This is a pseudo-colored image of high-resolution gradient-echo MRI scan of a fixed cerebral hemisphere from a person with multiple sclerosis.
Credit: Govind Bhagavatheeshwaran, Daniel Reich, National Institute of Neurological Disorders and Stroke, National Institutes of Health
The immune system’s reaction to the common Epstein-Barr virus can ultimately damage the brain and contribute to multiple sclerosis (MS). This is shown by new research from Karolinska Institutet, published in Cell. The study provides new insight into the long-suspected link between Epstein-Barr virus (EBV) and MS.
Multiple sclerosis is a chronic inflammatory disease in which the immune system attacks the central nervous system and causes nerve damage. It has long been known that everyone who develops MS has had an infection with the Epstein-Barr virus (EBV) – a common virus that often infects young people, sometimes causing glandular fever but often without any obvious symptoms.. Exactly how this virus contributes to MS has long been unclear.
The new study shows that when the immune system fights EBV, certain T cells – which normally attack the virus – can also react to a protein in the brain called Anoctamin-2 (ANO2). This phenomenon is called molecular mimicry – immune cells mistaking the body’s own proteins for those of the virus.
The researchers found that these cross-reactive T cells are significantly more common in people with MS than in healthy controls. The study builds on previous research showing that misdirected antibodies after EBV infection may play a role.
“Our results provide mechanistic evidence that immune responses to EBV can directly damage the brain in MS. It is a complex neurological disease, and it may be that the molecular mechanisms vary between patients,” says the study’s first author, Olivia Thomas, assistant professor at the Department of Clinical Neuroscience at Karolinska Institutet.
The study is based on analyses of blood samples from people with MS and compared with healthy controls. The researchers were able to isolate T cells that react to both the EBV protein EBNA1 and ANO2 from people with MS. In addition, experiments in a mouse model showed that these cells can exacerbate MS-like symptoms and cause damage to the brain.
According to the researchers, the results may help explain why some people develop MS after an EBV infection while others do not.
“The discovery opens up new treatments that target these cross-reactive immune cells. Since several EBV vaccines and antiviral drugs are now being tested in clinical trials, the results may be of great importance for future preventive and therapeutic efforts,” says Professor Tomas Olsson, who led the study together with Associate Professor Andre Ortlieb Guerreiro-Cacais at the same institution.
Rates of multiple myeloma (MM), the second most common blood cancer in the United States, are increasing and are twice as high in men than in women. A new study published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society, provides insights that may help to explain this disparity.
To investigate the sex difference in MM, researchers analyzed data on 850 patients with newly diagnosed MM enrolled in the Integrative Molecular And Genetic Epidemiology (IMAGE) study at the University of Alabama at Birmingham.
Compared with female patients, male patients were more likely to have advanced (International Staging System stage III) disease at the time of diagnosis. Males were also more likely to have high myeloma load—serum monoclonal protein (an abnormal protein produced by cancerous blood cells), more organ failure (especially kidney failure), and bone damage. Men were less likely than women to have low bone mineral density, and myeloma-defining features tended to differ between the two sexes. These differences were apparent even after taking numerous factors into account – including race, age, body mass index, education, income, smoking, and alcohol use.
Analyses suggested that certain chromosomal abnormalities that lead to initiation of myeloma occurring more often in younger males may help to explain some of the differences seen in this study.
“This research suggests that sex-specific mechanisms promote multiple myeloma pathogenesis, which may account for the excess risk seen in men,” said lead author Krystle L. Ong, PhD, of the O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham. “These findings may be used to improve risk stratification, diagnosis, and tailored treatments for both men and women with newly diagnosed multiple myeloma or related early precursor conditions.”
Just five extra minutes of moderate intensity physical activity a day or sitting half an hour less could make a measurable difference for public health, according to a new study published in The Lancet.
Researchers analysed data from more than 135 000 adults in Norway, Sweden, USA, and the UK to understand how small, realistic changes in daily habits affect mortality. Using device-measured physical activity, the team estimated how many deaths could be prevented if people moved a little more or spent less time sitting.
