Circulating Tumor Cells As Prognostic Markers in Neuroendocrine Tumors

2013 ◽  
Vol 31 (3) ◽  
pp. 365-372 ◽  
Author(s):  
Mohid S. Khan ◽  
Amy Kirkwood ◽  
Theodora Tsigani ◽  
Jorge Garcia-Hernandez ◽  
John A. Hartley ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Neuroendocrine Tumors ◽  
Prognostic Markers ◽  
Prognostic Significance ◽  
Elevated Serum ◽  
Progression Free Survival ◽  
Tumor Grade ◽  
Immunomagnetic Separation ◽  
Tumor Burden

Purpose To determine the prognostic significance of circulating tumor cells (CTCs) in patients with neuroendocrine cancer. Patients and Methods In this single-center prospective study, 176 patients with measurable metastatic neuroendocrine tumors (NETs) were recruited. CTCs were measured using a semiautomated technique based on immunomagnetic separation of epithelial cell adhesion molecule–expressing cells. Results Overall, 49% patients had ≥ one CTC, 42% had ≥ two CTCs, and 30% had ≥ five CTCs in 7.5 mL blood. Presence of CTCs was associated with increased burden, increased tumor grade, and elevated serum chromogranin A (CgA). Using a 90-patient training set and 85-patient validation set, we defined a cutoff of < one or ≥ one as the optimal prognostic threshold with respect to progression-free survival (PFS). Applying this threshold, the presence of ≥ one CTC was associated with worse PFS and overall survival (OS; hazard ratios [HRs], 6.6 and 8.0, respectively; both P < .001). In multivariate analysis, CTCs remained significant when other prognostic markers, grade, tumor burden, and CgA were included. Within grades, presence of CTCs was able to define a poor prognostic subgroup. For grade 1, HRs were 5.0 for PFS (P = .017) and 7.2 for OS (P = .023); for grade 2, HRs were 3.5 for PFS (P = .018) and 5.2 for OS (P = .036). Conclusion CTCs are a promising prognostic marker for patients with NETs and should be assessed in the context of clinical trials with defined tumor subtypes and therapy.

scholarly journals Prognostic Threshold for Circulating Tumor Cells in Patients With Pancreatic and Midgut Neuroendocrine Tumors

2020 ◽  
Author(s):  
Dalvinder Mandair ◽  
Mohid S Khan ◽  
Andre Lopes ◽  
Luke Furtado O’Mahony ◽  
Leah Ensell ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Neuroendocrine Tumors ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Multivariate Logistic Regression Analysis ◽  
Progression Free Survival ◽  
Free Survival ◽  
Optimum Threshold

Abstract Background Circulating tumor cells (CTCs) are detectable in patients with neuroendocrine tumors (NETs) and are accurate prognostic markers although the optimum threshold has not been defined. Objective This work aims to define optimal prognostic CTC thresholds in PanNET and midgut NETs. Patients and Methods CellSearch was used to enumerate CTCs in 199 patients with metastatic pancreatic (PanNET) (90) or midgut NETs (109). Patients were followed for progression-free survival (PFS) and overall survival (OS) for a minimum of 3 years or until death. Results The area under the receiver operating characteristic curve (AUROC) for progression at 12 months in PanNETs and midgut NETs identified the optimal CTC threshold as 1 or greater and 2 or greater, respectively. In multivariate logistic regression analysis, these thresholds were predictive for 12-month progression with an odds ratio (OR) of 6.69 (P &lt; .01) for PanNETs and 5.88 (P &lt; .003) for midgut NETs. The same thresholds were found to be optimal for predicting death at 36 months, with an OR of 2.87 (P &lt; .03) and 5.09 (P &lt; .005) for PanNETs and midgut NETs, respectively. In multivariate Cox hazard regression analysis for PFS in PanNETs, 1 or greater CTC had a hazard ratio (HR) of 2.6 (P &lt; .01), whereas 2 or greater CTCs had an HR of 2.25 (P &lt; .01) in midgut NETs. In multivariate analysis OS in PanNETs, 1 or greater CTCs had an HR of 3.16 (P &lt; .01) and in midgut NETs, 2 or greater CTCs had an HR of 1.73 (P &lt; .06). Conclusions The optimal CTC threshold to predict PFS and OS in metastatic PanNETs and midgut NETs is 1 and 2, respectively. These thresholds can be used to stratify patients in clinical practice and clinical trials.

