Oncology reviews
Venous thromboembolism in radiation therapy cancer patients: Findings from the RIETE registry

https://doi.org/10.1016/j.critrevonc.2017.03.006Get rights and content

Highlights

  • 13% Of patients with cancer-associated thrombosis received a radiotherapy treatment.

  • A higher rate of pulmonary embolism recurrence was observed in radiotherapy group.

  • A higher rate of cerebral bleeding was observed in radiotherapy group.

Abstract

Background

Cancer patients are at high risk of venous thromboembolism, particularly during cancer treatment. Conversely to chemotherapy, data on the epidemiology and clinical features of venous thromboembolism during radiation therapy are scarce. There is lack of evidence on the influence of radiation therapy (RT) on outcome in cancer patients with acute venous thromboembolism (VTE).

Methods

We used the RIETE (Registro Informatizado de Enfermedad ThromboEmbolica) database to assess the clinical characteristics and outcome of prospectively-collected consecutive patients with cancer-associated thrombosis occurred during the course of radiation therapy for cancer. Death, venous thromboembolism recurrences and major bleeding rates during long-term follow-up according to cancer site and treatment were compared

Results

9284 Patients with active cancer and VTE were enrolled in RIETE: 4605 with pulmonary embolism (PE) and 4679 with deep vein thrombosis (DVT). In all, 1202 (13%) were receiving RT. This last sub-population had a higher rate of PE recurrences and a similar rate of DVT recurrences or major bleeding than those not receiving RT. Patients on RT had a higher rate of cerebral bleeding.

Conclusions

In this cohort of cancer patients with VTE, a significant proportion of them received RT before VTE, the latter experienced a higher risk of cerebral bleeding.

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

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    1

    A full list of the RIETE investigators is given in the Appendix A.

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