The findings suggest that even modest changes matter. For the least active individuals, adding just five minutes of moderate-to-vigorous physical activity per day could prevent about 6% of deaths. When applied across the population – excluding the most active – this figure rises to 10%.
Reducing sedentary time also showed benefits, though smaller. Sitting 30 minutes less each day could prevent around three percent of deaths among the least active and seven percent across the population.
Maria Hagströmer, professor at the Department of Neurobiology, Care Sciences and Society. Photo: Ulf Sirborn.
“These results show that small steps can have a large impact,” says Maria Hagströmer, professor at the Department of Neurobiology, Care Sciences and Society and co-author of the study. “You don’t need to run marathons—just a few extra minutes of brisk walking each day can make a difference.”
Ing-Mari Dohrn, docent at the same department and also a co-author of the study, adds: “Our study focuses on realistic changes. For many people, reducing sitting time or adding short bouts of activity is more achievable than large lifestyle modifications.”
The researchers emphasise that these changes are not a substitute for regular exercise but highlight how small adjustments can contribute to better health at the population level.
Killer T cells surround a cancer cell. Credit: Alex Ritter, Jennifer Lippincott Schwartz and Gillian Griffiths, National Institutes of Health (CC BY 2.0).
Adult patients with an aggressive form of leukaemia will be able to receive a breakthrough immunotherapy, which was invented by University College London researchers, on the NHS within weeks following approval for use by the UK’s National Institute for Health and Care Excellence (NICE).
The CAR T-cell therapy – known as ‘obe-cel’ and marketed as Aucatzyl – involves taking a patient’s immune cells and reprogramming them in a lab to identify and target their cancer, before returning them to the body as ‘living medicine’.
Obe-cel is a second-generation CAR T cell therapy invented by scientists from the UCL Cancer Institute, led by Dr Martin Pule, and has delivered promising results in treating patients with acute lymphoblastic leukaemia (ALL), an aggressive blood cancer.
The therapy has reduced immune toxicity and persists for longer in blood cancer patients, overcoming two common limitations of earlier CAR T cell therapies. Aucatzyl was taken through clinical trials and is manufactured by UCL spinout business Autolus, which was set up with the help of UCL Business, the commercialisation company of UCL.
The development of CAR T cell therapy has had long-standing support from the National Institute for Health and Care Research (NIHR) UCLH Biomedical Research Centre (BRC).
NHS England today announced that the personalised therapy would be available on the NHS within weeks through specialist centres.
Dr Claire Roddie, one of the team who developed the treatment from UCL Cancer Institute and UCLH consultant haematologist, said: “I am delighted to hear of NICE’s decision. Many more patients now stand to benefit from CAR-T cell therapy on the NHS.
“We have been working on proving the safety and efficacy of this drug since 2017 and it has brought together clinical and research teams from UCL and UCLH, with support from government and arm’s-length bodies like the NIHR and the BRC as well as the pharmaceutical industry.
“The many, many people involved in this work can feel immensely proud of this achievement which will help save the lives of many more patients.”
Eligible patients will receive two doses of CAR-T therapy intravenously, ten days apart, with the treatment being delivered at specialist CAR-T centres across the country.
The treatment will be available to people aged 26 and over with B-cell acute lymphoblastic leukaemia which has returned or not responded to previous treatment.
It is estimated that it could be administered to around 50 patients each year in England.
In a clinical trial, 77% of patients saw their cancer enter remission after treatment with obe-cel, with half of those showing no signs of detectable cancer after three and a half years.
The treatment – which has been researched, developed and manufactured in the UK – was also found to have lower toxicity and was less likely to cause serious side effects than other CAR (chimeric antigen receptor) T-cell therapies.
Dr Anne Lane, UCL Business CEO, said: “This cutting-edge personalised immunotherapy has been on a 10-year journey starting with research by clinical academics in UCL’s Cancer Institute who, with the support of UCL Business, established Autolus, a spinout company dedicated to developing, trialling and bringing AUCATZYL® to market. That journey has required vision, tenacity and over £800m. Today that has hugely paid off and will benefit people across the UK. It’s an inspiring demonstration of what can be achieved when university academics, NHS hospitals and investors work together.”
