Promising results showcase benefits of MCED lab tests and provide hope for continued advancements
In impressive new research, Johns Hopkins School of Medicine has developed a clinical laboratory blood test that detects the presence of cancer years before symptoms present, aiding physicians with early diagnosis and treatment.
The identification of cancer cells comes via bloodstream analysis showing genetic materials shed by tumors and showcases the promise of multicancer early detection screening (MCED) to spot all types of cancer in early stages.
“Three years earlier provides time for intervention. The tumors are likely to be much less advanced and more likely to be curable,” Yuxuan Wang, MD, PhD, lead researcher and assistant professor of oncology at Johns Hopkins, told SciTechDaily.
Kimmel Cancer Center, Ludwig Center, the Bloomberg School of Public Health also participated in the study with the support of the National Institutes of Health (NIH).
Senior study author Nickolas Papadopoulos, PhD, professor of oncology at Johns Hopkins School of Medicine and senior author of the study, notes that an appropriate course of clinical care will be required following any positive result from the new cancer diagnostic blood test. (Photo copyright: Johns Hopkins.)
Johns Hopkins Study Details
To complete their research, the scientists studied plasma samples that came from the NIH study on Atherosclerosis Risk in Communities (ARIC), which was created to examine cardiovascular disease risk factors in heart failure, strokes, and heart attacks, SciTechDaily reported.
The researchers analyzed the samples using “highly accurate and sensitive sequencing techniques to analyze blood samples from 26 participants in the ARIC study who were diagnosed with cancer within six months after sample collection, and 26 from similar participants who were not diagnosed with cancer, ” SciTechDaily noted.
At the time of sample gathering, eight of the study participants had received a positive score on the MCED test. Six of them provided additional blood samples dating back 3.1 to 3.5 years. Four of those samples showed mutations, SciTechDaily reported.
Value of MCED Screening
While the sample size in the Johns Hopkins study is small, results of the tests give patients and their physicians a head start on identifying appropriate treatments and demonstrate the strides already made with MCED screening.
MCED tests are relatively new, and while they continue to lack FDA-approval, their ability to discern various types of cancer and provide advanced detection with helpful results make them a promising approach to early cancer screening, the American Cancer Society (ACS) notes.
“For cancers of all stages, therapies are more effective with a lower disease burden,” the scientists wrote in Cancer Discovery.
MCED tests use blood, saliva, urine, or other body fluids to seek out cancer signs through RNA, DNA, or proteins from abnormal cells that may be cancerous. Current screening can assist with cervical, breast, colorectal, prostate, or lung cancer, the ACS added.
Spotting Cancer Earlier
The Johns Hopkins scientist believe detection beyond three years early is likely. “In four of these six participants, the same mutations detected by the multicancer early detection test could be identified, but at 8.6- to 79-fold lower mutant allele fractions. These results demonstrate that it is possible to detect [circulating tumor DNA] more than three years prior to clinical diagnosis and provide benchmark sensitivities required for this purpose,” the Cancer Discovery study notes.
“Detecting cancers years before their clinical diagnosis could help provide management with a more favorable outcome,” Nickolas Papadopoulos, PhD, professor of oncology at Johns Hopkins School of Medicine and senior author of the study, told SciTechDaily.
“Of course, we need to determine the appropriate clinical follow-up after a positive test for such cancers,” he added.
Findings could reduce the need for self-reporting in future nutritional studies and lead to new clinical laboratory testing
Clinical laboratory testing may one day influence whether a person snacks on a bag of chips every day or chooses to eat healthy foods instead.
Researchers at the National Institutes of Health (NIH) reported that they have identified biomarkers in blood and urine that can indicate an individual’s consumption of ultra-processed foods (UPF).
Scientists discovered a signature that is predictive of a dietary pattern that’s high in ultra-processed food, study leader Erikka Loftfield, PhD, MPH, epidemiologist and principal investigator with the NIH, told the Associated Press (AP).
