Developing a 'better than MRI scan' test for ependymoma

Project title: Developing a biomarker for minimal residual disease in ependymoma

Funded by The Little Princess Trust and administered by CCLG
Lead investigator: Dr Madhumita Dandapani, University of Nottingham
Award: £87,678.73
Awarded July 2021

Ependymoma (EPN) is a challenging malignant brain tumour affecting 40 children per year in the UK. Treatment includes complete tumour removal and radiotherapy. Half the patients with no disease after treatment on MRI relapse within 2 years. This suggests that have low level or minimal residual disease (MRD) despite treatment. Developing an accurate MRD detection test could help select patients who would benefit from further continuation chemotherapy, thereby improving survival.

Cancer cells have altered cellular processes (collectively called metabolism) which differ from normal cells, giving them a survival advantage. Analysis of tumour using a very sensitive technique called liquid chromatography-mass spectrometry (LC-MS) can detect specific biochemical (metabolomic) abnormalities. EPN arises adjacent to where the cerebrospinal fluid (CSF), that bathes the brain, is made. Therefore, CSF-based LC-MS analysis could be a powerful tool to detect MRD in EPN. It could also identify underlying abnormal pathways in tumours, leading to new treatments.

Our preliminary data shows that CSF LC-MS is feasible with few drops of CSF and the profile in EPN is unique. CSF microscopy is a crude test currently used and samples are available to develop this new test. Our main aims are:-

  1. To develop a CSF-based LC-MS ‘liquid biopsy’ test for MRD in EPN
  2. To identify abnormal metabolic pathways underlying these biochemical changes that could be targeted, thus leading to new treatments.

This will be the largest CSF-based LC-MS study in EPN and will develop a ‘liquid biopsy’ test consisting of a panel of metabolites (biomarkers) specific to EPN. We will also test if biomarker levels correlate with disease burden.

Clinical benefit: If successful, this pioneering test could be used in clinical practice to measure MRD in EPN and select patients who need further chemotherapy. This project could also develop less toxic, more effective treatments, improving outcomes for children.