Blood-tests for neuroblastoma clinical trials to guide next-generation cancer treatments.
In 2021, Neuroblastoma UK awarded £469,093 in research funding to an international team of leading clinician-scientists to explore how blood tests (biomarker testing) could be used in clinical trials to improve outcomes for children with neuroblastoma.
Professor Louis Chesler’s research grant was co-funded by Neuroblastoma UK (£454,093) and Children’s Cancer Research Fund (also known as Friends of Rosie) (£15,000) as part of Neuroblastoma UK’s 2021 Grant Round.
Neuroblastoma is an aggressive childhood cancer, most commonly affecting children under the age of five. Those diagnosed with high-risk neuroblastoma often undergo intensive treatment that can lead to lifelong side effects. Even with such treatment, approximately 15% of children experience a relapse. There is a critical need for more accurate testing to help guide treatment and improve outcomes.
Why was this grant selected by Neuroblastoma UK?
Neuroblastoma UK strives to facilitate research that will lead to more effective treatments and ultimately a cure for every child diagnosed with neuroblastoma.
This 36 month research project was funded due to its potential to transform neuroblastoma treatment by filling a major gap in clinical trials. Molecular changes that could be detected prior to, and on treatment would represent ‘biomarkers’ of great clinical and diagnostic importance. To be used clinically, the technology needs to be evaluated formally, hence the importance and need of this project. The grant brought together respected leaders in the neuroblastoma research across three countries and four cancer centres to share scientific samples in order to extensively cross validate against standard tissue based samples and plasma samples. Constructing shared libraries for the participating laboratories and a common interpretation of test technologies across countries.
What is the importance of this research?
To treat children with neuroblastoma more effectively, it's essential to understand how aggressive their cancer is and whether they are at high risk of relapse. These insights guide treatment decisions. Currently, the only way to obtain detailed information about a tumour is through tissue biopsies - an invasive and sometimes dangerous procedure. Blood tests could offer a safer, less invasive, and potentially more accurate alternative.
Although advanced blood-based tests capable of detecting multiple biological markers already existed, they had not been applied in standard clinical trials for neuroblastoma. Before these tests could be used in such trials, the technology needed to be formally evaluated for their power and accuracy, as well as cross-compared against various test types to understand what they can, and cannot measure.
Once validated, these blood tests could revolutionize future clinical trials and improve outcomes for children undergoing treatment for neuroblastoma. In particular the focus was to detect the genetic alterations of ALK (anaplastic lymphoma kinase) , a gene that often plays a role in neuroblastoma cases and a separate test to detect presence of abnormally lengthened telomeres (in lay terms - cancer cells which keep protective caps on the end of chromosomes so that they do not shorten , which would normally trigger cell death to cancer cells).
Who were the leading researchers?
The project was carried out by an international team of leading clinician-scientists.
Professor Louis Chesler and Dr Sally George from The Institute of Cancer Research in Surrey, formed the collaborative team of industry leaders from four organisations. The team that spanned three countries included; Dr. Gudrun Schleiermacher from Institut Curie in Paris, Professor Godelieve Tytgat from the Prinses Máxima Center for Pediatric Oncology in Utrecht, Professor John Anderson from Great Ormond Street Hospital in London.
What are the outcomes?
Thanks to the grant provided by Neuroblastoma UK and Children’s Cancer Research Fund, scientists have been able to evaluate the accuracy and reliability of the blood-tests, making them ready for use in clinical trials when they are appropriately integrated into a clinical workflow.
The legacy of this research will also contribute to further collaboration across the UK and Europe. Helping to bring together field leaders and creating a more standardised way of testing cancerous DNA across Europe and the UK. This will support future collaboration, accelerating progress for the next generation of clinical trials.
What is the future impact?
Blood-tests are now being implemented in clinical trials including the SIOPEN pragmatic clinical trial to ‘Monitor Neuroblastoma Relapse with Liquid Biopsy Sensitive Analysis’ (MONALISA). This promising clinical trial hopes to improve early detection of relapse, overall survival rates, outcomes for patients and changes in care strategy.
Dr. Gudrun Schleiermacher from Institut Curie said, “For patients with neuroblastoma, the funding by Neuroblastoma UK and Children’s Cancer Research Fund, for blood based biomarker analyses represents a unique opportunity for validation of techniques and alignment of all analytical steps for the analysis of cell free DNA extracted from liquid biopsies. The funding has enabled us to make important progress and is a major step towards implementation of these analyses in the routine follow up of patients with high risk neuroblastoma’
Sally George from The Institute of Cancer Research said, “This funding has enabled us to develop the infrastructure to work much more closely together across Europe to develop liquid biopsy tests that are accredited for clinical use. In addition, we have also developed new liquid biopsy tests to detect aggressive subtypes of neuroblastoma. Working together in this way to develop these tests will help more children to be able to benefit these tests in the near future.”
For more information on liquid biopsies read the Stratified Medicine Paediatrics report.
