Oncology reviewsVenous thromboembolism in radiation therapy cancer patients: Findings from the RIETE registry
Introduction
Venous thromboembolism (VTE) represents a relevant cause of morbidity and mortality in patients with cancer. Population-based studies estimated that patients with active cancer are at a 4–6 fold higher risk to develop VTE than those without cancer (Heit et al., 2000, Khorana and Connolly, 2009). Besides the specific risk linked to cancer, receiving a treatment for cancer is recognized as an additional risk factor for VTE (Horsted et al., 2012). Recent surgery, immobility and the use of chemotherapy or hormonal therapy have been recognized as additional risk factors for VTE in patients with cancer (Prandoni et al., 2005, Seng et al., 2012), but the influence of radiation therapy (RT) has been less explored. In recent years, there has been some concern about the potential toxicity induced by radiation (Chargari et al., 2014, Darby et al., 2013), via cellular destruction and inflammatory prothrombotic processes caused by ionizing radiation (Goldin-Lang et al., 2007a, Goldin-Lang et al., 2007b).
RT may be initiated in early stages of cancer, when the risk of VTE is high (Blom et al., 2005), or as part of radical treatments for localized tumors, with or without chemotherapy. In addition, RT is a common palliative treatment in patients with advanced malignancies to control pain, treat unresectable cerebral tumors, brain metastases or medullar compression. The potential link between RT and VTE has been recently reported in case reports and small series of patients (Guy et al., 2015). As a consequence, there is growing evidence suggesting that RT may influence the outcome in cancer patients receiving anticoagulant therapy for VTE.
The RIETE (Registro Informatizado de Enfermedad TromboEmbólica) Registry is an ongoing, multicenter, international (Spain, Italy, France, Israel, Portugal, Germany, Switzerland, Czech Republic, Macedonia, Greece, Canada and Ecuador), observational registry of consecutive patients with acute symptomatic, objectively confirmed VTE. RIETE was initiated in Spain in 2001, and six years later the database was translated into English, with the aim to expand the Registry to other countries (Farge et al., 2015, Lecumberri et al., 2013, Muñoz-Torrero et al., 2011, Muriel et al., 2014, Nieto et al., 2010). The goal was to allow physicians worldwide to use the database to select the most appropriate therapy for their patients. The aim of the current study was to compare the clinical characteristics, treatment strategies and clinical outcome of cancer patients with VTE, according to the use of RT.
Section snippets
Patient entry criteria
Consecutive patients with symptomatic, acute deep venous thrombosis (DVT) or pulmonary embolism (PE) were enrolled in RIETE. DVT was objectively confirmed with ultrasonography or phleboscanner or contrast venography. Pulmonary embolism was confirmed by objective testing consisting of high probability ventilation/perfusion (V/Q) scan, intermediate V/Q scan with DVT, or positive contrast-enhanced, pulmonary embolism-protocol, helical chest computerized tomography.
Patients were excluded if they
Results
As of May 2015, 9284 patients with active cancer and VTE were enrolled in RIETE. Of these, 1202 (13%) were receiving RT. Patients on RT were 3 years younger and less likely to have renal insufficiency or recent surgery than those not receiving RT, but more likely to have thrombocytopenia, recent immobilization, use of estrogens, corticosteroids or non-steroidal anti-inflammatory drugs (Table 1). Among patients with PE, there were no differences in the proportion of those presenting with
Discussion
There is a lack of evidence in the literature to guide the optimal therapy (drugs, dose and even duration) for cancer patients with acute VTE receiving RT. Consequently, anticoagulation practice remains non-standardized and highly variable. Our findings, obtained from a large series of consecutive patients with active cancer and VTE, reveal that during the course of anticoagulant therapy patients receiving RT had an over two-fold higher risk for cerebral bleeding. This is important because a
Conflict of interest statement
The authors have no conflicts to declare
Acknowledgements
We express our gratitude to Sanofi Spain for supporting this Registry with an unrestricted educational grant. We also express our gratitude to Bayer Pharma AG for supporting this Registry. Bayer Pharma AG’s support was limited to the part of RIETE outside Spain which accounts for 22.49% of the total patients included in the RIETE Registry. We also thank the RIETE Registry Coordinating Center, S & H Medical Science Service, for their quality control data, logistic and administrative support and
References (33)
- et al.
Hemostatic radiotherapy in carcinoma of the uterine cervix
Int. J. Gynaecol. Obstet. Off. Organ Int. Fed. Gynaecol. Obstet.
(1995) - et al.
Cardiotoxicity research in breast cancer patients: past and future
Am. J. Cardiol.
(2014) - et al.
Ionizing radiation increases concentration of plasma von Willebrand factor in Cebus Apella Paraguayanus monkeys
Thromb. Res.
(1997) - et al.
Prevention of venous thromboembolism: american college of chest physicians evidence-based clinical practice guidelines (8th edition)
Chest
(2008) - et al.
Ionizing radiation induces upregulation of cellular procoagulability and tissue factor expression in human peripheral blood mononuclear cells
Thromb. Res.
(2007) - et al.
Radiation-induced carotid artery atherosclerosis
Radiother. Oncol. J. Eur. Soc. Ther. Radiol. Oncol.
(2014) - et al.
Endothelial activation with prothrombotic response in irradiated microvascular recipient veins
J. Plast. Reconstr. Aesthet. Surg. JPRAS
(2010) - et al.
Effects of age on the risk of dying from pulmonary embolism or bleeding during treatment of deep vein thrombosis
J. Vasc. Surg.
(2011) - et al.
Survival effects of inferior vena cava filter in patients with acute symptomatic venous thromboembolism and a significant bleeding risk
J. Am. Coll. Cardiol.
(2014) - et al.
Fatal bleeding in patients receiving anticoagulant therapy for venous thromboembolism: findings from the RIETE registry
J. Thromb. Haemost.
(2010)
Cancer and venous thromboembolism
Lancet Oncol.
Radiation-induced cardiovascular diseases: is the epidemiologic evidence compatible with the radiobiologic data? Int
J. Radiat. Oncol. Biol. Phys.
Mast cells and ionizing radiation induce a synergistic expression of inflammatory genes in endothelial cells by a mechanism involving p38(MAP kinase and (p65) NF-κB activation
Radiat. Res.
Malignancies, prothrombotic mutations, and the risk of venous thrombosis
JAMA
Increased deposition of von Willebrand factor in the rat heart after local ionizing irradiation
Strahlenther. Onkol. Organ Dtsch. Röntgenges. Al
Long-term activation of the pro-coagulant response after neoadjuvant chemoradiation and major cancer surgery
Br. J. Cancer
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A full list of the RIETE investigators is given in the Appendix A.