Lymphoma Testing

The Low Down on New Cancer Screening Tests

By Kim Freeman, DVM, DACVIM (Oncology)
Veterinary Cancer & Surgery Specialists
www.vcsspdx.com/

A screening test for early detection of cancer could be helpful if properly used. However, as with any test, it is important to understand how it works in order to understand the benefits and limitations. With the development of several new cancer screening tests on the market, it can be challenging to know how and when to use them. I will highlight two of them due to their accessibility.

Idexx Cancer Dx for canine lymphoma

According to Idexx, the Cancer Dx is “a revolutionary new canine cancer diagnostic test available to help you detect lymphoma earlier”. Please understand that this means the goal of this test is to serve as a SCREENING tool. This is NOT a test to confirm lymphoma in a patient with enlarged lymph nodes. It does not replace cytology or histopathology. If you speak with an oncologist that works for Idexx, they will tell you the same thing. This is a test to screen “sick pets” and “at-risk” breeds of dogs. According to Idexx, that means dogs over 7 years of age or high risk breeds that are over 4 years old.

Case selection is important. Testing every patient that walks in the clinic regardless of their age or breed will significantly influence the results. If you run the test on too many patients, you will start to increase the number of FALSE POSITIVES that you see in your patient population. This is called a Type I error. False positives are horrifying. A false positive is when the results incorrectly indicate the presence of disease when it is actually absent. Suddenly, the client is panicking. You are panicking. If the dog has a normal physical, you will have to recommend a barrage of diagnostic tests to look for this cancer. This can be stressful and expensive. Or wait a grueling 2 months to repeat this test to confirm it is real?! You also need to be prepared to have this conversation with the client, preferably BEFORE you run the test, rather than being on your heels in the aftermath of a false positive.

In a set of 2635 Cancer Dx tests run by Idexx, 17 dogs (0.6%) had results consistent with lymphoma. While lymphoma is one of the most common cancers in dogs, careful case selection is also very important because it impacts the proportion of all tested individuals who actually have the disease (population prevalence). If case selection is poor (young dogs; asymptomatic dogs that are not ‘at risk’ breeds), then the more samples that are run, the more likely we are to see false positives. For all of you statistics nerds, you already know that indiscriminate testing actually lowers the positive predictive value because of the low prevalence of disease in the whole population.

The Idexx Cancer Dx has a 79% sensitivity rate and 99% specificity rate. The sensitivity of the test is its ability to correctly identify individuals with lymphoma (true positives). Remember, that means 21% of the time the Idexx Cancer Dx test result is negative for dogs that actually have lymphoma. The good news is that the specificity is high, which means that if the test is negative, then there is a 99% chance the test is correct!

Another important question we must address as a clinical community is what to do with true positives without grossly detectable disease or clinical signs. This test has been shown to detect disease up to 4 months prior to clinical signs or obvious disease presents. That means there is a chance that you will have to continue to monitor and repeat diagnostics in some patients. Understanding the utility and significance of early detection in otherwise healthy patients is still challenging to know how to use in day to day practice. We don’t know if early detection can improve outcome… yet.

Of the dogs that tested positive with the Cancer Dx test, when additional diagnostics were done to confirm the diagnosis, there were a range of disorders detected including: lymphoma, acute and chronic leukemias, other lymphoproliferative neoplasias, myeloma related disorders, a suspect mast cell tumor, and extramedullary plasmacytoma. For the dogs with lymphoma or leukemia, this test DOES NOT tell you the grade of disease (acute vs chronic). It does not differentiate between high grade and low grade or indolent lymphoma. The treatment and prognoses for these conditions widely vary. This is why I do not know of an oncologist that would (or should) treat a dog prior to onset of clinical disease and without a cytologic or histologic diagnosis.

One side bonus is that the Cancer Dx test can provide a phenotype for lymphoma in 56% of samples tested. It will pick up 65% of B cell phenotypes and 8.7% T cell phenotypes. However it is not as proficient at this as PARR or flow cytometry, and it cannot differentiate between subtypes of B and T-cell lymphoma (including indolent forms like T-zone) in the way other tools like cytology, flow cytometry and histopathology can.

In a clinically ill dog, I would argue that cytology is fundamentally a better test to diagnose lymphoma and truly understand what type of cancer you are dealing with. Not all lymphomas are created equal – a conversation for another day.

Currently, there are no peer reviewed publications on the data from Idexx about this test. Idexx has not disclosed the technology or specific molecular markers that they are using to run this test. We have no idea how it works.

Antech Element i+ Nu. Q

Antech’s in-clinic analyzer now allows veterinarians to run a point of care Nu.Q® test. This test rapidly detects and quantifies nucleosomes in canine plasma. An elevated nucleosome concentration can serve as a biomarker to raise suspicion for certain types of cancer, especially lymphoma and hemangiosarcoma. This test is looking for active disease in sick or healthy patients. However, again it is NOT a confirmatory test for cancer. If a test is positive, additional diagnostics must be done to obtain a diagnosis. And, negative test also does not mean a pet does not have cancer. Non-cancerous conditions can have a positive Nu. Q result including but not limited to: immune-mediated disease, sepsis, trauma, and other inflammatory conditions. This test cannot differentiate between inflammatory diseases and cancer. While this test does not need to be run on a fasted patient, an unfasted sample can lead to false positive results and the test should be re-run following an 8 hour fast.

Without understanding the limitations of this test, it may be easy for some clinicians to mistake a positive result for a true diagnosis of severe disease. This is especially important when families are considering irreversible decisions like euthanasia based on the results of a single test. Please do not use any screening test to make a decision about euthanasia.

There are a lot of new tools out there, and when it comes to early cancer screening tests, there are an abundance of factors to consider before reaching for one. If you are wondering whether to implement one of these tests or a related diagnostic tool in your practice, please reach out to the developer and to your local specialists to gather more information and arm yourself with the facts to help your clinic and your clients make a fully informed decision. The oncologists at Veterinary Cancer & Surgery Specialists, Drs. Kim Freeman, Susie Kang, and Ross Luethcke, are always happy to respond to questions via phone or email (503-908-1492 oг info@vcsspdx.com).