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Urine test for bladder cancer could replace thousands of invasive procedures each year

Written by Louise Stanley on . Posted in Cancer outcomes, Clinical trials, Early diagnosis and detection.

Birmingham researchers funded by Cancer Research UK and liquid biopsy company Nonacus have developed a new urine test for bladder cancer, which could reduce the need for invasive and time-consuming procedures to diagnose the disease.

The test will use highly sensitive liquid biopsy technology developed by Nonacus in conjunction with  a panel of biomarkers developed and validated by Mr Rik Bryan and Dr Douglas Ward from the Bladder Cancer Research Centre at BHP founder-member the University of Birmingham, to detect the presence of bladder cancer by finding DNA from tumour cells present in the urine.

The biomarker panel, which consists of 443 genetic mutations that are common in bladder cancer has been validated in a deep sequencing study recently published in European Urology Oncology.

In this study, which was funded by Cancer Research UK and the Medical Research Council, the researchers used the test to analyse urine from 165 people with bladder cancer that had experienced haematuria (blood in the urine), and successfully detected the disease in 144 of them (87%).

The researchers also looked at using the test in 293 patients who had already been treated for bladder cancer and were being monitored for the cancer returning. In this setting, the test returned a higher proportion of false positive results compared to when used in the haematuria clinic (37.5% vs 15.2%), with 99 positive urine tests without a tumour being seen by cystoscopy on the same day. However, during their follow up monitoring, the patients who had those positive results had almost 3-times higher (11% vs 4%) rates of the cancer returning within 24 months indicating that the test could help detect recurrent disease before it is visible by cystoscopy (the camera inspection of the bladder). Further research is needed for the test to be used for surveillance.

Lead researcher Mr Richard Bryan said: “Even though cystoscopy is good at detecting bladder cancer, it’s invasive and time consuming for patients, so we need a better way to diagnose patients. In the future our test could be an easier way to get people with bladder cancer diagnosed faster, and could mean that tens of thousands of cystoscopies on healthy patients can be avoided each year.”

Iain Foulkes, Executive Director of Research and Innovation at Cancer Research UK said “These findings show that this urine test could help diagnose bladder cancer more easily. Early detection of cancer is key for improving patient outcomes and research like this could help identify the patients that need treatment soonest, while easing the pressures of diagnostic procedures on the NHS. We look forward to seeing how the test performs in the next clinical trial.”

The researchers are working in partnership with Nonacus, a provider of genetic testing products for precision medicine and liquid biopsy, to turn their approach into a clinical test for patients to be used within the NHS, and will start a clinical study funded by Cancer Research UK and involving over 3000 patients to evaluate just how powerful the test is at reducing the number of cystoscopies.

Each year, over 300,000 cystoscopies are carried out in England, however, around 80% of patients with haematuria who’ve had cystoscopy are found to have no cancers or abnormalities1,2.  The researchers believe that using the urine test in haematuria clinic could reduce the number of patients requiring a cystoscopy by at least 45%.

Funding boost to help improve ovarian cancer survival rates

Written by Louise Stanley on . Posted in Cancer outcomes, Early diagnosis and detection, Health inequalities.

BHP’s newest member NHS Trust has been given a charity grant of £100,000 to help improve survival rates of women with ovarian cancer.

The Pan-Birmingham Gynaecological Cancer Centre, based at SWBH’s City Hospital, is working jointly with University of Cambridge to boost the uptake in genetic testing, especially in Black, Asian and Minority Ethnic communities (BAME) where survival rates are low.

The project, called the Demonstration of Improvement for Molecular Ovarian cancer testing (DEMO), will create information about genetic testing in various languages both in leaflet and video format. The project will also improve the quality of the sample taken to aid diagnosis when there is suspicion of ovarian cancer by establishing a guidance document for all healthcare professionals involved in the process.

Dr Elaine Leung, Clinical Lecturer and Specialist Registrar at the Pan-Birmingham Gynaecological Centre which is run by Sandwell and West Birmingham NHS Trust, said: “This is a much-needed project reaching those diverse communities in the area.

