MBRS-29. IN-VIVO METABOLITE PROFILES FOR THE NON-INVASIVE AND RAPID IDENTIFICATION OF MOLECULAR SUBGROUP IN MEDULLOBLASTOMA

Molecular subgroup is now influencing risk stratification and disease management in medulloblastoma. Tissue metabolite profiles have shown promise in identifying the four consensus subgroups. A smaller number of metabolites can be measured non-invasively in patients using magnetic resonance spectroscopy (MRS). We investigated if a classifier constructed from tissue metabolites could be applied to in-vivo metabolite profiles to accurately predict subgroup non-invasively. Machine learning was used to construct a classifier with tissue concentrations from 10 metabolites reliably detected in-vivo. Retrospectively acquired diagnostic in-vivo MRS was available for 37 cases from four treatment centres. Although we identified WNT tumours by the presence of GABA with 100% accuracy in tissue, GABA was not reliability quantified in this in-vivo dataset. Therefore the classifier was developed using tissue profiles of known molecular subgroup (determined using DNA methylation array) from group 3(n=20), group 4(n=34) and SHH(n=23). The cross-validated accuracy of the tissue classifier was 86%. When applied to in-vivo metabolite profiles, subgroup was predicted non-invasively with an overall accuracy of 76%. Group 3 had the highest proportion of incorrectly classified cases (4/11), followed by SHH (2/10), and group 4 (3/16), largely due to differences in measuring lipids, glutamate, glutamine and hypotaurine in-vivo. We have established the feasibility of non-invasive metabolite profiling to identify medulloblastoma subgroups. With the ongoing optimization of MRS to target specific metabolites including GABA, we can further improve accuracy. Rapid, non-invasive preoperative diagnosis of subgroup will offer opportunities to stratify early therapeutic intervention especially surgery, avoiding long-term sequalae and improving quality of survival.