New Take on an Old Problem: Tackling VTE With Biomarkers, Risk Models, and Novel Drugs

Marijke Vroomen Durning, RN
Published: Wednesday, Mar 01, 2017
Alok Khorana, MD

Alok Khorana, MD

Despite advances in the oncology field, venous thromboembolism (VTE) remains a significant problem for patients with cancer. VTE, manifesting as deep vein thrombosis and pulmonary embolism (PE), is the second-leading cause of death among patients with cancer, after cancer itself.1 It can also cause significant delays in treatment, and affect short- and long-term survival.

Although VTE is not a new problem in oncology, it is poised to become a more pressing one. The overall incidence of VTE among US adults is projected to double by 2050, and cancer is among the comorbidities significantly associated with its prevalence.2 The reasons that cancer increases the risk of VTE appear to be related to the manner in which a malignancy affects at least 1 of 3 aspects of the Virchow triad for the formation of VTE: stasis (eg, extended bed4 rest; blockage of blood flow caused by the tumor), vessel damage (eg, tumor invasion; introduction of devices such as central catheters), and hypercoagulability. Genetics also plays a role in VTE, as it does in some cancers.3

VTE among patients with cancer was first reported in 1823 by Jean Baptist Bouillaud and again in 1865 by Armand Trousseau. Ironically, Trousseau died in 1867 of VTE, possibly related to gastric cancer.5

In recent years, efforts to understand the underlying causes of VTE have focused on identifying biomarkers and creating risk stratification models to help predict which patients may develop VTEs and, thus, which individuals would benefit from prophylaxis. In October 2016, the International Initiative on Thrombosis and Cancer (ITAC) published the latest set of guidelines on VTE that include a detailed analysis of clinical trial evidence regarding novel oral agents.6

New oral anticoagulants have emerged as an attractive potential alternative for patients with cancer who develop VTE and their efficacy and safety are being investigated currently. Some experts, however, believe that clinicians are underusing current tools for managing VTE; therefore, educating patients, families, and providers about the signs and symptoms of VTE is of paramount importance since their awareness can save lives.

Defining VTE Risk Factors

Patients with cancer and those who have had previous VTE are among the highest risk groups for VTE. And, although all patients with cancer are at some risk of developing VTE, some cancers carry a higher risk (Table).

“Which kind of cancer they have is one of the most important factors. Patients with hematologic malignancies, like lymphoma; lung cancer; gastrointestinal (GI) cancer, especially of the stomach and pancreas; genitourinary cancer (GU) cancer, although not prostate cancer as much as the other GU cancers, kidney cancer; and gynecologic cancers have the highest risk,” said Mary Cushman, MD, a spokesperson for the American Society of Hematology (ASH) in an interview with OncologyLive.® She is a hematologist who is medical director of the Thrombosis and Hemostasis Program at the University of Vermont Medical Center, and professor at the university’s Larner College of Medicine.®

The estimated incidence of VTE in oncology is about 15% but, according to Rachel P. Rosovsky, MD, a hematologist at Massachusetts General Hospital and director of the Education Committee for the National Pulmonary Embolism Response Team (PERT) Consortium, it can range anywhere from 4% to 30%. Consistent numbers are difficult to determine because different studies investigating the relationship between cancer and VTE have used different parameters.

In addition to the risk from cancer, once a patient with cancer has had a VTE, he or she is at increased risk of having another, with more serious consequences. “Cancer patients with VTE are 2 to 3 times more likely to have recurrent VTE than noncancer patients with VTE and are 2 to 6 times more likely to have hemorrhagic complications,” Rosovsky explained in an interview.

“In addition to the cancer in and of itself, having advanced or metastatic disease places patients at a higher risk of developing VTE,” Rosovsky said. A large retrospective study in the Netherlands that looked at 66,329 patients found that patients with distant metastases had a 1.9-fold increased risk of VTE compared with patients without metastases. 7 “Cancer patients with VTE are also more likely to have shorter survivals,” Rosovsky pointed out. A Danish study showed that patients with cancer who developed VTE had a 1-year survival of 12% compared with 36% in patients with cancer without VTE. 8

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