scholarly journals Prognostic value of circulating tumor cells in patients with bladder cancer: A meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254433
Author(s):  
Hui Jiang ◽  
Xiujuan Gu ◽  
Zhihua Zuo ◽  
Gang Tian ◽  
Jinbo Liu
Keyword(s):  
Bladder Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
Number Of Patients ◽  
Registration Number

Background Circulating tumor cells (CTCs) have been considered diagnostic and prognostic biomarkers for urothelial cancer. However, the prognostic role of CTCs in bladder cancer (BC) remains controversial. Here, we conducted a meta-analysis to evaluate the prognostic significance of CTCs for patients with BC. Methods All studies relevant to this topic were searched in the PubMed, Embase, and Web of Science databases. The hazard ratio (HR) and 95% confidence interval (95% CI) were set as effect measures. The outcomes were overall survival (OS), cancer-free survival (CSS), progression-free survival (PFS)/time to progression (TTP), and disease-free survival (DFS)/recurrence-free survival (RFS)/time to first recurrence (TFR). All analyses were conducted in STATA 15.1. Results Eleven eligible studies comprising 1,062 patients with BC were included in this meta-analysis. Overall analyses showed that CTC-positive patients had poorer survival (OS: HR 3.88, 95% CI 2.52–5.96, p < 0.001; CSS: HR 3.89, 95% CI 2.15–7.04, p < 0.001) and more aggressive progression (PFS/TTP: HR 5.92, 95% CI 3.75–9.35, p < 0.001; DFS/RFS/TFR: HR 4.57, 95% CI 3.34–6.25, p < 0.001) than CTC-negative patients. Subgroup analyses according to the number of patients, detection method, positivity rate, and follow-up time revealed that the presence of CTCs predicted a high risk of mortality and disease progression in most subgroups. Conclusion The meta-analysis confirmed that CTCs are a promising prognostic biomarker of poor survival and aggressive tumor progression for patients with BC. Prospero registration number CRD42021224865.

scholarly journals Circulating Tumor Cells Expressing Krüppel-Like Factor 8 and Vimentin as Predictors of Poor Prognosis in Pancreatic Cancer Patients

2021 ◽  
Vol 28 ◽  
pp. 107327482110271
Author(s):  
Peng Zhu ◽  
Hui-Ying Liu ◽  
Fu-Chen Liu ◽  
Fang-Ming Gu ◽  
Sheng-Xian Yuan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Prognostic Significance ◽  
Immunomagnetic Separation ◽  
Mesenchymal Transition

Background: Circulating tumor cells (CTCs) with an epithelial-mesenchymal transition phenotype in peripheral blood may be a useful marker of carcinomas with poor prognosis. The aim of this study was to determine the prognostic significance of CTCs expressing Krüppel-like factor 8 (KLF8) and vimentin in pancreatic cancer (PC). Methods: CTCs were isolated by immunomagnetic separation from the peripheral blood of 40 PC patients before undergoing surgical resection. Immunocytochemistry was performed to identify KLF8+ and vimentin+ CTCs. The associations between CTCs and time to recurrence (TTR), clinicopathologic factors, and survival were assessed. Univariate and multivariate analyzes were performed to identify risk factors. Results: Patients with CTCs ( n = 30) had a higher relapse rate compared to those without ( n = 10) (70.0% vs 20.0%; P < 0.01). The proportion of KLF8+/vimentin+ CTCs to total CTCs was inversely related to TTR ( r = −0.646; P < 0.01); TTR was reduced in patients with > 50% of CTCs identified as KLF8+/vimentin+ ( P < 0.01). Independent risk factors for recurrence were perineural invasion and > 50% KLF8+/vimentin+ CTCs (both P < 0.05). Conclusion: Poor prognosis can be predicted in PC patients when > 50% of CTCs are positive for KLF8 and vimentin.