Using data on the biomarkers—metabolites left after the body breaks down food—the researchers devised a “poly-metabolite score” that could potentially “reduce the reliance on, or complement the use of, self-reported dietary data in large population studies,” according to an NIH press release.
This will be helpful because, according to the AP, “Typical nutrition studies rely on recall: asking people what they ate during a certain period. But such reports are notoriously unreliable because people don’t remember everything they ate, or they record it inaccurately.”
“Limitations of self-reported diet are well known. Metabolomics provides an exciting opportunity to not only improve our methods for objectively measuring complex exposures like diet and intake of ultra-processed foods, but also to understand the mechanisms by which diet might be impacting health,” said Loftfield in the press release.
Thus, it’s conceivable that one day clinical laboratory testing could affect people’s food choices and help to improve their health.
“There’s a need for both a more objective measure and potentially also a more accurate measure,” Erikka Loftfield, PhD, MPH, epidemiologist and principal investigator with the NIH, told the Associated Press. (Photo copyright: National Cancer Institute.)
Study Methodology
The findings were based in part on an earlier study of 718 AARP members, aged 50-74, who agreed to submit blood and urine samples. The participants also completed dietary recall reports.
“The researchers found hundreds of metabolites that correlated with the percentage of energy from ultra-processed foods in the diet,” the NIH press release noted. “Using machine learning, researchers identified metabolic patterns associated with high intake of ultra-processed foods and calculated poly-metabolite scores for blood and urine separately.”
To test their findings, the researchers referred to a 2019 NIH study involving 20 adults aged 18 to 50. Under carefully controlled conditions, these participants spent two weeks consuming high levels of ultra-processed foods, followed by two weeks consuming no ultra-processed foods. As with the AARP cohort, they also submitted blood and urine samples. The poly-metabolite score proved to be an accurate measure of which diets they had consumed, the researchers reported.
The researchers acknowledged limitations in the study that will necessitate further research. “Study participants were older US adults whose diets may vary from other populations,” the authors noted. “Poly-metabolite scores should be evaluated and iteratively improved in populations with diverse diets and a wide range of UPF intake.”
Ultra-Processed Foods Defined
The NIH defines ultra-processed foods as “ready-to-eat or ready-to-heat, industrially manufactured products, typically high in calories and low in essential nutrients.” Diets high in these foods have been associated with “increased risk of obesity and related chronic diseases, including some types of cancer,” the press release noted.
In identifying these foods, the researchers cited a 2019 paper published in the journal Public Health Nutrition (PHN). The paper relied on the NOVA classification system, which makes a distinction between “processed” and “ultra-processed” foods. The latter typically contain “food substances never or rarely used in kitchens,” or cosmetic additives “whose function is to make the final product palatable or more appealing,” the PHN paper noted.
“From sugary cereals at breakfast to frozen pizzas at dinner, plus in-between snacks of potato chips, sodas and ice cream, ultra-processed foods make up about 60% of the US diet,” the AP reported in an earlier story. “For kids and teens, it’s even higher—about two-thirds of what they eat.”
Discovery could lead to new clinical laboratory testing for cancer screening in new mothers
Any clinical laboratory test that returns unexpected results is worth looking into more deeply. Such was the case with a recent study conducted by the National Institutes of Health (NIH), which investigated cases of pregnant women who received “unusual” results to prenatal lab tests conducted at a dozen labs in North America.
Following cancer screening protocols that included rapid whole-body magnetic resonance imaging, NIH scientists discovered “previously undetected cancers in 48.6% of pregnant people who had abnormal results for prenatal cell-free DNA (cfDNA) testing used to screen for chromosomal disorders in the fetus,” according to an NIH news release.
“They looked like healthy young women, and they reported themselves as being healthy,” Diana Bianchi, MD, head of the Prenatal Genomics and Therapy Section for the Medical Genetics Branch at the NIH’s National Human Genetics Research Institute, and senior author of the government study, told the Associated Press (AP).
