Cerebrospinal fluid (CSF) liquid biopsy has been recently recommended by the National Comprehensive Cancer Network (NCCN) as a molecular diagnostic tool for central nervous system (CNS) lymphoma that offers a minimally invasive method to detect key biomarkers when traditional diagnostics are limited by sensitivity or feasibility. This brief report describes the clinical use of two novel CLIA/CAP-approved CSF liquid biopsy tests from Belay Diagnostics, Summit™ and Vantage™, to aid in the diagnosis and management of CNS lymphoma. Results from both tests were reviewed for 50 CSF samples in the context of clinical information provided with the test order. Summit™ and Vantage™ detected clinically significant alterations in CNS lymphoma-associated genes such as MYD88, CD79B, and TP53 as well as MGMT methylation when other modalities (e.g., CSF cytology, MRI, or brain biopsy) were inconclusive. In several cases of suspected secondary CNS lymphoma, Summit™ detected pathogenic genomic variants as well as mild to high levels of aneuploidy, suggesting CNS involvement. Belay testing impacted management in 41 of 50 (82%) cases by informing CNS lymphoma diagnosis, stratification, or progression as well as therapeutic response with an overall false negative rate of 18% (2/11). This report contributes to the growing body of literature that demonstrates how comprehensive molecular profiling of CSF enhances detection and characterization of CNS lymphoma and offers a promising adjunct to conventional diagnostics.
Larson et al. (Mon,) studied this question.