Professor Peter Johnson, NHS National Clinical Director for Cancer, said: “This cutting-edge therapy has shown real promise in trials and could give patients with this aggressive form of leukaemia a chance to live free from cancer for longer – and, for some, it could offer the hope of a cure.
“This ‘living medicine’ boosts a patient’s own immune system and then guides T-cells towards the cancer to kill it – it is fantastic to have another pioneering option available on the NHS, adding to our range of CAR-T therapies which are helping people with blood cancers live longer, healthier lives.”
Harry, a 19-year-old student from Harrogate, was treated with obe-cel for B-cell ALL as part of a clinical trial in 2024. He said: “I feel so lucky to have had access to such a wondrous treatment. Not only did it work better than my doctors thought it would, it worked without many of the horrible side effects you can get from other treatments.
“I think it’s brilliant obe-cel is now available on the NHS for people over the age of 26. The biggest thing it offers is hope. When you’re facing a situation like mine, hope is the most valuable thing you can have.”
Health Minister Ashley Dalton said: “This pioneering treatment is excellent news for patients and their families, demonstrating how the NHS is at the forefront of medical innovation.
“Our 10 Year Health Plan is about harnessing our world-leading life sciences sector to deliver treatments like this – innovative therapies that save lives.
“By supporting new treatments with fewer side effects and shorter hospital stays, we’re building an NHS fit for the future whilst cementing the UK’s position as a global leader in medical research.”
Fiona Bride, interim Chief Commercial Officer and Director of Medicines Value & Access at NHS England, said: “This is a success story that’s made in Britain, and shows how collaboratively we can bring to life the ambition of the 10 Year Health Plan, showcasing how the UK’s competitive edge in life sciences can translate to better outcomes and treatments for NHS patients.
“The journey of obe-cel from scientific research in a UK university to a safe, clinically and cost-effective treatment set to be delivered through the NHS specialist CAR-T network is a remarkable one and I am grateful to colleagues who have played their part along the way.”
Acute lymphoblastic leukaemia is an aggressive cancer in the blood and bone marrow, with around 800 people being diagnosed in the UK every year, around half of which are in adults.
Data shows patients with aggressive forms of the cancer receiving chemotherapy, the current routine standard of care, live for just 10 months on average after treatment.
The therapy will be fast tracked to patients more quickly than the standard 90-day implementation period thanks to interim funding from the NHS’s Cancer Drugs Fund.
Strengthening Limpopo’s post-crash emergency response has been one of the most powerful achievements of the Limpopo Road Safety Programme (LRSP). Through a combined focus on updated clinical training, advanced rescue skills and improved operational systems, Projects 12 and 12.1 have reshaped how Emergency Medical Services (EMS) teams respond in the critical minutes after a crash – from the first emergency call to hospital handover.
Updating clinical skills to strengthen frontline emergency care
Across South Africa, the Clinical Practice Guidelines (CPGs) for emergency care have been substantially updated, including a major revision in 2018. These updates incorporated new evidence, improved patient outcomes, and standardised practice across the health system, shifting toward more user-friendly formats such as clinical decision-support tools. For Limpopo’s EMS, this presented both an opportunity and a challenge: although the guidelines were available, many personnel had not yet received training to apply them consistently in the realities of roadside emergencies. Project 12 addressed this need directly, rolling out comprehensive CPG training across all five districts. EMS practitioners were equipped with updated algorithms for trauma, medical, paediatric and obstetric emergencies, along with enhanced assessment, triage and stabilisation skills.
This clinical uplift aligned perfectly with major system improvements. In the 2023/2024 financial year, the Limpopo Department of Health procured more than 500 new, modern ambulances, significantly expanding the provincial fleet. The LRSP ensured this investment translated into real-world impact: EMS personnel were trained not only on updated CPGs but also to use the new vehicles and onboard equipment to their full potential; optimising monitoring, patient loading, scene workflow and en-route care. Modern ambulances combined with modern knowledge dramatically strengthened the quality of emergency care.
