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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]