INNV-56. The use of liquid biopsy in cerebrospinal fluid for early diagnosis of leptomeningeal disease and primary central nervous system malignancy: a single academic institution experience

The recent development of a cerebrospinal fluid (CSF) based assay for use in clinical practice has led to improvements in diagnosis of central nervous system (CNS) malignancy, both primary and secondary. This assay has emerged as a new and promising technique for minimally invasive diagnosis and therapy monitoring. We present a single institution experience of using Belay SummitTM, an assay designed to detect mutations and aneuploidy from tumor-derived DNA in CSF for diagnosis and management of primary and secondary CNS malignancy, in forty five patients between October 2024 and June 2025. CSF was collected via lumbar puncture and analyzed by both institutional cytology and the Summit assay. Nineteen cases were analyzed for primary brain tumor. Of these, one returned positive with TP53 mutation, one returned positive for a TERT mutation, two returned positive for an IDH-1 mutation, and two returned positive with mutations consistent with primary CNS lymphoma. Of the remaining patients, all were deemed to not have active CNS malignancy. Twenty six cases were assessed for leptomeningeal disease (LMD) due to clinical and/or imaging suspicion. Of these twenty six, eighteen yielded a diagnosis of LMD. Comparative institutional cytology result was negative for sixteen of these eighteen patients, despite imaging and neurologic exam findings consistent with LMD. Although additional prospective studies are needed to better select the proper use of liquid biopsy in CNS malignancy, the Belay SummitTM assay has provided useful information for the early diagnosis of primary CNS malignancy and LMD. It provides a useful analysis of a tumor mutation profile to help guide appropriate CNS directed therapy for primary CNS tumors and disseminated CNS malignancy.