Longitudinal glioma monitoring via cerebrospinal fluid cell-free DNA: one patient at a time

Response assessment in patients with high-grade gliomas is challenging due to the limitations of current imaging techniques and the difficulty in obtaining longitudinal tissue samples. Cell-free DNA (cfDNA) is under evaluation as a candidate monitoring biomarker, but it has limited sensitivity in plasma due in part to the blood-brain barrier. Our study aims to address these challenges by evaluating how intracranial cerebrospinal fluid (CSF) can be acquired longitudinally for disease monitoring. In these initial cases, we find that intracranial CSF cfDNA can feasibly be obtained throughout treatment via CSF access devices in patients with high-grade gliomas. We report on our initial experiences serially evaluating copy number burden, tumor fraction, and tumor-associated variant allele frequencies (VAFs). We also highlight the questions and challenges that will need to be answered before CSF cfDNA can become routinely deployable for patients with high-grade gliomas.Current methods for glioma response assessment are limited. This study aimed to assess the technical and clinical feasibility of molecular profiling using longitudinal intracranial CSF from patients with gliomas.