Table 4.
The combination of CTC counts with other clinical parameters: its performance and clinical utility in cancer management.
| Application | Cancer | Aim | Combinations | Parameter | Cutoff Value | AUC/Outcome | References |
|---|---|---|---|---|---|---|---|
| Cancer diagnosis | Breast cancer | Distinguish breast cancer patients from benign and healthy participants | CTC + tumor blood markers | CTC | 2 cells/mL blood | 0.845 | [147] |
| CEA | >5 ng/ml | 0.623 | |||||
| CA125 | >35 U/ml | 0.477 | |||||
| CA15-3 | >25 U/ml | 0.58 | |||||
| CTC + CEA | 0.866 | ||||||
| CTC + CA125 | 0.848 | ||||||
| CTC + CA15-3 | 0.873 | ||||||
| CTC + CEA + CA125 | 0.868 | ||||||
| CTC + CEA + CA15-3 | 0.874 | ||||||
| CTC + CA125 + CA15-3 | 0.873 | ||||||
| CTC + CEA + CA125 + CA15-3 | 0.874 | ||||||
| Early-stage (I-II) breast cancer diagnosis | CTC + tumor imaging data | CTC | 2 cells/4 mL blood | 0.855 | [23] | ||
| US (Ultrasound) | 4 b | 0.861 | |||||
| MMG (Mammogram) | 4 b | 0.759 | |||||
| CTC + US | 0.922 | ||||||
| CTC + MMG | 0.899 | ||||||
| Lung cancer | Early-stage (I-II) lung cancer diagnosis | CTC + tumor blood markers | CTC | 2 cells/3.2 mL blood | 0.825 | [148] | |
| CEA | >5 ng/ml | 0.541 | |||||
| CA125 | >35 U/ml | 0.565 | |||||
| CYFRA21-1 | >3.3 ng/ml | 0.587 | |||||
| SCC | >1.5 ng/ml | 0.509 | |||||
| CEA + CA125 + CYFRA21-1+ SCC | >1.5 ng/ml | 0.647 | |||||
| CTC + CEA + CA125 + CYFRA21-1 + SCC | 0.854 | ||||||
| Distinguish MPN patients from BPN patients | CTC | 2 cells/3.2 mL blood | 0.813 | ||||
| CEA | >5 ng/ml | 0.546 | [22] | ||||
| CA125 | >35 U/ml | 0.588 | |||||
| CYFRA21-1 | >3.3 ng/ml | 0.596 | |||||
| SCC | >1.5 ng/ml | 0.551 | |||||
| CEA + CA125 + CYFRA21-1 + SCC | 0.67 | ||||||
| CTC + CEA + CA125 + CYFRA21-1 + SCC | 0.853 | ||||||
| Distinguish benign from pulmonary nodules <2 cm | CTC + tumor imaging data | CTC | 6.05 cells/4 mL blood | 0.843 | [27] | ||
| CT | 0.83 | ||||||
| CTC + CT | 0.918 | ||||||
| Lung cancer diagnosis in patients with SPNs | CTC + tumor blood markers + tumor imaging data | CTC | 6 units/6 mL blood | 0.78 | [61] | ||
| CEA | 2.09 ng/ml | 0.626 | |||||
| Size (mm) (CT imaging) | 8 mm | 0.572 | |||||
| NT (CT imaging) | −600 HU | 0.626 | |||||
| Site (CT imaging) | 0.555 | ||||||
| CTC + CEA | 0.734 | ||||||
| CTC + CEA + NT | 0.827 | ||||||
| CTC + CEA + NT + Size + Site | 0.841 | ||||||
| Colore-ctal cancer | Colorectal cancer screening | CTC + tumor blood markers + cancer screening test | CTC | 23 cells/mL blood | 0.8602 | [24] | |
| CEA | >5 ng/ml | Detection rate: 30.3% | |||||
| iFOBT | The false-positive rate of iFOBT: 56.3% | ||||||
| CTC + CEA | Detection rate: 89.9% | ||||||
| CTC + iFOBT | Reduced false-positive rate of iFOBT to 18.8% | ||||||
| Pancre-atic cancer | Pancreatic ductal adenocarcinoma diagnosis | CTC + tumor blood markers | CTC | ≥2 cells/3.2 mL blood | 0.85 | [63] | |
| CA19-9 | ≥37 U/ml | 0.8 | |||||
| CTC + CA19-9 | 0.95 | ||||||
| Prognosis evaluation of the cancer | Breast cancer | Predict outcomes in metastatic breast cancer patients at baseline | CTC + CTC-related |
CTC | ≥5 cells/7.5 mL blood | PFS: HR 1.74 OS: HR 1.84 |
[25] |
| CTC + CTC clusters | ≥5 cells + ≥1 CTC-cluster/7.5 mL blood | PFS: HR 5.16 OS: HR 7.79 |
|||||
| Colorectal cancer | Predict recurrence for patients at all colorectal cancer stages | CTC + CTC-related + tumor blood markers |
CTC | >3 cells/2 mL blood | Recurrence rate: 32% | [26] | |
| CEA | > 5 ng/ml | Recurrence rate: 24% | |||||
| CA19-9 | > 37 ng/ml | Recurrence rate: 36.4% | |||||
| CTC clusters | >0 | Recurrence rate: 45.2% | |||||
| CTCs + CEA | Recurrence rate: 45.5% | ||||||
| CTCs + CA19-9 | Recurrence rate: 57.1% | ||||||
| CTCs With CTC clusters | Recurrence rate: 64.7% | ||||||
| CTCs + CEA + CA19-9 + With CTC clusters | Recurrence rate: 100% | ||||||
| Digestive tract cancer | Predict postoperative recurrence of cancer |
CTC + tumor blood markers | CTC | 6.87 cells/7.5 mL blood | 0.831 | [152] | |
| CEA mRNA | 3816.20 copies/mL | 0.912 | |||||
| CTC + CEA mRNA | 0.965 | ||||||
| Others | Lung cancer | Tumor invasiveness prediction |
CTC + tumor imaging data | FR + CTC Tumor volume (AI-assisted diagnosis system, ScrynPro) FR + CTC + tumor volume |
9.75 FU/3 mL blood | 0.659 | [153] |
| 118 mm^3 | 0.698 | ||||||
| 0.841 | |||||||
| Colorectal cancer | Metastasis prediction |
CTC + CTC-related + tumor blood markers | CTC CEA CTC + CEA |
≥3 cells/7 mL blood | 0.664 | [62] | |
| >5 ng/ml | 0.78 | ||||||
| 0.837 |
US, ultrasound; MS, Mammogram; CT, computed tomography; NT, Nodule type; HU, Hounsfield units; U, units; FR + CTC, folate-receptor-positive circulating tumor cell; FU, folate-receptor unit; AI, artificial intelligence.