As cancer cells grow ​and proliferate in the body, they shed DNA and protein that circulate in the blood. In a presentation at the American Association for Cancer Research (AACR) Virtual Annual Meeting I given April 28, researchers discussed data on two different strategies for detecting signs of cancer via blood tests, also sometimes called liquid biopsies. (The AACR publishes Cancer Today.)

A test being developed by Grail, a company based in Menlo Park, California, is able to identify not only whether some people are likely to have cancer but also what type of cancer they might have. Researchers presented data showing the test was able to detect signs of cancer in nearly half of people who had symptoms of cancer and did indeed go on to be diagnosed with cancer. The test was able to identify a cancer’s tissue of origin most of the time.

Another group of researchers presented data on DETECT-A, the first study to use a multicancer screening blood test to actively guide patients’ care. The test, which was used in around 10,000 women without a history of cancer, identified cancers in 26 patients. Fifteen of these women were diagnosed after getting full-body diagnostic PET-CT scans prompted by the blood test. The other 11 women developed symptoms of cancer and underwent other imaging before their blood test results prompted action. The blood test is being developed by Thrive Earlier Detection Corp., which is based in Baltimore and Cambridge, Massachusetts.

Both tests rarely flagged people as having likely cancer who did not in fact appear to have cancer, easing concerns that such tests might lead to further unnecessary tests and procedures.

“The ability to identify cancers through blood testing is one of the most exciting advances in cancer diagnostics,” said Nick Papadopoulos, a researcher at the Johns Hopkins University School of Medicine in Baltimore, in his presentation on the DETECT-A study. “Liquid biopsies provide an opportunity to develop minimally invasive tests that could identify multiple types of cancer.”

Detecting Cancer’s Origins

For early detection to be useful, doctors must be able to pinpoint where in the body the cancer might be located so they can do further tests. David D. Thiel, a urologist and researcher at the Mayo Clinic in Jacksonville, Florida, presented data on the Grail test, which analyzes DNA shed from cancer cells.

The current version of the test looks at patterns of chemical tags called methylation on DNA found in the blood. Methylation, a form of epigenetic modification, helps regulate gene expression and determine the identity of different types of cells. Cancer cells have unusual patterns of methylation on their DNA, and these patterns vary by cancer type.

To develop the Grail test and hone its accuracy, researchers collected blood and tissue from more than 15,000 people the U.S. and Canada, some of them recently diagnosed with cancer and some without a cancer diagnosis. The group published a study March 30, 2020, in Annals of Oncology showing that their methylation-based test identified less than 1% of people without known cancer as having suspected cancer and predicted presence of cancer and cancer type in some people who did have cancer.

In the AACR presentation, Thiel focused on a group of 303 people who had not been diagnosed with cancer when they gave blood for the study but who had concerning symptoms or imaging results that their doctors planned to follow up on with biopsy or surgery within six weeks of the blood draws.

The researchers split this group in two, using machine learning to improve their algorithm for use in the second group based on their test’s performance in the first group. In its second, more accurate iteration, the test identified 47% of the people who were ultimately diagnosed with cancer as having signs of cancer in their blood. Among the people identified as having signs of cancer, the test got the type of cancer right 97% of the time.

The test’s accuracy varied by cancer type and stage. When patients with kidney cancer were excluded, the test identified 59% of the patients with cancer. The test identified 79% of all cancers that were stage II or higher. None of the people who were predicted by the test not to have cancer received a cancer diagnosis after their surgery or biopsy.

“Overall these findings suggest this cell-free DNA multicancer early detection test could potentially be utilized to accelerate cancer diagnosis by directing diagnostic workup to predicted tissue of origin among individuals with high suspicion of cancer,” Thiel said in his presentation. The hope is that eventually the test will also be used alongside current guideline-recommended screening in patients without signs of cancer, Thiel said.

Putting Liquid Biopsy to the Test

Papadopoulos presented data from the first study to use the results of a multicancer screening test to guide care for patients. The results of the study were also described in a paper published in Science​ in conjunction with the session at the AACR meeting.

Papadopoulos helped develop a blood test called CancerSEEK that detects mutations in DNA found in cancer cells, as well as proteins that have elevated levels in cancer cells. For the DETECT-A study, Papadopoulos and his colleagues studied an early version of the test in around 10,000 women between the ages of 65 and 75 without a history of cancer. The women were all being treated in the Geisinger Health System, which has locations in Pennsylvania and New Jersey.

In past studies of multicancer early detection tests, researchers have generally not given the patients or their doctors any test results to act on. They’ve often focused instead on developing and validating the tests using large groups of people they already know to have cancer.

For DETECT-A, the researchers intervened based on patients’ testing results. They did full-body diagnostic PET-CT scans in those who showed signs of cancer in two consecutive blood tests and were recommended for scanning by a panel of experts. The blood test used for DETECT-A does not determine where cancers originated, but the PET-CT scans were able to tell doctors where possible cancers were located. Based on scan results, the doctors were then able to do further testing, such as biopsies, for cancer.

In the end, 127 study participants had positive blood tests and underwent imaging to further look for cancer. Of these patients, 64 had imaging results that suggested possible cancer and 26 were later diagnosed with cancer. Seventeen of the 26 patients’ cancers were localized or regional, and lymphoma and ovarian, lung, uterine, thyroid, colorectal, breast, kidney and appendix cancer were all represented.

The researchers meanwhile followed up with each patient a year after enrollment in the study to see how they were doing. At the time the data were analyzed, they had done one-year follow-ups with 93% of participants.

The researchers found that 24 additional women were diagnosed with cancer during the follow-up period after undergoing standard screening tests, and 46 additional women were diagnosed with cancer via other processes, mainly after developing symptoms of cancer.

A total of 38 patients who did not turn out to have cancer underwent further testing based on their full-body PET-CT scans. Most of these were noninvasive or minimally invasive procedures, but three patients underwent a surgery that did not result in a cancer diagnosis. These three patients turned out to have benign or precancerous conditions.

Papadopoulos pointed out that the version of the CancerSEEK test used in the study is an old version of the test and that a newer version of the test is less likely to yield false positives and false negatives.

“Our goal was to detect screen-detected cancer complementary to standard-of-care screening,” said Papadopoulos. “Indeed, the number of screen-detected cancers was doubled, and people were not discouraged from undergoing standard-of-care screening based on surveys conducted in individuals within the study population.”

Show Us the Survival Statistics

Both tests hold promise as screening tests for cancer types for which screening is not currently available, and as supplements to screening tests that are already routinely used. But further study of the tests is needed, according to researcher and pathologist David G. Huntsman of the University of British Columbia in Vancouver, who discussed both presentations during the session.

When applying a screening test to a healthy population, there is potential to harm people by causing unnecessary anxiety, follow-up testing, procedures and even overtreatment of cancers. Data on whether the screening tests lengthen life will help determine how often screening leads to detection and treatment of cancers that would have otherwise gone on to harm patients.

“Diagnostic odysseys can cause harm, so tissue specificity is needed, and both studies show tremendous progress in this regard,” Huntsman said. “But ultimately—and both studies have shown we’re moving in the right direction but we’re not there—we need to show proof of overall survival.” 

Kate Yandell is the digital editor of Cancer Today.​


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