Khorana Score Predicts Cancer Patients’ Thrombosis Risk

Results aid decision-making about anticoagulant therapy

Thrombosis and cancer are integrally linked. Patients with cancer carry a fourfold increase in thrombosis risk, with chemotherapy elevating the risk even higher.

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For the past eight years, Alok Khorana, MD, Director of the Gastrointestinal Malignancies Program at Cleveland Clinic’s Taussig Cancer Institute since April 2013, has been studying this link. In 2008, he published what has become a seminal paper in the field of thrombosis and cancer, detailing a risk score protocol that helps predict a cancer patient’s risk of venous thromboembolism (VTE).

The Khorana score, as it known, predicts thrombosis risk based on a collection of simple variables — type of cancer, body mass index (BMI) and complete blood count (platelet, leukocyte, hemoglobin).

“Not only is the score effective for assessing risk, but it is also easy to use because expensive tests are not required,” says Dr. Khorana. “It is data everyone already has for their patients.”

Each variable in the score is assigned a value. Elevated pre-chemotherapy platelet counts greater than 350,000/mcL, BMI of at least 35 kg/m2, and cancer types such as stomach and pancreas cancer each raise the risk, for example.

Cancer patients with a Khorana score of 3 or greater are at high risk for developing blood clots. “Our initial study of 4,000 patients also showed that patients who are at high risk of developing clots experience shorter progression-free survival and early mortality,” Dr. Khorana says..

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Studies confirm effectiveness

Today, nearly 10,000 patients in the United States and Europe have been part of clinical studies assessing the effectiveness of the Khorana score in predicting the risk of cancer-associated thrombosis. “Since our first study, multiple institutions have validated the score in predicting blood clot risk,” he says. “All of the studies show it works exceedingly well.”

In June 2013, the American Society of Clinical Oncology (ASCO) issued guidelines affirming the use of a slightly modified Khorana score as a well-established risk calculator for thromboembolism. Specifically, new ASCO guidelines recommend that patients with cancer be assessed for VTE risk at the time of chemotherapy initiation and periodically thereafter.

The guidelines also suggest that physicians consider using the score when deciding if VTE prophylaxis is an appropriate intervention for a particular patient. This is an important recommendation because several randomized clinical trials, including the Prophylaxis of Thromboembolism During Chemotherapy Trial (PROTECHT) and the SAVE-ONCO investigation, the largest thromboprophylaxis study ever conducted in cancer patients, have recently demonstrated that outpatient anti-coagulation prophylaxis is feasible, safe and effective.

But it remains unclear which cancer patients should be selected for VTE prophylaxis. The ASCO guidelines suggest that only those ambulatory cancer patients at high risk for VTE receive anti-coagulation therapy on a prophylactic basis.

New use: predicting mortality in cancer

The score’s main use is to assess risk of blood clots and to inform a recommendation for anticoagulation prophylaxis.

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“The new use of the score is that it is predictive of mortality,” explains Dr. Khorana. A European analysis of more than 1,500 patients with a variety of cancers determined that higher Khorana scores correlate with higher mortality rates independent of the presence of blood clots.

After two years of follow-up, patients with a Khorana score of 0 had a 27 percent mortality rate; those with a Khorana score of 3 or more had a 63 percent mortality rate, a fourfold higher mortality rate after adjustment compared with patients with a score of 0.

Validating results

This study based in Vienna, Austria, was performed in patients with several types of cancers. Dr. Khorana and others are conducting other investigations in specific cancer types to validate the score’s efficacy and usefulness in those patient populations.

Dr. Khorana’s research group has already performed two studies using the score in patients with gastrointestinal cancers. While the results are pending publication, Dr. Khorana explains that “when we look purely at colorectal cancer patients, who are the patients I treat personally, it appears highly effective in predicting mortality in that population.”