Adding Value to Liquid Biopsy for Brain Tumors: The Role of Imaging

SIMPLE SUMMARY: Clinical management in neuro-oncology has shifted to an integrated method that combines molecular profiles with histopathological and imaging data. Liquid biopsy is a non-invasive method that captures the molecular diversity of the whole tumor by detecting specific tumor biomarkers that circulate in body fluids like the cerebrospinal fluid. However, the limited presence and short half-life of tumor-derived biomarkers, especially in central nervous system (CNS) tumors, have restricted the use of liquid biopsy in clinical settings. Here, we review the diverse clinical applications of liquid biopsy in CNS tumors and discuss the added value of imaging in enhancing the release and detection of circulating tumor biomarkers. ABSTRACT: Clinical management in neuro-oncology has changed to an integrative approach that incorporates molecular profiles alongside histopathology and imaging findings. While the World Health Organization (WHO) guideline recommends the genotyping of informative alterations as a routine clinical practice for central nervous system (CNS) tumors, the acquisition of tumor tissue in the CNS is invasive and not always possible. Liquid biopsy is a non-invasive approach that provides the opportunity to capture the complex molecular heterogeneity of the whole tumor through the detection of circulating tumor biomarkers in body fluids, such as blood or cerebrospinal fluid (CSF). Despite all of the advantages, the low abundance of tumor-derived biomarkers, particularly in CNS tumors, as well as their short half-life has limited the application of liquid biopsy in clinical practice. Thus, it is crucial to identify the factors associated with the presence of these biomarkers and explore possible strategies that can increase the shedding of these tumoral components into biological fluids. In this review, we first describe the clinical applications of liquid biopsy in CNS tumors, including its roles in the early detection of recurrence and monitoring of treatment response. We then discuss the utilization of imaging in identifying the factors that affect the detection of circulating biomarkers as well as how image-guided interventions such as focused ultrasound can help enhance the presence of tumor biomarkers through blood–brain barrier (BBB) disruption.