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Drug dosing technology to improve children’s cancer treatment

A new project has been launched in collaboration with BHP founder-member the University of Birmingham aimed at aiding more precise drug dosing in children with cancer.

Children receiving chemotherapy treatment each process the drugs differently, leading to inconsistencies in drug concentrations in the blood (known as drug exposure).

Patients may not receive enough of the drug or in some cases may experience side effects following anthracycline treatment, predominantly in the form of dose-related cardiotoxicity.

A multidisciplinary team of experts working on the project, called ChromaDose, will develop a diagnostic drug monitoring tool to aid dose optimisation, enabling children receiving anthracycline chemotherapy – a type of the drug most commonly used to treat childhood lymphomas and leukaemias – to benefit from a personalised approach to treatment.

The technology behind ChromaDose, which is being led by UCL, will enable clinicians to calculate the patient’s drug exposure. Nurses administering the chemotherapy drug would collect a few drops of blood at different times following administration. These samples are then inserted into the ChromaDose bedside device using an innovative cassette design.

The machine automatically measures the amount of medicine within each blood drop and identifies the patient’s pharmacokinetic response (movement of drugs into and around the body), allowing ChromaDose to calculate the patient’s drug exposure.

Co-lead Professor Pamela Kearns, of the University of Birmingham, explained: “In 2021, there are nearly half a million survivors of childhood cancer in Europe and two thirds live with long term side effects from their treatment.

“One way to improve the side effect profile of a drug is to be more precise in the dosing. ChromaDose has the potential to allow us to individualise the dose of chemotherapy drugs to maximise effect on the tumour while minimising the side effects.

“I am looking forward to working with the team to move ChromaDose into clinical practice as a substantial step towards personalised medicine for children with cancer.”

Overall project lead Dr Stefan Guldin, of UCL Chemical Engineering, further explained: “We have come a long way from the first experiments in the lab to this unique opportunity to bring our technology into the clinic. The team we have been able to assemble in ChromaDose makes me confident that we can achieve our ambitious goals.”

Academics currently have the individual components which have shown promise when operated manually in a laboratory. They will now work to integrate these elements into an automated companion monitoring tool that will be able to provide reliable results within 30 minutes from insertion of the sample.

“The challenge of developing a fully-automated in-vitro diagnostic device for biochemical analysis on the ward cannot be underestimated,” explained Dr Alaric Taylor, Innovation & Design Lead at Vesynta Ltd, a UCL start-up. “Safety, performance, user experience and regulatory compliance are all competing factors.

“However, I believe that working within the ChromaDose consortium, with input and support from each and every stakeholder, makes the delivery of this technology possible.”

Co- lead Professor Gareth Veal, of the University of Newcastle, commented: “We have made great strides over a number of years in providing a national therapeutic drug monitoring service to support dosing decisions being made for childhood cancer patients across the UK.

“The development of a point-of-care diagnostic device funded through the i4i project could have a real impact on utilising drug monitoring approaches as routine cancer patient care in the future.”

The research team are working with a diverse group of stakeholders including children, parents, nurses, doctors, educators, designers, scientists and engineers. The Young Persons Advisory Groups at Great Ormond Street Hospital and North England were actively involved in the project planning stage, with over 60 participants, and remain important collaborators throughout the project. Additionally, parents and wider families of children who have experienced cancer will contribute through the Paediatric Oncology Reference Team.

Stakeholder satisfaction and user scenarios analysis will aid the translation of the ChromaDose innovation into the NHS healthcare system. This work is supported by partners at the National Institute for Health Research (NIHR) funded London In-Vitro Diagnostic Co-operative at Imperial College London. The expert team will map pathways for clinical integration alongside early stage health economic analysis, ensuring patient benefit is delivered rapidly and cost-effectively.

The ChromaDose project is funded by an NIHR i4i Product Development Award, which provides £980,000 for a nationwide multi-disciplinary team to conduct intensive research and development over 30 months. As project capstone, the team will seek regulatory approval from the notified body for widespread adoption.

