Circulating tumour cells predict survival in gastric cancer patients: a meta-analysis

Abstract

Aim of the studyThe prognostic value of the detection of circulating tumour cells (CTCs) in gastric cancer has been studied intensely in recent years. However, the application of different technologies led to inconsistent results between the studies. Here, we performed a meta-analysis of published studies to summarise the evidence.Material and methodsMedline and ISI Web of Knowledge were searched up to March 2013 using “circulating tumor cells” and “gastric cancer” as search terms. Hazard ratio (HR) with 95% confidence intervals (CIs) for prognostic outcomes and clinical characteristics were extracted from each study. Pooled hazard ratios (HR) and odds ratios (OR) were calculated using random or fixed-effects models.ResultsTwelve studies enrolling 774 patients were included. The combined HR estimate for overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were 1.41 (95% CI: 1.28–1.62), 2.99 (95% CI: 2.01–4.45) and 1.64 (95% CI: 1.02–2.62), respectively. Subgroup analysis concerning detection methods and sampling time showed that results of RT-PCR for the OS group and RT-PCR for the DFS group suggest a prognostic significance of CTC detection (pooled HR [95% CI]: 1.45 [1.28–1.65], I2 = 38%, p = 0.13; 2.99 [2.01–4.45], I2 = 0%, p = 0.32). In addition, results of the baseline CTC detection group also indicated a significant prognostic value to predict OS and DFS (pooled HR [95% CI]: 1.47 [1.19–1.82], I2 = 38%, p = 0.14; 2.99 [2.01–4.45], I2 = 0%, p = 0.32). We simultaneously found that the detection of CTCs correlated with pathological stage (pooled OR [95% CI]: 2.95 [1.65–5.28], I2 = 56%, p = 0.03), lymph node status (pooled OR [95% CI]: 2.26 [1.50–3.41], I2 = 37%, p = 0.09), the depth of invasion (pooled OR [95% CI]: 3.21 [1.38–7.43], I2 = 72%, p = 0.002), and distant metastasis (pooled OR [95% CI]: 2.68 [1.25–5.73], I2 = 43%, p = 0.15).ConclusionsDetection of CTCs is associated with poorer prognosis in gastric cancer patients.

Long-term prognostic impact of circulating tumour cells in gastric cancer patients

“…The enumeration of CTCs is particularly important in gastric cancer, which is the second leading cause of cancer-related death worldwide. Our current data indicate that detection of CTCs may indeed be a useful prognostic indicator for use in patients with gastric cancer, and are consistent with previous reports[25,26]. …”

Prognostic Role of the Circulating Tumor Cells Detected by Cytological Methods in Gastric Cancer: A Meta-Analysis

“…The result of our meta-analysis solved the controversies from two independent meta-analyses [7, 9] and demonstrated the prognostic role of CTCs detected by cytological methods in gastric cancer. Cytological methods may avoid false positive results from nonneoplastic and contaminated samples which was frequent in molecular methods, and they were able to count the number of CTCs and recognize viable and functional CTCs [33], so they may provide us with a more accurate result by using the cytological methods.…”

“…Currently, the major techniques used to identify CTCs can be divided into two aspects, the cytological methods (such as CellSearch, immunocytochemistry, flow cytometry, and immune-magnetic and fluorescence-activated cell sorter) and the molecular methods (mainly the PCR) [3]. Although meta-analyses have shown that the presence of CTCs in peripheral blood of patients with gastric cancer was associated with poor prognosis and clinical characteristics [7–9], most studies involved in these meta-analyses used the molecular methods and the prognostic value of CTCs detected by cytological methods remains controversial. The pooled HR on OS from two meta-analyses showed different results for CTCs positive patients when detected by cytological methods (HR = 2.00, 95% CI: 0.1.28–3.13 [7]; HR = 1.67, 95% CI: 0.57–4.92 [9], resp.)…”

“…Although meta-analyses have shown that the presence of CTCs in peripheral blood of patients with gastric cancer was associated with poor prognosis and clinical characteristics [7–9], most studies involved in these meta-analyses used the molecular methods and the prognostic value of CTCs detected by cytological methods remains controversial. The pooled HR on OS from two meta-analyses showed different results for CTCs positive patients when detected by cytological methods (HR = 2.00, 95% CI: 0.1.28–3.13 [7]; HR = 1.67, 95% CI: 0.57–4.92 [9], resp.) and the number of the involved studies was very little (two and three, resp.).…”

Detecting Tumor Metastases

“…Regarding treatment response, a meta-analysis considering 12 relevant studies demonstrated that prior to treatment CTCs correlated with lymph node status, distant metastasis, and disease staging, however, post-treatment CTCs only correlated with staging (Ma et al, 2012). Including the earlier mentioned meta-analysis, a number of meta-analyses were conducted in different cancers such as gastric cancer (Wang, Wei, Zou, Qian, & Liu, 2016), metastatic breast cancer (Lv et al, 2016), ovarian cancer (Cui, Kwong, & Wang, 2015; Zhou et al, 2015), head and neck (Wang, Cui, Xue, Tong, & Li, 2015), colorectal cancer (Huang et al, 2015), liver cancer (Jin, Peng, & Wu, 2013), prostate cancer (Wang et al, 2011), bladder and urothelial cancer (Wang et al, 2011), and positive correlations with CTCs were established.…”