“With the support of our patient representatives, the materials we co-create will be in an easy-to-understand format in both written and video form, which will give women a better understanding of the link between cancer and genetic testing.

“It’s important to ensure women know that genetic testing is similar to early detection and can help prolong life – we have already seen evidence of this through other studies.

“It helps to provide tailored treatments for patients and ultimately can mean surviving an ovarian cancer diagnosis.

“The lack of informed decision-making resources for women whose first language is not English could be a contributor to the low rates of testing within these communities. The team will co-produce information in multiple languages, as well as exploring why some groups of women are more likely to decline genetic testing.”

The project has been funded by health charity Ovarian Cancer Action and is part of a wider national initiative which includes funding for five other NHS cancer centres.

The Pan-Birmingham Gynaecological Cancer Network delivers cancer care to more than two million people in the West Midlands.

The project also builds on the team’s previous experience with the genetic testing studies, looking at BRCA testing in women with a new diagnosis of ovarian cancer before it became mainstream practice.

Lisa Bird, a former cancer patient who is part of the project, said: “When I was in my thirties I was diagnosed with ovarian cancer, which was a large shock.  My first line treatment successfully got me into remission but I wanted to know what options would be available to me if I came out of remission.

“I investigated treatment options and found that there were some treatments only available to those that have the BRCA 1 and 2 genes.  I also wanted to know if other family members were at an increased genetic risk of also getting ovarian cancer, so that I could warn them of the symptoms and ensure that they received better monitoring by their GPs.

“I’m really pleased to be part of the DEMO project team that will encourage more patients to have these same tests. I’m passionate that anyone affected by ovarian cancer should be able to have this genetic knowledge so that their healthcare teams can give them the best treatments available to them as quickly as possible. I really believe that the results of this project will help to provide patients with ovarian cancer, with a greater chance of an extended life.”

close up of a female child's blue eyes

Genetic diagnosis leads the way in childhood eye cancer treatment

Written by Louise Stanley on . Posted in Cancer outcomes, Early diagnosis and detection.

Experts from BHP member Birmingham Women’s and Children’s NHS Foundation Trust have transformed the treatment of children’s eye cancer with pioneering new research.

Dr Trevor Cole and Dr Amy Gerrish are the first in the country to develop a treatment called Cell-free DNA for the care of retinoblastoma – a rare type of cancer which typically develops in early childhood and affects around 50 children in the UK every year.

The specialist service based in our Children’s Hospital is one of the top centres in the world for treating the condition.

Until recently, diagnosing the genetic cause of retinoblastoma was only possible if the affected eye was removed as part of a treatment. However, thanks to research carried out by our team, we can now diagnose the genetic cause without removing the eye.

This procedure involves using a tiny volume of fluid taken carefully from the inside of the eye (a tenth of a millilitre) to predict whether the child’s other eye will be affected or any of their siblings or future children. Now, genetic diagnosis is even possible during pregnancy.

Dr Cole said: “Those who carry the germline Rb1 mutation that causes retinoblastoma have a 50 per cent risk of passing it to their children. However, non-invasive prenatal diagnosis is now possible in most pregnancies shown to be at risk of inheriting the gene mutation.”

Kirstie McLaughan, from High Wycombe, mum to three-year-old Aria and Kaleb, aged nine, underwent prenatal testing at our hospital when she was pregnant with her daughter.

“My partner, Callum, was diagnosed with retinoblastoma as a child, so we knew there was a risk that our children would develop the condition. In June 2012, my son was diagnosed with retinoblastoma, and we were transferred to Birmingham Children’s Hospital to begin treatment.”

Kaleb was told he was out of risk at the age of three following treatment our specialist retinoblastoma centre. “We couldn’t have asked for better care,” added Kirstie. “They really are an amazing team at the Eye Department. They couldn’t have done any more; they were so welcoming and friendly and were always on the other end of the phone should I have any questions or worries.”

When Kirstie found out a few years later that she was pregnant with their daughter, Aria, she knew there was a 50 per cent chance she would also inherit the gene that causes the condition. However, doctors at Birmingham Women’s Hospital could carry out genetic testing during pregnancy, taking a simple blood test from Kirstie.