scholarly journals Relationship of Circulating Tumor Cells to Tumor Response, Progression-Free Survival, and Overall Survival in Patients With Metastatic Colorectal Cancer

2008 ◽  
Vol 26 (19) ◽  
pp. 3213-3221 ◽  
Author(s):  
Steven J. Cohen ◽  
Cornelis J.A. Punt ◽  
Nicholas Iannotti ◽  
Bruce H. Saidman ◽  
Kert D. Sabbath ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Immunomagnetic Separation ◽  
Prognostic Information ◽  
Free Survival

PurposeAs treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells (CTCs) could predict clinical outcome in patients with mCRC.Patients and MethodsIn a prospective multicenter study, CTCs were enumerated in the peripheral blood of 430 patients with mCRC at baseline and after starting first-, second-, or third-line therapy. CTCs were measured using an immunomagnetic separation technique.ResultsPatients were stratified into unfavorable and favorable prognostic groups based on CTC levels of three or more or less than three CTCs/7.5 mL, respectively. Patients with unfavorable compared with favorable baseline CTCs had shorter median progression-free survival (PFS; 4.5 v 7.9 months; P = .0002) and overall survival (OS; 9.4 v 18.5 months; P < .0001). Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Conversion of baseline unfavorable CTCs to favorable at 3 to 5 weeks was associated with significantly longer PFS and OS compared with patients with unfavorable CTCs at both time points (PFS, 6.2 v 1.6 months; P = .02; OS, 11.0 v 3.7 months; P = .0002). Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival (18.8 v 7.1 months; P < .0001). Baseline and follow-up CTC levels remained strong predictors of PFS and OS after adjustment for clinically significant factors.ConclusionThe number of CTCs before and during treatment is an independent predictor of PFS and OS in patients with metastatic colorectal cancer. CTCs provide prognostic information in addition to that of imaging studies.

scholarly journals The Distribution of Circulating Tumor Cells Is Different in Metastatic Lobular Compared to Ductal Carcinoma of the Breast—Long-Term Prognostic Significance

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1718
Author(s):  
Ulrik Narbe ◽  
Pär-Ola Bendahl ◽  
Kristina Aaltonen ◽  
Mårten Fernö ◽  
Carina Forsare ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Ductal Carcinoma ◽  
Lobular Carcinoma ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Prognostic Effect ◽  
Serial Sampling ◽  
Distinguishing Features

Background: Invasive lobular carcinoma (ILC) has distinguishing features when compared to invasive ductal carcinoma of no special type (NST). In this study, we explored the distributional and prognostic characteristics of circulating tumor cells (CTCs) in metastatic ILC and NST. Materials and methods: Patients were included in an observational trial (ClinicalTrials.gov NCT01322893) with ILC (n = 28) and NST (n = 111). CTC count (number/7.5 mL blood) was evaluated with serial sampling (CellSearch). The primary endpoint was progression-free survival (PFS). Results: The CTC counts were higher in ILC (median 70) than in NST cases (median 2) at baseline (p < 0.001). The evidence for ≥5 CTCs as a prognostic factor for PFS in ILC was weak, but stronger with higher cut-offs (CTC ≥ 20: hazard ratio (HR) 3.0, p = 0.01) (CTC ≥ 80: HR 3.6, p = 0.004). In NST, however, the prognostic effect of CTCs ≥5 was strong. Decline in CTC count from baseline to three months was associated with improved prognosis in ILC and NST. Conclusions: The number of CTCs is higher in ILC than in NST, implying that a higher CTC cut-off could be considered for ILC when applying the CellSearch technique.

