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 ◽  
...  

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.

2013 ◽  
Vol 31 (3) ◽  
pp. 365-372 ◽  
Author(s):  
Mohid S. Khan ◽  
Amy Kirkwood ◽  
Theodora Tsigani ◽  
Jorge Garcia-Hernandez ◽  
John A. Hartley ◽  
...  

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.


PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254433
Author(s):  
Hui Jiang ◽  
Xiujuan Gu ◽  
Zhihua Zuo ◽  
Gang Tian ◽  
Jinbo Liu

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.


Author(s):  
Dalvinder Mandair ◽  
Mohid S Khan ◽  
Andre Lopes ◽  
Luke Furtado O’Mahony ◽  
Leah Ensell ◽  
...  

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.


2018 ◽  
Vol 7 (12) ◽  
pp. 5910-5919 ◽  
Author(s):  
Arutha Kulasinghe ◽  
Joanna Kapeleris ◽  
Rebecca Kimberley ◽  
Stephen R. Mattarollo ◽  
Erik W. Thompson ◽  
...  

2020 ◽  
Vol 21 (4) ◽  
pp. 1475
Author(s):  
Vera Cappelletti ◽  
Elena Verzoni ◽  
Raffaele Ratta ◽  
Marta Vismara ◽  
Marco Silvestri ◽  
...  

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.


2008 ◽  
Vol 43 (12) ◽  
pp. 2182-2185 ◽  
Author(s):  
Tatsuo Kuroda ◽  
Nobuyuki Morikawa ◽  
Kentaro Matsuoka ◽  
Akihiro Fujino ◽  
Toshiro Honna ◽  
...  

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