Decision is part of UK effort to diagnose 75% of all cancers at stage I or stage II by 2028 and demonstrates to pathologists that the technology used in liquid biopsy tests is improving at a fast pace
Pathologists and medical laboratory scientists know that when it comes to liquid biopsy tests to detect cancer, there is plenty of both hope and hype. Nevertheless, following a successful pilot study at the Christie NHS Foundation Trust in Manchester, England, which ran from 2015-2021, the UK’s National Health Service (NHS) is pushing forward with the use of liquid biopsy tests for certain cancer patients, The Guardian reported.
NHS’ decision to roll out the widespread use of liquid biopsies—a screening tool used to search for cancer cells or pieces of DNA from tumor cells in a blood sample—across the UK is a hopeful sign that ongoing improvements in this diagnostic technology are reaching a point where it may be consistently reliable when used in clinical settings.
The national program provides personalized drug therapies based on the genetic markers found in the blood tests of cancer patients who have solid tumors and are otherwise out of treatment options. The liquid biopsy creates, in essence, a match-making service for patients and clinical trials.
Liquid Biopsy Genetic Testing for Cancer Patients
“The learnings from our original ‘Target’ study in Manchester were that genetic testing needs to be done on a large scale to identify rare genetic mutations and that broader access to medicines through clinical trials being undertaken across the country rather than just one site are required,” Matthew Krebs, PhD, Clinical Senior Lecturer in Experimental Cancer Medicine at the University of Manchester, told The Guardian.
Krebs, an honorary consultant in medical oncology at the Christie NHS Foundation Trust, led the Target National pilot study.
“This study will allow thousands of cancer patients in the UK to access genetic testing via a liquid biopsy. This will enable us to identify rare genetic mutations that in some patients could mean access to life-changing experimental medicines that can provide great treatment responses, where there are otherwise limited or no other treatment options available.”
Detecting cancers at earlier stages of disease—when treatment is more likely to result in improved survival—has become a strategic cancer planning priority in the UK, theBMJ noted.
“The NHS is committed to diagnosing 75% of all cancers at stage I or II by 2028, from around 50% currently,” the BMJ wrote. “Achieving such progress in less than a decade would be highly ambitious, even without disruption caused by the COVID-19 pandemic. In this context, considerable hope has been expressed that blood tests for circulating free DNA—sometimes known as liquid biopsy—could help achieve earlier detection of cancers.”
The Guardian noted that the UK’s initiative will use a liquid biopsy test made by Swiss-healthcare giant Roche.
“We can’t guarantee that we will find a fault in the genetic code of every cancer patient we recruit, or that if we do, there will be a suitable drug trial for them,” Matthew Krebs, PhD (above), lead scientist of the NHS’ Target National pilot study, told The Guardian. “However, as we learn more about the genetics of cancer in this study, it will help doctors and scientists develop new treatments to help people in the future. Ultimately, we hope liquid biopsy testing will be adopted into routine NHS care, but we need studies such as this to show the benefit of the test on a large scale and provide the evidence that patients can benefit from being matched to targeted medicines on the basis of the blood test.” (Photo copyright: Cancer Research UK Manchester Centre.)
In her article “The Promise of Liquid Biopsies for Cancer Diagnosis,” published in the American Journal of Managed Care (AJMC) Evidence-based Oncology, serial healthcare entrepreneur and faculty lecturer at Harvard Medical School Liz Kwo, MD, detailed the optimism surrounding the “revolutionary screening tool,” including its potential for:
identifying mechanisms of resistance to therapies,
measuring remaining disease after treatment,
assessing cancer relapse or resistance to treatment, and
eliminating risk surrounding traditional biopsies.
The AJMC article estimated the liquid biopsy market will be valued at $6 billion by 2030. However, Kwo also noted that clinical adoption of liquid biopsies in the US continues to face challenges.
Welch compared the investor hype surrounding liquid biopsies to that of the now-defunct blood testing company Theranos, which lured high-profile investors to pour millions into its unproven diagnostic technology.
