Prognostic value of circulating tumor cells detected with the CellSearch System in patients with gastric cancer: evidence from a meta-analysis

Abstract

Background: Circulating tumor cells (CTCs) have been proposed as a marker for predicting the prognosis of cancer. However, the prognostic value of CTCs detected with the CellSearch System in patients with gastric cancer (GC) remains controversial. We performed a meta-analysis of available studies to investigate this topic.

Methods: Two authors systematically searched the studies independently in PubMed, Science Citation Index, Cochrane Database, Embase, and the references in relevant studies (up to September 2017) using keywords. Our meta-analysis was performed in Stata software, version 12.0 (2011; Stata Corp, College Station, TX, USA), with the risk ratio (RR), hazard ratio (HR), and 95% CI as the effect measures. Subgroup analyses and meta-regression were also conducted.

Results: Seven studies (including eight sets of data) containing 579 patients with GC from four countries were included in this meta-analysis. The pooled results showed CTC-positive status detected by the CellSearch System was significantly associated with poor overall survival (HR =2.09, 95% CI [1.71, 2.55], P<0.001, I²=31.5%) and progression-free survival (HR =2.11, 95% CI [1.25, 3.57], P=0.005, I²=75.6%) of patients with GC, regardless of sampling time. The disease control rate of CTC-positive group was lower than that of CTC-negative group for both baseline and intra-therapy, although no statistical difference existed at both sampling time points (baseline: 69.5% versus 81.8%, RR=0.79, 95% CI [0.54, 1.16], P=0.23, I²=68.0%; intra-therapy: 50.0% versus 85.9%, RR=0.24, 95% CI [0.02, 3.13], P=0.28, I²=87.4%).

Conclusion: Our meta-analysis demonstrated that CTCs detected with the CellSearch System from the peripheral blood had significant prognostic value and might predict poor response to chemotherapy for patients with GC.

Keywords: chemotherapy; circulating tumor cells; gastric cancer; meta-analysis; prognosis.

Figure 1

Flow chart of study selection. Note: Copyright ©2009. Adapted from Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. Abbreviation: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Figure 2

Summary estimates of HR for OS and PFS of GC patients with CTC positivity. Notes: (A) Forest plot of OS. (B) Forest plot of PFS. Weights are from random-effects analysis. Abbreviations: CTCs, circulating tumor cells; GC, gastric cancer; HR, hazard ratio; OS, overall survival; PFS, progression-free survival.

Figure 3

Summary estimates of RR for DCR of patients with CTC positivity. Note: Weights are from random-effects analysis. Abbreviations: CTCs, circulating tumor cells; DCR, disease control rate; RR, risk ratio; W, week.

Figure 4

Process of exploring the potential sources of heterogeneity on PFS. Notes: (A) Galbraith plot for PFS. (B) Forest plot for PFS after Uenosono et al (1) (2013) is omitted. (C) Change of heterogeneity before and after Uenosono et al (1) (2013) is omitted. Weights are from random-effects analysis. P^d value for heterogeneity. Abbreviations: HR, hazard ratio; PFS, progression-free survival; SE, standard error.

Figure 5

Funnel plots of included studies reporting OS and PFS. Notes: (A) Begg’s funnel plot on OS. (B) Egger’s funnel plot on OS. (C) Begg’s funnel plot on PFS. (D) Egger’s funnel plot on PFS. Abbreviations: HR, hazard ratio; OS, overall survival; PFS, progression-free survival; SE, standard error; SND, standard normal deviate.