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Table 2 Clinical applications of CTCs in recent three years (from 2020 to 2022)

From: Detection of circulating tumor cells: opportunities and challenges

Cancer Type

CTCs Utility

Detection Methods

Molecular Characteristic

Main Findings/Purposes

Trial Identifier

Reference

breast cancer

prognostic value

CellSearch® system

PI3KCA, ESR1

the detection of 5 cells/7.5 mL of blood is the best cutoff point to stratify the patients’ prognosis

NA

[133]

prognostic value; recurrence monitoring

an epithelial cell adhesion molecule–based, positive-selection microfluidic device

NA

the presence of circulating tumor DNA and circulating tumor cells after NAC in patients with early-stage TNBC was associated with significantly inferior distant DFS, DFS, and OS

NCT02101385

[134]

therapeutic monitoring

CellSearch® system

NA

a 50% reduction in baseline apoptotic CTC count represents the optimal cut-off to differentiate between therapy response and disease progression

NA

[135]

prognostic value

CellSearch® system

HER2, CK

CTC heterogeneity in the blood of patients is inversely associated with OS.

NA

[136]

prognostic value; guiding therapy

CellSearch® system

HER2

first-line HER2-targeted therapy of mBC seems to reduce CTC levels greater than endocrine or chemotherapy; anti-HER2 therapy seems to be associated with lower overall CTC levels.

NA

[44]

guiding therapy

CellSearch® system

HER2

HER2 + CTCs ≥2 associated with shorter survival and higher risk for disease progression (HR 2.16)

NA

[137]

guiding therapy

CellSearch® system

PD-L1

CTC and platelet PD-L1 expression could predict which patients should receive immune checkpoint inhibition and as a pharmacodynamics biomarker during treatment

NA

[138]

prognostic value

CellSearch® system

NA

mortality is on the number of CTC/7.5 mL WB in patients with mBC starting first-line chemotherapy

NCT00382018

[139]

prognostic value

density-based isolation

TWIST1, CD24, CD44, and ALDH1

TWIST1 in EpCAM+ cells had a significant lower DFS and OS

NA

[140]

prognostic value; therapeutic monitoring

CellSearch® system

NA

the addition of bevacizumab was associated with a PFS benefit regardless of CTC count, but an OS benefit was only observed in CTC-positive patients

NCT00601900

[141]

prognostic value

GILUPI CellCollector

NA

evaluate the predictive value of CTC in NAC among locally advanced breast cancer patients.

NCT03732339

No Results Posted

lung cancer

diagnostic value

ISET®

NA

the ISET Rarecells test used in this study had too low a sensitivity to be used as a reliable lung cancer screening tool for patients at high-risk

NCT02500693

[142]

prognostic value

EpCAM-independent

NA

the high number of CTC predicted adverse prognosis

NA

[143]

prognostic value

CytoploRare Kit

NA

preoperative CTC concentration is an independent and sensitive biomarker of prognosis in patients with NSCLC

NA

[144]

prognostic value

Microsieve membrane filter device

NA

evaluates the use of ctDNA and CTCs in predicting disease activity and drug response in lung cancer patients

NCT04254497

No Results Posted

guiding therapy; therapeutic monitoring

ISET®

ALK

detection by FISH analysis and prevalence of escaping mutations in circulating tumor cells for the non-invasive management of lung cancer patients

NCT02372448

No Results Posted

gastric cancer

prognostic value; guiding therapy

CellSearch® system

HER2

HER2-expression on CTCs was an independent prognostic factor for both OS and PFS; the potential clinical utility of trastuzumab combined chemotherapy in patients with HER2-positive CTCs even if they are histologically HER2-negative

NA

[145]

prognostic value

Ficoll

FGFR2

patients with FGFR2-positive CTCs (≥5 cells/10 mL blood) had significantly worse RFS

NA

[146]

prognostic value

Ficoll

CEA

the number of EpCAM - /CEA + cells was higher in patients with stage II–IV than in patients with stage I; a lower number of CTCs indicated a higher 3-year RFS.

