Accepted Article
Received Date : 14-Mar-2014 Accept Date: 01-Sep-2014 Article type : Recommendations and Guidelines
Prevention of VTE in Cancer Outpatients: guidance from the SSC of the ISTH
Alok A. Khorana1, Hans-Martin Otten2, Jeffrey I. Zwicker3, Gregory C. Connolly4, Dominique Farge-Bancel5 and Ingrid Pabinger6, for the Subcommittee on Haemostasis and Malignancy
1
Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
2
Department of Internal Medicine, Slotervaart Hospital, Amsterdam, Netherlands
3
Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard
Medical School, Boston, Massachussetts, USA 4
James P. Wilmot Cancer Center and Department of Medicine, University of Rochester,
Rochester, New York, USA
5
Assistance Publique-Hôpitaux de Paris, Internal Medicine and Vascular Disease Unit, Saint-
Louis Hospital; INSERM U 796, Paris 7 Diderot University, France 6
Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical
University of Vienna, Austria
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an 'Accepted Article', doi: 10.1111/jth.12725 This article is protected by copyright. All rights reserved.
Accepted Article
Corresponding author: Alok A. Khorana, M.D., F.A.C.P. 9500 Euclid Ave, R35
Cleveland, OH 44195 USA Email: [email protected]
Key words: venous thromboembolism, prevention, risk factors, cancer, multiple myeloma SCOPE Venous thromboembolism (VTE) is highly prevalent in patients with active malignancy,
although risk varies widely [1, 2]. A majority of cancer-associated VTE occurs in the outpatient setting and multiple randomized controlled trials (RCTs) have focused on outpatient thromboprophylaxis [3]. However, event rates in these RCTs have varied widely and there is no consensus on how to select patients for prophylaxis. This statement provides guidance on thromboprophylaxis for cancer outpatients. The format of ISTH guidance statements has previously been described [4]. Briefly, this
guidance outlines factors that may influence decision-making in individual patients. It is not based on a systematic review; such guidelines have recently been published [5, 6]. Definitions 1. Cancer outpatient. Patients with malignancy receiving outpatient systemic anti-neoplastic therapy. Patients in remission, on hormonal therapy alone, hospitalized or post-surgical are excluded. 2. Thromboprophylaxis. Use of anticoagulant and/or anti-platelet agents but not mechanical prophylaxis or vena cava filters.
This article is protected by copyright. All rights reserved.
Accepted Article
Selection of Patients Risk assessment is key, given wide variation in event rates in RCTs. Approaches to
identifying risk include: a) cancer site, b) biomarkers, or c) a validated risk assessment tool. The majority of RCTs have used site of cancer as the main criterion for assigning risk with additional risk factors such as advanced disease and chemotherapy. PROTECHT and SAVE-ONCO included patients with selected solid tumors [7, 8], PRODIGE focused on patients with malignant glioma [9] and FRAGEM and CONKO-004 focused on patients with pancreas cancer [10-12]. Two studies evaluated thromboprophylaxis in myeloma patients receiving thalidomide or lenalidomide-based regimens [13, 14]. Microtec selected patients based on primary site and biomarker-based risk stratification [15]. The development of a risk assessment tool to predict cancer-associated VTE proceeded
separately from trials of prophylaxis. The Risk Score developed by Khorana et al (“Khorana Score”) includes a combination of easily available variables (Table 1) [16]. It was externally validated in a prospective population by the Vienna CATS group and multiple others [17, 18] and meets criteria for a Level 1 clinical decision rule [19]. Although a majority of RCTs showed adequate relative risk reduction of VTE, event rates
in studies with broad populations were quite low. For instance, in PROTECHT, 2% of nadroparin-treated patients trea and 3.9% of placebo-treated patients had thromboembolism (single-sided P=0.02) [8]. In contrast, in FRAGEM which focused on pancreas cancer, VTE during treatment fell from 23% to 3.4% (p = 0.002), with a risk ratio of 0.145 [95% CI (0.0350.612)] [10]. [number needed to treat (NNT) = 6 ]. Although none of the studies demonstrated a
This article is protected by copyright. All rights reserved.
