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Page 12 of 18 Huang et al. J Cancer Metastasis Treat 2019;5:34 I http://dx.doi.org/10.20517/2394-4722.2018.94

Ref. [99] [83] [100] [80] [101] [102] [103] [104] [105] [106] [107] [108] [109] [110] [111] [112] [77] [78] [81] [82] [85]

P value log-rank P = 0.54 NR NR < 0.001 0.002 0.03 0.008 0.11 NR 0.034 < 0.001 0.014 NR 0.002 NR NR Log-rank P < 0.001 NR NR < 0.001 0.04

OS HR (95%CI) 1.53 (0.41-5.79) NR NR 2.13 (1.63-2.79) 3.58 (1.59-8.07) 3.55 (1.1-11.5) 3.07 (1.33-7.05) 2.9 (0.7-11.4) NR 0.4 (0.2-0.9) 3.463 (1.82-6.58) 4.8 (1.37-16.8) 3.1 (1.5-6.3) 6.5 (2.0-21.3) NR NR (pre-/post+) 7.38 (3.19-17.08) NR NR 3.16 (2.23-4.48) 0.12 (0.02-0.91)

Post/During Therapy P value log-rank P = 0.005 NR NR < 0.001 0.013 0.88 NR 0.016 0.05 0.486 0.022 0.031 NR 0.003 NR NR Log-rank P < 0.00 0.004 0.005 < 0.001 0.008

PFS
HR (95%CI) 4.22 (1.67-10.67) NR NR 1.94 (1.52-2.47) 2.49 (1.12-5.11) 0.92 (0.30-2.78) NR 4.3 (1.2-14.4) 1.9 (1-3.5) 0.7 (0.3-1.7) 2.152 (1.11-4.16) 3.9 (1.13-12.7) 4.8 (2.4-9.7) 3.84 (1.6-9.3) NR NR (pre-/post+) 2.49 (1.51-4.10) 2.82 (1.39-5.75) 2.425 (1.131-4.477) 3.78 (2.33-6.13) 0.17 (0.05-0.62)

Treatment CT Neoadjuvant CT NR First line CT CT CT CT First-line CT CT CT CT drug exposure no treatment CT NR NR Drug and adjuvant CT surgery radiotherapy CT ICIT

P value NR < 0.001 < 0.0001 NR 0.003 0.09 0.006 0.016 < 0.001 0.001 NR 0.101 NR 0.001 0.0013 0.23 Log-rank P < 0.001 NR NR < 0.001 0.20

OS IBC: inflammatory breast cancer; MBC: metastatic breast cancer; CRC: colorectal cancer, NSCLC: non-small-cell lung cancer, SCLC: small-cell lung cancer; GC: gastric cancer; GGEA: gastric and gastroesophageal adenocarcinomas; GEC: gastroesophageal cancer; EC: esophagogastric cancer; MM: metastatic melanoma; HR: hazard ratios; CI: confidence interval; PFS: progressi
HR (95%CI) NR 3.93 (2.81-5.45) 2.78 (2.42-3.19) NR 2.96 (1.14-6.81) 1.97 (0.89-4.37) 5.32 (1.62-17.50) 3.1 (1.2-8.2) 3.4 (1.8-6.3) 0.3 (0.2-0.6) NR 2.7 (0.82-8.89) 1.8 (1.2-2.9) 4.1 (1.7-9.5) 4.4 (1.7-11.7) 0.52 (pre+/post+) 10.57 (3.92-28.56) NR NR 3.43 (2.21-5.33) 0.46 (0.14-1.52)

Baseline

P value NR < 0.001 < 0.0001 NR 0.001 0.61 0.01 0.16 0.001 < 0.001 NR 0.133 NR 0.000 NR 0.91 Log-rank P < 0.001 0.153 NR < 0.001 0.95

PFS
HR (95%CI) NR 3.73 (2.82-4.90) 1.92 (1.73-2.14) NR 3.39 (1.67-6.83) 0.82 (0.38-1.78) 3.93 (1.38-11.15) 2.4 (1-5.7) 2.4 (1.4-4.1) 0.3 (0.2-0.6) NR 2.5 (0.76-8.27) 1.6 (1.0-2.4) 4.96 (2.2-11.2) NR 1.06 (pre+/post+) 3.73 (1.96-7.12) 2.17 (0.75-6.31) NR 3.16 (2.23-4.48) 0.97 (0.47-2.3)
Table 1. Presence of CTCs and clinical outcome in cancer patients

Patient Ratio 27% 12.6% 46.9% 53.6% 26% 28% 32% 23.2% 60% 50% 41% 67% 46% 69.4% 46.5% 37.5% 20.6% 79% 45.5% NR NR

CTC cut- off ≥ 1 CTC/ 7.5 mL ≥ 2 CTC/ 7.5 mL ≥ 5 CTC/ 7.5 mL ≥ 5 CTC/ 7.5 mL NR/7.5 mL ≥ 2 CTC/ 7.5 mL ≥ 2 CTC/ 7.5 mL ≥ 5 CTC/ 7.5 mL ≥ 5 CTC/ 7.5 mL ≥ 5 CTC/ 7.5 mL ≥ 3 CTC/ 7.5 mL > 2 CTC/ 8 mL ≥ 2 CTC/ 7.5 mL all marker (+) vs. others > 17 CTC/ 7.5 mL > 2 CTC/ 7.5mL > 1 CTC/ 7.5mL > 1 CTC/ 2.5mL 3 CTCs/ 3.2 mL 56% 48

Patient number 63 1,574 1,944 595 50 75 59 43 83 56 106 24 106 62 43 22 1,087 138 99 453 49 chemotherapy; NR: not reported; ICIT: immune checkpoint inhibition therapy

Technique CellSearch CellSearch CellSearch CellSearch qRT-PCR Immuno- fluorescence CellSearch CellSearch CellSearch CellSearch CellSearch FACS-ICC CellSearch qRT-PCR IsoFlux platform CellSearch CellSearch ISETdevice- CTCBIOPSY NEim- FISH CellSearch/ CD45-FISH Digital CTC Assay

Tumor type IBC (stage III) Breast Cancer MBC MBC CRC (stage IV) mCRC NSCLC (stage III/IV) NSCLC (stage IIIB/IV) SCLC SCLC AGC AGC GGEA GGEA GEC EC BC CRC (stage I-III) Cervical cancer Lung cancer MM