“Effective cancer screening requires more than early detection. It also requires that starting therapy earlier helps people live to older ages than they would if they started treatment later,” he wrote. “If that doesn’t happen, liquid biopsies will only lead to people living longer with the knowledge they have a potentially incurable disease without extending their lives. These people would be subjected to cancer therapies and their toxicities earlier, but at a time when they would otherwise be experiencing no cancer-related signs or symptoms.”
And so, while there’s much excitement about the possibility of a minimally invasive way to detect cancer, anatomic pathology groups and clinical laboratories will have to wait and see if the hype and hope surrounding liquid biopsies is substantiated by further research.
Proof of vaccination, masking, and availability of on-site testing will continue to be measures taken at in-person events for pathologists and medical laboratory professionals
Organizers of in-person clinical laboratory conferences face an interesting dilemma as they plan events in 2022: Where do they draw the line with COVID-19 safety protocols?
On one hand, the surge of cases caused by the SARS-CoV-2 Omicron variant seems to be in its waning stages and large swaths of the population are vaccinated. On the other hand, clinical laboratory and anatomic pathology events want potential registrants to have confidence that it is safe to travel and attend the gatherings.
One lab industry conference producer who happens to be knee-deep in preparing for an in-person meeting this spring is Robert Michel, Editor-in-Chief of The Dark Report and Founder of the 27th Annual Executive War College on Laboratory and Pathology Management. This informative event takes place on April 27-28 in New Orleans and includes COVID-19 protocols to protect attendees.
The CDC chart above shows the daily number of new COVID-19 cases in the US for the six-month period ending Feb. 28, 2022. Clinical laboratory managers should note that the number of new cases is at its lowest level since the Omicron variant showed up early this year.
“It’s important for all those planning to attend this year’s Executive War College to know that screening COVID-19 protocols will be in place to ensure the health and safety of all participants,” Michel noted. “We did a large lab conference in the fall of 2021 that included protocols for COVID-19 and the attendees told us they appreciated the protection provided by those protocols.”
After a significant rise in COVID-19 cases in January 2022 due to the Omicron variant, current daily case levels now are lower than they were six months ago before the new variant hit, according to numbers from the federal Centers for Disease Control and Prevention (CDC).
The in-person 2021 Executive War College, which took place in San Antonio on Nov. 2-3, 2021, followed the CDC’s recommendations:
COVID-19 protocols included a daily set of questions and a temperature check for all speakers and attendees before they were allowed to enter the conference area.
CLIA-complex rapid PCR COVID-19 tests were available for individuals whose temperature and answers to the screening questions indicated the need for such testing.
Attendees used an app to answer the daily screening questions and upload proof of vaccination.
“At last fall’s Executive War College, approximately 400 attendees were screened on each of the three days before entering the conference area and not one rapid COVID-19 test was needed,” Michel said. “Not only is that an outstanding outcome, but a number of attendees also told us they appreciated our efforts to keep them safe and protect their health.”
The 2022 Executive War College will follow the CDC’s updated COVID-19 guidelines, along with any state and local directives in effect as of April 27.
Although 300 attendees were expected at the 2021 Executive War College, 400 registered and participated.
Proof of Vaccination Has Been Required at Other Clinical Lab Industry Events
Organizers of other clinical lab conferences also have dealt with COVID-19 safety protocols. For example, the American Clinical Laboratory Association (ACLA) will hold its annual meeting in Washington, D.C., on March 9. COVID-19-related requirements for attendees will include proof of vaccination uploaded to a vaccine verification vendor and proof of a negative PCR test taken within 72 hours prior to the event.
The annual meeting of the American Society of Clinical Pathology (ASCP) occurs later this year in September in Chicago—too early yet to publish protocols. Last year’s ASCP conference in Boston was a hybrid event, offering both in-person and virtual options. Those who attended in person needed to upload proof of vaccination to a third-party vendor and were required to wear masks. On-site COVID-19 testing was available.
Revived Corporate Travel Could Boost Clinical Laboratory Conferences
The path back to live events across all industries has not been easy given various COVID-19 surges, political divisiveness over masking, frozen corporate travel budgets, and corporate policies banning or limiting employee travel.
Conference organizers throughout the United States universally hope those barriers will lower as 2022 progresses.