“I had non-invasive prenatal testing when I was pregnant with Aria. The test meant that if my daughter also had retinoblastoma, we could begin treatment right away,” explained Kirstie. “Luckily, the test came back all clear. It was such huge relief. It meant I didn’t have added worry or stress during my pregnancy.

“The team are amazing. The difference in testing available from when Kaleb was treated to when Aria was born really is extraordinary; their research is outstanding.”

Back in 2020, the team won the Ulverscroft David Owen Prize for this ground-breaking research.

Dr Cole and Dr Gerrish’s Cell-free DNA in retinoblastoma research is leading the way in transforming how we treat children’s eye cancer, providing significant savings for the NHS and less stress for patients and their families.

AI identifies patients with heart failure that respond to beta-blocker treatment

Written by Louise Stanley on . Posted in Early diagnosis and detection, Health inequalities, Inflammation and chronic disease.

Researchers at BHP founder-member the University of Birmingham have developed a new way to identify which patients with heart failure will benefit from treatment with beta-blockers.

Heart failure is one of the most common heart conditions, with substantial impact on patient quality of life, and a major driver of hospital admissions and healthcare cost.

The study involved 15,669 patients with heart failure and reduced left ventricular ejection fraction (low function of the heart’s main pumping chamber), 12,823 of which were in normal heart rhythm and 2,837 of which had atrial fibrillation (AF) – a heart rhythm condition commonly associated with heart failure that leads to worse outcomes.

Published in The Lancet, the study used a series of artificial intelligence (AI) techniques to deeply interrogate data from clinical trials.

The research showed that the AI approach could take account of different underlying health conditions for each patient, as well as the interactions of these conditions to isolate response to beta-blocker therapy. This worked in patients with normal heart rhythm, where doctors would normally expect beta-blockers to reduce the risk of death, as well as in patients with AF where previous work has found a lack of effectiveness. In normal heart rhythm, a cluster of patients was identified with reduced benefit from beta-blockers (combination of older age, less severe symptoms and lower heart rate than average). Conversely in patients with AF, the research found a cluster of patients who had a substantial reduction in death with beta-blockers (from 15% to 9% in younger patients with lower rates of prior heart attack but similar heart function to the average AF patient).

The research was led by the cardAIc group, a multi-disciplinary team of clinical and data scientists at the University of Birmingham and fellow BHP founder-member University Hospitals Birmingham, aiming to integrate AI techniques to improve the care of cardiovascular patients. The study uses data collated and harmonized by the Beta-blockers in Heart Failure Collaborative Group, a global consortium dedicated to enhancing treatment for patients with heart failure.

First Author Dr Andreas Karwath, Rutherford Research Fellow at the University of Birmingham and member of the cardAIc group, added: “We hope these important research findings will be used to shape healthcare policy and improve treatment and outcomes for patients with heart failure.”

Corresponding author Georgios Gkoutos, Professor of Clinical Bioinformatics at the University of Birmingham, Associate Director of Health Data Research UK Midlands and co-lead for the cardAIc group, said: “Although tested in our research in trials of beta-blockers, these novel AI approaches have clear potential across the spectrum of therapies in heart failure, and across other cardiovascular and non-cardiovascular conditions.”

Corresponding author Dipak Kotecha, Professor & Consultant in Cardiology at the University of Birmingham, international lead for the Beta-blockers in Heart Failure Collaborative Group and co-lead for the cardAIc group, added: “Development of these new AI approaches is vital to improving the care we can give to our patients; in the future this could lead to personalised treatment for each individual patient, taking account of their particular health circumstances to improve their well-being.”

The research used individual patient data from nine landmark trials in heart failure that randomly assigned patients to either beta-blockers or a placebo. The average age of study participants was 65 years, and 24% were women. The AI-based approach combined neural network-based variational autoencoders and hierarchical clustering within an objective framework, and with detailed assessment of robustness and validation across all the trials.

The research was presented this week at the ESC Congress 2021, hosted by the European Society of Cardiology – a non-profit knowledge-based professional association that facilitates the improvement and harmonisation of standards of diagnosis and treatment of cardiovascular diseases.

radiographer looks at cross sectional MRI images of a human skull

UHB and Cambridge University Hospitals win government funding for ground-breaking AI in radiotherapy

Written by Louise Stanley on . Posted in Cancer outcomes, Early diagnosis and detection.