By 2025, the system advanced even further with the introduction of a Computer-Aided Dispatch (CAD) system, enabling more efficient call-taking, improved dispatch decision-making, clearer communication and better tracking of EMS resources across districts. The CAD system, together with updated CPGs and a modern ambulance fleet, created a tightly integrated platform for faster, smarter and more coordinated EMS response. For the first time, Limpopo could align clinical best practice, operational intelligence and fleet capacity into one cohesive system.
Introducing advanced rescue skills for high-severity crash scenes
Yet, while clinical updates and dispatch improvements strengthened core EMS response, Limpopo still faced a critical need for specialised capacity at high-severity crash scenes, especially those involving vehicle entrapment. Project 12.1 filled this gap by introducing the province’s first Advanced Vehicle Rescue Short Course, delivered by EPIC EM and the University of Johannesburg. Over seven intensive days, participants trained in vehicle stabilisation, extrication techniques, hydraulic tool use, and multi-casualty scene management, blending theory with realistic, high-pressure simulations. Many described the training as transformative, giving them the competence and confidence to manage complex incidents on Limpopo’s regional and mining routes.
Together, these interventions have created a step change in Limpopo’s post-crash care system. Today, EMS teams arrive at crash scenes equipped with modern ambulances, updated clinical guidance, advanced rescue skills and a CAD-supported operational network that ensures faster and more coordinated response. Patients benefit from safer extrication, quicker stabilisation and better continuity of care during the “golden hour”. Beyond improving skills, the programme has strengthened morale, professionalism and a culture of excellence within EMS.
Projects 12 and 12.1 have left a lasting legacy: a provincial emergency response system that is smarter, faster and better prepared to save lives on Limpopo’s roads.
Red blood cells and serum separate after spinning in a centrifuge in the UVM Vaccine Testing Center. (Photo: Andy Duback)
The world’s first single-dose vaccine to prevent dengue fever has been approved for licensure in one of the largest countries affected by the disease, following 16 years of research contributions by scientists at the University of Vermont (UVM) Vaccine Testing Center, in partnership with the US National Institutes of Health (NIH) and the Johns Hopkins Bloomberg School of Public Health (JHSPH).
Dengue is the most common mosquito-borne disease worldwide, with nearly half the world’s population living in places with the risk of dengue. Along with high fever and severe muscle and bone pain, the virus can lead to shock, bleeding, and death. With more than 100 million cases reported annually, dengue poses a growing risk throughout the globe. Brazil recorded 5.9 million cases of dengue and more than 6000 deaths in 2024.
The new vaccine has now been licensed for use in Brazil under the name Butantan-TV. On November 26 the Instituto Butantan, a biologic research centre in São Paulo, announced that the vaccine will be incorporated into Brazil’s national immunisation program. Additional global approvals are anticipated as the vaccine is developed through other pharmaceutical partners including Merck and the Serum Institute of India.
In addition to the vaccine approval, a promising new antiviral medication designed to prevent infection and illness in individuals exposed to dengue virus will now advance, thanks to clinical trials at the UVM Vaccine Testing Center and JHSPH. The findings were published in the November 26 issue of the New England Journal of Medicine (NEJM).
“These milestones represent a turning point in global dengue prevention and treatment,” said UVM Vaccine Testing Center founder Beth Kirkpatrick, M.D., professor and chair of the Department of Microbiology and Molecular Genetics at the Robert Larner, M.D. College of Medicine at the University of Vermont. “We are proud of the role UVM has played in advancing science that will save lives worldwide.”