Accepted Article
survival benefit, in FRAGEM, lethal VTE at
Received Date : 14-Mar-2014 Accept Date: 01-Sep-2014 Article type : Recommendations and Guidelines
Prevention of VTE in Cancer Outpatients: guidance from the SSC of the ISTH
Alok A. Khorana1, Hans-Martin Otten2, Jeffrey I. Zwicker3, Gregory C. Connolly4, Dominique Farge-Bancel5 and Ingrid Pabinger6, for the Subcommittee on Haemostasis and Malignancy
1
Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
2
Department of Internal Medicine, Slotervaart Hospital, Amsterdam, Netherlands
3
Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard
Medical School, Boston, Massachussetts, USA 4
James P. Wilmot Cancer Center and Department of Medicine, University of Rochester,
Rochester, New York, USA
5
Assistance Publique-Hôpitaux de Paris, Internal Medicine and Vascular Disease Unit, Saint-
Louis Hospital; INSERM U 796, Paris 7 Diderot University, France 6
Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical
University of Vienna, Austria
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an 'Accepted Article', doi: 10.1111/jth.12725 This article is protected by copyright. All rights reserved.
Accepted Article
Corresponding author: Alok A. Khorana, M.D., F.A.C.P. 9500 Euclid Ave, R35
Cleveland, OH 44195 USA Email: [email protected]
Key words: venous thromboembolism, prevention, risk factors, cancer, multiple myeloma SCOPE Venous thromboembolism (VTE) is highly prevalent in patients with active malignancy,
although risk varies widely [1, 2]. A majority of cancer-associated VTE occurs in the outpatient setting and multiple randomized controlled trials (RCTs) have focused on outpatient thromboprophylaxis [3]. However, event rates in these RCTs have varied widely and there is no consensus on how to select patients for prophylaxis. This statement provides guidance on thromboprophylaxis for cancer outpatients. The format of ISTH guidance statements has previously been described [4]. Briefly, this
guidance outlines factors that may influence decision-making in individual patients. It is not based on a systematic review; such guidelines have recently been published [5, 6]. Definitions 1. Cancer outpatient. Patients with malignancy receiving outpatient systemic anti-neoplastic therapy. Patients in remission, on hormonal therapy alone, hospitalized or post-surgical are excluded. 2. Thromboprophylaxis. Use of anticoagulant and/or anti-platelet agents but not mechanical prophylaxis or vena cava filters.
This article is protected by copyright. All rights reserved.
Accepted Article
Selection of Patients Risk assessment is key, given wide variation in event rates in RCTs. Approaches to
identifying risk include: a) cancer site, b) biomarkers, or c) a validated risk assessment tool. The majority of RCTs have used site of cancer as the main criterion for assigning risk with additional risk factors such as advanced disease and chemotherapy. PROTECHT and SAVE-ONCO included patients with selected solid tumors [7, 8], PRODIGE focused on patients with malignant glioma [9] and FRAGEM and CONKO-004 focused on patients with pancreas cancer [10-12]. Two studies evaluated thromboprophylaxis in myeloma patients receiving thalidomide or lenalidomide-based regimens [13, 14]. Microtec selected patients based on primary site and biomarker-based risk stratification [15]. The development of a risk assessment tool to predict cancer-associated VTE proceeded
separately from trials of prophylaxis. The Risk Score developed by Khorana et al (“Khorana Score”) includes a combination of easily available variables (Table 1) [16]. It was externally validated in a prospective population by the Vienna CATS group and multiple others [17, 18] and meets criteria for a Level 1 clinical decision rule [19]. Although a majority of RCTs showed adequate relative risk reduction of VTE, event rates
in studies with broad populations were quite low. For instance, in PROTECHT, 2% of nadroparin-treated patients trea and 3.9% of placebo-treated patients had thromboembolism (single-sided P=0.02) [8]. In contrast, in FRAGEM which focused on pancreas cancer, VTE during treatment fell from 23% to 3.4% (p = 0.002), with a risk ratio of 0.145 [95% CI (0.0350.612)] [10]. [number needed to treat (NNT) = 6 ]. Although none of the studies demonstrated a
This article is protected by copyright. All rights reserved.
Accepted Article
survival benefit, in FRAGEM, lethal VTE at
