Publisher Health

The human brain’s adaptability to internal and external changes, known as neural plasticity, forms the foundation for understanding cognitive functions like memory and learning, as well as various neurological disorders. New research conducted by a team led by Dr. PARK Joo Min of the Center for Cognition and Sociality within the Institute for Basic Science (IBS) unveils a novel technique that could transform the treatment landscape for brain disorders. The team developed a non-invasive brain stimulation method called Patterned Low-Intensity Low-Frequency Ultrasound (LILFUS), which holds tremendous potential for inducing long-lasting changes in brain function.
Traditionally, magnetic and electrical brain stimulation methods have been used to modulate brain function. However, these methods come with inherent limitations that restrict their spatial resolution and penetration depth, making it challenging to precisely stimulate specific brain regions with optimal efficacy. More invasive methods, such as those that require surgical procedures, exhibit superior control and therapeutic effects for specific deep brain stimulation, but they come with risks such as tissue damage, inflammation, and infection. These limitations have fueled the search for alternative approaches that can overcome these constraints and provide more efficient and precise modulation of brain function.
In the latest study unveiled by the IBS, researchers used ultrasound to enable precise stimulation of specific brain areas. Unlike electromagnetic waves, ultrasound has the advantage of being able to penetrate deep into the brain tissues. The researchers discovered that ultrasound stimulation can modulate neural plasticity — the brain’s ability to rewire itself — through the activation of key molecular pathways. Specifically, the study pinpointed the ultrasound’s effect on mechanosensitive calcium channels in astrocytes, which controls the cells’ ability to uptake calcium and release neurotransmitters.
LILFUS was designed based on specific ultrasound parameters that mimic the brainwave patterns of theta (5 Hz) and gamma (30 Hz) oscillations observed during learning and memory processes. The new tool allowed the researchers to either activate or deactivate specific brain regions at will — intermittent delivery of the ultrasound was found to induce long-term potentiation effects, while continuous patterns resulted in long-term depression effects.
One of the most promising aspects of this new technology is its ability to facilitate the acquisition of new motor skills. When the researchers delivered ultrasound stimulation to the cerebral motor cortex in mice, they observed significant improvements in motor skill learning and the ability to retrieve food. Interestingly, researchers were even able to change the forelimb preference of the mice. This suggests potential applications in rehabilitation therapies for stroke survivors and individuals with motor impairments.
The implications of this research extend far beyond motor function. It may be used to treat conditions such as depression, where altered brain excitability and plasticity are prominent features. With further exploration, LILFUS could be adapted for various brain stimulation protocols, offering hope for various conditions ranging from sensory impairments to cognitive disorders.
Dr. Park stated, “This study has not only developed a new and safe neural regulation technology with long-lasting effects but has also uncovered the molecular mechanism changes involved in brainwave-patterned ultrasound neural regulation.” He further conveyed, “We plan to continue follow-up studies to apply this technology for the treatment of brain disorders related to abnormal brain excitation and inhibition and for the enhancement of cognitive functions.”

A drug can make life safer for children with food allergies by preventing dangerous allergic responses to small quantities of allergy-triggering foods, according to a new study led by scientists at the Stanford School of Medicine.
The research will be published Feb. 25 in the New England Journal of Medicine. The findings suggest that regular use of the drug, omalizumab, could protect people from severe allergic responses, such as difficulty breathing, if they accidentally eat a small amount of a food they are allergic to.
“I’m excited that we have a promising new treatment for multifood allergic patients. This new approach showed really great responses for many of the foods that trigger their allergies,” said the study’s senior author, Sharon Chinthrajah, MD, associate professor of medicine and of pediatrics, and the acting director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford Medicine.
“Patients impacted by food allergies face a daily threat of life-threatening reactions due to accidental exposures,” said the study’s lead author, Robert Wood, MD, professor of pediatrics at Johns Hopkins University School of Medicine. “The study showed that omalizumab can be a layer of protection against small, accidental exposures.”
Omalizumab, which the Food and Drug Administration originally approved to treat diseases such as allergic asthma and chronic hives, binds to and inactivates the antibodies that cause many kinds of allergic disease. Based on the data collected in the new study, the FDA approved omalizumab for reducing risk of allergic reactions to foods on Feb. 16.