Kirkpatrick served as principal investigator for the umbrella research funding award that supported early-stage clinical trials and immunology research on the vaccine at UVM. Kirkpatrick and colleagues began studying the candidate tetravalent (four-serotype) dengue vaccine in 2009 in collaboration with leaders in the dengue field: JHSPH professor Anna Durbin, M.D., and NIH virologist Steven Whitehead, Ph.D. Whitehead and colleagues at the NIH designed the candidate vaccine. Since 2009, more than 27 clinical trials have been conducted at UVM and JHSPH to develop this vaccine, yielding many major scientific and immunologic insights.
At UVM, the new dengue antiviral treatment investigation was led by Kristen Pierce, MD, co-director of the Vaccine Testing Center and professor of medicine, and by Durbin’s team at JHSPH. About 80 volunteers participated in clinical trials at the two sites.
The volunteers were randomly assigned to receive either the treatment or a placebo prior to receiving a dose of a mild strain of dengue virus. The study data published in NEJM showed that the treatment, an oral pan-dengue small molecular antiviral called Mosnodenivir, inhibits replication of dengue virus and prevents infection. An oral antiviral drug would be extremely useful during outbreaks and could be utilized by travelers and persons who are not able to receive a vaccine.
A test that rapidly detects signs of inflammatory bowel disease (IBD) in stool samples could improve future diagnosis and monitoring of the condition, a study suggests.
Microscopy images of colon tissue samples from IBD patients under remission (left) and with active disease (right). Granzyme A, indicated by green fluorescence, is elevated in the intestinal tract of IBD patients with active disease. Credit: Emily Thompson.
Scientists have developed a tool to measure the activity of a molecule linked to gut inflammation within faecal samples. The optical tool, known as a luminescent reporter, lights up when it detects the molecule, with higher readouts indicating increased activity and inflammation.
The new technique could boost the accuracy of stool sample tests for IBD, reducing the need for invasive, expensive procedures, experts say.
Gut inflammation
IBD is a chronic illness where the body’s immune system mistakenly attacks the digestive tract, leading to long-lasting inflammation. Diagnosis and monitoring of the condition often rely on colonoscopies, where a small camera is used to examine the gut.
Current IBD stool tests measure general markers of inflammation, such as the protein calprotectin, so a positive result requires further investigation to confirm the source.
University of Edinburgh researchers studied gut tissue from IBD patients and identified high levels of an enzyme – a molecule that speeds up chemical reactions in cells – called granzyme A (GzmA) in inflamed gut tissue compared with non-inflamed tissues.
Enzyme activity
GzmA is released by T cells; in IBD, T cells mistakenly see the gut as a threat and become overactive, which can lead to tissue damage and inflammation.
The research team developed a luminescent reporter to measure the activity of GzmA in stool samples. The reporter tool was tested on 150 samples from both IBD and healthy patients.
Combining the new reporting tool with the current common testing of faecal calprotectin levels was more successful in identifying IBD in patients than using faecal calprotectin scores alone.
Researchers say the ability to identify gut-specific inflammation is a step forward for IBD diagnosis, but caution further research is needed before it can be used in a clinical setting.
Spin-out company
The tool will form part of the assets of a new company in the process of spinning out of the University of Edinburgh, called IDXSense, supported by Edinburgh Innovations, the University’s commercialisation service.
The technique could also support the development of personalised IBD treatments in the future, with the ability to rapidly and accurately monitor gut inflammation levels in response to different therapies, experts say.
In a groundbreaking study published in the Proceedings of the National Academy of Sciences (PNAS), scientists at Pacific Northwest Research Institute (PNRI) have overturned a long-held belief in genetics: that inheriting two harmful variants in the same gene always worsens disease. Instead, the team found that, in many cases, two harmful variants can actually restore normal protein function.
The research focused on a human enzyme called argininosuccinate lyase (ASL), which plays a critical role in removing toxic ammonia from the body. Variants in ASL that decrease its activity cause one of the urea cycle disorders, a set of rare and potentially life-threatening metabolic diseases.
By experimentally measuring the functional impact of several thousand individual variants and variant combinations, PNRI researchers discovered that over 60% of pairs that were individually damaging could, together, bring enzyme activity back to healthy levels.
