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      Prognostic Value of Circulating Tumor Cells in Ovarian Cancer: A Meta-Analysis

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          Abstract

          Background

          The prognostic value of circulating tumor cells (CTCs) in ovarian cancer has been investigated in previous studies, but the results are controversial. Therefore we performed a meta-analysis to systematically review these data and evaluate the value of CTCs in ovarian cancer.

          Materials and Methods

          A literary search for relevant studies was performed on Embase, Medline and Web of Science databases. Then pooled hazard ratios (HRs) for survival with 95% confidence intervals (CIs), subgroup analyses, sensitivity analyses, meta-regression analyses and publication bias were conducted.

          Results

          This meta-analysis is based on 11 publications and comprises a total of 1129 patients. The prognostic value of the CTC status was significant in overall survival (OS) (HR, 1.61;95% CI,1.22–2.13) and progression-free survival (PFS)/disease-free survival (DFS) (HR, 1.44; 95%CI, 1.18–1.75). Furthermore, subgroup analysis revealed that the value of CTC status in OS was significant in "RT-PCR" subgroup (HR, 2.02; 95% CI, 1.34–3.03), whereas it was not significant in "CellSearch" subgroup (HR, 1.15; 95% CI 0.45–2.92) and "other ICC" subgroup (HR, 1.09; 95% CI 0.62–1.90). The presence of CTC was also associated with an increased CA-125 (OR, 4.07; 95%CI, 1.87–8.85).

          Conclusion

          Our study demonstrates that CTC status is associated with OS and PFS/DFS in ovarian cancer.

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          Reporting bias in medical research - a narrative review

          Natalie McGauran, Beate Wieseler, Julia Kreis … (2010)
          Reporting bias represents a major problem in the assessment of health care interventions. Several prominent cases have been described in the literature, for example, in the reporting of trials of antidepressants, Class I anti-arrhythmic drugs, and selective COX-2 inhibitors. The aim of this narrative review is to gain an overview of reporting bias in the medical literature, focussing on publication bias and selective outcome reporting. We explore whether these types of bias have been shown in areas beyond the well-known cases noted above, in order to gain an impression of how widespread the problem is. For this purpose, we screened relevant articles on reporting bias that had previously been obtained by the German Institute for Quality and Efficiency in Health Care in the context of its health technology assessment reports and other research work, together with the reference lists of these articles. We identified reporting bias in 40 indications comprising around 50 different pharmacological, surgical (e.g. vacuum-assisted closure therapy), diagnostic (e.g. ultrasound), and preventive (e.g. cancer vaccines) interventions. Regarding pharmacological interventions, cases of reporting bias were, for example, identified in the treatment of the following conditions: depression, bipolar disorder, schizophrenia, anxiety disorder, attention-deficit hyperactivity disorder, Alzheimer's disease, pain, migraine, cardiovascular disease, gastric ulcers, irritable bowel syndrome, urinary incontinence, atopic dermatitis, diabetes mellitus type 2, hypercholesterolaemia, thyroid disorders, menopausal symptoms, various types of cancer (e.g. ovarian cancer and melanoma), various types of infections (e.g. HIV, influenza and Hepatitis B), and acute trauma. Many cases involved the withholding of study data by manufacturers and regulatory agencies or the active attempt by manufacturers to suppress publication. The ascertained effects of reporting bias included the overestimation of efficacy and the underestimation of safety risks of interventions. In conclusion, reporting bias is a widespread phenomenon in the medical literature. Mandatory prospective registration of trials and public access to study data via results databases need to be introduced on a worldwide scale. This will allow for an independent review of research data, help fulfil ethical obligations towards patients, and ensure a basis for fully-informed decision making in the health care system.
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            Meta-analysis of the prognostic value of circulating tumor cells in breast cancer.

