Liquid Biopsy Strategies to Distinguish Progression from Pseudoprogression and Radiation Necrosis in Glioblastomas

Liquid biopsy for the detection and monitoring of central nervous system tumors is of significant clinical interest. At initial diagnosis, the majority of patients with central nervous system tumors undergo magnetic resonance imaging (MRI), followed by invasive brain biopsy to determine the molecular diagnosis of the WHO 2016 classification paradigm. Despite the importance of MRI for long-term treatment monitoring, in the majority of patients who receive chemoradiation therapy for glioblastoma, it can be challenging to distinguish between radiation treatment effects including pseudoprogression, radiation necrosis, and recurrent/progressive disease based on imaging alone. Tissue biopsy-based monitoring is high risk and not always feasible. However, distinguishing these entities is of critical importance for the management of patients and can significantly affect survival. Liquid biopsy strategies including circulating tumor cells, circulating free DNA, and extracellular vesicles have the potential to afford significant useful molecular information at both the stage of diagnosis and monitoring for these tumors. Here, current liquid biopsy-based approaches in the context of tumor monitoring to differentiate progressive disease from pseudoprogression and radiation necrosis are reviewed.