TABLE 1.
Representative studies relating circulating tumor cell (CTC) detection for various clinical applications in gastrointestinal (GI) tract cancers.
| CTCs for patient classification in GI tract cancers | |||||
|---|---|---|---|---|---|
| Study | GIC type | Feature | Platform used | Level (quantitative or qualitative) | Summary |
| Sastre et al. (2008) | CRC | Tumor stage (I–IV) | CellSearch system | >2 CTC per 7.5 mL blood | Only tumor stages correlated with CTC detection rates even when >2 or >3 CTCs were considered positive CTC cut-off |
| Bork et al. (2015) | CRC | Tumor stage (I–III) | CellSearch system | >1 CTC per 7.5 mL blood | Proportion of patients with positive CTC count increase as the stage increases |
| Bork et al. (2015) | CRC | Tumor stage (IV) | CellSearch system | >2/>3 CTC per 7.5 mL of blood | Metastatic patients had higher CTC detection rates |
| Kang et al. (2017) | GC | Healthy vs GC group | Lab-on-a-disk method | 2 CTC per 7.5 mL of blood | GC patients could be distinguished from normal patients with a sensitivity and specificity of 85.3% and 90.3%, respectively |
| Kang et al. (2017) | GC | Early-stage GC | Lab-on-a-disk method | A scorable CTC count of at least 1 CTC per 7.5 mL of blood | 80% early-stage GC (T1,N0) had a scorable CTC count |
| Luo et al. (2018a) | HCC | Invasive HCC/Barcelona Clinic Liver Cancer (BCLC) | CanPatrol CTC analysis system | CTCs subgrouped as epithelial, mesenchymal, and mixed phenotypes | Mesenchymal and mixed CTC phenotypes associated with invasive or BCLC stages |
| Chen et al. (2019) | HCC | Tumor stage | FAST disk microfluidic system | 2 CTCs per 7.5 mL of blood | No strong association was found between the stages and CTC count |
| Chen et al. (2019) | HCC | Metastatic HCC | CanPatrol CTC analysis system | 3/>3 CTCs per 7.5 mL of blood | High CTC count can predict the risk of EHM in HCC patients |
| Wei et al. (2019) | PDAC | PDAC patients vs. healthy individuals | Microfluidic assay | 2/>2 vimentin + CTC per 4 mL of blood | 76% of PDAC patients had vimentin + CTCs |
| Song et al. (2021) | PDAC | Early-stage PDACs | Microfabricated porous filter-based CTC enrichment and flow cytometric enumeration after immunostaining | EpCAM + CTCs enumerated | EpCAM + CTCs and plectin-1 + CTCs evaluated in portal and peripheral blood in resectable PDAC patients may be used as potential diagnostic and prognostic markers |
| Plectin-1 + CTCs enumerated | |||||
| CTCs for prognostic and therapy response applications in GI tract cancers | |||||
|---|---|---|---|---|---|
| Study | GIC type | Platform used | Scoring characteristic | Enumeration window | Comment |
| Yokobori et al. (2013) | CRC | autoMACS Cell sorting and immunocytochemistry | Evaluation of PLS3-expressing CTCs | Pre-operative peripheral blood of CRC patients | PLS3-positive CTCs represented as independent prognostic markers |
| Lee et al. (2015) | Metastatic GC | Anti-EpCAM antibody-coated magnetic particles using the CTC Profiler (Veridex) | >5 CTCs per 5 mL of blood | During the start of various chemotherapy cycles | Positive CTC score associated with unfavorable PFS and OS |
| Li et al. (2016) | Advanced GC | CellSearch | >3 CTCs per 7.5 mL of blood | 6 weeks after chemotherapy | Predicted shorter PFS and OS |
| Liu et al. (2017) | Advanced GC | CELLection™ Epithelial Enrichment kit | >2 CTCs per 2 mL of blood | After the 1st cycle of chemotherapy | Predicted poor PFS and OS |
| Mu et al. (2014) | Early HCC | Negative enrichment of CTCs and CaptorTM system | 16 CTCs per 7.5 mL of blood | Pre- and post-operative enumeration was done | CTC count decreased after successful surgery |
| Fang et al. (2014) | Intermediate HCC | Enrichment of CTCs by anti-EpCAM antibody and enumeration by fluorescent imaging | >1 CTC per 7.5 mL of blood | Pre- and post-TACE status of CTCs was evaluated in all patients | CTC count had no significant difference between patients receiving TACE or without receiving TACE |
| Rau et al. (2020) | Progressive HCC | Enrichment of CTCs followed by immunostaining and counting | 50 CTCs per ml of blood represented progressive disease | CTC evaluated for both advanced and metastatic HCC | High CTC count represented a progressive HCC disease |
| Zhou et al. (2020) | Resectable HCC | CellSearch system | >1 CTC per 7.5 mL of blood | CTCs evaluated once after surgery | High CTC group reported high mVI counts and, therefore, more chances of recurrence |
| Su et al. (2022) | HCC | CytoSorter™ | >2 CTCs per 2 mL of blood | Start and end of triple therapy, i.e., anti-PD-L1 therapy, anti-angiogenic therapy, and intensity modulated radiotherapy (IMRT) | Lesser score of PD-L1+ CTC at baseline was predictive of higher ORR and higher OS. |
| Poruk et al. (2017) | Resectable PDACs | Isolation by the size of epithelial tumor (ISET), followed by immunofluorescence | Various TIC surface phenotypes on CTCs were evaluated | CTCs evaluated in PDAC patients undergoing surgery | Patients positive for one or more CTC-TIC phenotypes act as independent factors for reduced OS) and DFS |
| Court et al. (2018) | Resectable PDACs | NanoVelcro Microfluidic System | 3/>3 CTCs per 5 mL of blood | CTCs evaluated in PDAC patients undergoing surgery | High CTC count pre-operatively predicts chances of occult metastasis |
| Zhu et al. (2021a) | Resectable PDACs | Immunomagnetic separation and fluorescent cell counts | Various CTC phenotypes grouped according to desired fluorescent tags | CTCs evaluated in PDAC patients undergoing surgery | Patients having >50% CTCs as KLF8+/vimentin+ have reduced TTR and OS |
| Park et al. (2021) | Resectable PDACs | CD-PRIME platform | Various CD144/EpCAM/CK CTC surface phenotypes | CTCs evaluated in PDAC patients undergoing surgery | CTC positivity defined by EpCAM/CK+ CD44− was associated with higher chances of early or frequent recurrence and systemic recurrence |
CRC, colorectal cancer; GC, gastric cancer; HCC, hepatocellular carcinoma; PDAC, pancreatic ductal adenocarcinoma; CTCs, circulating tumor cells; EHM, extrahepatic metastasis; FAST, fluid-assisted separation technology; IMRT, intensity modulated radiotherapy; TACE, transarterial chemoembolization; OS, overall survival; PFS, progression-free survival; DFS, disease-free survival.