scholarly journals Significance of Circulating Tumor Cells Detected by the CellSearch System in Patients with Metastatic Breast Colorectal and Prostate Cancer

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
M. Craig Miller ◽  
Gerald V. Doyle ◽  
Leon W. M. M. Terstappen
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Treatment Options ◽  
Venous Blood ◽  
Metastatic Breast ◽  
Cellsearch System ◽  
Multicenter Studies ◽  
Real Time Analysis ◽  
Number Of Treatment

The increasing number of treatment options for patients with metastatic carcinomas has created a concomitant need for new methods to monitor their use. Ideally, these modalities would be noninvasive, be independent of treatment, and provide quantitative real-time analysis of tumor activity in a variety of carcinomas. Assessment of circulating tumor cells (CTCs) shed into the blood during metastasis may satisfy this need. We developed the CellSearch System to enumerate CTC from 7.5 mL of venous blood. In this review we compare the outcomes from three prospective multicenter studies investigating the use of CTC to monitor patients undergoing treatment for metastatic breast (MBC), colorectal (MCRC), or prostate cancer (MPC) and review the CTC definition used in these studies. Evaluation of CTC at anytime during the course of disease allows assessment of patient prognosis and is predictive of overall survival.

scholarly journals Detection of Circulating Tumor Cells

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Sanne de Wit ◽  
Guus van Dalum ◽  
Leon W. M. M. Terstappen
Keyword(s):  
Real Time ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Treatment Options ◽  
Time Analysis ◽  
Future Directions ◽  
Real Time Analysis ◽  
Number Of Treatment

The increasing number of treatment options for patients with metastatic carcinomas has created an accompanying need for methods to determine if the tumor will be responsive to the intended therapy and to monitor its effectiveness. Ideally, these methods would be noninvasive and provide quantitative real-time analysis of tumor activity in a variety of carcinomas. Assessment of circulating tumor cells shed into the blood during metastasis may satisfy this need. Here we review the CellSearch technology used for the detection of circulating tumor cells and discuss potential future directions for improvements.

scholarly journals Circulating Tumor Cells in Metastatic Breast Cancer: Clinical Applications and Future Possibilities

2020 ◽  
Vol 10 (9) ◽  
pp. 3311
Author(s):  
Maggie Banys-Paluchowski ◽  
Florian Reinhardt ◽  
Tanja Fehm
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Therapy Monitoring ◽  
Metastatic Breast ◽  
Study Groups ◽  
Clinical Applications ◽  
Response To Treatment ◽  
Cellsearch System

Circulating tumor cells (CTCs) have gained importance as an emerging biomarker in solid tumors in the last two decades. Several detection assays have been introduced by various study groups, with EpCAM-based CellSearch system being the most widely used and standardized technique. In breast cancer, detection of CTCs correlates with clinical outcome in early and metastatic settings. CTC persistence beyond first cycle of palliative chemotherapy indicates poor response to treatment in metastatic situation. Beyond prognostication and therapy monitoring, CTC counts can guide treatment decisions in hormone receptor positive HER2-negative metastatic breast cancer. Furthermore, CTC-based therapy interventions are currently under investigation in clinical trials. In this review, we focus on the current state of knowledge and possible clinical applications of CTC diagnostics in patients with metastatic breast cancer.

Detection of circulating tumor cells (CTCs) in patients with hepatocellular carcinoma (HCC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15037-15037 ◽  
Author(s):  
B. C. Zee ◽  
C. Wong ◽  
T. Kuhn ◽  
R. Howard ◽  
W. Yeo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Control Procedure ◽  
Significant Prognostic Factor ◽  
Breast Cancer Patients ◽  
Cellsearch System

15037 Background: Allard et al. (2004) has established the accuracy, sensitivity, reliability and linearity of circulating tumor cells (CTCs) detection using the CellSearch System. 57% prostate cancers, 37% breast cancers, 37% ovarian cancers, 30% colorectal cancers, and 20% lung cancers specimens had >= 2 CTCs per 7.5 mL of blood. Only 0.3% healthy non-malignant disease subjects had >= 2 CTCs per 7.5 mL of blood. Cristofanilli et al.(2004,2005) have shown that CTCs at baseline and first follow-up were a significant prognostic factor for survival in metastatic breast cancer patients. However, HCC data on CTCs are not available. Methods: 20 locally advance or metastatic HCC patients who had not received prior treatment had been recruited after informed consent and 7.5 mL of blood were collected using the CellSave Preservative tubes (Veridex LLC, Raritan, NJ) that prevents CTCs degradation. The CellSearch system (Veridex LLC) similar to the previous studies was used to analyze the specimen. The CellSearch system consists the CellPrep system, the CellSearch Epithelial Cell Kit, and the CellSpotter Analyzer. All the procedures and interpretation of results followed closely with the quality control procedure of Veridex LLC including accreditation of trained laboratory personnel. Results: 13/20 (65%) had locally advanced disease and the rest had metastatic HCC. All patients had multiple lesions. 9/20 (45%) patients had detectable CTCs, 7/20 (35%) had >= 2 CTCs, and about 5/20 (20%) had 5 or more CTCs. For locally advanced HCC 4/13 (31%) patients had >= 2 CTCs per 7.5 mL of blood. For HCC patients with metastatic diseases 3/7 (43%) patients had >= 2 CTCs per 7.5 mL of blood. Conclusions: HCC patients with locally advance or metastatic disease had detectable CTCs in 7.5 mL of blood. We expected that the performance of CTCs in HCC is similar to that of breast cancer. Future study of using CTCs as prognostic factor at baseline and during treatment for HCC is being planned. No significant financial relationships to disclose.

