Quality of Life in Cancer Patients Undergoing Anticoagulant Treatment for Venous Thromboembolism: The Quavitec Study
Authors: Farge Dominique , Falvo Nicolas , Resche-Rigon Matthieu , Berremili Toufek , Couturaud Francis , Bensaoula Okba , Védrine Lionel , Bonnet Isabelle , Péré-Vergé Denis , Coudurier Marie , Li Veronique , Cajfinger Francis 
Published: October 2019

Abstract
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<0.0001) and 8.3 [-8.3;33] in the EORTC global Health status/QoL score (p<0.0001), with no change in VeinsQoL. Logistic regression identified the pattern of change in QoL in the first three months of anticoagulation as a strong predictor of QoL scores at the M6 follow-up (MOS SF-36, p<0.0001; EORTC, p<0.0001; veinesQoL, p<0.0001). Tumor histology (p=0.005), CVC (p=0.024), absence of acute infection (p=0.034), and being ambulatory as opposed to bedridden (p=0.045), were additional predictive factors in the MOS SF-36.
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.