“With the fast-spreading Omicron triggering another round of setbacks to start 2022, event planners now are betting on spring to finally mark a turning point for the hard-hit industry,” MarketWatch reported on Feb. 4. “Their hopes hinge on American corporations taking a note from the recovery already under way for domestic air travel for leisure purposes, with the linchpin being a robust revival of trade show attendance and other in-person business gatherings.”
For Michel, offering actionable advice through well-thought-out sessions has been a cornerstone of the content offered each year at the Executive War College. He believes that approach will continue to be the strongest drawing point for clinical laboratory and pathology executives now considering attending the event.
“Our reading of the tea leaves is that across the profession of laboratory medicine, a great many managers, administrators, executives, and pathologists want to return to in-person conferences,” Michel noted. “Registrations for our April event are running ahead of 2019, and people tell us that they recognize the changes in healthcare and the lab marketplace because of the pandemic. They want to understand what’s driving current trends, like greater consumer involvement in lab testing and how to get private payers to reimburse claims for COVID-19 and genetic tests, as well as how a growing number of clinical laboratories are incorporating artificial intelligence solutions in both clinical care settings and lab operations.”
An estimated 80 pathologists will now work for larger pathology superlabs as part of the deals, bringing stiffer competition to independent anatomic pathology groups
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Consolidation among private practice anatomic pathology groups continues with news that two large regional pathology groups decided to sell to larger pathology companies. The first transaction announced was on Dec. 16, 2021, when Sonic Healthcare of Sydney, Australia, disclosed that it had acquired Dallas-based ProPath. Sales price and other terms were not announced.
The second transaction happened last month. On Jan. 24, Nashville-based PathGroup announced it had bought Pathology Consultants of Greenville, S.C. Price and terms of this transaction also were not disclosed.
Pathology Consolidation Continues
The decision by two of the nation’s leading regional pathology groups to sell themselves to larger pathology entities confirms that the trend of consolidation is continuing within the pathology profession. It is also a sign that smaller pathology groups will find it increasingly difficult to compete and stay profitable as new technologies transform the surgical pathology profession, such a digital pathology platforms.
ProPath was considered a financially strong regional super-group, as it operates facilities in three states and has 50 pathologists and 500 employees. Sonic noted that ProPath’s annual revenue was about $110 million.
Sonic Healthcare also purchased Aurora Diagnostics in 2018 for $540 million. That deal brought it 32 pathology practice sites and added 220 pathologists to its roster.
With its acquisition of Pathology Consultants, PathGroup adds 30 pathologists and 100 employees. Prior to this acquisition, PathGroup said it had 225 pathologists.
“We will continue providing highly specialized pathology expertise, as well as a broad range of clinical and molecular pathology services,” PathGroup CEO Ben Davis. MD, said of the Pathology Consultants acquisition. (Photo copyright: ProPath)
Maintaining Independence Gets Tougher
Anatomic pathologists will want to understand why two major regional pathology groups have decided to give up their independence and sell to a larger company. The reasons are several and include:
Need for cash to purchase the equity of retiring baby boomer pathologist partners in the group.
Challenges in recruiting new pathologists to the group.
Need for capital to acquire digital pathology capabilities and other needed advanced diagnostic technologies.
Access to managed care contracts as private health plans continue to narrow their provider networks.
It should be noted that graduating pathology residents and fellows are tech-savvy and want to work in practices that have all the latest technologies in histology, scanning, and digital pathology. This observation plays into the consolidation of the market.
Scientists working to sequence all 1.66 million animal species say this is a missed opportunity to better understand our own genetics; such research would identify biomarkers useful for clinical laboratory testing
For 23 years, the world’s genomic scientists have been on a mission to sequence the genomes of all animal species. And they’ve made great progress. However, according to a recent study conducted by researchers at Washington State University (WSU) and Brigham Young University (BYU), only a fraction of the sequences are from invertebrate species. And that, according to the study’s authors, is “overlooking huge swathes of diversity and opportunity.”
The push to sequence the whole genomes of all animals began in 1998 with the sequencing of the Caenorhabditis elegans roundworm, according to a WSU news release. It was the first animal genome sequence, but it was not to be the last. Nearly 25 years later, genomic scientists have sequenced about 3,300 animal genomes. And while that’s a lot of genomic sequences, it’s a drop in bucket of the approximately 1.7 million animal species on the planet.