Birmingham’s brain tumour centre awarded Tessa Jowell Centre of Excellence status

The brain tumour centre at BHP founder-member University Hospitals Birmingham (UHB) has been recognised as a Tessa Jowell Centre of Excellence following rigorous expert-led assessments by the Tessa Jowell Brain Cancer Mission.

With more than 12,000 people diagnosed every year with a primary brain tumour in the UK[i], and 300 new patients seeking treatment at UHB, the award has been introduced to recognise hospitals for their excellence in patient care. It represents a step change in the neuro-oncology landscape across the UK.

UHB was measured on a range of criteria, including its excellent clinical practice and training opportunities; emphasis on patient quality of life; providing clinical trials and offering a high standard of research opportunities. Led by a committee of experts in the field and virtual site visits, the assessments were backed up by patient feedback about the care they received.

At least 88,000 British people are currently living with a brain tumour but over 5,000 people a year will lose their lives to it[ii]. The “Excellence” status provides reassurance about the availability of excellent care within the NHS and positive recognition for its staff at UHB who, despite the challenges of the Covid-19 pandemic, continue to go above and beyond for their patients. Due to the strain Covid-19 has placed on the NHS, UHB’s brain tumour centre now offers virtual clinics for patients.

Founded to design a new national strategy for brain tumours, the Tessa Jowell Brain Cancer Mission is committed to helping as many hospitals as possible achieve the “Excellence” status in the future. To achieve this, the mission is launching the Tessa Jowell Academy, a national platform allowing hospitals to share best-practice to improve their services, as well as one-year fellowships for doctors to further specialise in brain tumours.

Jess Mills, Co-Founder of the Tessa Jowell Brain Cancer Mission and Tessa’s daughter, said: “Mum’s mission throughout 50 years of her political life was to tackle systemic inequality. So, it was tragic whilst fitting, that her final campaign was a call to arms to create universal equality in access to excellence in cancer care throughout the NHS. It is with immeasurable pride that just 3 years later, the Tessa Jowell Brain Cancer Mission has begun the real-world translation of that vision into reality. 

“We are thrilled to have awarded University Hospitals Birmingham for its excellent ongoing work for patients and commitment to support other centres in reaching the same level of Excellence. Shockingly, the UK still has one of the worst cancer survival rates in Europe, but in time, the Tessa Jowell Centres will make the UK a global leader in the treatment and care of brain tumour patients. We have a long way to go until the cutting edge of science is delivered to every patient, but this is a huge and transformational first step.”

Colin Watts, Professor of Neurosurgery at BHP founder member the University of Birmingham and Honorary Consultant Neurosurgeon at UHB, said: “We are delighted that our model of patient-centred, consultant-led, research-orientated care for brain cancer patients has been recognised in this way. This award is a tribute to the whole multidisciplinary team who put patients at the centre of everything they do and take real pride in delivering best practice for everyone.

“It is a privilege to be to be  given this status from TJBCM partner organisations and we are very proud to affiliate ourselves with this recognition. We have worked hard as a team over the years to develop and improve patient care and will always strive to make a difference wherever possible. We will continue this process collaboratively by sharing and developing best practice within our service, externally and between other service providers for this cohort of patients.”

Cally Palmer, NHS England National Cancer Director, said: “This award is a fitting tribute to Tessa Jowell and her dedication to excellence in cancer care, as well as to all the NHS staff who have worked tirelessly throughout the pandemic to continue to provide life-saving cancer services, and it is great to see NHS hospitals across the country being recognised as centres of excellence. NHS services are open and ready to help those who need cancer care, and I encourage anyone who is experiencing any worrying symptoms to contact their GP immediately to improve chances of a successful recovery.”

