Value Of Circulating Tumor Cells In Patients Research Articles

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.

The diagnostic value of circulating tumor cells for lung cancer

Background:Circulating tumor cells (CTCs) have become a potential diagnostic tumor marker and have the potential for wide clinical applications. However, the diagnostic parameters vary among previous studies. A systematic review of the literature and meta-analysis were conducted to assess the diagnostic value of CTCs for lung cancer.Methods:Eligible studies were searched in PubMed, Medline, Cochrane Library, and Embase databases. The included studies assessed the diagnostic value of CTCs in patients with lung cancer up to September 30, 2018. A total of 1601 patients in 8 studies were included in the meta-analysis. We calculated the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) to investigate the diagnostic value of CTCs for lung cancer. STATA version 12.0 and Meta-DiSc version 1.4 software were used to analyze the data.Results:The pooled sensitivity was 0.75 (95% CI: 0.73–0.78), the specificity was 0.89 (95% CI: 0.86–0.92), the PLR was 6.29 (95% CI: 3.98–9.96), and the NLR was 0.24 (95% CI: 0.14–0.42). Furthermore, the pooled DOR of CTCs for lung cancer was 27.73 (95% CI: 12.99–59.23). The summarized area under the ROC curve was 0.93 (95% CI: 0.90–0.95). The meta-regression analysis suggested that the heterogeneity was mainly attributed to the experimental methods. The results of the clinical diagnosis efficiency show that the diagnostic efficiency has increased significantly by testing CTCs for diagnosing lung cancer.Conclusion:The results of this meta-analysis suggest that CTCs are associated with a high diagnostic value for lung cancer. These findings require large-scale prospective studies to verify and evaluate the diagnostic value in the future.

Prognostic value of circulating tumor cells in patients with squamous cell carcinoma of the head and neck: a systematic review and meta-analysis.

The prognostic value of circulating tumor cells (CTCs) in patients with squamous cell carcinoma of the head and neck (SCCHN) is controversial. The objective of this study was to evaluate the prognostic value of CTCs in patients with SCCHN by conducting a meta-analysis. We systematically searched scientific literature published before June 10, 2014, using the PubMed, ScienceDirect, Cochrane Library, and EMBASE databases. Studies evaluating the correlation of CTC status with tumor-node-metastasis (TNM) disease stage, nodal involvement, and disease progression (recurrence or metastasis) in patients with SCCHN were selected for the analysis. Pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated using the fixed-effects model or the random-effects model in the presence of heterogeneity. Our analysis consisted of eight studies, enrolling a total of 433 patients. The disease progression (recurrence/metastasis) rate in the CTC-positive patients was significantly higher (OR 3.44; 95 % CI 1.87-6.33; p < 0.01) compared with the patients without disease progression. However, there was no significant difference between TNM disease stage III-IV and stage I-II in the presence of CTCs (OR 1.54; 95 % CI 0.87-2.72; p > 0.05). CTC status did not correlate with nodal involvement (OR 1.20; 95 % CI 0.67-1.90; p > 0.05). This meta-analysis indicates that detection of CTCs has a predictive value in patients with SCCHN, particularly those with tumor progression. The presence of CTCs in patients with SCCHN has a poor prognosis compared with the patients without CTCs. Detection of CTCs might be served as a prognosticator in patients with SCCHN. Further studies based on homogeneous populations are warranted to confirm these findings.

CD117⁺ cells in the circulation are predictive of advanced prostate cancer.

Circulating tumor cells (CTCs) are associated with cancer progression, aggressiveness and metastasis. However, the frequency and predictive value of CTCs in patients remains unknown. If circulating cells are involved in tumor aggressiveness and metastasis, then cell levels should decline upon tumor removal in localized cancer patients, but remain high in metastatic patients. Accordingly, proposed biomarkers CD117/c-kit, CD133, CXCR4/CD184, and CD34-positive cell percentages in the blood of patients undergoing radical prostatectomy for localized cancer were assessed by flow cytometry prior to intervention and 1-3 months postoperatively. Only circulating CD117⁺ cell percentages decreased after radical prostatectomy, increased with cancer progression and correlated with high PSA values. Notably, postoperative CD117⁺ levels did not decrease in patients experiencing biochemical recurrence. In a xenograft model, CD117-enriched tumors were more vascularized and aggressive. Thus, CD117 expression on CTCs promotes tumor progression and could be a biomarker for prostate cancer diagnosis, prognosis, and/or response to therapy.