All study participants were severely allergic to peanuts and at least two other foods. After four months of monthly or bimonthly omalizumab injections, two-thirds of the 118 participants receiving the drug safely ate small amounts of their allergy-triggering foods. Notably, 38.4% of the study participants were younger than 6 years, an age group at high risk from accidental ingestions of allergy-triggering foods.
Allergies are common
Food allergies affect about 8% of children and 10% of adults in the United States. People with severe allergies are advised to fully avoid foods containing their allergy triggers, but common allergens such as peanuts, milk, eggs and wheat can be hidden in so many places that everyday activities such as attending parties and eating in restaurants can be challenging.

“Food allergies have significant social and psychological impacts, including the threat of allergic reactions upon accidental exposures, some of which can be life-threatening,” Chinthrajah said. Families also face economic impacts from purchasing more expensive foods to avoid allergens, she added.
In the best available treatment for food allergies, called oral immunotherapy, patients ingest tiny, gradually increasing doses of allergy-triggering foods under a doctor’s supervision to build tolerance. But oral immunotherapy itself can trigger allergic responses, desensitization to allergens can take months or years, and the process is especially lengthy for people with several food allergies, as they are usually treated for one allergy at a time. Once they are desensitized to an allergen, patients also must continue to eat the food regularly to maintain their tolerance to it — but people often dislike foods they were long required to avoid.
“There is a real need for treatment that goes beyond vigilance and offers choices for our food allergic patients,” Chinthrajah said.
Omalizumab is an injected antibody that binds and deactivates all types of immunoglobin E, or IgE, the allergy-causing molecule in the blood and on the body’s immune cells. So far, omalizumab appears able to provide relief from multiple food allergens at once.
“We think it should have the same impact regardless of what food it is,” Chinthrajah said.
Injections stave off severe reactions
The study included 177 children with at least three food allergies each, of whom 38% were 1 to 5 years old, 37% were 6 to 11 years old, and 24% were 12 or older. Participants’ severe food allergies were verified by skin-prick testing and food challenges; they reacted to less than 100 milligrams of peanut protein and less than 300 milligrams of each other food.

Two-thirds of the participants were randomly assigned to receive omalizumab injections, and one-third received an injected placebo; the injections took place over 16 weeks. Medication doses were set based on each participant’s body weight and IgE levels, with injections given once every two or four weeks, depending on the dose needed. The participants were re-tested between weeks 16 and 20 to see how much of each allergy-triggering food they could safely tolerate.
Upon re-testing, 79 patients (66.9%) who had taken omalizumab could tolerate at least 600 mg of peanut protein, the amount in two or three peanuts, compared with only four patients (6.8%) who had the placebo. Similar proportions of patients showed improvement in their reactions to the other foods in the study.
About 80% of patients taking omalizumab were able to consume small amounts of at least one allergy-triggering food without inducing an allergenic reaction, 69% of patients could consume small amounts of two allergenic foods and 47% could eat small amounts of all three allergenic foods.
Omalizumab was safe and did not cause side effects, other than some instances of minor reactions at the site of injection. This study marks the first time its safety has been assessed in children as young as 1.
More questions
More research is needed to further understand how omalizumab could help people with food allergies, the researchers said.
“We have a lot of unanswered questions: How long do patients need to take this drug? Have we permanently changed the immune system? What factors predict which people will have the strongest response?” Chinthrajah said. “We don’t know yet.”
The team is planning studies to answer these questions and others, such as finding what type of monitoring would be needed to determine when a patient gains meaningful tolerance to an allergy-triggering food.
Many patients who have food allergies also experience other allergic conditions treated by omalizumab, Chinthrajah noted, such as asthma, allergic rhinitis (hay fever and allergies to environmental triggers such as mold, dogs or cats, or dust mites) or eczema. “One drug that could improve all of their allergic conditions is exactly what we’re hoping for,” she said.
The drug could be especially helpful for young children with severe food allergies, she added, because they tend to put things in their mouths and may not understand the dangers their allergies pose, she added.
The drug could also make it safer for community physicians to treat food allergy patients, since it cannot trigger dangerous allergic reactions, as oral immunotherapy sometimes does. “This is something that our food allergy community has been waiting a long time for,” Chinthrajah said. “It’s an easy drug regimen to implement in a medical practice, and many allergists are already using this for other allergic conditions.”
