Clinical Value Of Circulating Tumor Cells Research Articles

Circulating tumor cells in oncology

Purpose of the study: to identify general patterns in the presence of detectable amounts of circulating tumor cells (CTCs) negatively correlated with the overall survival of patients and their ability to form metastases in distant tissues and organs, as well as to summarize the biological properties and interactions of CTCs with other cell types during intravasation, circulation, extravasation, and colonization, which involve changes in CTC phenotypes that are regulated by many signaling molecules, including cytokines and chemokines. Material and Methods. We analyzed publications available from PubMed (https://pubmed.ncbi.nlm.nih.gov), Scopus (https://www.scopus.com/), Web of Science (https://apps.webofknowledge. com/WOS_GeneralSearch), Cancer Tomorrow (https://gco.iarc.fr/tomorrow/en), and Global cancer observatory (https://gco.iarc.fr) databases between 2000–2021 using the keywords “circulating tumor cells”, “biomarker”, “metastasis” and others. Results. Monitoring of blood levels of CTCs can have exceptional prognostic and monitoring implications. Liquid biopsy to detect CTCs and their progeny can be used to diagnose cancer in the general population, as well as to predict biomarkers in cancer patients. The improvement in the CTC detection technology and clinical trials in large prospective studies will increase the clinical usefulness of these marker cells. Understanding of their biology and interactions with other cell types, especially with the immune cells, and the development of CTC immunotherapy also holds great promise in cancer therapy. Conclusion. Currently, CTCs are not routinely used in clinical practice, but research in this area continues to accumulate the data on the clinical validity of CTC detection. This is due to the feasibility of monitoring the patient’s condition using liquid biopsy for the CTC detection. We present an overview of the clinical value of CTCs as a biomarker, as well as key studies examining the clinical usefulness of CTCs.

Detection and Clinical Value of Circulating Tumor Cells as an Assisted Prognostic Marker in Colorectal Cancer Patients.

BackgroundCirculating tumor cells (CTCs) are cells that have been shed into the vasculature from a primary tumor and circulate in the bloodstream. It has been suggested that detecting CTCs could help the clinician to detect early metastasis or recurrence more effectively. This trial sets out to assess the detection and clinical value of CTCs as an assisted prognostic marker in patients with colon cancer and rectal cancer.MethodsA prospective cohort of patients with colorectal cancer (CRC) was enrolled from July 2015 to February 2018 in Shanghai Minimally Invasive Surgery Center, Shanghai, China. In this study, 149 patients with CRC were enrolled and underwent surgical treatment. There were 79 cases of colon cancer and 70 cases of rectal cancer, including 93 males and 56 females. To investigate the correlativity and clinical value of CTCs, the patients were statistically analyzed in different subgroups: colon cancer group vs rectal cancer group, and left hemicolon cancer group vs right hemicolon cancer group.ResultsThe results of analysis comparing CTC counts and clinical pathological features in colon and rectal cancer indicated that with increased tumor stage, the number of CTCs also increased, with significant statistical differences. CTC counts in patients with colon and rectal cancer showed positive correlations with TNM staging (P=0.001, 0.013, respectively), T staging (P=0.021, 0.001), N staging (P=0.014, 0.035) and M staging (P=0.018, 0.203). Detection of serum biomarkers in CTC-positive and CTC-negative groups indicated a significantly increasing expression in the CTC-positive group. To confirm the correlations between CTCs and histoembryological differences, analysis was conducted with the patients in two subgroups: left hemicolon cancer group and right hemicolon cancer group. The results showed that the positive rate of CTCs increased in both groups with the increase in tumor stage. The survival analysis indicated that there was a steep gradient in survival in the follow-up period, particularly in the CTC-positive group (P=0.000). Risk assessment curves showed that the change escalated more rapidly in the CTC-positive group. Furthermore, with the increase in T stage, changes in the survival curve and risk curve escalated more rapidly in the CTC-positive group.ConclusionIt was confirmed that in the left hemicolon cancer group, a much higher coincidence rate could be found on CTC-positive rate and clinicopathological features, than in the right hemicolon cancer group. The sensitivity of CTCs may be related to the histoembryological location of the tumor, lymphatic metastasis and the depth of infiltration. Monitoring CTCs may have value in evaluating clinical staging and estimating clinical prognosis.

Evaluation of therapeutic efficacy with CytoSorter® circulating tumor cell-capture system in patients with locally advanced head and neck squamous cell carcinoma.