Prognostic value of circulating tumor cells in patients with pancreatic cancer: a meta-analysis

Increasing scientific evidences suggest that circulating tumor cells (CTC) in peripheral blood may be a powerful predictor of survival in patients with pancreatic cancer. However, many existing studies have yielded inconclusive results. This meta-analysis aims to assess the prognostic value of CTC in patients with pancreatic cancer. An extensive literary search for relevant studies was conducted on PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CNKI, and CBM databases from their inception through July 1, 2013. The meta-analysis was then performed using the Stata 12.0 software. Crude hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated under a fixed or random effect model. Nine cohort studies were included in this meta-analysis with a total of 623 pancreatic cancer patients. This number included 268 CTC-positive patients and 355 CTC-negative patients. Our meta-analysis revealed that patients in the CTC-positive group were significantly associated with poor progression-free survival (PFS) (HR = 1.89, 95% CI = 1.25-4.00, P < 0.001). Furthermore, pancreatic cancer patients in the CTC-positive group also showed worse overall survival (OS) than those in the CTC-negative group (HR = 1.23, 95% CI = 0.88-2.08, P < 0.001). Subgroup analysis by ethnicity indicated that CTC-positive patients had poor OS among both Asian and Caucasian populations (all P < 0.05). Further subgroup analyses by detection and treatment methods also suggested that CTC-positive patients showed worser OS than CTC-negative patients in the majority of subgroups (all P < 0.05). No publication bias was detected in this meta-analysis. In conclusion, our meta-analysis suggests that CTC-positive pancreatic cancer patients may have worser PFS and OS than CTC-negative patients. Detection of CTC in peripheral blood may be a promising biomarker for the detection and prognosis of pancreatic cancer.

716 Differential Survival in Patients With Hepatitis B Virus-Related Hepatocellular Carcinoma (HBV/HCC) Compared to Hepatitis C Virus-Related Hepatocellular Carcinoma (HCV/HCC)

Background/Aims: Detection of circulating tumor cells (CTC) is associated with poor progression free and overall survival in patients with breast, prostate, and colon cancer. There is limited information about the prognostic value of CTC in patients with cholangiocarcinoma (CCA). The aim of this study are (1) to quantify circulating tumor cells in the peripheral blood of patients with CCA; and (2) to test the hypothesis that the presence of circulating tumor cells is associated with larger tumor burden of CCA and poor overall survival. Methods: A total of 45 patients with CCA seen at Mayo Clinic Rochester were prospectively enrolled between June 2010 and September 2012. 10 ml peripheral blood was drawn into CellSave Preservative Tubes. Blood samples were processed within 96 hours after the blood draw. The CellSearch system by Veridex was used for the capture, enrichment, identification and enumeration of CTC of epithelial origin in 7.5 ml of peripheral blood from the patients. The CellSearch system has an estimated sensitivity of approximately 20-30% for detecting CTC at a prognostic level . The association between baseline characteristics and detection of CTC was analyzed. Overall survival was estimated by the Kaplan Meier method and compared using the Log Rank test. Results: The mean age of patients was 61 and 29 (64%) patients were male. CTC were detected in 13 (28%) patients. Patients with CTC tended to have larger tumor size, more tumor nodules, a higher CA19-9 level, increased CEA, lymph node involvement, and metastatic disease compared to patients without CTC. (Table) There was no significant association between CTC and demography (age, gender, and race) or underlying liver dysfunction . There was a trend towards poorer survival in patients with CTC compared to patients without CTC (p=0.09). Conclusion: CTC are detectable in patients with cholangiocarcinoma. The presence of CTC was associated with tumor burden and metastatic cancer. The prognostic implications of CTC in patients with CCA need further validation in a larger patient group.

631 Circulating Tumor Cells Are Associated With More Advanced Disease in Cholangiocarcinoma

Background/Aims: Detection of circulating tumor cells (CTC) is associated with poor progression free and overall survival in patients with breast, prostate, and colon cancer. There is limited information about the prognostic value of CTC in patients with cholangiocarcinoma (CCA). The aim of this study are (1) to quantify circulating tumor cells in the peripheral blood of patients with CCA; and (2) to test the hypothesis that the presence of circulating tumor cells is associated with larger tumor burden of CCA and poor overall survival. Methods: A total of 45 patients with CCA seen at Mayo Clinic Rochester were prospectively enrolled between June 2010 and September 2012. 10 ml peripheral blood was drawn into CellSave Preservative Tubes. Blood samples were processed within 96 hours after the blood draw. The CellSearch system by Veridex was used for the capture, enrichment, identification and enumeration of CTC of epithelial origin in 7.5 ml of peripheral blood from the patients. The CellSearch system has an estimated sensitivity of approximately 20-30% for detecting CTC at a prognostic level . The association between baseline characteristics and detection of CTC was analyzed. Overall survival was estimated by the Kaplan Meier method and compared using the Log Rank test. Results: The mean age of patients was 61 and 29 (64%) patients were male. CTC were detected in 13 (28%) patients. Patients with CTC tended to have larger tumor size, more tumor nodules, a higher CA19-9 level, increased CEA, lymph node involvement, and metastatic disease compared to patients without CTC. (Table) There was no significant association between CTC and demography (age, gender, and race) or underlying liver dysfunction . There was a trend towards poorer survival in patients with CTC compared to patients without CTC (p=0.09). Conclusion: CTC are detectable in patients with cholangiocarcinoma. The presence of CTC was associated with tumor burden and metastatic cancer. The prognostic implications of CTC in patients with CCA need further validation in a larger patient group.