Table 1.

Clinical Applications of ctDNA in Primary and Metastatic CNS Tumors

Role	Application	Primary or Metastatic CNS Tumors	Methods	Reference
Diagnostic	Early detection	Medulloblastomas, ependymomas,and gliomas	WES	10
		Gliomas	qPCR	25
		Gliomas	Real-time PCR	42
		Diffuse gliomas	Targeted exome sequencing+ddPCR	8
		PCNSL	qPCR	44
		BM	Digital PCR and targeted amplicon sequencing	4
		LM	Cancer panel sequencing	4
		LM	NGS	61
		LM	Real-time PCR	58
		LM	ddPCR	7
		LM	ddPCR+NGS	5
		LM	Real-time MS-HRM+ real-time TaqMan PCR	62
		LM	Direct DNA sequencing	29
Predictive	Identification of therapeutic targets	LM	Direct DNA sequencing	29
		BM	WES	33
	BM	ARMS-PCR	60
		CPU	CellMax SMSEQ+NGS	68
	Identification of drug-resistant mutations	LM	NGS	61
		LM	Real-time PCR	69
		BM	NGS	9
	Monitoring treatment response	GBM and BMs	ddPCR	7
		Gliomas	Real-time PCR	42
		Glioblastoma	PCR	47
Prognostic	Estimation of the risk for recurrence or progression	Neuroblastoma	Real-time qPCR	10
		Medulloblastoma	PCR	56
	Monitoring tumor burden	GBM and BMs	ddPCR	7
		LM	NGS	61
		Metastatic breast cancer with BM	ddPCR+WES	72
		Melanoma+ECD	dPCR	32

Abbreviations: WES, whole exome sequencing; PCR, polymerase chain reaction; qPCR, quantitative PCR; ddPCR, droplet digital PCR; ARMS-PCR, allele refractory mutation system PCR; PCNSL, primary central nervous system lymphoma; LM, leptomeningeal metastasis; BM, brain metastasis; GBM, glioblastoma; CPU, cancer of unknown primary; NGS, next-generation exome; MS-HRM, methylation-sensitive high-resolution melting; ECD, Erdheim-Chester Disease.