Objective: This study aimed to investigate the feasibility of utilizing CytoSorter® system to detect circulating tumor cells (CTCs) and clinical value of CTCs in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC).Methods: 31 patients with LAHNSCC, 12 healthy volunteers, and 6 patients with benign tumor serving as controls were enrolled in this study. CTCs were enriched with the CytoSorter®, a microfluidic based immune capture system. CTC detection was performed before and after induction chemotherapy, as well as after surgery and/or radiotherapy. Correlations between CTC enumerations at different time points and survival outcome and recurrence risk were evaluated. The correlation between CTCs and clinicopathological characteristics was appraised. Follow-up of patients continued until March 2019.Results: While CTCs were not found in the controls, they were detected in 24 of 31 LAHNSCC patients. CTCs could be used to distinguish diseased people from the healthy (P<0.0001). CTCs were statistically associated with patient age (P=0.037, >60 years old vs<60 years old) and lymph node metastasis (P= 0.034, N0N1 VS N2N3). Most patients had significantly reduced CTCs at the end of treatment. Patients with partial remission of tumor after induction therapy had more CTCs than those with complete remission of tumor. Patients with higher CTCs counts prior to treatment had higher chance of developing local recurrence of tumor after treatment (P=0.0187).Conclusion: CTCs were successfully isolated in LAHNSCC patients using CytoSorter® system with better sensibility. CTCs can be used to differentiate LAHNSCC patients from those with benign HNSCC tumor or healthy volunteers, and as markers to monitor patient’s response to treatment and predict the local tumor recurrence after treatment. CTC detection at baseline has the greatest prognostic potency in LAHNSCC patients.

Clinical value of CTC in predicting the efficacy of treatment in breast cancer.

e12104 Background: Circulating tumor cells (CTCs) have proven to be underlying surrogate markers for several cancers. We aimed to investigate the diagnostic, predictive, and prognostic value of tCTCs using a four-CTC marker (CK19, surviving, Her2 and MUC1) real-time quantitative PCR (RT-PCR) assay in patients with breast cancer. Methods: In a previous study, we established a multimarker RT-PCR platform to detect and quantify CTC in colorectal cancer. By choosing four mRNA markers (CK-19/surviving/Her2/Muc1), we quantified CTC in the peripheral blood of 90 early operable breast cancer patients, 40 patients who had undergone surgery and received 6 cycles of follow-up of neoadjuvant chemotherapy, and 30 healthy volunteers. For early operable breast cancer patients, the CTC status at preoperative and postoperative time points was monitored. For the other 40 patients undergoing systemic adjuvant chemotherapy, the CTC status at six or more different time points was monitored. Results: CTCs were detected in 81% (73/90) of patients with early operable breast cancer. After surgery, 67.1% (49/73) of the patients switched to negative status. 36 out of 40 (90%) patients who received systemic adjuvant chemotherapy were CTC-positive. During follow-up, 31 out of 36 (86%,) patients became CTC-negative after 4 chemotherapy cycles. Among these 36 patients, four patients had relapsed within one year, and one had died. Three out of four relapsed patients, including the deceased one, switched into high CTC-positive status before diagnosed recurrence. Conclusions: The decrease of the levels of these CTC mRNA markers after surgery indicates that these CTC markers could be used as an indirect evaluation of tumor burden. The level of CTC mRNA markers could also help to evaluate therapeutic efficacy and disease progression.

Circulating tumor cells are correlated with disease progression and treatment response in an orthotopic hepatocellular carcinoma model.

Hepatocellular carcinoma (HCC) is a highly malignant tumor characterized by rapid progression, poor prognosis, and frequent hematogenous metastasis. A minimally invasive diagnostic biomarker that can predict disease progression and treatment response would be of extraordinary benefit. Therefore, we have investigated whether the number of circulating tumor cells (CTCs) is correlated with disease progression and treatment response in HCC. Here we report that the number of CTCs, monitored by in vivo flow cytometry (IVFC), is strongly correlated with disease progression and treatment response in a highly metastatic orthotopic nude mouse model of green fluorescent protein (GFP)-labeled HCC. Sorafenib treatment reduces the number of CTCs significantly. The decreased number of CTCs is consistent with low lung metastasis. This study has demonstrated a considerable clinical value of CTCs as a biomarker in predicting disease progression and monitoring therapeutic efficacy in patients with HCC.

