BIOM-36. DETECTION OF CIRCULATING TUMOR DNA (CTDNA) IN CEREBROSPINAL FLUID (CSF) IN PATIENTS WITH GLIOBLASTOMA TREATED IN PHASE I CLINICAL TRIAL

Abstract BACKGROUND As circulating tumor DNA (ctDNA) has been shown to be a source of tumor-specific biomarkers, liquid biopsy has emerged as a novel noninvasive tool in diagnosis, disease monitoring and treatment selection in several solid tumors. However, its use in brain tumors remains challenging because ctDNA is commonly not detected in blood. Thus, CSF (cerebrospinal fluid) has emerged as a potential source of ctDNA in the context of brain tumors. PATIENTS AND METHODS We prospectively evaluated the detection of ctDNA in CSF (CSF-ctDNA) +/- blood of patients with pre-treated MTAP-deleted glioblastoma, currently treated in a phase I clinical trial evaluating PRMT5 inhibitors. We did CSF samples at C2D15 and at progression, after patient’s oral and written consent. CSF was collected by lumbar puncture and analyzed with a panel of 35 genes including IDH1-2, TERT promoter and EGFR. Blood was collected, synchronously with CSF, by peripheral veinous punction and analyzed with the Foundation One Liquid CDx panel. RESULTS Between January and April 2024, five patients were included. All of them undergone initial surgical resection and received at least one previous systemic treatment associated with radiotherapy. At least one somatic mutation was identified in each patient, including EGFR amplification in 2/5 patients (40%). CSF was not available at baseline. One patient provided CSF only at progression. Four patients provided CSF at C2D15 on treatment, and among them, one patient was also collected at progression. At data cut-off, one patient was still on treatment. We identified a detectable level of CSF-ctDNA in only one patient with occipital tumor localization, with detection of EGFR amplification known at diagnosis. Synchronous blood analysis showed only clonal hematopoiesis variants. CONCLUSION We showed in this small cohort of patients that detection of CSF-ctDNA is technically feasible. The type of panel used might be optimized for this population especially to monitor patients as a potential surrogate biomarker for treatment response.