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 < .01) for PanNETs and 5.88 (P < .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 < .03) and 5.09 (P < .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 < .01), whereas 2 or greater CTCs had an HR of 2.25 (P < .01) in midgut NETs. In multivariate analysis OS in PanNETs, 1 or greater CTCs had an HR of 3.16 (P < .01) and in midgut NETs, 2 or greater CTCs had an HR of 1.73 (P < .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.

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 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.

sVEGFR2 and circulating tumor cells to predict for the efficacy of pazopanib in neuroendocrine tumors (NETs): PAZONET subgroup analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4140-4140 ◽  
Author(s):  
Enrique Grande ◽  
Oriol Casanovas ◽  
Julie Earl ◽  
Daniel E. Castellano ◽  
Rocio Garcia-Carbonero ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Somatostatin Analogues ◽  
Tumor Location ◽  
Circulating Endothelial Cells ◽  
Duration Of Treatment ◽  
Primary Tumors ◽  
Free Survival

4140 Background: The PAZONET trial (Grande et al, ESMO 2012) performed by the GETNE group analyzed the efficacy and safety of the use of pazopanib (800 mg/qd) in patients (pts) with progressive metastatic NETs that had been previously treated with other novel targeted agents. Here we report on the relationship between clinical outcome and circulating and tumor-related biomarkers. Methods: Kaplan-Meier analysis was used to correlate progression-free survival (PFS) with: blood circulating markers at baseline and after 12 weeks of treatment (VEGF-A and sVEGFR2 circulating plasma, Circulating Tumor Cells (CTC) and Circulating Endothelial Cells (CEC)), tumor functional status, Ki67, concomitant somatostatin analogues (SSA), chromogranin A (CgA) and primary tumor location. Results: 44 pts were enrolled, 42 were evaluable for response. sVEGFR2 decreased after 12 weeks of treatment (median decrease 20%, p<0.0001) and the duration of treatment with pazopanib was associated with a decrease in sVEGFR2 (p=0.0046). Pts with a decrease in sVEGFR2 of >20% and <=20% had a median progression-free survival (mPFS) of 12.6 and 9.1 months (mo) respectively (p=0.067). Pts with and without CTC at baseline had a mPFS of 5.8 and 9.1 mo respectively (p=0.12). VEGFA and CEC were not found to predict PFS. mPFS in the intention to treat population was 10.0 mo (95% CI 4.3-15.6). Significant differences in mPFS were found in concomitant SSA treatment (11.9 mo [10.6-13.2]) vs. pazopanib alone (4.8 mo [3.0-6.6]) (p=0.007); decrease of CgA (3.4 mo [0.0-6.8]) vs no decrease (11.2 mo [8.4-14.1]) (p=0.024) and pancreatic (12.8 mo [11.0-14.6]) vs gastrointestinal (10.0 mo [4.9-15.1]) vs other primary tumors (3.4 mo [0.0-7.0]). No differences in mPFS were seen in functioning (10.0 mo) and non-functioning tumors (9.3 mo) and Ki67 status (< 2% 10.0 mo, 3-10% 10.8 mo or >10% 4.1 mo). Conclusions: sVEGFR2 and baseline CTC are promising predictive biomarkers for pazopanib in NETs. The updated results confirm the efficacy of pazopanib as a sequencing treatment of pts with progressive NETs, particularly in those with pancreatic primary tumors. The combination of pazopanib and SSA seems to be synergistic. Clinical trial information: NCT01280201.

386 HIGH NUMBERS OF PORTAL VENOUS CIRCULATING TUMOR CELLS ACQUIRED VIA EUS PROVIDE PROGNOSTIC ASSISTANCE FOR PROGRESSION FREE SURVIVAL IN PANCREATICOBILIARY CANCERS

2019 ◽  
Vol 89 (6) ◽  
pp. AB78-AB79
Author(s):  
Eric Swei ◽  
Ernesto Llano ◽  
Christopher G. Chapman ◽  
Betty Li ◽  
Rene S. Bermea ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Progression Free Survival ◽  
Free Survival

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.

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