“This work shows that genetic variants don’t act independently in many important cases,” said Michelle Tang, PhD, PNRI Staff Scientist and lead author of the study. “For a defined group of genes, the default assumptions we use to predict disease risk simply don’t hold.”
This phenomenon is known as intragenic complementation. It occurs when damage caused by one variant is offset by another variant in a different part of the same protein. The mechanism was first proposed in 1964 by Francis Crick and Leslie Orgel, but until now had not been tested systematically or shown to be common or predictable at scale.
To make these interactions predictable, the research team developed an AI-based model that accurately forecasted whether two variants would restore protein function. The model achieved nearly 100% accuracy in predicting intragenic complementation in ASL as well as in a second human enzyme, fumarase, suggesting these rules apply broadly across the human genome.
“We’ve shown that, in many cases, two damaging variants can work together to restore protein function,“ said Aimée Dudley, PhD, PNRI Senior Investigator who led the study. “This kind of genetic interaction is not an isolated exception, but a widespread and underappreciated way that variants can interact, especially in rare disease contexts.”
The researchers estimate that approximately 4% of human genes have the structural features that allow this type of interaction. For these genes, standard genetic predictions can overestimate disease risk, particularly for people who carry two different variants in the same gene.
Vegetarian and vegan diets can support healthy growth when carefully planned with appropriate supplementation, finds a major new meta-analysis – the most comprehensive study to-date of plant-based diets in children.
A team of researchers, from Italy, USA and Australia, analysed data from over 48 000 children and adolescents worldwide who followed different dietary patterns, examining health outcomes, growth and nutritional adequacy. They found that vegan and vegetarian diets can be nutrient-rich and support healthy growth, but also carry a risk of deficiencies if key nutrients are not obtained through fortified foods or supplements.
The peer-reviewed study, published in Critical Reviews in Food Science and Nutrition, also suggests that plant-based diets may offer additional health benefits for children – including improved cardiovascular risk profiles – compared with omnivorous diets that include meat, fish and other animal-derived foods.
This large meta-analysis is the most comprehensive study to date of plant-based diets in children under 18 years of age, examining data from 59 studies across 18 countries. It compared lacto-ovo-vegetarian (which include dairy products and eggs, but exclude meat, fish and poultry) and vegan diets (which exclude all animal-derived foods) with omnivorous diets across a wide range of nutritional and health outcomes in 7280 lacto-ovo-vegetarians, 1289 vegans and 40 059 omnivores.
The study found that vegetarian children consumed more fibre, iron, folate, vitamin C and magnesium than omnivores, but they had lower intakes of energy, protein, fat, vitamin B12 and zinc. While evidence on vegan diets was more limited, similar patterns emerged.
“Notably, vitamin B12 didn’t reach adequate levels without supplementation or fortified foods, and calcium, iodine and zinc intakes were often at the lower end of recommended ranges, making them important nutrients to consider for children on plant-based diets,” explains the study co-author Dr Jeannette Beasley, an Associate Professor in the Departments of Nutrition and Food Studies and Medicine at New York University.
“Vegan children, in particular, had especially low calcium intake.”
Health benefits
Despite these risks, both vegan and vegetarian children displayed more favourable cardiovascular health profiles than omnivores, with lower total and low-density lipoprotein (LDL) cholesterol – the “unhealthy” form of cholesterol.
Growth and body composition measures indicated that children on plant-based diets tended to be leaner than omnivores: vegetarian children were slightly shorter and lighter, with lower body mass index (BMI), fat mass and bone mineral content. Vegan children also had shorter stature and lower BMI scores.
“Our analysis of current evidence suggests that well-planned and appropriately supplemented vegetarian and vegan diets can meet nutritional requirements and support healthy growth in children,” states lead-author Dr Monica Dinu, who focuses on exploring how nutrition shapes health and well-being at the Department of Experimental and Clinical Medicine, at the University of Florence, in Italy.