While cfDNA tests are not diagnostic, pathologists and clinical laboratory managers involved in genetic testing are likely familiar with them. The blood tests are used by expectant mothers to assess risk of a fetus with an abnormal number of chromosomes that could suggest disorders such as Down Syndrome, according to ARUP Laboratories.
Unexpected results from tests draw attention. This one seems to have a chance to get more traction with labs because the results point to a prenatal test having some success predicting cancer, even if incidentally.
“[The study participants] and their care providers need to take the results seriously and have additional testing because in that population there is a 48% risk of cancer,” Diana Bianchi, MD, senior author of the NIH study, told the AP. (Photo copyright: National Institutes of Health.)
Cancer Found in about Half of Those with Abnormal cfDNA
The NIH researchers started a long-term study, called IDENTIFY, to learn more about abnormal cfDNA results that could suggest cancer. Study participants must be:
Pregnant or postpartum with no known cancer.
Recipients of “unusual clinical cfDNA-sequencing results or results that are non-reportable (fetal aneuploidy status could not be assessed) from one of 12 different commercial laboratories,” they wrote in NEJM.
For the study’s initial cohort of 107 participants, researchers repeated cfDNA sequencing testing and coordinated standard medical diagnostic tests (such as Pap smears) and whole-body magnetic resonance imaging.
52 women (48.6%) were found to have “hidden cancers.”
32 had blood cancers.
20 had solid tumors in the breast, bile duct, colon, pancreas, lung, kidney, bone, and adrenal gland.
13 of the 20 with solid tumors were able to access “potentially curative treatments.”
55 women did not have cancer and may have obtained an unreliable cfDNA result.
“In this study, 48.6% of participants who received unusual or nonreportable clinical cfDNA-sequencing results had an occult cancer (cancer of unknown primary).
“Further study of DNA-sequencing patterns that are suggestive of occult cancer during prenatal screening is warranted,” the researchers wrote in NEJM.
Follow-Up Testing Needed
Cancers found in the study participants “included colorectal, breast, lung and pancreatic cancers, as well as lymphoma, cholangiocarcinoma and renal carcinoma. The screening test analyzes placental DNA fragments circulating in the maternal bloodstream to identify an extra chromosome or to determine the baby’s sex,” according to the NIH news release.
Bianchi told AP the study results also pointed to a “very chaotic” pattern in DNA-sequencing of women with cancer, and that more research is needed to find out who should be screened for cancer.
Clinical laboratories and pathologists who analyze cfDNA tests could take a leadership role in assessing current standards for the tests, determining how suspicious results are reported, and suggesting needed changes.
With more study, the technique could lead to new precision medicine pathology diagnostics and clinical laboratory tests
Researchers at Yale University have devised a new pathology tool that utilizes barcode technology to map the spatial relationships of ribonucleic acid (RNA) and proteins. This will be of interest to histopathologists who are responsible for examining clinical laboratory tissue samples and helping physicians diagnose disease.
Called Patho-DBiT (pathology-compatible deterministic barcoding in tissue), the Yale scientists claim their new tool can completely examine RNA and possibly aid in the diagnoses and treatment of cancer.
The technology, according to a Yale news release, “is unique in that it has microfluidic devices that deliver barcodes into the tissue from two directions creating a unique 2D ‘mosaic’ of pixels, providing spatial information that could be used to inform the creation of patient-specific targeted therapies.”
“It’s the first time we can directly ‘see’ all kinds of RNA species, where they are and what they do, in clinical tissue samples,” said Rong Fan, PhD, Harold Hodgkinson professor of biomedical engineering and pathology at Yale and senior author of the study.
“I think it’s going to completely transform how we study the biology of humans in the future,” said Rong Fan, PhD (above), Harold Hodgkinson professor of biomedical engineering and pathology at Yale and senior author of the study, in a Yale news release. The discovery could lead to new clinical laboratory screening tests and diagnostics for cancer. (Photo copyright: Yale University.)