NA

[147]

therapy monitoring

CTCBIOPSY

NA

compare both short-term and long-term treatment effect of laparoscopic vs. open approach on progressive gastric and rectal cancer, based on circulating tumor cell (CTC) test results and DFS

NCT02955173

No Results Posted

colorectal cancer

prognostic value

CellSearch® system

NA

elevated bCTCs and RASmut were associated with clinicopathologic features known to be associated with poor prognosis

NCT01640405NCT01640444

[148]

prognostic value

Density gradient isolation

CEACAM5

using CEACAM5 as a dynamic poor prognostic CTC biomarker in patients with mCRC; MSI-High was identified as an unfavorable prognostic factor for tumors in patients with mCRC

NA

[149]

therapy monitoring

EPISPOT

NA

a prospective study of a cohort of patients with metastatic colorectal cancer was conducted to demonstrate the predictive value of CTC counts for treatment response.

NCT01596790

No Results Posted

pancreatic cancer

guiding therapy; prognostic value

CellSearch® system

NA

patients with positive CTC (≥1) preoperatively had a poor prognosis despite successful tumor resection, a finding with high specificity.

NA

[150]

hepatocellular Carcinoma

prognostic value

CellSearch® system

NA

CTC count ≥3 was associated with a higher risk of postoperative extrahepatic metastases;

NA

[151]

prognostic value

CanPatrol

Nanog

the numbers of EpCAM mRNA+ CTCs and Nanog mRNA+ CTCs were strongly correlated with postoperative HCC recurrence

NA

[152]

prognostic value

CellSearch® system

NA

elucidate the association between the levels of CTC/CTC clusters and patients’ disease during the perioperative period; explore the molecular basis of CTC production in hepatocellular carcinoma.

NCT05297955

No Results Posted

renal cell carcinoma

prognostic value

CellSearch® system

NA

the presence of ≥3 CTCs at baseline is associated with a significantly shorter PFS and OS in patients with mRCC

NA

[153]

prognostic value

CanPatrol-ITMCTCs

NA

no differences in the OS and DFS between the different numbers of CTCs

NA

[154]

prostate cancer

guiding therapy

Streck tubes

AR-V7

patients with detectable nuclear-localized AR-V7 in CTCs had superior survival with taxanes over ARSIs

NA

[155]

prognostic value

VERSA

NA

a transcriptional profile detectable in CTCs can serve as an independent prognostic marker beyond AR-V7 in patients with mPC CTC can be used to identify the emergence of multiple ARSI resistance mechanisms.

NCT01942837

NCT02025010

[156]

prognostic value

AdnaTest®

AR; AR-V7

detection of AR-V7 in CTCs is independently associated with shorter PFS and OS with abiraterone or enzalutamide; men with AR-V7-positive disease experience clinical benefits from taxane chemotherapy

NA

[157]

prognostic value

Epic Sciences

AR

chromosomal instability of CTCs was associated with poor OS in patients treated with AR signaling inhibitors and taxanes.

NA

[158]

prognostic value

CellSearch® system

NA

low CTC detection rate in patients with locally advanced high-risk prostate cancer; the conversion of CTCs was significantly associated with stages T3 (P = 0.044) and N1 (P = 0.002); detection of CTCs was not significantly associated with overall survival (P > 0.40)

NCT01800058

[159]

bladder Cancer

prognostic value

Telomerase-based technique

NA

detect tCTC levels in bladder cancer patients in different cohorts; clarify how tCTC levels vary with the natural history of bladder cancer; observe whether tCTCs provide new information.

NCT02246738

No Results Posted

gestational choriocarcinoma

guiding therapy

NanoVelcro system

NA

patients with ≥4 CTCs were more likely to develop chemoresistance than those with < 4 CTCs (P < 0.001)

NA

[127]

gynaecological malignancy

prognostic value

CellSearch® system

NA

patients with ≥ 1 CTC at baseline had significantly shorter OS and PFS than CTC-negative patients

NA

[160]