September 21, 2018
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NHLBI grant to fund research toward prevention of cancer-related venous thromboembolism

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Photo of Alok Khorana
Alok A. Khorana

A $4.7 million grant from the NHLBI will support a Cleveland Clinic-led research consortium’s effort to develop a better risk-prediction tool for cancer-associated venous thromboembolism.

The 5-year grant will fund research led by Keith R. McCrae, MD, professor of molecular medicine at Case Western Reserve University and staff physician in the department of hematology and oncology at Cleveland Clinic, and Alok A. Khorana, MD, professor of medicine at Cleveland Clinic Lerner College of Medicine.

Research sites for the project include Cleveland Clinic’s Taussig Cancer Institute and Lerner Research Institute, as well as Beth Israel Deaconess Medical Center at Harvard Medical School and University of Cincinnati.

“About 20% of [patients with cancer] develop blood clots, which can cause stroke, hospitalization and delays in treatment. In fact, cancer-associated thrombosis is the second leading cause of death [among] patients with cancer,” Khorana said in a press release. “This grant will help us address the challenge of identifying who will develop blood clots and enable us to treat them proactively with blood thinners to prevent this complication.”

HemOnc Today spoke with Khorana about the incidence and impact of cancer-associated VTE, the research this grant will fund, and how the results will help clinicians and researchers better determine which patients are at risk.

 

Question: Can you provide context about incidence of cancer-associated VTE , as well as its impact on morbidity and mortality?

Answer: Thromboembolism is prevalent among patients with cancer. One in five will get a blood clot at some point during their illness. The clots can be in different areas of the body; however, most will be in the venous system. There also is a smaller incidence of arterial events, which include stroke or myocardial infarction. The consequences of thrombosis for patients with cancer are substantial and can lead to hospitalization and ED visits. A lot of studies document a link between venous and arterial thromboembolism and risk for short- and long-term mortality. Thrombosis has been shown to be the second leading cause of death among individuals with cancer, trailing only the malignancy itself.

 

Q: What research will this grant fund?

A: It is important to identify who will develop thromboembolism because clots are highly preventable with low-doses of anticoagulants. However, prophylactic anticoagulation is not a strategy that we want to use for every patient. The majority will not get a clot, and exposing those patients to anticoagulants can lead to bleeding and other side effects. This grant supports novel approaches to predict risk for cancer-associated VTE. The currently utilized risk-prediction approach is the Khorana Score. Although this score has been validated multiple times and has a high negative predictive value, it does not have a high positive predictive value. We feel this tool can be improved upon with novel biomarker data and other approaches..

 

Q: How will the research be conducted?

A: There are a couple different components. One is a discovery phase to identify novel candidate biomarkers. We have preliminary data that include molecules involved in the contact activation pathway, as well as complement activation. Part of the grant will focus on identifying if these can predict cancer-associated VTE. The second aim is to identify circulating micro-RNA profiles predictive of thrombosis. In preliminary data, we have identified a couple micro-RNA profiles that are predictive of cancer-associated thrombosis, and we want to see if these can be used in a broader population to further stratify risk. In the validation phase, we will evaluate these candidate biomarkers in blood specimens obtained from several hundred patients with cancer who participate in ongoing clinical trials to see if these candidate biomarkers are truly predictive and can enhance risk-prediction tools.

 

Q: How might the results help clinicians or researchers better determine who is at risk for cancer-associated VTE?

A: By completion of this grant, we think we will be able to better identify patients with cancer at risk for venous thromboembolism and potentially arterial thromboembolism. If we are able to do that, then we can better target patients for prophylaxis using anticoagulants in prophylactic doses. – by Jennifer Southall

 

For more information:

Alok A. Khorana, MD, can be reached at Cleveland Clinic, 10201 Carnegie Ave., CA60, Cleveland, OH 44195; email: khorana@ccf.org.

Disclosure: Khorana reports no relevant financial disclosures.