            Liling Zhang, Sabine Riethdorf, Gang Wu … (2012)
            The prognostic value of circulating tumor cells (CTC) detected in breast cancer patients is currently under debate. Different time points of blood collections and various CTC assays have been used in the past decades. Here, we conducted the first comprehensive meta-analysis of published literature on the prognostic relevance of CTC, including patients with early and advanced disease. A comprehensive search for articles published between January 1990 and January 2012 was conducted; reviews of each study were conducted and data were extracted. The main outcomes analyzed were overall survival (OS) and disease-free survival (DFS) in early-stage breast cancer patients, as well as progression-free survival (PFS) and OS in metastatic breast cancer patients. Pooled hazard ratio (HR) and 95% confidence intervals (CIs) were calculated using the random and the fixed-effects models. Subgroup and sensitivity analyses were also conducted. Forty-nine eligible studies enrolling 6,825 patients were identified. The presence of CTC was significantly associated with shorter survival in the total population. The prognostic value of CTC was significant in both early (DFS: HR, 2.86; 95% CI, 2.19-3.75; OS: HR, 2.78; 95% CI, 2.22-3.48) and metastatic breast cancer (PFS: HR, 1.78; 95% CI, 1.52-2.09; OS: HR, 2.33; 95% CI, 2.09-2.60). Further subgroup analyses showed that our results were stable irrespective of the CTC detection method and time point of blood withdrawal. Our present meta-analysis indicates that the detection of CTC is a stable prognosticator in patients with early-stage and metastatic breast cancer. Further studies are required to explore the clinical utility of CTC in breast cancer. ©2012 AACR
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              Progress and challenges in screening for early detection of ovarian cancer.

              Usha Menon, Heidi Jacobs (2004)
              Ovarian cancer is characterize by few early symptoms, presentation at an advanced stage, and poor survival. As a result, it is the most frequent cause of death from gynecological cancer. During the last decade, a research effort has been directed toward improving outcomes for ovarian cancer by screening for preclinical, early stage disease using both imaging techniques and serum markers. Numerous biomarkers have shown potential in samples from clinically diagnosed ovarian cancer patients, but few have been thoroughly assessed in preclinical disease and screening. The most thoroughly investigated biomarker in ovarian cancer screening is CA125. Prospective studies have demonstrated that both CA125 and transvaginal ultrasound can detect a significant proportion of preclinical ovarian cancers, and refinements in interpretation of results have improved sensitivity and reduced the false-positive rate of screening. There is preliminary evidence that screening can improve survival, but the impact of screening on mortality from ovarian cancer is still unclear. Prospective studies of screening are in progress in both the general population and high-risk population, including the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), a randomized trial involving 200,000 postmenopausal women designed to document the impact of screening on mortality. Recent advances in technology for the study of the serum proteome offer exciting opportunities for the identification of novel biomarkers or patterns of markers that will have greater sensitivity and lead time for preclinical disease than CA125. Considerable interest and controversy has been generated by initial results utilizing surface-enhanced laser desorption/ionization (SELDI) in ovarian cancer. There are challenging issues related to the design of studies to evaluate SELDI and other proteomic technology, as well as the reproducibility, sensitivity, and specificity of this new technology. Large serum banks such as that assembled in UKCTOCS, which contain preclinical samples from patients who later developed ovarian cancer and other disorders, provide a unique resource for carefully designed studies of proteomic technology. There is a sound basis for optimism that further developments in serum proteomic analysis will provide powerful methods for screening in ovarian cancer and many other diseases.
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                Author and article information

                Contributors
                Jeffrey Chalmers: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 22 June 2015
                Publication date Collection: 2015
                Volume: 10
                Issue: 6
                Electronic Location Identifier: e0130873
                Affiliations
                [001]Department of Clinical Laboratory, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
                The Ohio State University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: LS. Performed the experiments: YZ BB. Analyzed the data: YZ BB XY GX YM. Contributed reagents/materials/analysis tools: YZ BB XY GX YM. Wrote the paper: YZ BB.

                Article
                Publisher ID: PONE-D-14-53617
                DOI: 10.1371/journal.pone.0130873
                PMC ID: 4476582
                PubMed ID: 26098665
                SO-VID: 7c78c4af-b481-44d7-8572-dbbfd157e71d
                Copyright statement: Copyright @ 2015
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                Date received : 16 December 2014
                Date accepted : 26 May 2015
                Page count
                Figures: 8, Tables: 2, Pages: 14
                Funding
                This work was supported by National Natural Science Foundation of China (Lisong Shen 81372641, Yunlan Zhou 81401946, Xiangliang Yuan 81472244).
                Categories
                Subject: Research Article
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

                ScienceOpen disciplines: Uncategorized
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                ScienceOpen disciplines: Uncategorized

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