Table 1.

Recent advancement of techniques for detecting EGFR mutation using ctDNA in lung cancer.

Study team	Sample	Oncogene mutation	Sample size	Method	Conclusion
Wang et al.	Plasma	EGFR	68 (III/IV)	ARMS/Scorpion assay	Sensitivity (22.06%), specificity (96.97%), positive predictive value (88.24%), and negative predictive value (54.70%) [20]
Liu et al.	Plasma	EGFR	86 (III/IV)	ARMS	Sensitivity (67.5%), specificity (100%), and concordance rate was 84.9% [21].
Goto et al.	Plasma	EGFR	86 (III/IV)	ARMS/Scorpion assay	Sensitivity (43.1%), specificity (100%), positive predictive value (100%), negative predictive value (54.7%), and concordance ratio (66.3%) [22]
Kimura et al.	Plasma	EGFR	42 (advanced stage)	ARMS/Scorpion assay	Sensitivity (85.7%), specificity (94.2%), and concordance ratio (92.9%) [23]
Kimura et al.	Plasma	EGFR	27 (III/IV)	ARMS/Scorpion	Detection rate 48.1% [24]
Yung et al.	Plasma	EGFR	35 (III/IV)	Digital PCR	Sensitivity (92%) and specificity (100%) [28]
Brevet et al.	Plasma	EGFR	34 (III/IV)	Mass spectrometry genotyping	Detection rate 61% [51]
Hu et al.	Plasma	EGFR	24 (I/II/III/IV)	High-resolution melting analysis	Positive rate was 100% for patients in stages II–IV, 81.8% (9/11) for stage I. The sensitivity was 91.67% and specificity was 100% [52].
Zhao et al.	Plasma	EGFR	111 (I/II/III/IV)	Mutant-enriched PCR	Concordance ratio (71.2%), sensitivity (35.6%), and specificity (95.5%). Sensitivity varied according to the disease stage and pathological differentiation; early stage (10%) versus advanced stage (56%). Highly differentiated (20%) patients and moderately differentiated (19%) and poorly differentiated subgroup (77.8%) [31].
Jiang et al.	Plasma	EGFR	58 (III/IV)	Mutant-enriched PCR	Sensitivity (77.8%), specificity (100%), and concordance rate (93.1%), more sensitive than the nonenriched assay [32].
Bai et al.	Plasma	EGFR	230 (III/IV)	DHPLC	Sensitivity 81.8% and specificity 89.5% [57]
Kim et al.	Plasma	EGFR	35 (III/IV)	PNA-mediated PCR	Concordance in the serum and tumor samples was 17% [42].
Kim et al.	Plasma	EGFR	57 (III/IV)	PNA–LNA PCR clamp	Concordance in the serum and tumor samples was 87.7% [43].
Xu et al.	Plasma	EGFR	51 (III/IV)	ARMS/Scorpion assay	Sensitivity (50.0%)   Specificity (100%) [25]
				Mutant-enriched PCR	Sensitivity (25.0%)   Specificity (96.2%)
				DHPLC	Sensitivity (25.0%)   Specificity (92.3%)
			60 (III/IV)	Direct sequencing versus Mutant-enriched PCR	Sensitivity 18.3% versus 55.0% [33]
Kuang et al.	Plasma	EGFR −T790M	54 (III/IV)	ARMS/Scorpion assay	Detected in 54% of patients with prior clinical response to TKI and 29% of prior stable disease [19]
Taniguchi et al.	Plasma	EGFR −T790M	44 (III/IV)	BEAMing	82.6% detection rate in patient who developed PD after EGFR TKI and 43.5% detection rate in patients were never treated with EGFR TKI [48]
Sakai et al.	Plasma	EGFR −T790M	75 (III/IV)	Mass spectrometry genotyping	28% detection rate in patient who developed PD after EGFR TKI [50].
Kukita et al.	Plasma	EGFR	144 (III/IV)	Next-generation sequencers: Ion Torrent PGM	72.7% detection rate in exon 19 deletion, 78.2% detection rate in L858R or L861Q [66]
Couraud et al.	Plasma	EGFR (exons 18, 19, 20, and 21)	68 (I/II/III/IV)	Next-generation sequencers: Ion Torrent PGM	Sensitivity ranged from 55% (EGFR exon 19) to 100% (EGFR exon 18) Considering all amplicons, the sensitivity was 58% and the concordance rate was 68% [67].
Wei et al.	Saliva	EGFR	40 (III/IV)	EFIRM	Exon 19 Del (AUCs = 0.94, 95% CI, 0.82–1) and L858R (AUCs = 0.96, 95% CI, 0.90–1) [80]

ARMS: amplification-refractory mutation system; DHPLC: denaturing high performance liquid chromatography; PNA: peptide nucleic acid; PNA-LNA: peptide nucleic acid-locked nucleic acid; BEAMing: beads, emulsions, amplification, and magnetics; NGS: next-generation sequencing; Ion Torrent PGM: Ion Torrent Personal Genome Machine (PGM) System; EFIRM: electric field-induced release and measurement.