The research team included scientists from the Johns Hopkins University School of Medicine, the National Institutes of Allergy and Infectious Diseases, the Icahn School of Medicine at Mount Sinai, Massachusetts General Hospital, the University of North Carolina School of Medicine, the University of Arkansas for Medical Sciences and Arkansas Children’s Hospital, Emory University School of Medicine and Children’s Healthcare of Atlanta, University of Texas Southwestern Medical Center, Perelman School of Medicine at the University of Pennsylvania, Genentech/Roche, Novartis Pharmaceuticals Corporation, and Rho, Inc.
The research was funded by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, both part of the National Institutes of Health (grant numbers UM2AI130836, UM1AI130838, UL1TR003098, UM1TR004408, UM1AI130570, UM1AI130839, UM1AI130936,UM1TR004406, UL1TR002535, UM1TR004399, UL1TR001878, UM1AI130781, UL1TR002378 and UL1TR003107), and the Claudia and Steve Stange Family Fund. Genentech/Novartis provided the investigational product and monetary support to Johns Hopkins University and collaborated on the study design.

The drug does not completely prevent reactions, but it can reduce the risks posed by trace amounts of food allergens.The Food and Drug Administration approved a drug this month that cuts the risk of severe reactions in children and adults exposed to trace amounts of peanuts, tree nuts, milk, dairy and other food allergens — a move that could dramatically improve quality of life for people coping with these risks. The results of the clinical trial supporting the decision were published on Sunday.While the drug, Xolair, offers a new layer of protection to people who may have life-threatening reactions to common foods, and especially to those who are allergic to several foods, its use comes with important caveats.Does Xolair cure food allergies?No. Xolair is not a cure for food allergies, nor can it be used to treat acute reactions. People who take Xolair must continue to avoid foods that they are allergic to.But Xolair can significantly reduce the odds that people with severe food allergies will develop acute reactions if they ingest minute amounts of allergens, like peanuts or eggs in prepared foods, or are exposed to trace amounts in some other way.People must take the drug continuously in order to benefit from its protection. Even then, the drug does not entirely eliminate the risk.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Xolair cuts the risk of dangerous reactions after exposure to minute amounts of allergens, researchers reported. But children taking it still must avoid risky foods.A drug that has been used for decades to treat allergic asthma and hives significantly reduced the risk of life-threatening reactions in children with severe food allergies who were exposed to trace amounts of peanuts, cashews, milk and eggs, researchers reported on Sunday.The drug, Xolair, has already been approved by the Food and Drug Administration for adults and children over age 1 with food allergies. It is the first treatment that drastically cuts the risk of serious reactions — like anaphylaxis, a life-threatening allergic reaction that causes the body to go into shock — after accidental exposures to various food allergens.The results of the researchers’ study, presented at the annual conference of the American Academy of Allergy, Asthma and Immunology in Washington, were published in The New England Journal of Medicine.“For a certain population of food allergy patients, this medication will be life-changing,” said Dr. Robert A. Wood, the paper’s first author and director of the Eudowood Division of Pediatric Allergy, Immunology and Rheumatology at Johns Hopkins Children’s Center.“If you have a severe milk or egg allergy, or something that was not even part of this study — like garlic or mustard — you cannot eat in a restaurant, ever,” Dr. Wood said.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Published15 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Aurelia FosterHealth reporterThe House of Lords is being urged to throw out plans for non-doctor associate roles to be licensed by the same body as doctors. Under a planned new law, physician associates (PAs) will be regulated by the General Medical Council (GMC).The British Medical Association (BMA) believes this could lead to patients confusing the different roles, which it says could have “tragic consequences”.The Department of Health and Social Care has been approached for comment.There are about 3,200 PAs working in GP surgeries and hospitals in England, with 10,000 more planned in the next decade or so.They were introduced to help doctors with their work – examining and diagnosing patients and discussing treatments with them – although PAs are currently unregulated.Unlike doctors, they do not have to hold a medical degree, but they usually have a degree in a life science and have to undertake a two-year training course.Governments GMC to regulate physician associatesCall for physician associate clarity after misdiagnosis deathUK’s biggest GP chain replacing doctors with less-qualified medicsPhysician associates ‘not doctors’The BMA, the union representing doctors in the UK, believes that regulation by the GMC could