Tag Archives: Biomarkers

October 2023—Orders for cerebrospinal fluid testing for Alzheimer’s disease have grown at Mayo Clinic since spring 2020, when testing was first offered. When aducanumab was approved in May 2021, test orders jumped.

July 2023—When Butler Health System in early 2020 installed the Beckman Coulter DxA 5000 automation line, its hospitals were among the first in the country to do so. At the same time, Butler went live with the DxH 900 hematology analyzer.

May 2023—Behold the common coin. Note its two sides, its easy flippability. Here is Joseph Pizzolato, MD, with the first coin toss. Given the expanded use of biomarkers with a variety of tumors, and constantly evolving assays, how hard is it for medical oncologists to navigate testing? “It’s not difficult at all now,” says a cheerful Dr. Pizzolato, medical director of the comprehensive therapeutic unit of Sylvester Comprehensive Cancer Center, University of Miami Health System, as well as medical director of the Aventura satellite at Sylvester. With third-party companies integrating test ordering directly into electronic medical records, he adds, “It’s getting even easier to order tests and see the results.” Agreed, says his colleague Rhonda Yantiss, MD, director of surgical pathology, Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine. And therein lies the problem. “It’s kind of a mess,” she says. In practice, precision medicine is becoming both more and less precise.

May 2023—For fluid biomarkers in the diagnosis of Alzheimer’s disease, the pace of research and related industry and regulatory developments in the past year has been brisk.

April 2023—After years of excitement and scientific breakthroughs, the use of molecular testing to guide cancer therapeutics finally is coming into its own. Unfortunately, it appears to have landed in the wrong place at the right time. That place is a lonely spot, surrounded by gaps in economics and coverage, as well as knowledge, guidelines, ordering patterns, turnaround times, reporting, and the like. So plentiful are the gaps that, put together, they could form a vast, inhospitable space, a veritable Colorado Plateau, with molecular testing as a majestic, enticing but remote rocky pinnacle in the middle. Think Monument Valley. It’s worth the trek. The evidence in support of genomic profiling continues to grow. Simply put, “Patients with the right markers who get the right drugs do better,” says Neal Lindeman, MD, vice chair, laboratory medicine and molecular pathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine/New York Presbyterian Hospital. But as numerous studies are showing, the lag in testing is growing as well.

April 2023—Traumatic brain injury triage in the emergency department is badly in need of biomarkers—and ones that can change practice. “If biomarkers don’t change practice, they’re a waste of time,” said W. Frank Peacock IV, MD, professor of emergency medicine, vice chair of research, and research director, Department of Emergency Medicine, Baylor College of Medicine.

April 2023—How is the demand for biomarker tests linked to new oncology drugs playing out in your health system? It is one of several questions laboratory leaders answered in a March 7 Compass Group call led by Stan Schofield, VP and managing principal of the Compass Group and formerly of NorDx/MaineHealth. That and digital pathology and the cost of storage, staffing and wages, the release of results, and the financial implications of the end of the public health emergency were the topics of the day. The Compass Group is an organization of not-for-profit IDN system laboratory leaders who collaborate to identify and share best practices and strategies.

February 2023—Like a thriving expat, Deborah Dillon, MD, is comfortable moving within worlds both old and new. Specifically, as a breast and molecular pathologist at Brigham and Women’s Hospital, she appreciates the biomarkers she and her colleagues grew up with, so to speak, as well as those that are part of a more recently arrived-at scenery. Not everyone finds both worlds equally riveting. “A lot of people are much more interested in, and excited by, new markers,” she says. “When I talk to people from pharma, this is what they want to hear about.” So do many pathologists, oncologists, and patients—new markers and new therapies have a way of updating hopes. Dr. Dillon understands the persistent thrill of the new, why people want her to talk the language of PIK3CA, PARP inhibitors, MMR, NTRK fusions, ESR1, and the like. But as an in-demand speaker as well as in a recent interview with CAP TODAY, she also advocates for making the old—the longstanding trinity of ER, PR, and HER2—seem new again.

