This document describes a study that used circulating cell-free DNA (cfDNA) isolated from cerebrospinal fluid (CSF) to diagnose and monitor leptomeningeal disease. The researchers used a targeted sequencing panel to analyze 341 cancer genes in cfDNA from 53 patients. Results from CSF cfDNA analysis were compared to standard CSF cytopathology and MRI findings. CSF cfDNA analysis detected tumor-derived genetic alterations and was more sensitive than cytopathology. The study demonstrates that genomic analysis of CSF cfDNA can help facilitate early diagnosis of central nervous system tumors and guide treatment.