Liquid biopsies in patients with diffuse glioma.

Myron G Best,Nik Sol,Jaap C Reijneveld,Pieter Wesseling,Thomas Wurdinger,Sebastiaan Zijl

doi:10.1007/s00401-015-1399-y

Abstract

Diffuse gliomas are the most common malignant primary tumors of the central nervous system. Like other neoplasms, these gliomas release molecular information into the circulation. Tumor-derived biomarkers include proteins, nucleic acids, and tumor-derived extracellular vesicles that accumulate in plasma, serum, blood platelets, urine and/or cerebrospinal fluid. Recently, also circulating tumor cells have been identified in the blood of glioma patients. Circulating molecules, vesicles, platelets, and cells may be useful as easily accessible diagnostic, prognostic and/or predictive biomarkers to guide patient management. Thereby, this approach may help to circumvent problems related to tumor heterogeneity and sampling error at the time of diagnosis. Also, liquid biopsies may allow for serial monitoring of treatment responses and of changes in the molecular characteristics of gliomas over time. In this review, we summarize the literature on blood-based biomarkers and their potential value for improving the management of patients with a diffuse glioma. Incorporation of the study of circulating molecular biomarkers in clinical trials is essential for further assessment of the potential of liquid biopsies in this context.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-015-1399-y) contains supplementary material, which is available to authorized users.

Highlights

Diffuse gliomas are the most frequent primary malignant tumors of the central nervous system [182]
In this review on liquid biopsies in patients with diffuse glioma, we provide a concise discussion of the current state of the art of five blood-based liquid biopsy biosources [plasma; serum; extracellular vesicles; blood platelets; circulating tumor cells (CTCs)], followed by a more elaborate discussion regarding the potential of detecting circulating proteins, circulating nucleic acids (DNA, different forms of RNA) and of circulating tumor cells
Two studies that together included approximately 90 recurrent glioblastoma patients treated with bevacizumab plus irinotecan demonstrated that a decreased plasma protein level of vascular endothelial growth factor (VEGF), measured, respectively, eight weeks and 15 days after the start of the treatment, was associated with improved progression-free survival (PFS) and overall survival (OS) [46, 165]

Summary

Introduction

Diffuse gliomas are the most frequent primary malignant tumors of the central nervous system [182]. Wesseling Department of Pathology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands literature on blood-based biomarkers and their potential value for improving the management of patients with a diffuse glioma. Molecular markers obtained via liquid biopsies may allow for repeated assessment of molecular aberrations of the tumor and real-time treatment monitoring in patients with diffuse glioma.

Results

Conclusion