Serum HER2 in the context of circulating tumor cells in patients with metastatic breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10599-10599 ◽  
Author(s):  
Volkmar Mueller ◽  
Sabine Riethdorf ◽  
Brigitte Kathrin Rack ◽  
Wolfgang Janni ◽  
Peter A. Fasching ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Elevated Serum ◽  
Metastatic Breast ◽  
Serum Levels ◽  
Her2 Status ◽  
Cellsearch System ◽  
Prognostic Information

10599 Background: Circulating tumor cells (CTC) reflect an aggressive tumor behavior by hematogenous tumor cell dissemination. Overexpression of HER2 in breast cancer (BC) is associated with increased angiogenesis and therefore potentially linked to increased hematogenous tumor cell spread. The aim of the analysis was to investigate whether concentrations of serum HER2 (sHER2) deliver prognostic information in the context of CTC detection in metastatic BC patients. Methods: Blood was obtained in a prospective multicenter setting from 254 patients with metastatic BC at the time of disease progression. sHER2 was determined using a commercial ELISA-kit (Wilex). CTC were detected with the CellSearch system (Veridex). Patients received systemic treatment according to national and international guidelines including HER2-targeted treatment. Results: Five or more CTC were detected in 122 of 245 evaluable patients (49.8%).119 of 251 (47%) metastatic patients had serum sHER2 levels above 15ng/mL. Median PFS was 9.2 months (95%-CI: 9.9 – 13.0 mths) with elevated sHER2 versus 11.4 mths (9.9 – 13.0 mths) with non-elevated levels (p=0.07). OS was 17.4 mths (14.6 – 20.3 mths) vs. 26.5 mths (23.1-29.8 mths; p<0.01). In patients with 5 or more CTC, serum levels were above the cut-off for sHER2 in 61% vs. 33% in those with less than 5 CTC (p< 0.01). Patients with elevated sHER and 5 or more CTC hat a PFS of 9.1 mths (7.2 – 11.1 mths) and a OS of 14.5 mths (11.8 – 17.2 mths), those with non-elevated sHER2 and less than 5 CTC a PFS of 12.1 (10.1 – 14.1 mths) and a OS of 29.5 month (25.4 – 33.6 mths) (p=0.15 for PFS and p< 0.01 for OS). Including sHER2, CTC and established prognostic factors in the multivariate analysis, the presence of CTC, line of therapy, ER and HER2 status of the primary tumor remained independent predictors of OS. Conclusions: Elevated serum levels of sHER2 are associated with the presence of CTC and indicate poor clinical outcome. However, sHER2 has no independent prognostic value when presence of CTC were taken into account.

Detecting circulating tumor cells (CTCs) in patients with high-risk, localized prostate cancer using the CellSearch platform.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15178-e15178
Author(s):  
Sumanta Kumar Pal ◽  
Clayton Lau ◽  
Miaoling He ◽  
Przemyslaw Twardowski ◽  
Timothy G. Wilson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Gleason Score ◽  
Prognostic Value ◽  
Localized Prostate Cancer ◽  
Cellsearch System ◽  
Mesenchymal Transition ◽  
E Cadherin

