A simple spinal fluid test could detect hidden cancer cells that standard scans miss in children and young people with brain tumours. Around a third to a half of children with aggressive brain tumours relapse within two years, even when MRI scans show no remaining disease. This suggests that tiny amounts of tumour—minimal residual disease—survive treatment undetected. The current NHS test, which looks for tumour cells in cerebrospinal fluid collected after surgery, only catches a small minority of patients. The researchers have developed a different approach: instead of looking for cells, they measure the chemical by-products of tumour metabolism. They have already identified specific metabolites in spinal fluid that reliably signal the presence of medulloblastoma and ependymoma, even when the standard cell-based test is negative. If this work succeeds, it could lead to a simple, NHS-compatible immunoassay that detects residual disease across multiple brain tumour types. That would allow doctors to identify children who need additional treatment before relapse becomes visible, and to catch recurrence earlier when further therapy is more likely to work. The research is still at a validation stage, but the goal is a clinically usable diagnostic test.
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Brain tumours are the main cause of death in children and young people (CYP) under the age of 40 years. A significant proportion (30-50%) of paediatric high-grade (malignant) tumours relapse or reoccur within two years with the vast majority coming back in the same area despite evidence of a complete response on MRI scans. This suggests that there is minimal residual disease (MRD) present at the end of treatment. Finding better ways of detecting MRD could help identify patients who require additional treatment or continuation chemotherapy beyond standard-of-care (SOC), to reduce the risk of relapse. We also need to have a more sensitive method of detecting relapse early so that further treatments may be possible and effective. We know that tumour cells alter their metabolism to help them survive and evade the body's immune response. Metabolomics is the study or analysis of all the metabolites produced as a result of cellular processes. We have developed a novel metabolomics-based assay using cerebrospinal fluid (CSF) collected as part of SOC, to identify key metabolites that are specific to tumours. Thus far we have focused on two highly malignant tumours in children and young people called medulloblastoma (MB) and ependymoma (EPN). We have identified eighteen metabolites in CSF taken 14 days after surgery in tumour-specific levels, and sixteen of these metabolites are reliable biomarkers in patients (reproducible and clinically relevant). The current NHS SOC test involves collecting CSF at the same time point (day 14) and testing for the presence of tumour cells; this test is only positive in a small minority of patients who don't have other evidence of disease spread or metastasis. We can detect metabolomic signatures in patients whose cytology is negative. We know that the key metabolites that we identify correlate with that expressed in tumours in EPN and these also broadly correlate with MRI spectroscopy data.There is also published evidence of the role of the pathways involved in synthesising these metabolites in MB and EPN. It is important to note that we have some disease-specific metabolites that distinguish MB from EPN, but we also have common metabolites that are different from patients who don't have brain tumours but are broadly similar between MB and EPN. This is particularly exciting as we propose that these common metabolites could have greater value in detecting MRD across different brain tumour types. We are seeking funding through the MRC Developmental Pathway Gap Fund (DPGF) fund to expand this work across EPN and MB to validate our results. compare samples taken from the same patient at different time intervals to see if the metabolites fluctuate with disease burden. We have some pilot work ongoing at the moment which suggests it is conserved at relapse. identify tumour-specific metabolomic signatures for other types of brain tumours where CSF analysis is currently done as standard of care. characterise the CSF proteins mediating the production of these metabolites. This step aims to see if we can develop an immunoassay- based test for MRD using CSF for several tumour types which could be implemented easily within the NHS. It is anticipated that successful DPGF funding will help us achieve the above-listed objectives in readiness for a future developmental pathway funding scheme (DPFS) application to translate this work into a clinically validated test.
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