Table 2.

Comparison of technologies for ctDNA analysis

Scale of analysis	Technology	LoD, %	Advantage	Disadvantage
Single‐locus or multiplexed assays	Microfluidic or allele‐specific PCR		Rapid High sensitivity Suitable for detection of specific point mutations, copy number variations, short indels, and gene fusions Low cost	Monitoring for small number of known mutations
	Droplet digital PCR35, 36, 37	0.001
	Allele‐specific quantitative PCR38	<0.01
	BEAMing39	0.01
Targeted sequencing approaches	Amplicon sequencing		Genome profiling Monitoring for de novo resistance mutations Monitoring clonal evolution in response to therapy Sensitivity for disease burden could be increased by testing multiple loci in a single assay	Long time for analysis Expensive
	Safe‐SeqS40	0.10
	TAm‐Seq41	>2
	Hybridization capture
	CAPP‐Seq42	0.01
Genome‐wide analysis	Whole‐exome sequencing43, 44	>1‐3	Identifying structural variants Stratifying patient samples on the basis of disease burden Detecting the presence of chromosomal aberrations	Same as disadvantage of targeted sequencing approach
	Whole‐genome sequencing45	5‐10

BEAMing, beads, emulsions, amplification, magnetics; CAPP‐Seq, cancer personalized profiling by deep sequencing; cfDNA, cell‐free DNA; ctDNA, circulating tumor DNA; LoD, limit of detection; Safe‐SeqS, safe‐sequencing system; TAm‐Seq, tagged‐amplicon deep sequencing.