e15178 Background: Enumeration of circulating tumor cells (CTCs) using the CellSearch platform has prognostic value in patients with metastatic castration resistant prostate cancer. However, the prognostic value of CTC enumeration in high-risk, localized prostate cancer (HRLPC) remains undefined. Methods: Patients with HRLPC (defined by ≥1 of the following criteria: ≥ cT3a disease, Gleason score 8-10, or PSA > 20 ng/mL) who have chosen prostatectomy for their definitive management were prospectively identified. Patients were consented to receive 4 sequential 30 mL blood draws, each collected in 3 separate 10 mL EDTA tubes. The first 2 blood draws were conducted 2 weeks prior and immediately prior to surgery, while the second 2 blood draws were conducted 4-6 weeks and 3 months following surgery. Within 4 hrs of blood collection, the white blood cell (WBC) fraction was pooled and Ficoll purified. The WBC fraction was transferred to a CellSave tube, and CTCs were enumerated using the CellSearch system. Expression of CD133 and E-cadherin was characterized using the CellSearch system in patients with detectable CTCs. Results: Within 3 monthsof study initiation in Nov 2011, 19 of a planned 37 patients have been accrued. Median age in the cohort was 65 (range, 51-74), and the number of patients with Gleason score 8-10, ≥ cT3a disease, or PSA > 20 ng/mL was 16, 4, and 2, respectively. The majority of patients (17/19, or 89%) had only one high-risk feature. Mean baseline PSA for the cohort was 11.4 (range, 3.4-37). CTCs were detectable in 67% of patients prior to surgery, 27% of patients at 1 month following surgery and 67% of patients at 3 months following surgery. Amongst those patients with detectable CTCs, the median count was 3 (range, 1-7). Further, in these patients, CD133 and E-cadherin were detected in 44% and 46% of specimens assessed, respectively. Full details of these analyses will be provided at the time of the meeting. Conclusions: Using a modified methodology, CTC enumeration using the CellSearch platform is feasible in patients with HRLPC. Interestingly, markers of epithelial-mesenchymal transition and stem cell lineage are detectable in a proportion of patients with localized disease.

Expression of eIF4E relevant biomarkers detected in circulating tumor cells from metastatic NSCLC and prostate cancer patients using antibody-independent ApoStream technology.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13562-e13562
Author(s):  
Weiguo Wu ◽  
Jacky Woo ◽  
Vladislava O. Melnikova ◽  
Margaret Pace ◽  
Vishal Gupta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Expression ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Laser Scanning ◽  
Metastatic Breast ◽  
Invasive Approach ◽  
Metastatic Nsclc ◽  
Colorectal Cancer Patients

e13562 Background: Enumeration of circulating tumor cells (CTCs) is used clinically to monitor disease progression and has previously been shown to be an independent biomarker for predicting survival of metastatic breast, prostate, and colorectal cancer patients. Molecular characterization of CTCs is rapidly emerging as a minimally invasive approach to interrogate the genotype and phenotype of cancers. However, the use of EpCAM-based enrichment platforms relies on the expression of EpCAM thus limiting the type of tumor cells that can be recovered. ApoStream, is a novel, antibody-independent, dielectrophoretic field-flow fractionation based technology that recovers CTCs from cancer patient blood samples. Methods: A side-by-side comparison of EpCAM dependent CellSearch and ApoStream was performed for CTC enumeration in NSCLC and prostate cancer patients. A multiplexed immunofluorescent assay was developed for CTC (cytokeratin+/CD45-/DAPI+ cells) enumeration. CTCs recovered by ApoStream were evaluated for the expression of multiple eIF4E pathway biomarkers using quantitative laser scanning cytometry (LSC). Results: ApoStream isolated a significantly greater number of CTCs in both NSCLC and prostate cancer patients (NSCLC: range 9-1037, mean=407 by ApoStream versus a range of 30-340, mean=118 by CellSearch , p<0.05; prostate cancer: range 12-3490, mean=1472 by ApoStream versus a range of 16-2155, mean=502 by CellSearch , p<0.05). The eIF4E protein expression in CTCs was positively correlated with the CTC count. A trend toward correlation between the eIF4E protein expression level and the expression levels of Cyclin D1, Survivin and Bcl-2 was observed. Conclusions: The ApoStream platform recovers higher numbers of CTCs from the blood of metastatic NSCLC and prostate cancer patients compared to the EpCAM-dependent CellSearch platform. CTCs recovered by ApoStream are suitable for downstream molecular analyses paving the way for broader applications in translational cancer research.

Circulating tumor cells (CTCs) as a predictor of metastatic disease in patients with biochemical recurrence (BR) of prostate cancer with equivocal scan results.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 239-239
Author(s):  
Jeanny B. Aragon-Ching ◽  
Samuel J. Simmens ◽  
Steven R. Patierno ◽  
Robert S. Siegel
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Disease ◽  
Bone Biopsy ◽  
Treatment Options ◽  
Primary Treatment ◽  
Testosterone Levels ◽  
Number Of Patients ◽  
Bone Scans