November 2022—The lack of tools for assessing traumatic brain injury has long bedeviled physicians. There’s CT. And then? “This has been an unmet medical need for years,” says Ramon Diaz-Arrastia, MD, PhD, the John McCrea Dickson, MD, professor of neurology and director of the Clinical Traumatic Brain Injury Research Center, University of Pennsylvania Perelman School of Medicine. “As many of us know, it’s one of the major barriers that has hindered clinically advanced development of new therapies in TBI. And I think it’s pretty clear that the clinical evaluation alone leaves a lot to be desired.” “I am always frustrated that we have limited tools,” agrees Frederick Korley, MD, PhD, associate professor and associate chair for research in emergency medicine, University of Michigan Medical School, and scientific director, Massey TBI Grand Challenge, Weil Institute, University of Michigan. That’s now on the cusp of changing. Blood-based biomarkers for brain injury may not be bellying up to the bar just yet, but they are starting to raise the bar for how physicians assess TBI.

September 2022—It may not be the oldest story in the world, but in clinical laboratories it’s an oft-told tale: Tumor meets biomarker; drug meets companion diagnostic; both meet FDA approval; clinicians meet with patients offering new hope—and those in the lab are left trying to figure out how to make it all work. That story is playing out again in the realm of measuring tumor mutational burden. In mid-2020 the FDA approved pembrolizumab as a new treatment option in adult and pediatric patients with TMB-high (≥10 mutations/megabase) solid tumors, as determined by the FDA-approved FoundationOne CDx assay. “That doesn’t sound too controversial, right?” says Alain Borczuk, MD, vice chair of anatomic pathology and director of oncologic pathology, Northwell Health Cancer Institute. “It’s not the only way in, but it’s one of the ways in. If you’re arguing for your patient that this is the biomarker that makes them eligible for the drug, then the next questions will be, What was the number? And what was the test?” And it’s off to the races.

September 2022—Which biomarker for heart failure should be used—BNP or NT-proBNP—and does it matter? That’s the question Christopher W. Farnsworth, PhD, set out to answer in his “hot topic” talk (one of a trio) at the AACC meeting in July.

May 2022—Studies show promise for new approaches to biomarkers for myocarditis diagnosis, one of which is circulating micro­RNA mmu-miR-721. Another biomarker, sera soluble ST2 (sST2), which has been found to be clinically useful in predicting heart failure, could be added to existing biomarkers used to diagnose patients with myocarditis, interpreted according to sex and age. And serial high-sensitivity troponin measurements might be another approach to diagnosing and monitoring myocarditis.

October 2021—It’s not quite six degrees of Kevin Bacon, but the connection between Alzheimer’s disease biomarkers and equity in medicine is real (and far more important). It’s a trail researchers have been following for some time, but which has gained more prominence with the recent approval of a new drug for treating the disease (aducanumab) and the acknowledgment of racial disparities in CSF amyloid and tau biomarkers and their associated cutoffs.

September 2021—Beginning next year, CAP-accredited laboratories that perform HER2 immunohistochemistry in gastroesophageal adenocarcinoma or highly sensitive (hs) ALK in non-small cell lung cancer will be required to enroll in proficiency testing for those analytes.

August 2021—The FDA’s approval in June of a new drug to treat Alzheimer’s disease has incited motley responses, a sort of Grand Tour of emotions and reactions. As with any stormy action, the aftermath becomes clear only over time, during the hard work of cleaning up. What comes next?

February 2021—Absorbing new biomarkers into lung cancer workups makes for a complicated diplomacy. How best to balance so many rivals? Does it make the most sense for laboratories to try to do everything at once, a full-court press involving next-generation sequencing panels? Or is it more practical to add a new marker only as a new targeted therapy receives approval? Where do RNA-based assays fit in? What about IHC? When do you make the switch? Or do you? And how best to handle cell-free DNA tests (which seem to be the rogue states in all this)? How do you weight external factors, such as reimbursement, existing equipment and capital expenditures, and physician expertise? Driving this all are medical breakthroughs. As with all forms of statecraft, the latest incident can change everything. For lung cancer, the most recent advance comes from the ADAURA trial, which showed a significant benefit of using osimertinib to treat stage IB to IIIA EGFR-mutation positive non-small-cell lung cancer.

