Table 2.
cfDNA plasma concentration performance as a biomarker for lung cancer diagnosis.
| Study | Year | Assay | Study population | Diagnostic performance | |||
|---|---|---|---|---|---|---|---|
| Cut-off | S | E | AUC | ||||
| Sozzi (80) | 2001 | DNA DipStick TM Kit (Invitrogen, Carlsbad, CA) | 43 healthy controls 84 patients with radically resected NSCLC (47 ADCs, 25 SCC and 12 others) |
6–25 ng/ml | 75% | 86% | 0.844 |
| Stages: IA: 14; IB: 32; II: 15; III: 23 | |||||||
| Sozzi (81) | 2003 | RT-PCR using hTERT | 100 controls 100 consecutive patients with NSCLC (58 ADC, 34 SCC, 8 others) |
25 ng/ml | 46% | 99% | 0.940 |
| Stages: IA: 16; IB: 18; IIB: 25; IIIA: 33; IIIB: 5; IV: 3 | |||||||
| Gautschi (82) | 2004 | RT-PCR | 46 healthy controls 185 NSCLC patients (81 ADC, 49 SCC, 37 LCC and 18 undifferentiated) |
10 ng/ml | – | 98% | – |
| Stages: I-II: 19; III: 62; IV: 104 | |||||||
| Herrera (83) | 2005 | RT-PCR using human β-actin gene | 11 healthy volunteers; 38 esophageal cancer; 28 GERD 25 NSLC patients undergoing surgery |
14.0 μg/L | 48% | 100% | 0.630 |
| Stages: I: 10; II: 4; III: 3; IV: 1; Unknown: 7 | |||||||
| Ludovini (84) | 2008 | RT-PCR | 66 controls 76 consecutive patients with NSCLC undergoing surgery (37 SCC, 28 ADC and 11 LCC) |
3.25 ng/ml | 80% | 61% | 0.820 |
| Stages: I: 20; II: 40; IIIA: 11; IIIB: 5 | |||||||
| Szpechcinski (85) | 2015 | RT-PCR using human β-actin | 40 healthy volunteers 101 patients with chronic respiratory inflammation (34 COPD, 35 sarcoidosis, 32 asthma) 50 resectable NSCLC patients (24 ADC, 22 SCC and 4 others) |
2.80 ng/ml | 90% | 81% | 0.900 |
| Stages: I: 22; II: 20; IIIA: 8 | |||||||
| Szpechcinski (86) | 2016 | RT-PCR using human β-actin | 16 healthy controls 28 subjects with benign lung tumors 65 NSCLC patients (28 ADC, 27 SCC, 10 others) |
2.80 ng/ml | 86% | 61% | 0.800 |
| Stages: I: 30; II: 23, III: 12 | |||||||
| Sozzi (87) | 2009 | RT-PCR using hTERT | 1035 subjects included in a CT screening program (annually CT). During the 5-year follow-up period, 956 remained cancer free, 38 developed LC, and 41 developed other tumors | – | – | – | 0.496 |
| Paci (88) | 2009 | RT-PCR using hTERT | 79 healthy controls. 151 NSCLC patients (65 SCCl, 61 ADC, 12 bronchioloalveolar, 3 LCC, 2 typical carcinoid, 8 others) |
2 ng/ml | 86% | 47% | 0.790 |
| Stages: IS: 1; IA: 33; IB: 44; IIA: 5; IIB: 12; IIIA: 24; IIIB: 18; IV: 4 | |||||||
| Yoon (89) | 2009 | RT-PCR using human β-actin gene | 105 healthy controls 102 LC patients (67 ADC, 16 SCC, 10 SCLC and 9 others) |
– | – | – | 0.860 |
| Stages in SCLC: localized: 5; extensive: 4 Stages in NSCLC: I: 8; II: 2; III: 19; IV: 64 |
|||||||
| Van der Drift (90) | 2010 | RT-PCR using human β-actin gene | 21 controls 46 untreated NSCLC patients (21 SCC, 20 ADC, 5 LCC) |
>32 ng/ml | 52% | 67% | 0.660 |
| Stages: I: 11; II: 6; III: 12; IV: 15; Unknown: 2 | |||||||
| Catarino (91) | 2012 | RT-PCR using hTERT | 205 controls 104 NSCLC patients (38 SCC, 54 ADC and 12 others) |
20 ng/ml | 79% | 83% | 0.880 |
| Stages: I/II: 4; III/IV: 100 | |||||||
ADC, adenocarcinoma; AUC, area under the curve; E, specificity; hTERT, human telomerase reverse transcriptase gene; IS, in situ; LC, lung cancer; LCC, large cell carcinoma; NSCLC, non-small cell lung cancer; S, sensitivity; SCC, squamous cell carcinoma; RT-PCR, real time polymerase chain reaction.