Purpose: The aim of the study was to evaluate the association between clinicopathological and prognostic significance and circulating tumor cells (CTCs) in patients with head and neck cancer. Methods: We searched PubMed, MEDLINE, BioMed, and EMbase databases for studies that assessed the association between clinicopathological and prognostic significance and CTCs in patients with head and neck cancer. Studies obtained from search strategy were screened using pre-specified criteria, and necessary data were retrieved for meta-analysis. Results: Seventeen studies with 816 patients were eligible for combined analysis. Presence of CTCs in peripheral blood was significantly associated with N stage (OR 0.50, 95%CI [0.30, 0.81], n = 10, P = 0.005). Patients in the high-CTC group were significantly associated with poorer disease-free survival (DFS; HR = 1.73, 95%CI [1.01 - 2.96], P = 0.050) and poorer overall survival (OS; HR = 2.53, 95%CI [1.37 - 4.69] P = 0.003). Further analyses indicated strong prognostic powers of CTCs in non-RT-PCR group and pre-treatment group. Conclusion: Our meta-analysis indicates that presence of CTCs is associated with higher N stage and poorer prognosis in patients with head and neck cancer. The potential for further clinical application may be needed for further investigation.Purpose: The aim of the study was to evaluate the association between clinicopathological and prognostic significance and circulating tumor cells (CTCs) in patients with head and neck cancer. Methods: We searched PubMed, MEDLINE, BioMed, and EMbase databases for studies that assessed the association between clinicopathological and prognostic significance and CTCs in patients with head and neck cancer. Studies obtained from search strategy were screened using pre-specified criteria, and necessary data were retrieved for meta-analysis. Results: Seventeen studies with 816 patients were eligible for combined analysis. Presence of CTCs in peripheral blood was significantly associated with N stage (OR 0.50, 95%CI [0.30, 0.81], n = 10, P = 0.005). Patients in the high-CTC group were significantly associated with poorer disease-free survival (DFS; HR = 1.73, 95%CI [1.01 - 2.96], P = 0.050) and poorer overall survival (OS; HR = 2.53, 95%CI [1.37 - 4.69] P = 0.003). Further analyses indicated strong prognostic powers of CTCs in non-RT-PCR group and pre-treatment group. Conclusion: Our meta-analysis indicates that presence of CTCs is associated with higher N stage and poorer prognosis in patients with head and neck cancer. The potential for further clinical application may be needed for further investigation.
Cancer of the head and neck is the 6th most common cancer worldwide contributing 600,000 new cases of cancer every year and more than 95% of those cases are squamous cell carcinomas [
In clinical practice, patients with H&N cancer who have the same TNM stage and undergo similar treatments have various clinical outcomes due to the heterogeneity of the tumor, suggesting that the TNM staging system might be inadequate for prognostic prediction for H&N cancer. Therefore, development of new biomarkers as an adjunct to traditional staging system would facilitate establishing more appropriate patient-specific treatment strategies.
Recent researches have revealed that circulating tumor cells (CTCs) in peripheral blood may serve as a potential biomarker. CTCs, which were first reported by Ashworth in 1869 [
The aim of this study was to use a meta-analysis to comprehensively investigate the relationship between the presence of CTCs and clinicopathological significance of CTCs in H&N cancers, and to explore its potential prognostication impact.
PubMed, Embase, the Science Citation Index, Cochrane databases and the Ovid Database were systematically searched for studies investigating the tumor clinicopathological and prognostic relationship between CTCs and H&N cancer, with no restrictions on language, place of publication or date of publication (up to November 2015). The main search terms used were “circulating tumor cells”, “disseminated tumor cells”, “head and neck cancer”, “nasopharyngeal”, “nasal”, “oral”, “oropharyngeal”, “hypopharyngeal”, “laryngeal”, and “larynx”.
To make our analysis reliable, we screened the titles and abstracts for all searched papers, and full text was perused for potential eligible studies according to the following inclusion criteria: 1) containing patient cases of H&N cancer; 2) measuring the presence of CTCs in peripheral blood (PB); 3) investigating the clinicopathological and prognostic significance of CTCs in H&N cancer patients with at least one of the outcome measures of interest. Studies were excluded in our study: 1) duplicated publications; 2) no outcomes of interest that were provided or can’t be calculated for prognostic evaluation.
Two reviewers (Chen RW and Zhou Y) independently evaluated each papers and extracted data, and any disagreements were resolved via discussion, with a third investigator if necessary. The following information was extracted: first author, publication year, population characteristics (i.e., country, number, sex and age), tumor clinicopathological characteristics (i.e. anatomical sites, pathologic differentiation and TNM stage), sampling times (preoperative or postoperative), detection methods (RT-PCR array, Non-RT-PCR array including Cell Search system or immunocytochemistry), CTCs positive rate, detection markers, endpoints and survival data. For studies with multiple markers or detect methods, each of the cohorts was considered an independent data set. However, for those studies with multiple sample times (i.e. pre-treatment and intra/post-treatment), we use data from pre-treatment samples because those data were usually dependent from various treatment regimens.
Statistical analysis was performed using Review Manager 5.2 (Copenhagen: The Nordic Cochrane Centre; The Cochrane Collaboration, 2012). To evaluate the association between CTCs and clinicopathological characteristics, the estimated odd ratios (ORs) were extracted from enrolled publications. To statistically assess the prognostic significance (DFS and OS), we extracted the estimated hazard ratios (HRs) and associated 95% CIs when available. If the HR and its variance were not reported directly in the original study, these values were calculated from available reported data using software designed by Tierney JF [
The primary literature research initially yielded 2320 articles. After screening the titles, abstracts, language and other information, 2161 studies were excluded and 159 potential studies were reviewed further. An additional 137 studies were then excluded which were reviews (n = 18), laboratory studies (n = 97) or studies of other tumors (n = 22). Upon detailed evaluation of the remaining 22 studies, 5 studies had to be excluded because the outcome of interest could not be calculated. Finally, a total of 17 articles were considered to be appropriate for the meta-analysis (
The eligible 17 studies comprising 816 patients diagnosed as head and neck squamous cell carcinoma were published between 1999 and 2014 [