Table 6.

Main Advantages and Disadvantages of Using ctDNA, Circulating Tumor Cells and Exosomes as Biomarkers in Gliomas

	Advantages	Disadvantages
ctDNA	• Higher ctDNA levels compared with CTC – hard to make quantitative comparisons • Potential to fully represent spatial and temporal heterogeneity of tumor • Greater sensitivity than CTC or exosomes?	• Short half-life, <1.5 ha • Release mainly by cells undergoing necrosis or apoptosis • Lower sensitivity of ctDNA in blood vs CSF • Lower sensitivity of ctDNA in lumbar CSF vs cisternal CSFb
CTC	• Information at the protein, DNA and RNA levels • Potential value of quantification • New techniques in development to optimize isolation of CTC	• CTC are rare • May represent only parts of tumor heterogeneity • Limited number of surface markers for CTC enrichment • Process of isolation challenging
Exosomes	• Carry proteins, DNA, RNA, and miRNA • Able to cross the BBB • Stable under various conditions • Content protected from degradation • Released by living cells	• Release not exclusive from tumor cells • May represent only parts of tumor heterogeneity • Possible presence of contaminants by current isolation method • No specific isolation protocols • Dexamethasone inhibits EV release.

^aMay be different in CSF versus blood.

^bLimited amount of data.