Texidor, Rhonda

Abstract Background Leptomeningeal disease (LMD) remains a challenging complication of both solid tumors and hematologic malignancies, with diagnosis traditionally relying on cerebrospinal fluid (CSF) cytology, which has limited sensitivity. Circulating tumor DNA (ctDNA) analysis in CSF has emerged as a promising diagnostic and molecular profiling tool that may improve detection and guide treatment decisions. We will report real-world clinical experience using a CSF ctDNA assay (Menarini Silicon Biosystems) in routine neuro-oncology practice. Methods Retrospective analysis of over 100 CSF specimens obtained from patients with suspected or confirmed LMD will be conducted. Clinical data to be collected: patient demographics, tumor histology, indication for testing, and prior treatments. ctDNA assay results will be compared with conventional CSF cytology. Molecular alterations identified through ctDNA testing will be recorded, along with subsequent treatment decisions, including use of targeted therapies, systemic therapy modifications, radiation therapy, or intrathecal approaches. Preliminary clinical outcomes, including radiographic response, progression patterns, and survival trends, will be explored. Descriptive statistical methods will be used to summarize the findings. Results We anticipate that among analyzed specimens, ctDNA testing will provide clinically meaningful diagnostic yield across multiple tumor histologies. Concordance and discordance patterns between ctDNA results and conventional cytology will be evaluated, including cases in which ctDNA identified molecular alterations despite negative cytology. Actionable genomic findings in a subset of patients will be analyzed and presented. Early outcome observations that ctDNA-informed management may facilitate more personalized care will be reported. Conclusions CSF ctDNA analysis represents a feasible and informative adjunct to conventional cytology in the evaluation of patients with suspected LMD in real-world clinical practice. Beyond diagnostic support, molecular profiling from ctDNA may influence treatment selection and enable precision oncology approaches in this high-risk population. Prospective studies are warranted to define sensitivity, specificity, and the impact of ctDNA-guided interventions on clinical outcomes.