Q&A: Understanding sensitivity and specificity in canine lymphoma liquid biopsy

Liquid biopsy, which looks for markers of cancer in a blood or fluid sample, is bringing lymphoma-specific screening into canine wellness care. In the first episode of Cliff’s Edge, dvm360’s new veterinary oncology podcast, Pamela D. Jones, DVM, DACVIM (Oncology), DACVR (Radiation Oncology), spoke with host Craig A. Clifford, DVM, MS, DACVIM (Oncology), about the company’s Cancer Dx test for canine lymphoma.

In this first of 2 Q&As drawn from the episode, Jones explains how the test works, what its reported sensitivity and specificity mean for screening, common causes of false results, and how to interpret a T-cell phenotype. Performance figures are as described by Jones on behalf of IDEXX.

Editor's note: This dvm360 Q&A has been edited and consolidated from a verbal interview to better fit a written format while retaining the substance of the original conversation.

Craig A. Clifford, DVM, MS, DACVIM (Oncology): What is the IDEXX Cancer Dx test, and how does it work?

Pamela D. Jones, DVM, DACVIM (Oncology), DACVR (Radiation Oncology): For me as an oncologist, one of the exciting things about it is we’re really moving into cancer screening as a diagnostic tool. Previously, from private practice, our cancer screening generally involves physical exam, blood work, maybe chest x-rays, but there’s nothing specific. Cancer Dx is part of the new era, [as] I like to call it, and that is liquid biopsy. That’s where we take a blood sample or a sample of fluid from the body, and we look for markers in that sample of cancer somewhere within the body. This particular test, Cancer Dx, is a multiomics platform. It’s a combination of an immunoassay and molecular diagnostics for lymphoma in the body.

Clifford: Why does lymphoma lend itself to liquid biopsy?

Jones: Even [with] previous liquid biopsy tests that have come out in veterinary and human medicine, we find that systemic cancers like lymphoma are more detectable on this kind of test because they’re systemic; they’re in contact with the blood constantly, being part of the lymph system. Whereas solid tumors are a little bit tougher to detect with liquid biopsy because they’re not always completely exposed to blood and out there systemically.

Clifford: What does the test’s specificity mean for veterinarians?

Jones: I know none of us really appreciate stats, but some of us do. The biggest thing that I always say is that we push the specificity of this test very high. The specificity is 99%. When I think about specificity, I always take a step back and go, Okay, specificity, to me, identifies correctly those patients that do not have the disease as negative. The way to think about it when you’re talking cancer screening is that the risk of false positives is low. We push that as far as we can go. I wish it was 100, but it’s not. We’re always going to have a risk of false positives.

Clifford: What about sensitivity? Does a 79% sensitivity mean the test misses cases?

Jones: The sensitivity of the test is 79%. When I think about sensitivity, I think about [how] the test is going to correctly identify those that have the disease as positive. So 79%, and I always flip it right on its head. I go, Okay, 79% of the time. That means 1 out of 5 times, the test is not going to identify a patient that has the disease. And people immediately go, “Wow, 1 out of 5 times it’s going to miss it.” But I don’t worry about that, because we’re veterinarians and we’re never walking into any disease syndrome with 1 diagnostic test. We’re using our physical exam, we’re using our clinical history, we’re using all the things we know to say this patient has this disease or does not have the disease, no matter how positive a test is.

Clifford: Why would the test return a false-negative result?

Jones: Why would it come up false negative? There’s probably a lot of different reasons. When I think of lymphoma, we always try and put it into 1 disease, but the truth is, some lymphomas may not secrete the marker we’re picking up. Some lymphomas may not secrete it in high enough numbers, or maybe it’s a variable secretion depending on when the tumor’s letting [it] off from the cancer cells themselves. So there’s a lot of reasons why it may not pick up that particular marker.

You can listen to the full episode here!