lead to a “blurring of the lines” between PAs and doctors. In an open letter to the House of Lords ahead of a debate on Monday, the BMA’s chairman Prof Phil Banfield said: “PAs are not doctors. They do not hold a medical degree and are not medically trained, despite misleading statements made by some. “We know that patients are already confused about telling the difference between PAs and doctors, and this legislation will make this problem worse.”Keeping the GMC as the regulator exclusively of doctors would mean we retain the clear distinction between doctors and PAs.” The BMA believes PAs should instead be licensed by the Health and Care Professions Council (HCPC), which regulates other medical professionals such as paramedics and radiographers. Like the GMC, the HCPC’s function is to set standards, assure quality and investigate complaints.Under the same order, anaesthesia associates (AAs) working in the NHS would also come under the regulation of the GMC. AAs help anaesthetists, and should be supervised.An NHS spokesperson said: “Physician associates play an important role in supporting the NHS to provide high-quality care for patients, but this should always be with appropriate supervision and within the scope of their practice.”More on this storyGovernment wants to regulate NHS associate rolesPublished11 December 2023Unqualified medics given senior hospital rolesPublished21 November 2023Call for physician associate clarity after deathPublished15 July 2023GP chain swapping doctors for less qualified staffPublished13 June 2022Related Internet LinksThe BMANHS EnglandDepartment of Health and Social CareHouse of Lords – UK ParliamentThe BBC is not responsible for the content of external sites.

The F.D.A. recently approved the first therapy for patients in danger of losing their toes, fingers and other exposed parts of the body.The first time Dr. Peter Hackett saw a patient with frostbite, the man died from his wounds. It was in Chicago in 1971, and the man had gotten drunk and passed out in the snow, his fingers so frozen that gangrene eventually set in.Dr. Hackett later worked at Mount Everest Basecamp, on Denali, Alaska, and now in Colorado, becoming expert in treating cold-weather injury. The experience was often the same: There was not much to do about frostbite, except rewarm the patient, give aspirin, amputate in severe cases and, more often, wait and accept that six months later the patient’s body might “auto-amputate” by naturally shedding a dead finger or toe.His mentor in Anchorage used to say, “Frostbite January, Amputation July,” remembered Dr. Hackett, clinical professor at the Altitude Research Center at the University of Colorado’s Anschutz Medical Campus. “For centuries, there was nothing else to do.”This month, the Food and Drug Administration approved the first therapy for treatment of severe frostbite in the country. The drug, iloprost, is given intravenously for several hours a day over a little more than week. It works by opening blood vessels to improve circulation, limiting inflammation and stopping the formation of platelet clumps that can stop circulation and kill tissue. Most at risk are a person’s toes, fingers, ears, cheeks and nose.The approval of the treatment is as much scientific novelty as it is pharmaceutical industry moneymaking bonanza. Experts say there is not good data on how many people suffer severe enough frostbite to receive this therapy. But the cases could be as few as several dozens of people a year in the United States, according to Dr. Norman Stockbridge, head of the F.D.A.’s division of cardiology and nephrology in the agency’s Center for Drug Evaluation and Research, which approved the drug.“When you get down to people who get really frostbitten and really at risk of losing digits, it’s pretty uncommon,” Dr. Stockbridge said. Still, “it’s better to have a drug for this than nothing.”We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Appointment cancellations and financial distress have become a constant at Bethesda Pediatrics, a nonprofit medical clinic in East Texas that is heavily dependent on Medicaid, the health insurance program for the poor.On a recent Monday, the mother of a toddler who had a primary care appointment broke down in tears after learning the child had just lost Medicaid coverage, wondering how she could pay the bill.Another mother told Dr. Danny Price, the clinic’s lead pediatrician, that she was afraid to get her child a flu shot because of the $8 fee she would have to pay now that the child had been dropped from Medicaid. A child with depression did not show up, most likely, Dr. Price presumed, because of having lost Medicaid coverage.The uncertainty and panic at the clinic, tucked inconspicuously in a poor residential pocket of Tyler, Texas, highlight a little-examined consequence of the vast trimming of the Medicaid rolls since a policy that barred states from kicking anyone out of the program during the pandemic ended last spring. The loss of coverage has not only affected families, but is also threatening the financial stability of vital components of the American safety net.Medicaid payments are “the lifeblood of our health centers and their ability to serve,” said Dr. Kyu Rhee, the president and chief executive of the National Association of Community Health Centers, which treat roughly one in 11 people in the United States and rely on Medicaid and federal grants to provide a financial cushion for the uncompensated care they give uninsured patients.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

