Experimental Blood Test Detects Cancer Years Before Symptoms

Roxanne Nelson, RN, BSN

July 29, 2020

A blood test that may be able to detect cancer years before any symptoms appear is under development. The PanSeer assay, which detects methylation markers in blood, was used in healthy individuals and successfully detected five cancer types in 91% of samples from individuals who were diagnosed with cancer 1 to 4 years later.

"We can't say for sure that the patients didn't have any symptoms, but we detected the cancer years before they ever walked into the hospital," said study author Kun Zhang, PhD, a professor of bioengineering at the University of California, San Diego. "We were also able to follow up with patients, so we actually knew that they had cancer."

Zhang noted that they also followed the individuals whose tests indicated they were cancer free. "They were healthy at the time the samples were obtained, and they remained healthy," he said. "Follow-up was key to validating these data."

The PanSeer test is being developed by Singlera Genomics. Zhang is a cofounder and a paid consultant of the company.

The study was published online July 21 in Nature Communications.

Unique Among Tests

Several blood tests for the detection of cancer have been reported in recent years. A test developed by Grail was able to detect more than 50 types of cancer and also identified the tissues where the cancer originated. The CancerSEEK test identified eight common cancers by measuring circulating tumor DNA from 16 genes as well as eight protein biomarkers.

Findings regarding the CellMax Life FirstSight blood test were released last month. The test detected all 11 cases of colorectal cancer in a cohort of 354 patients and detected 40 of 53 advanced adenomas.

The latest study with the PanSeer assay is unique, say the investigators, because they had access to blood samples from patients who may have been completely asymptomatic and had not yet been diagnosed with cancer. Other blood tests have typically involved the use of specimens from people with a known diagnosis.

The specimens were collected as part of a 10-year longitudinal study that began in 2007 in China. Zhang and his team were able to test blood samples before individuals had experienced any signs or symptoms of cancer, and they were able to conduct long-term follow-up of the cohort.

Study Details

The PanSeer assay uses DNA methylation analysis and screens for a DNA signature called CpG methylation. The results of an early-stage proof-of-concept study were published 3 years ago (Nat Genet. 2017;49:635–642).

For the current study, data were drawn from the Taizhou Longitudinal Study, which included 123,115 individuals aged 25 to 90 years who provided blood samples for long-term storage from 2007 to 2014. Participants were monitored indefinitely for cancer occurrence using local cancer registries and health insurance databases.

The team identified 575 individuals who were initially asymptomatic and healthy but were subsequently diagnosed with one of five common cancer types (stomach, esophagus, colorectum, lung, or liver cancer) within 4 years of their initial blood sampling. The authors selected these five cancer types to study because the incidence rates of these cancers in this population are high and, taken together, account for the highest mortality.

The study design allowed the authors to evaluate specimens both from patients with cancer and from those who were healthy within the same cohort. Using 191 prediagnosis samples, 223 postdiagnosis samples, and 414 healthy samples, they created a training set and validation model.

A machine learning method was created to classify samples as being either from healthy individuals or from those with cancer, using blood samples from the training set. The final classifier achieved 88% sensitivity for postdiagnosis samples and 91% sensitivity for prediagnosis samples at a specificity of 95%.

Zhang feels that initially, it would be more appropriate to use the test for high-risk patients and to then evaluate the clinical benefit. "For any test, it is always more prudent to begin with a high-risk population," he said. "You want to see some benefit with the high-risk population first, and then it can slowly be extended to others at lower risk."

He emphasized that more rigorous testing is needing before the PanSeer assay is ready for clinical use. The logistics of designing and conducting a clinical trial that would include more than one cancer type would be very complicated. "The option was to break it down to five different studies," he said. "We decided to begin with colon cancer, and we are currently in the process of talking with the FDA and designing the study."

High Bar to Reach

Approached for comment, Benjamin Weinberg, MD, assistant professor of medicine, Division of Hematology and Oncology, the Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, noted that there is "quite a ways to go before this can be clinically actionable.

"A lot of us are looking at combining methylation with circulation tumor DNA and throw the kitchen sink at it, but as the paper nicely describes, there are pros and cons to all of these," he said.

Many tests of this type are in development. Weinberg explained that a circulating tumor DNA test for colon cancer may hit the market soon, pending FDA approval, although that test will be used in a different setting. "This is something that's used to assess for minimal residual disease in patients who have undergone surgery and appear to be 'cured' of the disease," he said. "The test is looking to see if there is any circulating tumor DNA being shed from whatever tumor is left behind."

The type of test that has piqued the most interest is one that is "tumor informed," meaning that the company receives tumor tissue and develops a personalized test of that tumor on the basis of tumor genetics. "That is a very targeted way of surveillance," said Weinberg, "But It would be very difficult to use a tumor-informed test on the population described in this study because you don't know if there is going to be a tumor or not."

The PanSeer test may also prove difficult to use in the clinic because it detects multiple cancers, Weinberg said. "If there is a positive finding, then which cancer do you look for?" he commented. "It has an issue in that regard, and that's the problem with this type of test, as it is easier if there is one site of origin."

Overall, the test was fairly sensitive and specific, with a very low false negative rate. Going forward, he noted, there is a very high bar for tests used as screening tools, although the authors do say that their focus is for use in a high-risk population.

"There would have to be a randomized trial, and the test will have to show a survival benefit," Weinberg said. He noted that it can sometimes be challenging to do so.

"Colonoscopy has been shown to be beneficial, but early mammography has become controversial, and prostate cancer is a whole different animal," he added. "And these are established tests, and they show how difficult this can be."

The Taizhou Longitudinal Study study was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Key Basic Research grants from the Science and Technology Commission of Shanghai Municipality, the International S&T Cooperation Program of China, the Municipal Science and Technology Major Project program, the International Science and Technology Cooperation Program of China, and the 111 Project (B13016). Funding for the DNA methylation assays was provided by Singlera Genomics. Zhang is a cofounder, equity holder, and paid consultant of Singlera Genomics, a company that is developing early cancer detection tests, including the PanSeer test. Weinberg is a speaker or a member of a speakers bureau for Taiho Pharmaceutical Co Ltd, Bayer HealthCare Pharmaceuticals, and Eli Lilly and Company; has received research grant from Novartis Pharmaceuticals Corporation; and has received travel reimbursement from Caris Life Sciences.

Nat Commun. Published online July 21, 2020. Full text

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