BIOM-71. UNLOCKING THE POTENTIAL OF LIQUID BIOPSY IN GLIOBLASTOMA: AN EXTENSIVE EVALUATION OF CIRCULATING BIOMARKERS

Abstract BACKGROUND Liquid biopsy offers a minimally invasive approach to monitor cancer progression through blood-based biomarkers including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs) and extracellular vesicles (EVs). While widely studied in systemic cancers, its application in glioblastoma (GBM) remains limited due to low ctDNA shedding and the absence of epithelial CTCs commonly targeted by standard CTC platforms. These challenges highlight the need for GBM-specific strategies to fully harness the potential of liquid biopsy in neuro-oncology. In this study, we performed an evaluation of circulating biomarkers present in GBM patients’ blood. METHODS Three blood collection tubes (BCTs) were drawn from 15 GBM patients. From each, plasma was removed by centrifugation for investigation of ctDNA. CTC and large EVs enrichment was performed using ANGLE’s Parsortix® device, that isolates cancer cells from blood based on size and deformability. The Parsortix® harvests from one BCT were stained using an RUO immunofluorescence assay targeting epithelial and mesenchymal markers, while the harvests from the other tubes and the DNA from plasma were used for investigation of genomic alterations including IDH1, IDH2, BRAF, EGFR. RESULTS 60% (9/15) of GBM patients had ≥1 CTC, all of mesenchymal phenotype (mean: 7, median: 6, range: 2–17). Homotypic clusters of CTCs were identified in 78% (7/9) of the CTC+ subjects with a range of 2–6 CTCs per cluster and a maximum of 2 clusters per subject. Extracellular vesicles were detected in 40% of the patients. Molecular analysis of CTC and ctDNA is currently underway. CONCLUSIONS This study demonstrated the successful isolation of CTCs and EVs from the blood of GBM patients. Ongoing analyses, including ctDNA testing and molecular characterization of CTCs, aim to verify whether ctDNA and/or CTCs can be used as informative biomarkers, ultimately guiding dynamic testing strategies to advance precision cancer therapies in neuro-oncology.