BIOM-48. UTILITY OF CIRCULATING TUMOR DNA (CTDNA) FROM CEREBROSPINAL FLUID (CSF) FOR PROGNOSIS OF PATIENTS WITH RECURRENT HIGH-GRADE GLIOMA

Abstract High-grade gliomas (HGGs) are the most aggressive primary brain tumors, and molecular characterization is vital for their diagnosis and treatment. Due to their location, tumor sampling is often challenging. Therefore, developing minimally invasive diagnostic methods is urgently needed. Here we report that circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) can identify key genomic alterations and track clonal evolution in HGGs. Detection of CSF ctDNA correlates with leptomeningeal disease and overall survival, indicating its potential for integration into clinical decision-making. Our study includes 313 samples from 253 patients with recurrent glioma treated at MSKCC who underwent CSF collection using the MSK-IMPACT targeted sequencing assay. 37% of genomic alterations were detected using our less stringent variant calling criteria and Gaussian Mixture Model to call copy number events. CSF ctDNA positivity was determined by the presence of at least one oncogenic disease-defining alteration or any shared alteration with the tumor. We found 212 CSF ctDNA positive (68%) and 101 CSF ctDNA negative (32%) samples. CSF ctDNA positivity was the highest amongst histone mutant tumors (96%). We noticed 44% of alterations shared between the tumor and the CSF, additionally, we noted considerable tumor evolution particularly within the growth signaling pathways (e.g. PDGFRA). Our cohort demonstrated that patients with positive CSF ctDNA had a significantly shorter overall survival compared to those who were CSF ctDNA negative (4.83 months vs 14.14 months, HR 2.4, p < 0.001). Radiographic findings such as enhancing disease and contact of the tumor with the ventricular space were positively associated with CSF ctDNA positivity. Additionally, CSF ctDNA was associated with positive cytology in 12/12 cases (100%). With our improved pipeline, we hypothesize CSF ctDNA may be used as a prognostic biomarker for survival, but confirmation requires further validation in a prospective study.