Prognostic value of circulating tumor cells and disseminated tumor cells in patients with ovarian cancer: a systematic review and meta-analysis

Journal of Ovarian Research, Jun 2015

Recent studies have shown diagnostic and prognostic values of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in various cancers, including ovarian cancer. We aimed to evaluate the association of CTCs and/or DTCs with the clinical outcomes of ovarian cancer. Clinical studies of CTCs/DTCs of ovarian cancer were included for systematic review and meta-analysis. A total of 236 studies were screened but only 16 qualified studies with 1623 subjects were included. Odds ratio (OR) showed CTCs/DTCs were not significantly associated with serous carcinoma (OR = 0.71 [0.49, 1.05]), lymph node metastasis (OR 1.14 [0.67, 1.93]), and residual disease (OR 1.45 [0.90, 2.34]); but significantly associated with advanced tumor staging (OR = 1.90 [1.02, 3.56]). The overall pooled hazard ratio (HR) of CTCs/DTCs on OS and PFS/DFS was 1.94 [1.56– 2.40] and 1.99 [1.59–2.50], respectively. Subgroup analyses revealed that CTCs were significantly associated OS (HR 1.97 [1.50-2.58]) and PFS/DFS (HR 2.52 [1.83-3.48]), while DTCs was significantly associated OS (HR 1.89 [1.33, 2.68]) and PFS/DFS (HR 1.60 [1.17, 2.19]). Meta-analysis showed strong relationship of CTCs/DTCs with advanced staging, treatment response and poor prognosis in patients with ovarian cancer.

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Prognostic value of circulating tumor cells and disseminated tumor cells in patients with ovarian cancer: a systematic review and meta-analysis

Cui et al. Journal of Ovarian Research Prognostic value of circulating tumor cells and disseminated tumor cells in patients with ovarian cancer: a systematic review and meta-analysis Long Cui 0 Joseph Kwong 0 Chi Chiu Wang 0 0 Department of Obstetrics and Gynecology, Prince of Wales Hospital, The Chinese University of Hongkong , Shatin, Hong Kong , China Recent studies have shown diagnostic and prognostic values of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in various cancers, including ovarian cancer. We aimed to evaluate the association of CTCs and/ or DTCs with the clinical outcomes of ovarian cancer. Clinical studies of CTCs/DTCs of ovarian cancer were included for systematic review and meta-analysis. A total of 236 studies were screened but only 16 qualified studies with 1623 subjects were included. Odds ratio (OR) showed CTCs/DTCs were not significantly associated with serous carcinoma (OR = 0.71 [0.49, 1.05]), lymph node metastasis (OR 1.14 [0.67, 1.93]), and residual disease (OR 1.45 [0.90, 2.34]); but significantly associated with advanced tumor staging (OR = 1.90 [1.02, 3.56]). The overall pooled hazard ratio (HR) of CTCs/DTCs on OS and PFS/DFS was 1.94 [1.56- 2.40] and 1.99 [1.59-2.50], respectively. Subgroup analyses revealed that CTCs were significantly associated OS (HR 1.97 [1.50-2.58]) and PFS/DFS (HR 2.52 [1.83-3.48]), while DTCs was significantly associated OS (HR 1.89 [1.33, 2.68]) and PFS/DFS (HR 1.60 [1.17, 2.19]). Meta-analysis showed strong relationship of CTCs/DTCs with advanced staging, treatment response and poor prognosis in patients with ovarian cancer. Ovarian cancer; Circulating tumor cells; Disseminated tumor cells; Prognosis - Introduction Ovarian cancer is the most frequent cause of death amongst gynecological cancers worldwide. Majority of cases diagnosed in late stage of the disease and resulted in poor survival [1]. The five-year survival rate of patients with ovarian cancer is only around 30 % in Stage III or IV [2]. The reasons of delayed diagnosis are partly due to lack of sensitive signs and symptoms and effective screening methods [3]. Although survival has been improved with the use of cyto-reduction surgery along with platinum- and/or taxane-based chemotherapy, nearly 80 % eventually relapse within 5 years [4]. Therefore, methods that help detection of ovarian cancer in early stage and monitoring of tumor progression have great potential to improve survival of the patients. It was considered that ovarian cancer spreads primarily through direct dissemination in the abdominal cavity. While the presence of disseminated tumor cells (DTCs) in bone marrow of patients with ovarian cancer have been reported [5, 6]. However, bone marrow sampling is rather an invasive procedure, which is not widely accepted in the clincial management. In recent years, focus has been shifted to the detection of circulating tumor cells (CTCs) in peripheral blood. CTCs are tumor cells release from the primary tumor and then circulate through the bloodstream, resulting in spreading to different organs and subsequent outgrowth of the tumor cells in new microenvironment. These CTCs thereby have the potential to contribute to the development of local and systematic relapses [7]. Either DTCs or CTCs have potential to predict prognosis and to monitor treatment efficacy in cancer patients. Presence of CTCs has been reported in several solid tumors, including breast [8], colorectal [9], lung [10], kidney [11], esophageal [12], liver [13], prostate [14], and pancreatic cancers [15, 16]. Studies of CTCs/ DTCs in ovarian cancer patients had been investigated, most of them demonstrated that CTC or DTC is associated with poor clinical outcome [17–22]. However, other studies failed to show the positive correlation [5, 23, 24] and even demonstrated negative association in terms of progression free survival/disease free survival (PFS/DFS) and overall survival (OS) [25, 26]. The prognosis value of CTCs/DTCs in ovarian cancer remains controversial. A recent systematic review of CTCs and DTCs in ovarian cancer concluded the association of CTCs and DTCs with adverse clincopathological characteristics and poor clinical outcomes [27], but no appropriate statistics and detailed analysis were provided. The objective of this study was to conduct a metaanalysis of published clinical studies of CTCs/DTCs in ovarian cancer and to investigate the association of CTCs/ DTCs with clinical outcomes. Methods An independent systematic review of the literature across PubMed and EMBASE database was conducted on April 27, 2015. The search strategy included keywords such as “ovarian cancer”, “ovarian carcinoma”, “circulating tumor cell (s)”, “disseminated tumor cell (s)”, and “prognos*”. Only studies published in peer reviewed journals were included, data from letters and conference abstracts were not included. The study selection process is shown in Fig. 1 and search strategies and results are pro (...truncated)


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Long Cui, Joseph Kwong, Chi Wang. Prognostic value of circulating tumor cells and disseminated tumor cells in patients with ovarian cancer: a systematic review and meta-analysis, Journal of Ovarian Research, 2015, pp. 38, 8, DOI: 10.1186/s13048-015-0168-9