Parents: take an informed approach
Plant based diets remain entirely achievable for children and can offer environmental advantages as well as health benefits. The authors stress that families should not be discouraged from choosing vegetarian or vegan diets for ethical, environmental or health reasons. Instead, they recommend that parents approach these diets with informed planning and, where possible, seek support from clinicians such as dietitians and paediatric health professionals. With attention to a few key nutrients, these diets can fully meet children’s needs during periods of rapid growth while reducing nutritional risks.
“We hope these findings offer clearer guidance on both the benefits and potential risks of plant-based diets, helping the growing number of parents choosing these diets for health, ethical or environmental reasons,” Dr Dinu adds.
More research needed, but balance is key
The authors also emphasise the need for clear, evidence-based guidance to support families with planning healthy plant-based diets for children, who may have higher nutritional needs during periods of rapid growth and development.
However, the researchers caution that these results are limited by the cross-sectional design of most included studies, variability in methods and populations, and challenges in accurately assessing children’s dietary intake.
“In conclusion,” says fellow co-author Dr Wolfgang Marx, from the Food & Mood Centre, at Deakin University, Australia, “while well-planned vegetarian and vegan diets are nutritionally adequate and beneficial for adults, there is far less clarity about their suitability for children – leading to inconsistent or even conflicting advice for parents.
“Our findings suggest that a balanced approach is essential, with families paying close attention to certain nutrients – particularly vitamin B12, calcium, iodine, iron and zinc – to ensure their children get everything they need to thrive.”
Adding breast magnetic resonance imaging (MRI) to a diagnostic mammogram did not reduce five-year cancer recurrence rates for patients with stage I/II hormone receptor (HR)-negative breast cancer, according to researchers at The University of Texas MD Anderson Cancer Center.
The Phase III Alliance A011104/ACRIN6694 trial found that five-year locoregional recurrence rates were 6.8% in patients who received an MRI as part of a diagnostic work-up and 4.3% in those who did not. These data were presented today at the San Antonio Breast Cancer Symposium (SABCS) by principal investigator Isabelle Bedrosian, MD, professor of Breast Surgical Oncology (Abstract GS2-07).
“We have long assumed that finding more breast cancer on an MRI and removing it with surgery would help lower the chance of a patient’s cancer coming back,” Bedrosian said. “When you look at our findings alongside earlier trials, the message is clear: adding MRI before surgery doesn’t improve results for patients – and may not have to be used as a standard part of the diagnostic process.”
No additional MRI benefit in this group
The trial enrolled 319 patients between 2014 and 2018 with newly diagnosed stage I or II HR-negative breast cancer. These patients were eligible for lumpectomy and did not have germline BRCA1/2 mutations, bilateral breast cancer or a history of prior breast cancer. All patients had undergone diagnostic mammography with or without ultrasound prior to trial enrolment. Patients were randomly assigned to undergo additional imaging by breast MRI (161 patients) or to receive no further imaging (158 patients).
Not only did breast MRI not impact five-year recurrence rates, but there were also not significant differences between groups for five-year distant recurrence-free survival nor overall survival.
A small subset of patients with tumour subtypes (HR- HER2+ and HR-HER2-) and those over the age of 50 at diagnosis also showed no benefit to MRI.
Pre-op MRI not finding anything important
Breast MRI is a common part of the diagnostic evaluation because it can reveal cancer that mammography might not detect. However, the evidence that it improves surgical outcomes for patients has been limited.
“We believe the reason MRI did not reduce recurrence rates may be twofold,” Bedrosian said. “It is possible that MRI didn’t uncover many lesions that mammography hadn’t already found, or perhaps identifying and surgically removing those additional lesions was not important to reducing risk of the cancer coming back. It’s possible that in the group that did not receive MRI, radiation and chemotherapy effectively treated the occult areas of disease”.
Experts are now analysing how often breast MRI identified additional lesions in the trial population to better understand why breast MRI did not impact oncologic outcomes.
Study limitations
Limitations included that most patients involved in the trial had breast cancer that hadn’t spread to their lymph nodes, which may partly explain why recurrence rates were low overall. Despite being open to women of all ages, the study enrolled mostly older women who may have been less likely to benefit from breast MRI.
