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.

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).

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.”