The magazine’s Ethicist columnist on whether it’s appropriate to offer an unsolicited medical diagnosis.When our neighbor died a few months ago, his companion was grief-stricken. Although she lives separately in a rural town an hour away, they spoke every day. We knew her hardly at all, but she asked us to keep an eye on the now-vacant home, which she will eventually inherit.Now she comes periodically to sort through our neighbor’s possessions and prepare the house for sale. In doing so, it has become apparent that he was a hoarder, and she has turned to us again — for help in understanding the value of many of his things and for physical help with the sorting of them. She is overwhelmed. Her movements are slow, her decisions are hesitant and her stamina is limited.I happen to be a retired neurologist. Over the course of many days spent helping and observing her, I’ve become convinced she has Parkinson’s disease. I concluded that much of the slowness and hesitancy we initially attributed to her shock and emotional fatigue is, instead, a result of her as-yet-undiagnosed neurological illness. With the passage of time, I am increasingly confident of my observations.There’s been no occasion to mention my professional background, and I’m now uncertain about whether I should tell her about it and my clinical impressions. Her disease, at its current stage, is likely to be successfully managed with oral medication. However, it is neither obvious that she will have access to skilled neurological care nor that she will be willing to seek it. And a new diagnosis of Parkinson’s, without prompt treatment, on top of her recent loss and the challenges that have followed, may further overwhelm her. My wife is in favor of my informing her, because treatment would benefit her quality of life. I’m hesitant, as there has been no invitation to become more involved in her personal life, and I cannot provide her with a supportive doctor-patient relationship. What would you recommend? — Name WithheldFrom the Ethicist:You offer two reasons for not saying anything. One is that she hasn’t asked for your involvement in her personal life. Given that she knows nothing of your qualifications, though, she has had no cause to. The second is that the information might bring her distress without any benefit. But as a former professional in the field, you’re in a position to reduce that risk by advising her how to access the necessary care. Treatment that could help alleviate her symptoms would be the best outcome. Surely you would want to know if you had a treatable medical condition.I wonder whether you’re worried that if you tell her what you’ve noticed, you’ll be drawn into her life in demanding ways. After all, you’ve probably spent a lot more time in your neighbor’s house than you had expected. But you can draw a clear boundary here: You’re not her doctor and you’re not going to be her doctor. You happen to be qualified to give her some medical counsel that could lead to treatment and substantially improve her ability to function. You’re not offering to be her Virgil through the underworld of neurological care.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Violence against teachers is likely to be higher in schools that focus on grades and test scores than in schools that emphasize student learning, a new study has found.
Researchers surveyed over 9,000 U.S. teachers shortly before and during the height of the COVID-19 pandemic about their perception of the instructional emphasis in their schools. Participants also reported whether they had been subjected to physical, verbal or property violence — by students, parents, colleagues and/or administrators.
Results showed that a school culture focused on performance was associated with higher levels of all types of teacher-directed violence before and during COVID-19, while school emphasis on mastery of material was related to lower levels of violence aimed at educators.
“What was really striking was this performance culture predicted all kinds of increased violence by students, whether it be physical violence, verbal threatening or property violence,” said Eric Anderman, lead author of the study and professor of educational psychology at The Ohio State University.
“It wasn’t the mastery part. It was when there’s this focus on grades and test scores — ‘you’ve got to get good grades, school is all about grades’ — that’s when kids acted out against teachers.”
Given the evidence that nearly half of U.S. teachers are highly unsatisfied, the authors concluded that fostering a school culture of deep engagement in learning could make students happier and teachers safer.
The study was published online Feb. 20 in the Journal of School Violence.

Anderman and colleagues surveyed a total of 9,363 teachers of pre-K to high school classes in suburban, urban and rural districts across the United States over two time periods: between fall 2019 and March 2020, and during the 2020-2021 academic year.
