Liquid biopsies for the monitoring of gliomas and brain metastases in adults

Abstract

Clinical evaluation and MR imaging are currently the cornerstone of brain tumor progression monitoring. However, this is complicated by the occurrence of treatment effects such as pseudoprogression and radionecrosis. While essential for patient management, the distinction from true progression remains a significant challenge. Moreover, MR imaging provides limited real-time insights into tumor heterogeneity, genetic divergence, and treatment resistance. Although surgical histopathological biopsies can yield additional valuable information, they are not always conclusive, invasive, and therefore, not suitable for longitudinal measurements. In the era of precision medicine, there is a critical need for minimally invasive, accurate, and cost-effective monitoring methods for both primary brain tumors and brain metastases. Liquid biopsies have emerged as a potential candidate. Various analytes, including circulating nucleic acids, extracellular vesicles, platelet RNAs, and circulating tumor cells, can be obtained from whole blood and its derivatives, as well as other body fluids such as cerebrospinal fluid. In this narrative review, we outline the potential of liquid biopsies for the management of gliomas and brain metastases in adults and emphasize their utility in monitoring disease progression and treatment response. We discuss the most studied biofluids and analytes, along with their respective advantages and downsides. Furthermore, we address key considerations for future research and biobanking to pave the way for clinical implementation.

Keywords: Biomarkers; Brain metastases; Brain tumors; Glioma; Liquid biopsy; Monitoring.

Fig. 1

Overview of blood-based biomarkers in glioma and brain metastasis, including ctDNA (1), RNA (2), platelet mRNA (3), extracellular vesicles (4) and circulating tumor cells (5). a Primary tumor with cancer cells which intravasate (CTCs), cells secrete EVs, necrotic and apoptotic cells shed nucleic acids (ctDNA, RNA) in circulation; b Brain metastasis formation by CTCs; c Brain metastasis derived CTCs; d Glioma derived CTCs, EVs, ctDNA, RNA

Fig. 2

The ideal theoretical liquid biopsy for monitoring treatment response in brain tumors as compared to MR-imaging