Circulating tumor cells (CTCs) in metastatic breast cancer: Biological value beyond tumor burden

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 615-615 ◽  
Author(s):  
M. Cristofanilli ◽  
V. Guarneri ◽  
V. Valero ◽  
H. A. Fritsche ◽  
K. R. Broglio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Prognostic Value ◽  
Tumor Biology ◽  
Prognostic Significance ◽  
Metastatic Breast ◽  
Tumor Burden ◽  
Risk Of Death

615 Background: The detection of circulating tumor cells (CTCs) can predict progression-free (PFS) and overall survival (OS) in patients with metastatic breast cancer (MBC). We evaluated the prognostic significance of baseline CTCs in relation to standard measures of tumor burden. Furthermore, we assessed if the prognostic value of CTCs was related to any particular molecular phenotype. Patients and Methods: One hundred twenty-three consecutive MBC patients (pts) evaluated prospectively between 12/2000 and 5/2005 were included in this analysis. CTCs from 7.5 mL of whole blood were isolated and enumerated using CellSearch system. Prognostic value was determined by analyzing the following factors, baseline level of CTCs (negative: <5 CTCs/7.5 mL; positive: ≥ 5 CTCs/7.5 mL), age (50 yrs<vs. >/=50 yrs), hormonal receptor (HR), Her-2/neu status, metastatic site (visceral vs. non-visceral), Swenerton score, CA27.29 levels, and previous chemotherapy for MBC (none vs. pre-treated), Results: Median age was 52 years (range 24–88) and the median follow-up was 7.7 months (range 0–53.4 months). The median OS for the alive pts was 17.5 months. Fifty-two pts (42%) had positive CTCs and abnormal CA27.29 was detected in 80 pts (66%). The median OS for patients with negative vs. positive CTCs were 28.3 months (range 1.28 - 31.24) and 12.8 months (range 1.71 to 36.83) respectively (p=0.0001). In the multivariable model, HR status, CTCs, and CA27.29 level were the only factors significantly related to OS. CTCs demonstrated the strongest predictor for OS and were associated with 2.53 times the risk of death (p = 0.003). The prognostic value of CTCs was independent of line of treatment, site of recurrence and phenotype of the disease. Conclusions: CTCs demonstrated prognostic value independent of standard measures of tumor burden and phenotypic characteristics of the disease. CTCs are an important marker of tumor biology in metastatic breast cancer. No significant financial relationships to disclose.

scholarly journals The prognostic significance of circulating tumor cells in head and neck and non-small-cell lung cancer

2018 ◽  
Vol 7 (12) ◽  
pp. 5910-5919 ◽  
Author(s):  
Arutha Kulasinghe ◽  
Joanna Kapeleris ◽  
Rebecca Kimberley ◽  
Stephen R. Mattarollo ◽  
Erik W. Thompson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Head And Neck ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cell Lung Cancer ◽  
Prognostic Significance ◽  
Small Cell ◽  
Small Cell Lung

Microfluidic Assaying of Circulating Tumor Cells and its Correlation with Muscle Invasiveness and Tumor Grade of Urothelial Bladder Cancer

2021 ◽  
Author(s):  
Guanghou Fu ◽  
Kok Suen Cheng ◽  
Anqi Chen ◽  
Zhijie Xu ◽  
Xiaoyi Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Risk Stratification ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Tumor Grade ◽  
Invasive Bladder Cancer ◽  
Low Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Abstract Background: Bladder cancer is characterized by its frequent recurrence and progression. Effective treatment strategies need to be based on an accurate risk stratification, in which muscle invasiveness and tumor grade represent the two most important factors. Traditional imaging techniques provide preliminary information about muscle invasiveness but are lacking in terms of accuracy. Although as the gold standard, pathological biopsy is only available after the surgery and cannot be performed longitudinally for long-term surveillance. Methods: In this work, we developed a microfluidic approach that interrogates circulating tumor cells (CTCs) in the peripheral blood of bladder cancer patients to reflect the risk stratification of the disease. Results：In a cohort of 48 bladder cancer patients comprising 33 non-muscle invasive bladder cancer (NMIBC) cases and 15 muscle invasive bladder cancer (MIBC) cases, the CTC count was found to be considerably higher in the MIBC group compared with the NMIBC group (4.67 vs. 1.88 CTCs/3 mL, P=0.019), and was significantly higher in high-grade bladder cancer patients verses low-grade bladder cancer patients (3.69 vs. 1.18 CTCs/3mL, P=0.024). Conclusions: This microfluidic assay of CTCs is believed to be a promising complementary tool for the risk stratification of bladder cancer.Trial registration: This research was conducted under the approval of the Ethics Committee of the First Affiliated Hospital at Zhejiang University School of Medicine with the Registration No. 2015-218.

