Can the new test be trusted?

February 17, 2023 – In January 2022, Anthony Arenz, 51, of Mesa, AZ, breathed a sigh of relief.

It blood test for which it is shown 50 types of cancer – known as The Galleri test – did not detect any positive signs.

It will be welcome news for everyone, but especially for firefighters, whose job increases the risk of developing cancer by 9%. 14% greater risk dying from it than the average person. The Mesa unit had already lost two soldiers cancer in the previous 3 years. Both were more than a decade younger than Arenz.

But when the city of Mesa offered more free screenings, including full-body MRIs to firefighters in their 50s, Arenz initially shrugged it off. With Galerie’s negative test in hand, he didn’t want to spend any more time dwelling on it.

However, he began to feel a creeping guilt that he had missed a test that many of his fellow victims had not been offered. He tried to calm his anxiety with research. A glance at the company’s website did not give him peace. According to Grail Bio, maker of the Galleri test, a “No cancer signal detected” result does not rule out cancer.

Arenz ordered his free MRI.

The results left him with severe, stage I kidney cancer. Galleri had missed the test.

Arenz received his free Galleri test a cancer screening program funded by the City of Mesa at the Winsor Cancer Center in Scottsdale. Led by Vershali Shukla, a radiation oncologist and co-owner of Vincere, the program screens first responders in more than 10 Arizona cities at no cost to them.

Vincere started using Galleri shortly after the consumer test launched in June 2021. Since then, the first responder program has become the largest commercial user of the test in North America.

But Galleri’s ability to detect cancer and, perhaps more importantly, the consequences of false positives, have been under scrutiny since the test began. Galleri, which has not yet been approved by the FDA, is still so new that few know what false results actually look like and how common they can be.

“Okay” but “not ready yet”

After conducting the test on nearly 2,000 first responders, Shukla can offer some insight into the true value of the test in high-risk populations.

“Cancer screening is a very difficult problem,” he says. And “Honestly, the tests are good, but not ready yet [for wider use]”.

Arenz wasn’t the only firefighter who got a surprise after passing Galleri’s test.

In nearby Phoenix, Mike Curtis, 51, knew his cancer risk was high, but he wasn’t too worried. Curtis had been fighting fires since he was 17, and his father, also a firefighter, died of cancer at age 58.

He had taken Vincere Cancer Center out of the all-free screening service since the program started in late 2018, well before Shukla started using Galleri in 2021. His last lung scan was clear. But he did the Galleri test just to stay alert.

His result was a shock. The test revealed signs of cancer.

Curtis decided not to tell anyone, not even his wife. He would bear the bad news alone until he was sure.

Shukla, however, immediately doubted the results of the blood tests. He rushed to do some further tests. A week later, and after a scan of Curtis’ abdomen and pelvis, her hump was confirmed. Gallery’s test was wrong, Curtis did not have cancer.

The price of his peace of mind. Extensive work at a price of $4,000. Fortunately, the bill was covered by the screening program.

Overall, in just 18 months of using the blood test, Shukla has encountered only one other false positive out of nearly 2,000 Galleri results.

He also detected two positive cancer signals with Galleri, which were confirmed by further tests. One was chordoma, a rare type of bone cancer, and the other was squamous cell carcinoma of the head and neck. Galleri caught them both too early, in time for treatment.

But for Shukla, the false negatives were particularly “scary”. Arenz was just one of 28 cancers that missed the blood test. And since 500 negative tests have yet to be validated, the 28 false negatives may be an underestimate.

In his experience, a binary test result—a simple positive or negative cancer signal—is an oversimplification of risk, he says. It “gives a false impression that you do or do not have cancer” when the test itself is inconclusive.

Whitney Jones, MD, Grail’s senior medical director, agrees that the test isn’t meant to stand alone in cancer detection. Galleri’s goal is to “complement other exhibitions, not replace them,” he says.

According to Galleri’s data and analysis of Shukla’s experience, the test’s specificity exceeded 99%. This means that the test successfully reduces false positives.

