Table 3.

Selected studies investigating the predictive role of CTCs in advanced NSCLC patients treated with chemotherapy. Abbreviations: NSCLC, non-small cell lung cancer; CTC, circulating cancer cell; Chemo, chemotherapy; Pts, patients; FISH, fluorescence in situ hybridization; PFS, progression-free survival; OS, overall survival; PD, progressive disease; TKI, tyrosine kinase inhibitor; RR, response rate; mo., months; vs., versus.

Study	Analysis Time-Point	Patients (n)	Therapeutic Approach	Detection Method	Predictive Relevance
Krebs et al. [28]	At baseline and after 1st cycle	101	Chemo	CellSearch	Pts with <5 CTCs count at the second time point in comparison with those with ≥5 CTCs: PFS: 6.9 vs. 2.4 mo., p = 0.012 OS: 8.9 vs. 3.9 mo., p = 0.003
Xu et al. [31]	Before the 1st, 2nd, and 3rd cycle	66	Chemo	CellSearch	A statistically significant difference between CTC value, a modification after 2 courses and PD was observed (p = 0.028)
Muinelo-Romay et al. [74]	Before the 1st, 2nd, and 5th cycles of chemo	43	Chemo	CellSearch	Pts with ≥2 CTCs at 2nd cycle had superior rates of PD and poorer PFS (4.2 mo. vs. 8.5 mo., p = 0.016)
Gorges et al. [95]	At baseline and every 12 weeks	50	Chemo	GILUPI CellCollector	Treatment response during therapy was associated with significant decreases in CTC counts (p = 0.001)
J Li et al. [83]	At baseline, before 2 and 4 cycle of chemo or after 1 and 2 months of targeted therapy	100	Chemo Targeted therapy (anti-EGFR)	Negative enrichment of immune magnetic beads and FISH	The changes in CTC levels before and after the 2nd cycle of chemo were correlated with the DCR: 38% in CTC-positive pts vs. 62% in CTC-negative pts (p < 0.001)
Tamminga et al. [92]	At baseline	86	Chemo (n = 52) TKI (n = 34)	CellSearch	Pts with CTCs vs. pts without CTCs: RR: (a) TKI: 25% vs. 73% (p = 0.02) (b) chemo: 35% vs. 51% (p = 0.05) PFS: 3.3 mo. vs. 8 mo., p = 0.01 OS: 5.2 mo. vs. 12.1 mo., p = 0.03
Wang et al. [94]	At baseline, at cycle 1 and cycle 4, and at PD	150	Chemo	CellSearch	Pts with persistent negative CTCs had longer PFS (5.7 mo. vs. 3.0 mo.) and OS (13.1 mo. vs. 5.6 mo.) compared with pts with persistent positive CTCs, which was not impacted by chemotherapy. Chemotherapy decreased CTC from 36.0% to 13.7%
Zhou et al. [85]	Before the 1st and the 3rd cycle	59	Chemo	CellSearch	No correlation between the change of CTC counts and response to chemotherapy was observed
Hirose et al. [76]	At baseline	33	Chemo	CellSearch	No differences in response rates to cytotoxic chemotherapy between CTC-positive patients and CTC-negative patients.