BIOM-07. DEVELOPING A CEREBROSPINAL FLUID-BASED BIOMARKER FOR MINIMAL RESIDUAL DISEASE AND RELAPSE IN PAEDIATRIC BRAIN TUMOURS USING METABOLOMIC METHODS

Abstract

Abstract BACKGROUND Many paediatric brain tumours have poor outcomes due to relapse (50% in ependymoma and 30% in medulloblastoma) following treatment. Most of these occur within two years, suggesting persistent minimal residual disease (MRD) below the imaging detection threshold. Diagnosing MRD at the end-of-treatment or early relapse using a sensitive, minimally-invasive liquid biopsy could improve outcomes. Extracting metabolites arising from aberrant cancer metabolism, from cerebrospinal fluid (CSF) is promising because of the proximity of tumour to CSF. METHODS Liquid chromatography coupled with tandem high-resolution mass spectrometry (LC-MS/MS) using 25µl CSF extracted with 75µl methanol was shown to differentiate malignant paediatric brain tumours (n=47;day 14 samples) from controls (n=49). RESULTS Ependymomas (n=33) differed from medulloblastomas (n=14). Eighteen metabolites were identified as differentially abundant between tumours and controls with 14 metabolites being increased in abundance in tumours. These included amino acids and derivatives (n=8), metabolites in one carbon metabolism (n=1), carnitine cycle (n=2), aerobic glycolysis (n=2), purine catabolism (n=2), ascorbate degradation (n=1) and creatinine synthesis (n=2). From those, betaine/creatinine ratio gave an area under the curve (AUC) of 0.96 (excellent) in receiver operating curve analysis. Using a cut-off ratio of 0.1775 for discriminating brain tumours from controls, had sensitivity and specificity of 92% and 89%. Medulloblastomas were largely similar to ependymomas; nevertheless, three metabolites could discriminate between them, and met the criteria of corrected p<0.05. A ratio of glutarate semialdehyde/malic acid had AUC of 0.85 (good). With a cut-off ratio of 0.0422, the sensitivity and specificity were 79% and 82%. CONCLUSION This is the first CSF-based metabolomics study in ependymoma and third in medulloblastoma. Ratios of CSF metabolites can be used as biomarkers to detect brain tumours sensitively and specifically. This work will further be developed into a liquid biopsy test for the detection of MRD and early tumour recurrence.