More Precise Cancer Diagnoses
“As a physician who has been diagnosing cancer, I was surprised by how much more I can see using this pathology tool,” said Mina Xu, MD, professor of pathology at Yale School of Medicine and one of the authors of the study. “I think this deep molecular dive is going to advance our understanding of tumor biology exponentially. I really look forward to delivering more precise and actionable diagnoses.”
According to the Yale study, the Patho-DBiT tool has many beneficial capabilities. They include:
Dissecting spatiotemporal dynamics of lymphomagenesis at the single-cell level.
FFPE tissue involves the fixation of tissues by utilizing formalin and embedding tissue samples in paraffin wax. This method allows for the long-term preservation of tissue morphology and cellular details and is commonly used in histopathology.
In the past, the RNA within FFPE samples have been susceptible to fragmentation during the paraffin-embedding process and degradation issues. These samples may also experience chemical modifications which could result in resistance to the enzymatic reactions necessary for proper sequencing.
“There are millions of these tissues that have been archived for so many years, but up until now, we didn’t have effective tools to investigate them at spatial level,” said the study’s first author Zhiliang Bai, PhD, a postdoctoral associate in Rong Fan’s lab at Yale. “RNA molecules in these tissues we’re looking at are highly fragmented and traditional methods can’t capture all the important information about them. It’s why we’re very excited about Patho-DBiT.”
Targeted Therapies
The team is encouraged by their research and the future potential for Patho-DBiT. They believe the technology may be useful in creating targeted therapies and helping understand the metamorphosis of low-grade tumors to more aggressive ones. They conceive their tool may assist in developing ways to prevent the progression of cancers.
“It is very exciting that Patho-DBiT-seq is also capable of generating spatial maps of noncoding RNA expression,” said Jun Lu, PhD, associate professor of genetics at Yale and another of the study’s authors. “Noncoding RNAs are often in regions of our genomes that were previously thought of as junk DNA, but now they are recognized as treasured players in biology and diseases such as cancer.”
The research included faculty members from several departments at Yale and was supported by the National Institutes of Health (NIH). The technology is now licensed to biotechnology company AtlasXomics of New Haven, Ct., for further development.
More research and studies are needed to validate the findings of this research, but the Patho-DBiT tool could prove to be useful for the preservation of tissue samples and become essential in the diagnoses and treatment of cancers.
List also includes precision oncology, liquid biopsies, and early diagnosis of pancreatic cancer
Pathologists and clinical laboratory managers will be interested to learn that in a recently updated article the World Economic Forum (WEF) identified a dozen important recent breakthroughs in the ongoing fight to defeat cancer, including some related to pathology and clinical laboratory diagnostics.
The article noted that approximately 10 million people die each year from cancer. “Death rates from cancer were falling before the pandemic,” the authors wrote. “But COVID-19 caused a big backlog in diagnosis and treatment.”
The Swiss-based non-profit is best known for its annual meeting of corporate and government leaders in Davos, Switzerland. Healthcare is one of 10 WEF “centers” focusing on specific global issues.
Here are four advances identified by WEF that should be of particular interest to clinical laboratory leaders. The remaining advances will be covered in part two of this ebrief on Wednesday.
“Our study represents a major leap in cancer screening, combining the precision of protein-based biomarkers with the efficiency of sex-specific analysis,” said Novelna founder and CEO Ashkan Afshin, MD, ScD (above), in a company press release. “We’re not only looking at a more effective way of detecting cancer early but also at a cost-effective solution that can be implemented on a large scale.” The 12 breakthroughs listed in the World Economic Forum’s updated article will likely lead to new clinical laboratory screening tests for multiple types of cancer. (Photo copyright: Novelna.)
Novelna’s Early-Stage Cancer Test
Novelna, a biotech startup in Palo Alto, Calif., says it has developed a clinical laboratory blood test that can detect 18 early-stage cancers, including brain, breast, cervical, colorectal, lung, pancreatic, and uterine cancers, according to a press release.