239 Background: Staging for BR is challenging since the yield of computed tomography (CT) and bone scans are low, especially in patients with low prostate specific antigens (PSA) levels. We examined the utility of circulating tumor cells (CTCs) to predict metastatic disease in a cohort of patients who presented with BR (Aragon-Ching, et. al. ASCO GU 2011;abstr 60). Methods: 33 pts enrolled from May 2010 to September 2011 with BR, defined as patients (pts) who have undergone primary treatment with PSA rise to >/= 0.2 from a prior undetectable level for prior prostatectomy or > 2 mg/dl rise from post-nadir radiotherapy, were included. PSA doubling time (PSADT), scan results, Gleason scores, age, testosterone levels were all obtained. CTCs were evaluated in 7.5 mL of peripheral blood using the CTC CellSearch test. BR patients with equivocal CT and/or bone scan results who were biopsiable and consentable underwent bone biopsy to confirm metastatic disease. Results: The median age for 33 patients was 71 y/o (range: 51 – 91), median PSA of 1.7 ng/mL (range 0.2 – 65.8), testosterone levels of 315.5 ng/dL (range: 31 – 727), Gleason score of 7, hemoglobin of 13.78 g/dL, BMI of 27.72 and alkaline phosphatase of 68 IU/L. Prostatectomy was the primary treatment in 23 pts, radiotherapy in 9 pts and Cyberknife in 1 pt. Median PSADT varied between 0.35 to 55.2 months. Only a small number of patients had either biopsy confirmed metastatic disease (n=2) or detectable CTC (n=3). Both of the 2 patients with metastatic disease had detectable CTC (sensitivity = 1.00, 95% CI: .34, 1.00). For the patients without signs or confirmation of metastatic disease, 30/31 had no detectable CTC (specificity = .97, 95% CI: .84, .99). Conclusions: While most pts with BR have negative blood CTCs, patients with detectable CTCs and equivocal findings on scans should raise suspicion and prompt a search for metastatic disease, given increasing available treatment options for metastatic prostate cancer. However, the limited number of patients may preclude reliable statistical evaluation of CTCs in this population. Supported by IRG-08-091-01 from ACS to GWU Cancer Institute.

Dramatically Elevated Circulating Tumor Cell Numbers in a Patient With Small Cell Neuroendocrine Carcinoma of the Prostate

2010 ◽  
Vol 134 (1) ◽  
pp. 120-123
Author(s):  
Fanny Chan ◽  
Oscar Goodman ◽  
Louis Fink ◽  
Nicholas J. Vogelzang ◽  
David Pomerantz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Specific Antigen ◽  
Metastatic Breast ◽  
Circulating Tumor Cell ◽  
Small Cell ◽  
Castration Resistant Prostate Cancer ◽  
Normal Prostate ◽  
Castration Resistant

Abstract Detection of circulating tumor cells in whole blood is a useful prognostic tool for patients with castration-resistant prostate cancer, as well as for patients with metastatic breast cancer and colorectal carcinoma. In this report, we present the case of a patient with neuroendocrine small cell prostate cancer with normal prostate-specific antigen levels throughout the course of disease but who had markedly elevated circulating tumor cells, as detected with the CellSearch (Veridex) system.

scholarly journals Epithelial-to-mesenchymal transition of tumor cells: cancer progression and metastasis

2021 ◽  
Author(s):  
Vasileios Vardas ◽  
Eleni Politaki ◽  
Evangelia Pantazaka ◽  
Vassilis Georgoulias ◽  
Galatea Kallergi
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Metastatic Breast ◽  
Cellsearch System ◽  
Mesenchymal Transition ◽  
Specificity And Sensitivity

Detection and characterization of circulating tumor cells (CTCs) with an epithelial-to-mesenchymal transition (EMT) phenotype is very important as it can contribute to the identification of high-risk for relapse and death patients. However, most of the methods are underestimating CTC numbers, due to their dependence on epithelial markers. In the current study, we evaluated the EMT phenotype in CTCs isolated from breast cancer (BC) patients, using the CellSearch system. Spiking experiments for the evaluation of the specificity and sensitivity of our method were performed using HeLa cells. Sixty-five breast cancer (BC) patients (47 early and 18 metastatic) were enrolled in the study. Vimentin is a mesenchymal marker which indicates tumoral cells acquiring invasive and malignant properties. We studied the vimentin (VIM) expression using the extra channel of the CellSearch system and an anti-vimentin antibody conjugated with FITC. In our present results, we reported the percentage of circulating tumor cells that expressed vimentin in early and in metastatic breast cancer patients. Interestingly, the incidence of cells with a CK-VIM+CD45- phenotype was detected in both settings. These cells were detected in 31.4% of CK-negative (11/35) and 82.3% of CK-positive (10/12) early BC patients. The corresponding numbers for metastatic disease were 15.4% (2/13) and 100% (5/5), respectively. Our results suggest that in CTC-negative patients, potentially undetectable tumor cells could be identified using the FDA-approved CellSearch system, based on the (CK-VIM+CD45-)-phenotype, offering additional information regarding the metastatic dissemination in cancer patients. Further experiments evaluating more biomarkers are necessary to elucidate the mechanisms that regulate tumorigenesis and metastasis.

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