 Visceral thrombosis CVC-associated thrombosis Bleeding n=292 n=100 n=392 All 44 (15.1) 11 (11.0) 55 (14.0) Major 16 (5.5) 7 (7.0) 23 (5.9) Thrombocytopenia n=290 n=100 n=390 (n platelets/mm3) 53 (18.3) 15 (15.0) 68 (17.4) All n=65 n=17 n=82 < 50,000 22 5 27 Drop > 50% 15 2 17 Deaths n=301 n=107 n=408 All 102 (33.9) 44 (41.1) 146 (35.8) Cause of death* n=100 n=44 n=144 LMWH treatment** 1# 0 1## Cancer 87 39 126 Sepsis 4 1 5 Bleeding 4 1 5 Antineoplastic treatment 1 0 1 PE 0 1 1 Other 7 3 10 *Multiple causes of death may have been reported in the same patient; **fatal bleeding reported as LMWH-related; #n=99; ## n=143 Kaplan-Meier estimate of the probability of bleeding at 6 months was 15.9% while corresponding estimates were 18.1% for thrombocytopenia and 34.5% for deaths. Of the five (3.5%) patients who reported fatal bleedings one was reported as related to the LMWH treatment. No heparin-induced thrombocytopenia was reported in the study. Conclusion Clinical outcomes were consistent with previous observations in this patient population except a lower incidence of VTE recurrence compared with previous studies. Study results tend to confirm the favorable efficacy and safety profile of LMWH for the long-term treatment of patients with cancer-associated VTE, when used according to recommended treatment duration and respecting contra-indications. Schulman. J Throm Haemost. 2005 Apr;3(4):692-4.Farge J Thromb Haemost. 2013 Jan;11(1):56-70.Debourdeau P, J Thromb Haemost. 2013 Jan;11(1):71-80 Disclosures Farge: Pfizer: Research Funding; LEO Pharma: Research Funding. Debourdeau:Pfizer: Research Funding; LEO Pharma: Research Funding. Cajfinger:Pfizer: Research Funding; LEO Pharma: Research Funding.

Venous thromboembolism (VTE) is a major therapeutic issue in cancer. Advances in this field and heterogeneities in clinical practices prompted us to establish guidelines related to VTE treatment and to central venous catheter thrombosis (CVCT) management. in cancer patients according to the SOR Standards, Options: Recommendations (SOR) methodology for the development of evidence-based Clinical Practice Guidelines (CPG) as endorsed by the French National Cancer Institute. Methods: After reviewing the published studies on the topics between 1999 and 2007, a first version of the guidelines was based on the levels of evidence derived from analysis of the 38 out of 418 selected studies for VTE treatment and the 40 out of 175 selected studies for the CVCT management. The recommendations were classified as Standards or Options and then peer-reviewed by 65 independent experts. Detailed methodology is available at www.sor-cancer.fr Standards in cancer patients: The treatment of VTE should be based on Low Molecular Weight Heparins (LMWH) at curative doses for at least 3 months. During the initial treatment (up to 10 days), there are no specific requirements and all drugs approved (including LMWH, Unfractionnated Heparin (UFH), fondaparinux and danaparoid) may be used. Beyond the first 10 days, VTE treatment should be based on LMWH at curative doses for at least 3 and optimally for 6 months, as validated with the following drugs and dosage regimens: dalteparin 200 IU/kg once daily for one month, then 150 IU/kg once daily; enoxaparin 150 IU/kg once daily; and tinzaparin 175 IU/kg once daily. In case of: severe renal impairment, UFH should be used rapidly followed by Vitamins K Antaogonist (VKA) for at least 3 months; severe Pulmonary Embolism (hemodynamic failure), the indications and usages of thrombolytic drugs are the same as in non-cancer patients; absolute contra-indication to anticoagulation or VTE recurrence despite optimal anticoagulation, vena cava filters (VCF) should be considered; intracranial malignancies, VTE treatment is the same as in cancer patients with non-intracranial tumors. CVCT treatment relies on long term use of LMWH. In case of severe renal failure, UFH with early AVK must be used. Treatment is to be continued as long as the catheter is maintained. This can only be achieved if the catheter is functional, well positioned, not infected and if adapted anticoagulation has resumed the CVCT. If catheter withdrawal is necessary, there is no standard concerning the anticoagulation management. CVCT prophylaxis relies on positioning the catheter distal extremity at the “superior vena cava - right atrium” junction. Systematic CVCT anticoagulant prophylaxis is not recommended. Options: Treatment of VTE: If LMWH administration for 3 months is impossible, short-term use of LWMH followed by VKA for at least 3 months may be proposed. It is recommended to administer LMWH for 3 to 6 months; LMWH should be used according to the same curative dosage regimen as during the first 3 months. Beyond the first 6 months, the anticoagulant treatment should be continued as long as the cancer is active or treated. In the event of a first VTE episode secondary to a transient risk factor and if the cancer is not active nor treated, anticoagulation may be discontinued after 6 months. The choice between LMWH and VKA depends on their benefit-risk ratio (influenced by drug interactions, chemotherapy, invasive procedures, and general health status) and acceptability. If a VCF is considered, a retrievable VCF may be discussed. CVCT treatment: If another catheter has to be inserted, prior evaluation of the venous circulation by scanner or ultrasound examination is recommended. If prolonged use of LMWH is impossible, VKA can be proposed. In case of severe superior vena cava syndrome, fibrinolytics can be used in the absence of contra-indications. Treatment by LMWH can be stopped 6 weeks after catheter withdrawal in non active cancer or after 3 to 6 months of LMWH followed by VKA in the other cases. CVCT prophylaxis: Right side catheter insertion and vein localisation by ultrasonography are preferred. Conclusion: The French recommendations further support the 2006 Italian and the 2007 North American guidelines on VTE treatment in cancer patients and were extended to the use of VCF and treatment of patients with intracranial malignancies. In addition, we provide recommendations on CVCT treatment in cancer patients.