BRAINatomy 2
International paediatric team receives second investment of $5m to further expand the BRAINatomy project
More than 75 per cent of children with brain tumours survive in the long term, often thanks to receiving treatment in the form of radiotherapy. Although radiotherapy remains one of the most effective means of treating childhood brain cancers, it can result in a series of short and long-term side effects. These side effects occur due to healthy tissue surrounding the tumour being affected by radiation which can result in effects from problems with physical growth to developmental problems with learning.
Incepted by The University of Manchester in collaboration with The Christie NHS Foundation Trust, the Royal Manchester Children’s Hospital, patient advocates from Manchester and from Brainstrust, international collaborators at St Jude Children’s Research Hospital (USA) and the University Medical Centre Groningen (Netherlands), and funded through a Stand Up To Cancer®-Cancer Research UK Pediatric Cancer New Discoveries Challenge grant, the BRAINatomy project was established to improve the outcomes for children diagnosed with brain tumours. Co-led by Professor Martin McCabe, a child cancer specialist from The University of Manchester, BRAINatomy 1 began in 2021 with the aim of identifying parts of children’s brains that are most sensitive to radiotherapy damage, and where radiotherapy delivery causes the greatest side-effects.
The BRAINatomy 1 team identified subunits within the brain where the dose of radiotherapy received correlated with observed changes in brain function, through image-based data mining (IBDM) methods. This work provided an ‘atlas’, i.e. a database of areas of the brain to specifically avoid during radiotherapy to minimise treatment side-effects.
Manchester researchers who were led by Professor Marianne Aznar also identified that radiation delivered to the hypothalamus was seen to correlate with reductions in processing speed; linked closely to how well children perform at school.
Finally, the team identified significant inflammation of some parts of the brain after radiotherapy, and differences in the biological effects of proton therapy and conventional radiotherapy in different brain compartments.
After developing this ‘atlas’ the team realised that further research was needed to identify additional subunits and investigate the long-term effects of other radiotherapy techniques. For more information about BRAINatomy 1, please read our impact case study.
“Childhood cancers remain a major clinical unmet need. It’s great news for Manchester that we have been awarded this significant second phase of funding. We are making good progress towards our ambitious goal, and we hope this research will lead to safer radiotherapy treatments for childhood brain tumours as well as new treatments that could help more young people to survive this type of cancer in the future. The award is also a proud recognition of Manchester’s reputation as a world-leading centre in cancer research. We’re excited to have been awarded this second round of funding to help more young people across the world with this devastating disease.”
Professor Martin McCabe
University of Manchester and Honorary Consultant Paediatric Oncologist, The Christie NHS Foundation Trust
BRAINatomy 2
Four years later, a second investment of $5 million USD has been received to enable the team to further continue the BRAINatomy project in BRAINatomy 2. This next stage of the project will be looking to use the methodology developed by Professor Marianne Aznar and colleagues to study the effects of proton therapy in children treated at St Jude, The Christie and University Medical Center Groningen. BRAINatomy 2 also extends the collaboration to include colleagues at Princess Máxima Center, the national children’s cancer hospital in the Netherlands. Proton therapy is a newer type of radiotherapy that can deliver more targeted dose to tumour while avoiding more of the healthy brain.
Our main focuses for the second round of funding will be to study where in children’s brains the effects of proton therapy are most damaging for cognitive function, to see if it is possible to re-direct proton therapy to deliver effective therapy while protecting the most sensitive brain regions, to investigate the impact of detecting hormone deficiencies caused by radiotherapy earlier than we currently do, and to see whether we can help to protect brain function by reducing brain inflammation around the time of radiotherapy. This research could be a real game-changer for generations to come as we develop ways to deliver radiotherapy accurately to tumours but avoid sensitive areas of the brain and ultimately give patients much better lives.
Professor Martin McCabe
Lead scientist
The study seeks to continue earlier work on the hypothalamus by the lead investigator at St Jude Children’s Research Hospital, Professor Tom Merchant, by using a clinical trial to identify when radiotherapy begins to affect this part of the brain and provide doctors information on when hormone replacement therapy should be administered.
The team have also found evidence to suggest that exposure to radiotherapy can activate immune cells in different parts of the brain, which can cause further damage to regions in the brain such as the hypothalamus. Another arm of this study will use a clinical trial to look at using anti-inflammatory drugs to reduce the instance of this phenomenon.
Finally, the team will investigate the use of Proton Beam Therapy (PBT) vs traditional Radiotherapy (which uses high energy x-rays/ photons) and assess how each treatment option affects children’s and young people’s brains.
“It can be challenging to analyse data from large patient cohorts while retaining all the information contained in each patient’s individual radiotherapy plan. By using advanced data mining methods, we can spot patterns at a very detailed level, providing extremely valuable information on how to design future treatments.”
Professor Marianne Aznar
Professor of Radiation Oncology Physics, University of Manchester/The Christie hospital
Cancer Research UK Chief Executive Michelle Mitchell said: “Thanks to research, more than three in four children and young people diagnosed with a brain tumour in the UK survive for at least five years*. Every extra moment that they can spend with their families is precious and we want those moments to be as comfortable as possible.”
“Many young people who survive their cancer face long-term side effects, such as fertility problems or loss of hearing, because of their treatment. These problems often persist for the rest of their lives.
The research from The University of Manchester highlights that, as well as developing new treatments with fewer side effects, we must also focus on making the treatments and interventions we already have better for children and their families.
Across the UK, we support researchers who are dedicated to making sure that children and young people will see a future where they can lead longer, healthier lives, free from the fear of cancer.”
Partnership
This success of this project is reliant on ongoing collaborations between teams at The University of Manchester, The Christie NHS Foundation Trust, the Royal Manchester Children’s Hospital, Cancer Research UK Clinical Trials Unit, Birmingham, St Jude Children’s Research Hospital, Memphis, USA, and Netherlands based Princess Maxima Hospital and University Medical Centre Groningen.
This research is possible thanks to funding from Stand Up To Cancer in the US and Cancer Research UK’s Stand Up To Cancer initiative.
This MCRC blog was written using information from the following sources: