Minimum Technical Preanalytical, Patient, and Clinical Context Data Elements for Cerebrospinal Fluid Liquid Biopsy: Recommendations for Public Database Submissions

PURPOSE: Blood-based liquid biopsy has enabled minimally invasive molecular profiling in patients with solid tumors. For cancers of the CNS, however, the use of peripheral blood for cell-free DNA (cfDNA) detection and sequencing has proved challenging because of scant levels of tumor-derived material shed into systemic circulation. An alternative is to use cerebrospinal fluid (CSF), which contains a greater concentration of tumor-derived cfDNA in patients with brain tumors (BTs). CSF liquid biopsy is a relatively nascent field, with critical unanswered questions regarding preanalytical variables that may affect assay performance. In an effort to identify and standardize key preanalytical variables, the Blood Profiling Atlas in Cancer (BLOODPAC) Consortium launched a BT Working Group in 2022. METHODS: We reviewed protocols for CSF sample collection and processing used by expert Working Group members at their respective academic institutions and diagnostic companies, as well as the available literature on CSF liquid biopsy. Through a collaborative and iterative process, we developed a list of key preanalytical variables for cfDNA-based CSF liquid biopsy in patients with primary and metastatic brain malignancies. RESULTS: The Working Group agreed on a recommended list of preanalytical minimum technical data elements, clinical context data elements, and patient context data elements for cfDNA-based CSF liquid biopsy in patients with CNS malignancies. A subset of variables were considered to be of critical priority and are designated as required annotations to submissions of cfDNA-based CSF liquid biopsy sample data into the BLOODPAC Data Commons. CONCLUSION: We propose a list of preanalytical variables relevant for cfDNA-based CSF liquid biopsy, with the overarching goal of encouraging routine collection and reporting of these variables in future studies.