Clinical Utility and Application of Liquid Biopsy Genotyping in Lung Cancer: A Comprehensive Review

Figures & data

Figure 1 Comparison between tissue and liquid biopsy: advantages and limitations.

Abbreviations: ctDNA, circulating tumor DNA; cfDNA, cell-free DNA; mRNA, messenger RNA; miRNA, micro RNA.

Table 1 ctDNA plasma detection of EGFR mutation

Reference	Method of Detection	Study Design/Sample Size	Sensitivity	Specificity	Concordance/OPA Between Tissue and Liquid Biopsy
Douillard J et al^Citation91	QUIAGEN therascreen EGFR RGQ PCR Kit	Prospective, single‐arm Phase IV study (IFUM study); N = 652	65.7%	99.8%	94.3%
Reck M et al92^Citation92	QUIAGEN therascreen EGFR RGQ PCR Kit; Cobas EGFR mutations test version 2; Cycleave; PNA‐LNA PCR Clamp; other	Multicenter (ASSESS study); N = 1162	46%	97%	89%
Wu YL et al^Citation93	QUIAGEN therascreen EGFR RGQ PCR Kit	Phase III, Prospective (Lux‐Lung 3 and 6 stud‐ ies); N = 334 (plasma); N = 287 (serum)	60.5% (plasma) 28.6% (serum)	n.r.	n.r.
Han B et al94^Citation94	Cobas EGFR mutations test version 2	Multicenter (IGNITE study); N = 2561	46.9%	95.6%	80.5%
Karlovich et al^Citation96	Cobas EGFR mutations test version 2; BEAMing (Symex Inostics GmbH)	Prospective, multi‐ centre, observational and phase‐1 TIGER‐X; N=153	(Cobas/BEAMING) Activating mutations: 73%/82% T790M: 64%/73%	(Cobas/BEAMING) Activating mutations: 100% T790M: 98%/50%	(Cobas/BEAMING) Activating mutations: 80% T790M: 86%/67%
Oxnard et al^Citation28	BEAMing (Sysmex Inostics GmbH)	Retrospective (AURA Phase I) N = 216	T790M: 70% L858R: 86% Del 19: 82%	T790M: 69% L858R: 97% Del 19: 98%	n.r.
Sacher et al^Citation97	Droplet digital PCR (ddPCR)	Prospective; N = 180 (120 newly diag‐ nosed + 60 acquired resistance)	L858R: 74% Del 19: 82% T790M: 77%	L858R: 100% Del19:100% T790M: 63%	L858R: 80% Del19: 91% T790M: 40%
Zheng D et al^Citation98	Droplet digital PCR (ddPCR)	N=117	T790M: 81%	T790M: 100%	88%

Abbreviations: N.R., not reported; NSCLC, Non-small cell lung cancer; EGFR, Epidermal growth factor receptor; ddPCR, Droplet digital polymerase chain reaction; BEAMing, Beads, emulsion, amplification, and magnetics; OPA, overall percent agreement.

Table 2 Meta‐analysis on the diagnostic accuracy of liquid biopsy for detecting EGFR mutations

Reference	Study Design (N of Patients)	Sensitivity	Specificity	Concordance/OPA Between Tissue and Liquid Biopsy
Luo et al^Citation100	20 studies (N=2012)	67.4%	93.5%	n.r.
Qiu M et al^Citation101	27 studies (N=3110)	62%	95.9%	n.r.
Mao et al^Citation102	25 studies (N=2605)	61%	90%	79%
Zhou et al^Citation103	32 studies (N=4527)	70%	98%	n.r.
Passiglia et al^Citation104	21 studies (N=1639)	67%	80%	n.r.

Abbreviations: OPA, overall percent agreement; n.r., not reported.

Figure 2 Potential applications of liquid biopsy in both localized and metastatic non-small cell lung cancer.

Abbreviations: b-TMB, blood tumor mutational burden; ctDNA, circulating tumor DNA; MRD, minimal residual disease.

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