In a small “proof of concept” study, scientists at the company reported that the test identified 93% of stage 1 cancers among men with 99% specificity and 90% sensitivity. Among women, the test identified 84% of stage 1 cancers with 85% sensitivity and 99% specificity.
The researchers collected plasma samples from 440 individuals diagnosed with cancers and measured more than 3,000 proteins. They identified 10 proteins in men and 10 in women that correlated highly with early-stage cancers.
“By themselves, each individual protein was only moderately accurate at picking up early stage disease, but when combined with the other proteins in a panel they were highly accurate,” states a BMJ Oncology press release.
The company says the test can be manufactured for less than $100.
“While further validation in larger population cohorts is necessary, we anticipate that our test will pave the way for more efficient, accurate, and accessible cancer screening,” said Novelna founder and CEO Ashkan Afshin, MD, ScD, in the company press release.
Precision Oncology
According to the National Institutes of Health’s “Promise of Precision Medicine” web page, “Researchers are now identifying the molecular fingerprints of various cancers and using them to divide cancer’s once-broad categories into far more precise types and subtypes. They are also discovering that cancers that develop in totally different parts of the body can sometimes, on a molecular level, have a lot in common. From this new perspective emerges an exciting era in cancer research called precision oncology, in which doctors are choosing treatments based on the DNA signature of an individual patient’s tumor.”
“These advanced sequencing technologies not only extend lifespans and improve cure rates for cancer patients through application to early screening; in the field of cancer diagnosis and monitoring they can also assist in the formulation of personalized clinical diagnostics and treatment plans, as well as allow doctors to accurately relocate the follow-up development of cancer patients after the primary treatment,” Wang wrote.
Based in China, Genetron Health describes itself as a “leading precision oncology platform company” with products and services related to cancer screening, diagnosis, and monitoring.
Liquid and Synthetic Biopsies
Liquid biopsies, in which blood or urine samples are analyzed for presence of biomarkers, provide an “easier and less invasive” alternative to conventional surgical biopsies for cancer diagnosis, the WEF article notes.
These tests allow clinicians to “pin down the disease subtype, identify the appropriate treatment and closely track patient response, adjusting course, if necessary, as each case requires—precision medicine in action,” wrote Merck Group CEO Belén Garijo, MD, in an earlier WEF commentary.
The WEF article also highlighted “synthetic biopsy” technology developed by Earli, Inc., a company based in Redwood City, Calif.
As explained in a Wired story, “Earli’s approach essentially forces the cancer to reveal itself. Bioengineered DNA is injected into the body. When it enters cancer cells, it forces them to produce a synthetic biomarker not normally found in humans.”
The biomarker can be detected in blood or breath tests, Wired noted. A radioactive tracer is used to determine the cancer’s location in the body.
“Pancreatic cancer is one of the deadliest cancers,” the WEF article notes. “It is rarely diagnosed before it starts to spread and has a survival rate of less than 5% over five years.”
The test is based on a technology known as high-conductance dielectrophoresis (DEP), according to a UC San Diego press release. “It detects extracellular vesicles (EVs), which contain tumor proteins that are released into circulation by cancer cells as part of a poorly understood intercellular communication network,” the press release states. “Artificial intelligence-enabled protein marker analysis is then used to predict the likelihood of malignancy.”
The test detected 95.5% of stage 1 pancreatic cancers, 74.4% of stage 1 ovarian cancers, and 73.1% of pathologic stage 1A lethally aggressive serous ovarian adenocarcinomas, they wrote.
“These results are five times more accurate in detecting early-stage cancer than current liquid biopsy multi-cancer detection tests,” said co-senior author Scott M. Lippman, MD.
Look to Dark Daily’s ebrief on Wednesday for the remainder of breakthroughs the World Economic Forum identifies as top advancements in the fight to defeat cancer.