But here’s where the missed opportunity comes in. According to the WSU news release, “Vertebrates account for 54% of all genome sequencing assemblies, despite representing only 3.9% of animal species. In contrast, the invertebrates of the Arthropoda phylum, which includes insects and spiders, comprise only 34% of current datasets while representing 78.5% of all species.”
“We are interested in ourselves, and that’s not necessarily a bad thing,” said Paul Frandsen, PhD (above), in the news release. Frandsen is Assistant Professor of Genetics, Genomics, and Biotechnology at Brigham Young University and one of the study authors. “But to begin to understand entire ecosystems,” he continued, “we have to start sampling more of the variety of life to gain a clearer picture. Vertebrates are important components of ecosystems, but arguably insects and many other small creatures probably play an even more important role because they’re down at the base of the food web.” (Photo copyright: Brigham Young University.)
The scientists analyzed the best available genome assemblies found in GenBank, the world’s most extensive genetic database. They found that 3,278 unique animal species across 24 phyla, 64 classes, and 258 orders have been sequenced and assembled to date.
They also found that sequencing efforts have focused heavily on species that most resemble humans. The Hominidae, a taxonomic family of primates that includes humans as well as great apes, bonobos, chimpanzees, orangutans, and gorillas, has the most contiguous genome data assembled.
The team discovered that vertebrates account for 54% of the animal genome sequencing that has been performed even though they make up less than four percent of known animal species. By comparison, invertebrates of the Arthropoda phylum, which represent 78.5% of all animal species, comprise only 34% of the completed animal genome sequencing. And yet, the Arthropoda phylum is the largest phylum in the animal kingdom and includes insects, spiders, scorpions, centipedes, millipedes, crabs, crayfish, lobsters, and barnacles.
“With genome assemblies accumulating rapidly, we want to think about where we are putting our efforts. It’s not being spread evenly across the animal tree of life,” said lead author Scott Hotaling, PhD, post-doctoral researcher at WSU, in the news release. “Invertebrates are still very underrepresented, which makes sense given that people seem to care more about vertebrates, the so-called ‘charismatic megafauna.’”
The team discovered that only five arthropod groups: ants, bees, butterflies, fruit flies, and mosquitos, were well represented in genome sequencing. The longest genome sequenced so far belongs to the Australian lungfish, the only surviving member of the family Neoceratodontidae.
1,100 Years to Sequence All Eukaryotic Life
The scientists also discerned that animal genome assemblies have been produced by 52 countries on every continent with permanent inhabitants. The majority of animal genome sequencing (77%) that is being performed is mostly occurring in developed countries located in the Northern Hemisphere, often referred to as the Global North. Nearly 70% of all animal genome assemblies have been produced by just three countries: the United States, China, and Switzerland.
There are geographic differences between regions regarding the types of animals being sequenced and assembled with North America concentrating on mammals and insects, Europe focusing on fish, and birds being the main type of animals sequenced in Asia.
The scientists would like to see more animal genome sequencing happening in countries from the Global South, or Southern Hemisphere, particularly in tropical regions that contain a myriad of diversity among animal species.
“If we want to build a global discipline, we need to include a global people,” Hotaling said. “It’s just basic equity, and from a pure scientific standpoint, the people who live in areas where species are being sequenced have a lot of knowledge about those species and ecosystems. They have a lot to contribute.”
But the WSU/BYU scientists found that many species in GenBank only have low-quality assemblies available. They noted that “the quality of a genome assembly is likely the most important factor dictating its long-term value.”
Fortunately, several animal genome sequencing ventures have been announced in recent years, so the amount of available data is expected to rise exponentially. These projects include:
The Earth BioGenome Project (EBP) which aspires to sequence and catalog the genes of all the eukaryotic species on the planet within ten years.
The Vertebrate Genomes Project which seeks to generate high-quality assemblies for 70,000 extant vertebrate species.
The Bird 10K Project that seeks to generate assemblies for all extant birds.
The i5K Project which plans to produce 5,000 arthropod genome assemblies.