A machine learning technology that helps cut the time patients wait for life-saving cancer treatment has been successful in the latest round of the Artificial Intelligence (AI) in Health and Care Award.

BHP founder member University Hospitals Birmingham, working in partnership with Addenbrooke’s Hospital, part of Cambridge University Hospitals (CUH) is one of 38 organisations singled out for funding.

The AI Award is making £140 million available over four years to accelerate the testing and evaluation of artificial intelligence technologies which meet the aims set out in the NHS Long Term Plan.

Over the next year, UHB will work with CUH to leverage Microsoft Project InnerEye’s open-source AI toolkit to differentiate tumour and healthy tissue on cancer scans (called ‘segmenting’), prior to radiotherapy treatment. The aim of this AI Award project is to evaluate how this could save clinicians’ time, reduce the time between the scan and commencing treatment, and scale this to four NHS Trusts.

Dr Kal Natarajan, UHB consultant clinical scientist, said: “I’m really looking forward to working with colleagues in Birmingham and Cambridge on this project.

“The technology has tremendous potential to transform radiotherapy care, helping patients to be treated quicker and ensure clinicians spend their time as effectively as possible.”

Dr Raj Jena, CUH oncologist and project lead, said: “I am so pleased that our project has been awarded government funding to take it to the next level. AI has the capacity to deliver so much behind-the-scenes routine work, enabling doctors to spend more time face-to-face with patients, and shortening the time that patients have to wait for treatment.

“We believe this is first time an NHS hospital has trained its own medical imaging AI for its own patients and our aim is to assist other radiotherapy departments to use the models for their patients.”

Up to half of the UK population will be diagnosed with cancer at some point in their lives. Of those, half will be treated with radiotherapy, often in combination with other treatments such as surgery, chemotherapy, and increasingly immunotherapy.

Radiotherapy involves focusing high-intensity radiation beams to damage the DNA of hard cancerous tumours while avoiding surrounding healthy organs. This is a critical tool in the fight against cancer, with around 40% of cured patients undergoing precision radiotherapy.

Radiotherapy is most effective when treatment takes place as soon as possible. However, segmenting the tumour targets and healthy tissue on image scans is a key step that is currently performed manually by doctors, taking several hours per patient.

Microsoft’s recent peer-reviewed research paper in JAMA Network Open shows that clinicians could segment prostate and head & neck cancer images up to 13 times faster when using InnerEye machine learning assistance, with an accuracy similar to that of human experts.

Javier Alvarez-Valle, from Microsoft Research Cambridge, said: “We are delighted that CUH and UHB are able to use our open-source software to build their own AI models, for the benefit of their patients. This NHSX AI Award paves the way for more NHS Trusts to reduce cancer treatment times using assistive AI, and to help alleviate the workload of clinicians.”

Already, over 17,000 stroke patients and over 25,000 patients with diabetes or high blood pressure have benefited from the first round of the AI in Health and Care Award since September, where £50 million was given to 42 AI technologies.

The AI Award is one of the programmes that make up the NHS AI Lab, led by NHSX and delivered in partnership with the Accelerated Access Collaborative (AAC) and National Institute for Health Research (NIHR).

Urine test for bladder cancer to be developed by University of Birmingham and Nonacus

Written by Louise Stanley on . Posted in Cancer outcomes, Early diagnosis and detection.

BHP founder-member the University of Birmingham and Nonacus, a provider of genetic testing products for precision medicine and liquid biopsy, have partnered to develop a non-invasive test for bladder cancer. The test, which is expected to be available by mid-2022, will use highly sensitive liquid biopsy technology developed by Nonacus, and a panel of biomarkers validated by Dr Rik Bryan and Dr Douglas Ward from the University’s Bladder Cancer Research Centre, to diagnose the disease from urine samples.