scholarly journals Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression

2020 ◽  
Vol 21 (4) ◽  
pp. 1475
Author(s):  
Vera Cappelletti ◽  
Elena Verzoni ◽  
Raffaele Ratta ◽  
Marta Vismara ◽  
Marco Silvestri ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Response Prediction ◽  
Surface Proteins ◽  
Cell Recovery ◽  
Epithelial Cell Surface

Circulating tumor cells (CTCs) are promising biomarkers for prognosis, therapeutic response prediction, and treatment monitoring in cancer patients. Despite its epithelial origin, renal cell carcinoma (RCC) shows low expression of epithelial markers hindering CTC-enrichment approaches exploiting epithelial cell surface proteins. In 21 blood samples serially collected from 10 patients with metastatic RCC entering the TARIBO trial, we overcame this limitation using the marker-independent Parsortix™ approach for CTC-enrichment coupled with positive and negative selection with the DEPArray™ with single cell recovery and analysis for copy number alterations (CNA) by next generation sequencing NGS. Two CTC subpopulations were identified: epithelial CTC (eCTC) and non-conventional CTC (ncCTC) lacking epithelial and leukocyte markers. With a threshold ≥1CTC/10 mL of blood, the positivity rates were 28% for eCTC, 62% for ncCTCs, and 71% considering both CTC types. In two patients with detectable eCTCs at baseline, progression free survival was less than 5 months. In an index case, hierarchical structure by translational oncology (TRONCO) identified three clones among 14 CTCs collected at progression and at baseline, each containing cells with a 9p21.3loss, a well-known metastasis driving subclonal alteration. CTCs detection in RCC can be increased by marker-independent approaches, and CTC molecular characterization can allow detection of subclonal events possibly related to tumor progression.

scholarly journals Circulating Tumor Cells in Pancreatic Cancer: Current Perspectives

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1659 ◽  
Author(s):  
Verena Martini ◽  
Sylvia Timme-Bronsert ◽  
Stefan Fichtner-Feigl ◽  
Jens Hoeppner ◽  
Birte Kulemann
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Prognostic Markers ◽  
Cancer Prognosis ◽  
Detection Methods ◽  
Ductal Adenocarcinoma ◽  
Detection Tool ◽  
The Usa ◽  
New Biomarkers

Pancreatic cancer is the fourth leading cause of cancer-related death in the USA and Europe; early symptoms and screenings are lacking, and it is usually diagnosed late with a poor prognosis. Circulating tumor cells (CTCs) have been promising new biomarkers in solid tumors. In the last twenty years (1999–2019), 140 articles have contained the key words “Circulating tumor cells, pancreatic cancer, prognosis and diagnosis.” Articles were evaluated for the use of CTCs as prognostic markers and their correlation to survival in pancreatic ductal adenocarcinoma (PDAC). In the final selected 17 articles, the CTC detection rate varied greatly between different enrichment methodologies and ranged from 11% to 92%; the majority of studies used the antigen-dependent CellSearch© system for CTC detection. Fifteen of the reviewed studies showed a correlation between CTC presence and a worse overall survival. The heterogeneity of CTC-detection methods and the lack of uniform results hinder a comparison of the evaluated studies. However, CTCs can be detected in pancreatic cancer and harbor a hope to serve as an early detection tool. Larger studies are needed to corroborate CTCs as valid biomarkers in pancreatic cancer.

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