The authors of the PNAS paper noted that there are currently only about four genome assemblies happening each day and, at that rate, the sequencing of all eukaryotic life will not be completed until the year 3130.
So, microbiologists, clinical laboratory professionals, and genomic scientists have plenty of time to get up to speed.
These findings hint at the role of pre-existing conditions in raising the risk of an individual having a severe case of COVID-19 once infected
At the University of Michigan, a team of pathologists have been researching the factors that might cause some patients infected by SARS-CoV-2 to suffer persistent respiratory problems, often described as “long COVID.” They have identified factors that place some individuals at higher risk for these problems.
Little is known about how the SARS-CoV-2 coronavirus affects the body long-term. Millions of people who have survived COVID-19 infections are living with chronic symptoms, including persistent respiratory problems such as shortness of breath. However, until now, it was not clear what may be causing these symptoms in some people but not others, even after the coronavirus has completely cleared their bodies.
Now, anatomic pathologists at Michigan Medicine, formerly the University of Michigan Health, believe they may have discovered what is causing ongoing respiratory problems in some patients who have recovered from the COVID-19 infection—pre-existing conditions.
The researchers examined lung biopsies from COVID-19 patients who continued to experience lingering symptoms. They discovered in some individuals lung damage that was present prior to contracting the virus.
“Some of the early publications and popular press around long COVID has implied or assumed that once you had COVID, everything that happens next is COVID-related,” said anatomic pathologist and senior author of the study Jeffrey Myers, MD (above), Vice Chair for Clinical Affairs and Quality at Michigan Medicine, in a news release. “Of course, that might or might not be true,” he added. (Photo copyright: University of Michigan.)
The research team analyzed lung biopsies from 18 COVID-19 survivors who were still experiencing respiratory symptoms or had abnormal computed tomography (CT) scans after the virus was no longer present in their bodies. The researchers found ground glass opacities on the radiological scans of 14 of those patients.
According to the news release, this finding indicates there were “areas of the lungs that appear as a cloudy gray color as opposed to the dark color of normal air-filled lungs, on a chest X-ray or CT scan.”
The biopsies exhibited evidence of pre-existing lung scarring and proof of diffuse alveolar damage, which is typically seen in patients with acute respiratory illnesses. Only five of the patients examined in the study were known to have lung disease prior to their COVID-19 diagnoses.
The researchers found that the most common condition present in these 18 patients was usual interstitial pneumonia (UIP). This condition, also known clinically as idiopathic pulmonary fibrosis (IPF), is a common form of pulmonary fibrosis that is characterized by progressive scarring and stiffening of both lungs.
“We were seeing a lot of UIP, which isn’t the pattern we tend to associate with acute lung injury,” said Kristine Konopka, MD, Clinical Associate Professor at Michigan Medicine and lead author of the study, in the news release. “So, we think these are patients who had lung disease prior to COVID and maybe they just weren’t being followed by primary care physicians. They then had COVID, are still sick, and their UIP is finally being picked up.”
Could Patients Have Lung Disease and Not Know it?
“The notion,” Myers noted in the news release, “that a person could have chronic lung damage and not know it was unheard of until relatively recently.” He also explained that UIP/IPF is a progressive disease that gets worse with time and that an infection like COVID-19 can accelerate the illness to a more serious condition known as an acute exacerbation of IPF, which can lead to death.
“SARS-CoV-2 comes along and does to the lung, from a pathology perspective, exactly what happens with an acute exacerbation,” Myers said.
The researchers also stated that it’s impossible to determine for certain whether the SARS-CoV-2 virus caused the UIP/IPF without the existence of full clinical histories of the patients prior to their COVID-19 diagnoses. They hope their research will motivate clinicians to be cautious before automatically attributing respiratory symptoms to long COVID in survivors of the virus. It is possible that the lung damage was present prior to the coronavirus.
“You shouldn’t make assumptions but [instead] ask the right questions, the first of which would be ‘I wonder if this is really COVID?’ What you do after that depends on the answer to that question,” he added.
This research is an example of how pathologists can add insight and value into the deeper understanding of the processes involved in specific diseases. Dark Daily invites any of our readers who are aware of other pathologist-authored studies or published papers about COVID-19 to alert us to the availability of those works.