October 2020—With MGMT gene promoter methylation observed in about 50 percent of glioblastomas, it remains a biomarker of strong clinical interest in routine practice, even though it’s not the sole determinant in decisions related to therapy. PCR and pyrosequencing are the most commonly used assays, and there’s a technique that is not yet mainstream but gaining interest, said Tejus A. Bale, MD, PhD, assistant attending pathologist in the Department of Neuropathology and Diagnostic Molecular Pathology, Memorial Sloan Kettering Cancer Center. Dr. Bale spoke June 30 in the first of a series of Association for Molecular Pathology webinars on emerging and evolving biomarkers.

June 2020—Testing rates for actionable biomarkers in metastatic non-small cell lung cancer patients are below where they should be, and the overlap of PD-L1 expression with genomic targets causes confusion for oncologists and patients, said Geoffrey R. Oxnard, MD, oncologist at Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School, in a recent CAP TODAY webinar.

February 2020—Cost-effectiveness analysis of health care diagnosis and treatment, unfortunately connoting quotas and spartan budgets, may not have the best reputation among the general public.

January 2020—Since the Journal of Irreproducible Results arrived on the scene in 1955, founded by a physicist and a virologist, its parodies of scientific research have amused and skewered many in the scientific community. But in the world of clinical research, irreproducibility is a less than whimsical idea.

October 2019—Chlorinated lipids have been shown to be new potential biomarkers for sepsis, and continuing research into their role could lead to faster diagnosis, said David A. Ford, PhD, of Saint Louis University School of Medicine, at this year’s AACC annual meeting. Dr. Ford, a professor of biochemistry and molecular biology, discovered chlorinated lipids in 2002, and at the AACC meeting he shared recent research on the association between chlorinated lipids and lung injury and death in sepsis patients.

March 2018—The central idea of the film Minority Report—that a “precrime” police unit can predict and prevent crimes—still mostly inhabits the realm of science fiction. Luckily, in medicine, researchers studying “predisease” can make headway on prevention by analyzing the laboratory test results from samples collected years earlier, when patients showed no clinical symptoms, that might have been able to predict disorders such as chronic kidney disease (CKD) in those patients.

December 2016—Matt Damon in Interstellar. Julia Roberts in The Player. Gene Hackman in Young Frankenstein. When movie stars appear in uncredited parts, it’s usually for a cameo, not a leading role. But in diagnostics, an uncredited or off-label use of an assay might be its main use—possibly even its most clinically important use.

October 2016—An automated immunoassay has been created for symmetric dimethylarginine, or SDMA, a biomarker that can detect chronic kidney disease between 10 to 17 months earlier than creatinine, with 100 percent sensitivity and 91 percent specificity. And, unlike with creatinine, a patient’s muscle mass does not influence the biomarker’s reliability.

November 2015—Cardiologist James Januzzi Jr., MD, sounds like he could be running for political office. Are you going to settle for something different? Or is it time to demand something better?

August 2015—Forget the lone tree falling down, unnoticed and thus possibly soundless, in the forest. For pathologists and medical oncologists, the more meaningful philosophical question involves breast cancer biomarkers. If a biomarker looks promising in research, will its impact be felt in clinical practice?

July 2015—Getting the upper hand on chronic kidney disease requires taking maximum advantageof existing CKD biomarker capabilities. It also means discovering new markers, though the trick is finding those that can expand treatment options. Some believe fibroblast growth factor-23 has the potential to fit that bill, with one researcher calling it “among the most exciting new targets in chronic kidney disease.”

June 2015—Last fall, the FDA cleared Astute Medical’s NephroCheck to pinpoint critically ill adults likely to manifest moderate to severe acute kidney injury within 12 hours. The urine biomarker test’s investigators believe NephroCheck will give clinicians the early warning signs they need to head off impending cases of AKI, though it remains to be seen whether that hoped-for prevention will bear out in clinical outcomes studies. One important laboratory hurdle to widespread use of the test is that it is performed on a countertop instrument separate from the automated line used for all other urinalyses.

November 2013—Like turning around an ocean-going tanker, changing widely accepted testing practices in kidney disease, one of the nation’s most common disorders, may have to be done gradually. But the latest study comparing the biomarkers cystatin C and creatinine, published in the Sept. 5 New England Journal of Medicine (2013;369:932–943), is the most sweeping study to date and should provide new impetus to wider use of cystatin C.