MP79-18 RESULTS OF THE CLINICAL TRAIL IN-VIVO ISOLATION OF CTCS IN PROSTATE CANCER PATIENTS BY A CELLCOLLECTOR

You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 2014MP79-18 RESULTS OF THE CLINICAL TRAIL IN-VIVO ISOLATION OF CTCS IN PROSTATE CANCER PATIENTS BY A CELLCOLLECTOR Gerit Theil, Kersten Fischer, Andre Schumann, Kathrin Haublod, Catrin Boehm, Thomas Krahn, Klaus Luecke, Nils Morgenthaler, and Paolo Fornara Gerit TheilGerit Theil More articles by this author , Kersten FischerKersten Fischer More articles by this author , Andre SchumannAndre Schumann More articles by this author , Kathrin HaublodKathrin Haublod More articles by this author , Catrin BoehmCatrin Boehm More articles by this author , Thomas KrahnThomas Krahn More articles by this author , Klaus LueckeKlaus Luecke More articles by this author , Nils MorgenthalerNils Morgenthaler More articles by this author , and Paolo FornaraPaolo Fornara More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2521AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Circulating tumor cells (CTCs) in the blood stream play a critical role in establishing metastases. The clinical value of CTCs as a biomarker may help to assess the treatment efficacy. The detection of CTCs in the blood of patients with prostate cancer might therefore, in addition to their prognostic value, serve as liquid biopsy, complementing or replacing prostate-specific antigen (PSA) determination in predicting and monitoring the response to different therapies. However, capturing these rare cells from whole blood is still a major challenge that needs significant improvement. The aim was to demonstrate proof of concept of in vivo CTC isolation in Prostate cancer patients (PCa). METHODS A medical device (CellCollector) was inserted in a cubital vein for 30 minutes. The interaction of target CTCs with the CellCollector was mediated by antibodies to the epithelial cell adhesion molecule (EpCAM). To confirm binding of CTCs to the wire, immunohistochemical staining against Cytokeratin and CD45 was performed. There were 226 applications of the device in 16 metastasized PCa (PCa-m) with up to 8 wire applications per patient, 24 localized PCa (PCa-l) with up to 3 wire applications per patient as well as 19 men with benign prostate hypertrophy (BPH) and 21 women as control group with only one wire application. CTC counts from 22 PCa patients with 71 applications were directly compared to the CellSearch technology. RESULTS We obtained in vivo isolation of CTCs in 73 of 98 applications to PCa patients (74.5 %). The sensitivity for metastasized PCa was (86.2%) and for local PCa (57.5%), respectively. In PCa-l patients we observed prior radical prostatectomy (n=18) and 6 (n=15) and 12 (n=7) months after surgery CTC numbers on average of 18.2, 2.8 and 1.4, respectively. For the CellSearch® measurements, a blood draw of 7.5 ml blood was performed. We found in 77.5% (55/71) applications the patient to be positive for CTCs using the CellCollector™. In contrast the CellSearch® system resulted only in 42.2% (30/71) in the detection of CTCs. In addition we found a correlation of the CTC levels detected by the CellCollector™ and the PSA level during treatment. CONCLUSIONS We demonstrate the use of CTCs besides PSA during therapy adjustment in PCa patients. In summary, the CTC detection rate of the CellCollector in PCa-m and PCa-l in comparison to the CellSearch® method increased by 26% and 45%. Further molecular genetic CTC characterization as well as multiple antibody coating at the CellCollector will assume crucial information for therapy decisions. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e936-e937 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Gerit Theil More articles by this author Kersten Fischer More articles by this author Andre Schumann More articles by this author Kathrin Haublod More articles by this author Catrin Boehm More articles by this author Thomas Krahn More articles by this author Klaus Luecke More articles by this author Nils Morgenthaler More articles by this author Paolo Fornara More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Detecting circulating tumor cells: current challenges and new trends.

Circulating tumor cells (CTCs) in the blood stream play a critical role in establishing metastases. The clinical value of CTCs as a biomarker for early cancer detection, diagnosis, prognosis, prediction, stratification, and pharmacodynamics have been widely explored in recent years. However, the clinical utility of current CTC tests is limited mainly due to methodological constraints. In this review, the pros and cons of the reported CTC assays are comprehensively discussed. In addition, the potential of tumor cell-derived materials as new targets for CTC detection, including circulating tumor microemboli, cell fragments, and circulating DNA, is evaluated. Finally, emerging approaches for CTC detection, including telomerase-based or aptamer-based assays and cell functional analysis, are also assessed. Expectantly, a thorough review of the current knowledge and technology of CTC detection will assist the scientific community in the development of more efficient CTC assay systems.