International research team that developed swarm learning believe it could ‘significantly promote and accelerate collaboration and information exchange in research, especially in the field of medicine’
“Swarm Learning” is a technology that enables cross-site analysis of population health data while maintaining patient privacy protocols to generate improvements in precision medicine. That’s the goal described by an international team of scientists who used this approach to develop artificial intelligence (AI) algorithms that seek out and identify lung disease, blood cancer, and COVID-19 data stored in disparate databases.
Since 80% of patient records feature clinical laboratory test results, there’s no doubt this protected health information (PHI) would be curated by the swarm learning algorithms.
In their study they wrote, “Fast and reliable detection of patients with severe and heterogeneous illnesses is a major goal of precision medicine. … However, there is an increasing divide between what is technically possible and what is allowed, because of privacy legislation. Here, to facilitate the integration of any medical data from any data owner worldwide without violating privacy laws, we introduce Swarm Learning—a decentralized machine-learning approach that unites edge computing, blockchain-based peer-to-peer networking, and coordination while maintaining confidentiality without the need for a central coordinator, thereby going beyond federated learning.”
What is Swarm Learning?
Swarm Learning is a way to collaborate and share medical research toward a goal of advancing precision medicine, the researchers stated.
The technology blends AI with blockchain-based peer-to-peer networking to create information exchange across a network, the DZNE news release explained. The machine learning algorithms are “trained” to detect data patterns “and recognize the learned patterns in other data as well,” the news release noted.
“Medical research data are a treasure. They can play a decisive role in developing personalized therapies that are tailored to each individual more precisely than conventional treatments,” said Joachim Schultze, MD (above), Director, Systems Medicine at DZNE and Professor, Life and Medical Sciences Institute at the University of Bonn, in the news release. “It’s critical for science to be able to use such data as comprehensively and from as many sources as possible,” he added. This, of course, would include clinical laboratory test results data. (Photo copyright: University of Bonn.)
Since, as Dark Daily has reported many times, clinical laboratory test data comprises as much as 80% of patients’ medical records, such a treasure trove of information will most likely include medical laboratory test data as well as reports on patient diagnoses, demographics, and medical history. Swarm learning incorporating laboratory test results may inform medical researchers in their population health analyses.
“The key is that all participants can learn from each other without the need of sharing confidential information,” said Eng Lim Goh, PhD, Senior Vice President and Chief Technology Officer for AI at Hewlett Packard Enterprise (HPE), which developed base technology for swarm learning, according to the news release.
An HPE blog post notes that “Using swarm learning, the hospital can combine its data with that of hospitals serving different demographics in other regions and then use a private blockchain to learn from a global average, or parameter, of results—without sharing actual patient information.
“Under this model,” the blog continues, “‘each hospital is able to predict, with accuracy and with reduced bias, as though [it has] collected all the patient data globally in one place and learned from it,’ Goh says.”
Swarm Learning Applied in Study
The researchers studied four infectious and non-infectious diseases:
They used 16,400 transcriptomes from 127 clinical studies and assessed 95,000 X-ray images.
Data for transcriptomes were distributed over three to 32 blockchain nodes and across three nodes for X-rays.
The researchers “fed their algorithms with subsets of the respective data set” (such as those coming from people with disease versus healthy individuals), the news release noted.
Findings included:
90% algorithm accuracy in reporting on healthy people versus those diagnosed with diseases for transcriptomes.
76% to 86% algorithm accuracy in reporting of X-ray data.
Methodology worked best for leukemia.
Accuracy also was “very high” for tuberculosis and COVID-19.
X-ray data accuracy rate was lower, researchers said, due to less available data or image quality.
“Our study thus proves that swarm learning can be successfully applied to very different data. In principle, this applies to any type of information for which pattern recognition by means of artificial intelligence is useful. Be it genome data, X-ray images, data from brain imaging, or other complex data,” Schultze said in the DZNE news release.
The scientists say hospitals as well as research institutions may join or form swarms. So, hospital-based medical laboratory leaders and pathology groups may have an opportunity to contribute to swarm learning. According to Schultze, sharing information can go a long way toward “making the wealth of experience in medicine more accessible worldwide.”