However, the sensitivity of the test was much lower. Shukla’s data measured a sensitivity of 6.7% among first responders. That means the test misses about 93 out of every 100 cancers. Agreed The latest Grail data In more than 6,300 people over the age of 50, the sensitivity of the test was 29%.

Specificity and sensitivity are measurements used to validate a test and demonstrate confidence in its ability to detect a target disease. A test with high specificity can correctly identify patients without the condition, while a test with high sensitivity can correctly identify patients who do have the condition. But there are tradeoffs between sensitivity and specificity. One value increases at the expense of the other.

It’s normal for a cancer screening test to prioritize specificity, says Aparna Parikh, MD, an oncologist at Massachusetts General Hospital Cancer Center in Boston. In a test like Galleri, which is designed to be used with other screening tests, “at least we see good specificity, which is important because we don’t want false positives where the downstream effect on the patient can be high. “

Overall, Jones says, Grail Bio’s goal is to create a test that’s sensitive enough to catch the most dangerous cancers without flooding the healthcare system with false positives. In addition, he says, sensitivity varies by cancer type and tends to be lower for cancers that already have other screening tests available, as well as for earlier-stage disease.

But Galleri’s sensitivity values ​​are “a little scary,” said Ji-Hyun Lee, MD, PhD, director of quantitative sciences at the University of Florida Health Cancer Center. Lee, who is not affiliated with Grail, reviewed the company’s publicly available data as well as Shukla’s data for WebMD.

Although there is no definitive threshold for sensitivity, miss rates of up to 93% and 71% “give little confidence [accuracy of the] test,” Lee says.

Positive and negative predictive values, however, are more clinically relevant screening test criteria. These numbers indicate how likely the patient’s results are to be true, and therefore how worried they should be about a positive result and how much they should trust a negative result.

At First Responders, Shukla found that only half of Galleri’s positive tests were confirmed cancer cases. And Grail data analysis was discovered Only 38% of positive Galleri tests – 35 out of 92 people have been diagnosed with cancer.

In the general population, if only 38% of Galleri positives actually have cancer, the test “isn’t very useful for making a decision for the patient or providers,” Lee says.

Galleri can also be a costly prospect for patients, regardless of outcome, says Electra Pasquet, PhD, an epidemiologist and cancer screening expert at Ohio State University. A positive Galleri test requires a cascade of further diagnostic tests with no promise of payer coverage. For a negative result, Galleri recommends that the patient be screened again in a year, at an annual cost of $950 plus any follow-up tests when Galleri picks something up.

“If a provider wants to offer the Galleri test, all of those things, I think, have to be very clear,” Pasquet says.

After Galleri’s negative test, Arenz’s cancer didn’t slip through the cracks as he received other advanced imaging for free. But whether all doctors will go to such lengths to replicate Galleri’s results, even with negative patients, is unknown.

A negative result can give patients “a huge false sense of security,” Shukla says. And if the test is positive, the treatment is not straightforward, he says. Chasing cancer, especially one that isn’t really there, can be nerve-wracking and expensive.

So the question is: Why does Galleri test at all if it requires so much validation?

Parikh says a high-risk population like firefighters is ideal for Galleri and other liquid biopsy tests. But, he says, if it were to be used more widely in the general population, he would be “wary of the system’s ability to administer this test en masse.”

Shukla says it’s less about the results he’s getting today and more about making the test more effective for his patients in the future. First responders need a test like this, which can quickly identify many cancers, he says. But for it to improve, Grail needs more data for this high-risk population. That’s what he’s after.

Curtis has no regrets about taking the Galleri test. In her mind, the emotional toll of having cancer for a few days wasn’t too expensive. It’s part of cancer screening.

But he says it would have been a much more stressful experience if he had been financially responsible for the work, or if Shukla hadn’t been there to manage his case from start to finish.

Since it was free, Arents does not regret the Gallery either. But he tells his colleagues to check out the site, do their research and do more screening.

“Any medical center that just does this one test, you just have to be careful,” Shukla says. “It is not so easy.”

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