Bladder cancer is the seventh most common cancer in the developed world1. In the UK, over 100,000 people a year are referred to hospital clinics that investigate for bladder cancer, usually after passing blood in their urine (haematuria).  The first stage of investigation is usually cystoscopy, which involves inserting a camera into the bladder.   Of these 100,000 patients, around 12% are subsequently diagnosed with bladder cancer, normally after a second invasive procedure to extract a biopsy.

Dr Bryan, Director of the Bladder Cancer Research Centre,  commented: “While blood visible in the urine should always be investigated, over 80% of people who have a cystoscopy at a haematuria clinic are diagnosed with non-malignant conditions or have no abnormality.  Unfortunately, the remaining 20% will need a further invasive procedure to confirm diagnosis.  What is required is a highly sensitive and specific, non-invasive test that can rapidly determine those who need a biopsy and those who do not, and a urine test is the obvious place to start.”

While the ‘liquid biopsy’ approach is attractive, the low levels of tumour DNA in a background of DNA from normal tissues requires highly sensitive analytical techniques to obtain accurate results.  However, researchers at the University started their work in the knowledge that Nonacus had successfully pioneered commercial non-invasive prenatal tests to identify low-levels of fetal DNA in maternal blood samples.  Moreover, the company was developing methods to allow confident and sensitive calling of mutations from as little as 10ng of DNA.

The researchers used ‘deep sequencing’ of tumour DNA to identify mutations that are present in the majority of urothelial bladder cancers (UBCs).  Their work, which was funded by Cancer Research UK and an MRC Confidence in Concept grant, involved sequencing 23 genes from tumour samples collected from 956 newly diagnosed, treatment-naïve patients.  This deep sequencing of genes identified 451 unique mutations that were present in over 96% of tumours.  The researchers also demonstrated that these mutations were identifiable in urine samples collected at the same time as tumour sampling2.

As the researchers have shown, mutated DNA in a urine sample can be extracted from cancer cells shed into the urine from the lining of the urinary tract, or can be found as cell-free DNA fragments. However, extracting DNA from the cancer cells provides more reliable amounts of DNA for the test, especially when only small volumes of urine may be available. Coupling the mutation panel with the unique molecular identifiers and the proprietary target capture technology provided by the Nonacus Cell3 Target™ will provide a much more sensitive test than the existing PCR-based approach. The researchers are already working on validating this combination in a further 600 cases (including non-cancer cases) and they expect to publish data on sensitivity and specificity within six months.

Nonacus intends to launch the new bladder cancer test within 12 months, and the final product will include access to bioinformatics software to help with analysis.  The company expects the test will provide high sensitivity for all stages and grades of disease, and will ensure the test is available worldwide to laboratories, hospitals and clinics.

Promisingly, the original research also determined the influence of the mutations on cancer progression, time to recurrence, and overall and disease-specific survival in patients with non-muscle-invasive bladder cancer (NMIBC), and disease-specific survival in patients with muscle-invasive bladder cancer (MIBC), raising the possibility that the test could be used to stratify patients according to risk.

Chris Sale, CEO of Nonacus Ltd, commented:  “We expect this partnership to deliver better care and outcomes for patients by reducing the number of invasive procedures, providing earlier diagnosis and speeding up access to treatment for people with bladder cancer.”

Tony Hickson, Chief Business Officer at Cancer Research UK, said: “As funders of much of the world-class, cutting-edge cancer research happening in the UK, we offer unique opportunities to commercial partners looking for early involvement in new discoveries. Having Nonacus on board to help transform promising findings in the lab into a new non-invasive test to diagnosis bladder cancer is a testament to how commercial collaborations have the potential to transform the lives of patients. We are looking forward to seeing the next steps as the test is developed and rolled out to the UK and beyond.”

Allen Knight, Chair of Trustees, Action Bladder Cancer UK, said:  “This really is very exciting and has the potential to make an incredible difference for patients and for Bladder Cancer treatment. Currently urine tests do not ​accurately pick up bladder cancer, and invasive tests are required to confirm a diagnosis.  A urine test that can rapidly determine who needs these tests will be a very welcome development.  Many patients, myself included, find cystoscopies very uncomfortable at best, and they can have lasting side effects.  This research could pave the way for routine screening, common in other cancers, but unavailable at present for Bladder Cancer.”