The Khorana Score 10 Years Later

The future of VTE risk prediction in cancer

Since its introduction in 2008, the Khorana Score has helped clinicians worldwide calculate the risk of venous thromboembolism for an individual cancer patient.

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The Khorana Score uses readily available clinical information like the type of cancer, the complete blood count and a person’s body mass index. Part of its advantage lies in its ease of use.

Since Alok Khorana, MD, Vice Chair for Clinical Services at Cleveland Clinic Cancer Center, and colleagues introduced this tool a decade ago, it has been validated multiple times in different countries and incorporated into a number of society guidelines over the years. “At Cleveland Clinic, we’ve incorporated the score into the electronic medical record for early detection of potential clots,” says Dr. Khorana.

Though subsequent investigators dubbed it the ‘Khorana Score,’ Dr. Khorana credits its utility and longevity to the team of colleagues that helped develop this risk stratification and prediction tool including Charles W. Francis, MD, Gary H. Lyman, MD, MPH, Nicole M. Kuderer, MD, and Eva Culakova, PhD.

Updating the score

“Despite the score’s persistent relevance over the last decade,” says Dr. Khorana, “it is time to find new biomarkers to refine the score and increase its accuracy.”

Part of the tool’s popularity is its simplicity, so Dr. Khorana and team are proceeding carefully with updates to avoid adding unnecessary complexity. They address this balancing act between precision and practicality in an editorial published in The Lancet Haematology.

The team also wants to ensure that any update provides a very high positive predictive value – 70 percent or greater.

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Simplicity versus complexity

For example, in the same issue of The Lancet Haematology, a new VTE prediction model is proposed based on two factors: tumor site risk (low or intermediate versus high or very high) and D-dimer concentrations.

D-dimer assays are widely used in hospitals for other indications. “The test itself is not hard to order, and you can get results very quickly,” says Dr. Khorana. “However, D-dimers need to be ordered in most cases — it is not a test routinely collected for people with cancer. So it’s an extra step, which can be a challenge because you’re asking oncologists to add more to their workflow.”

This raises the question that if the new tool is more accurate — is it going to be more widely used? Dr. Khorana and team seek to strike a careful balancing act between clinical applicability and improved prediction.

Over the past decade, some investigators have suggested adapting the Khorana Score to specific cancer types. However, the score is only designed to look at a general cancer population. “We could certainly develop a better score for each type of cancer, but we could end up with 25 different scores that no one uses,” says Dr. Khorana.

Multiple applications over time

In a report in the journal Thrombosis Research, Dr. Khorana reviews more details of how clinicians and researchers have used the Khorana Score over the past decade. Initially, research was focused on discovering risk factors for VTE in people receiving outpatient chemotherapy. This research led to an appreciation that VTE is multifactorial and that identifying risk factors was insufficient. Thus, the team developed a risk stratification score.

Expanded uses for the score have emerged over the past decade. Examples include predicting VTE risk in inpatient cancer settings, designing subsequent thromboprophylaxis studies, targeting education about VTE to high-risk individuals and identifying a subgroup of cancer patients at risk for early mortality.

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Dr. Khorana also addresses the score’s possible future in this report. A potential adaption of the tool would involve identifying innovative biomarkers that contribute to precision medicine. “We would also like to address the knowledge gap regarding the risk of bleeding in patients treated with thromboprophylaxis, as well as learn more about how arterial events can lead to stroke and myocardial infarction in a cancer population,” says Dr. Khorana. 

Future studies

Dr. Khorana and team are currently studying whether the Khorana Score can be used to identify patients who might benefit from prophylaxis. Dr. Khorana is co-leading a trial with approximately 800 patients worldwide, assigning patients with a higher risk score to prophylaxis with an oral anticoagulant and comparing them with a placebo group.

They are also investigating genomics in lung cancer patients to try to improve risk prediction as well as evaluating circulating small RNA as a biomarker. Dr. Khorana just received a five-year NIH grant from the National Heart, Lung, and Blood Institute to assess these plasma biomarkers to improve cancer risk prediction. Keith McCrae, MD, staff in Hematology and Medical Oncology, is co-principal investigator on this grant.

Not only would a plasma biomarker for cancer be less invasive than taking tumor tissue for a biopsy, it could also be easier for monitoring treating response or progression over time.

The first decade of the Khorana score brought clinicians an easy to use prediction tool to assess their patients’ risk of VTE. With ongoing refinements, conversations and research, the tool should continue to help clinicians help their patients for years to come.