Table 1. Studies investigating circulating tumor cells in non-small cell lung cancer by ISET, CellSearch and folate receptor technique.
| Author (year) | Measurement method | Population | Outcome |
|---|---|---|---|
| Hofman (2011) (17) | CellSearch & ISET | 210 NSCLC patients undergoing surgery, stage I-IV | CellSearch (≥1 CTC): 82/210 positive (39%) ISET (≥1 CTC): 104/210 positive (50%) Both methods independently associated with diminished DFS |
| Krebs (2011) (12) | CellSearch | 101 NSCLC patients untreated stage III/IV, samples before and after treatment | ≥2 CTCs: 21 patients (21%) CTC ≥5 CTCs baseline and treatment CTC correlated with OS, PFS and disease stage |
| Krebs (2012) (18) | CellSearch & ISET | 40 patients stage III/IV, paired blood samples for comparison |
CellSearch (≥2 CTC): 9/40 positive (23%) ISET (≥1 CTC): 32/40 positive (80%) ISET: additionally CTC clusters and subpopulation of EpCAM- CTCs |
| Punnoose (2012) (15) | CellSearch | 41 patients NSCLC, stage III/IV Treated with erlotinib and pertuzumab |
≥1 CTC: 28/37 positive (78%) CTC count decrease correlated with DFS |
| Lou (2013) (5) | LT-PCR (folate α-receptors) | 72 NSCLC patients, stage I-IV 20 benign patients 24 healthy donors |
Threshold 8.5 CTU: detection of NSCLC: sensitivity 82%; specificity 93% |
| Nieva (2013) (14) | HD-CTC IF | 28 NSCLC patients with metastatic disease, 66 blood samples during course study |
≥1 CTC per 1 mL: 45 out of 66 (68%) blood samples CTC ≥5 per mL a HR OS 4.0 |
| Wendel (2013) (16) | HD-CTC | 78 NSCLC patients, chemotherapy-naïve, stage I-IV | ≥1 CTCs per 1 mL: 57/78 (73%) No correlation disease stage |
| Yu (2013) (6) | LT-PCR (folate α-receptors) |
153 NSCLC patients, stage I–IV, 64 benign disease 49 healthy controls |
Threshold 8.64 CTU per 3 mL: detection of NSCLC: sensitivity 73%; specificity 84% |
| Juan (2014) (11) | CellSearch | 37 NSCLC patients, stage IIIB/IV, measurements at baseline and after 2 months chemotherapy |
≥ 2 CTC: 9/37 positive (24%) ≥ 1 CTC: 15/38 (%) |
| Muinelo-Romay (2014) (13) | CellSearch | 43 NSCLC patients, stage IIIB or IV and undergoing first line chemotherapy |
≥1 CTC: 18/43 positive (42%) ≥5 CTC: 10/43 positive (23%) ≥5 CTCs correlated with OS and PFS |
| Chen (2015) (7) | LT-PCR (folate α-receptors) | Validation set: 237 NSCLC patients, stage I-IV 114 benign patients, 28 controls | Threshold 8.93 CTU per 3 mL: sensitivity of 76%; specificity 82% Correlated with disease stage |
| Wan (2015) (1) | LT-PCR (folate α-receptors) | 50 patients NSCLC, stage I-IV 35 benign patients 28 healthy subjects |
CTU correlated to disease stage |
| de Wit (2015) (19) | Modified CellSearch (+EPCAM- CTC) | 27 patients (24 NSCLC patients) | ≥1 EpCAM+ CTC: 11/27 (41%) ≥5: 4/27 (15%) ≥1 EpCAM- or EpCAM+ CTC: 20/27 (74%) ≥5: 11/27 (41%) EPCAM+ Cells ≥1 correlated with OS EPCAM- Cells no significant difference in OS |
All CTC numbers are in 7.5 mL of whole blood, unless stated otherwise. OS, overall survival; PFS, progression free survival; DFS, disease free survival; HR, hazard ratio; ISET, isolation by size of epithelial tumor method; EpCAM-CTCs, epithelial cell adhesion molecule negative circulating tumor cells; HD-CTC IF, high definition- CTC Immunofluorescence; LT-PCR, ligand targeted PCR; CTU, circulating tumor cell unit.