Among the types of violence teachers reported included objects being thrown at them, obscene remarks or gestures directed their way, and damage to personal or classroom property. When assessing school culture, they rated such statements as “Teachers believe all students can learn,” an indication of a climate focused on mastery, or “Teachers treat kids who get good grades better than other kids,” signaling a climate focused on performance and grades.
Statistical analysis of the data controlled for numerous variables to look specifically for the link between school climate and violence directed at teachers.
In addition to those connections, the study showed that this violence didn’t stop during and shortly after the COVID-19 lockdown. About 65% of surveyed teachers reported at least one incidence of verbal threats or property damage by students before the pandemic, compared to 32% and 26% of teachers reporting similar incidents, respectively, in 2020-21. Over half of teachers reported violence by parents before COVID-19, a figure that dropped to 29% early in the pandemic.
“The rates are lower, but the rates are still there,” Anderman said. “People say no one was in schools then. That’s not true. A lot of times teachers were in the building, but the students were at home. And some of the violence occurred over Zoom.”
Student violence toward teachers was more common overall, but the study showed the same relationship trend between school culture and rates of teacher-directed violence by parents, colleagues and administrators.

“If the school was really focused on grades, you had more instances of parents, colleagues and administrators doing things that were harmful to teachers,” Anderman said. “But if the school focused on mastery — if people in school said this is a place where we really encourage kids to learn as much as they can to master material — you for the most part get less of the colleagues and parents and administrators engaging in any type of violence perpetrated against teachers.”
Anderman described a mastery climate as one in which students who take longer than a peer to solve a math equation aren’t considered worse students, and where students who perform poorly on a test might be given a do-over to try to bring up their grade. With mastery, grades still matter — but encouraging kids to really learn is the larger goal.
On the other hand, pushing students to get good grades can lead to frustration, a major predictor of aggressive behavior, he said.
“This is something we can change that doesn’t cost millions of dollars to change,” Anderman said. “This is taking time to really think about when we’re talking to kids, how much are we stressing the grades? This is about changing the way we talk to kids about what learning is about and what is really important.”
This study was part of the work of the American Psychological Association Task Force on Violence Against Teachers and School Personnel.
Co-authors included Ohio State postdoctoral researchers Andrew Perry and Hyun Ji Lee, and task force members from DePaul University; the University of California, Los Angeles; the University of North Carolina at Chapel Hill; the Center for Justice Innovation; Rutgers University; and the University of California, Berkeley.

A new study identified a set of 140 genes that may help predict enhanced disease-free survival in patients with non-small cell lung cancer (NSCLC) treated with a combination of immunotherapy and low-dose radiation. The results, published in Cell Reports Medicine on Feb. 23, suggested that this “gene signature” could be used to identify a subclass of lung tumors that is more likely to be eradicated by immunotherapies.
Immunotherapy has saved countless lives but only 20 to 25 percent of patients respond to this treatment that activates a person’s own immune system to attack their cancer. Predicting who would benefit from this approach and why could help patients who have exhausted other options such as chemotherapy.
Studying a cohort of 60 patients with NSCLC, the team determined previously that adding a low dose of radiation to a course of durvalumab, an immune-boosting drug, promoted cancer-free survival in most of these individuals. Now, to assess why some tumors didn’t respond to the therapy, the researchers examined pretreatment tumor biopsies from this study cohort. They determined the gene expression profiles, which showed the specific genes that are turned up and those that turned down in each sample.
They compared the gene expression profiles of ten tumors that reached major pathologic response (MPR) — the elimination of more than 90 percent of the cancer cells in patients’ tumors — with combination treatment versus six that did not. They discovered the two groups of pretreatment tumors could be reliably distinguished by a set of genes with 135 of the genes turned up and 5 turned down. The majority of the 135 genes were associated with enhanced cell growth, suggesting the tumors that responded to the dual therapy were particularly aggressive.
The researchers were also able to examine how the gene expression profile changed in the responsive cancers before and after treatment. They found that in tumors displaying MPR, dual therapy not only reversed the activity of this 140-gene set, it also increased the activation of genes associated with cellular pathways involved in immunity and tissue repair.
The activity of the 140 genes which correlated with treatment response is particularly promising as clinicians could use the signature to identify people who would gain the maximum benefit from immunotherapy.
The researchers plan to test whether tumors with this aggressive gene signature have a better response to the combination therapy in a larger patient study.