Tessa Jowell Centres of Excellence:

      1. University Hospitals Birmingham
      2. Edinburgh Centre for Neuro-oncology
      3. King’s Health Partners of King’s College Hospital & Guy’s and St Thomas’s Hospitals in London
      4. Leeds teaching hospitals NHS Trust (Leeds General Infirmary and St James’s Hospital)
      5. Salford Royal Foundation Trust and The Christie (Manchester)
      6. Newcastle upon Tyne Hospitals NHS Foundation Trust
      7. Nottingham University Hospitals (NUH) NHS Trust
      8. St George’s University Hospital, Royal Marsden Hospital and Royal Surrey County Hospital
      9. University College London Hospitals NHS Foundation Trust

Over £700M is spent on cancer research in the UK every year, yet less than 2% of that is dedicated to brain tumours[iii]. The Mission will be supported by the All-Parliamentary Group on Brain Tumours chaired by Derek Thomas MP, to secure further support for NHS centres to enable more of them to achieve the “Excellence” status in the future. To kick-start additional monetary support, the Tessa Jowell Foundation, the charity set-up by Tessa’s family to lead the delivery of her legacy, has announced a fundraising appeal to raise £4M to enable the centres to excel after the network is launched.

[i] Cancer Research UK, https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/brain-other-cns-and-intracranial-tumours (Data: 2015-2017, UK)

[ii] Cancer Research UK, https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/brain-other-cns-and-intracranial-tumours#heading-Zero (Data: 2015–2017, UK). Accessed October 2020.

[iii] National Cancer Research Institute (NCRI) Cancer Research Database Data Package 2019

 

AI and advanced imaging could diagnose childhood brain tumours without biopsy

A study led by Birmingham Health Partners member organisations has found that combining advanced imaging and artificial intelligence techniques can accurately classify the characteristics of common types of childhood brain tumours – paving the way for more rapid non-invasive diagnosis.

Brain tumours in a particular part of the brain, called the posterior fossa, are the largest cause of death from cancer in children. There are three main types of tumour that occur in the posterior fossa, and being able to characterise them quickly and efficiently can be challenging without confirmation via a biopsy, which is invasive.

Now a new study, carried out in collaboration with researchers from WMG at the University of Warwick and published in Scientific Reports, has found tumour diagnostic classification can be improved by using an advanced and non-invasive imaging technique known as ‘diffusion weighted imaging’ in combination with machine learning (AI). This means that the tumour can be characterised and treated more efficiently.

Diffusion weighted imaging involves the use of specific advanced MRI sequences, as well as software that generates images from the resulting data which uses the diffusion of water molecules to generate contrast in MR image. Experts can then extract a ‘map’ which can be analysed to give more information about the tumour.

The study involved 117 patients at five primary treatment centres across the UK, with images taken using machines across 12 hospitals.  The images were analysed by both an experienced radiologist and an expert scientist in paediatric neuroimaging.  Analysis from the images were fed to AI algorithms to successfully discriminate the three most common types of paediatric posterior fossa brain tumours, non-invasively.

Professor Andrew Peet, NIHR Professor in Clinical Paediatric Oncology at BHP founder-members the University of Birmingham and Birmingham Women’s and Children’s NHS Foundation Trust, said: “When a child comes to hospital with symptoms that could mean they have a brain tumour, that initial scan is such a difficult time for the family and understandably they want answers as soon as possible.

“Here we have combined readily available scans with artificial intelligence to provide high levels of diagnostic accuracy that can start to give some answers.

“Previous studies using these techniques have largely been limited to single expert centres. Showing that they can work across such a large number of hospitals opens the door to many children benefitting from rapid non-invasive diagnosis of their brain tumour.

“These are very exciting times and we are working hard now to start making these artificial intelligence techniques widely available.”

Professor Theo Arvanitis, Director of the Institute of Digital Health at WMG, University of Warwick, and one of the authors of the study, added: “If this advanced imaging technique, combined with AI technology, can be routinely enrolled into hospitals it means that childhood brain tumours can be characterised and classified more efficiently, and in turn means that treatments can be pursued in a quicker manner with favourable outcomes for children suffering from the disease.”

The research was supported by Cancer Research UK, EPSRC Cancer Imaging Programme at the Children’s Cancer and Leukaemia Group, the Medical Research Council, National Institute for Health Research (NIHR), Children’s Research Fund, Poppyfields and Help Harry Help Others.