Relationship between circulating tumor cells and tumor response in colorectal cancer patients treated with chemotherapy: a meta-analysis

Abstract

Background: The prognostic value of circulating tumor cells (CTCs) in colorectal cancer (CRC) patients and their value in predicting tumor response to chemotherapy are controversial. The aim of this meta-analysis was to assess the prognostic and predictive value of CTCs in CRC patients treated with chemotherapy.

Methods: A comprehensive literature search for relevant studies was conducted in PubMed, Embase, the Cochrane Database, the Science Citation Index and the Ovid Database, and the reference lists of relevant studies were also perused for other relevant studies (up to April, 2014). Using the random-effects model in Stata software, version 12.0, the meta-analysis was performed using odds ratios (ORs), risk ratios (RRs), hazard ratios (HRs) and 95% confidence intervals (CIs) as effect measures. Subgroup and sensitivity analyses were also performed.

Results: Thirteen eligible studies were included. Our meta-analysis indicated that the disease control rate was significantly higher in CRC patients with CTC-low compared with CTC-high (RR = 1.354, 95% CI [1.002-1.830], p = 0.048). CRC patients in the CTC-high group were significantly associated with poor progression-free survival (PFS; HR = 2.500, 95% CI [1.746-3.580], p < 0.001) and poor overall survival (OS; HR = 2.856, 95% CI [1.959-4.164], p < 0.001). Patients who converted from CTC-low to CTC-high or who were persistently CTC-high had a worse disease progression (OR = 27.088, 95% CI [4.960-147.919], p < 0.001), PFS (HR = 2.095, 95% CI [1.105-3.969], p = 0.023) and OS (HR = 3.604, 95% CI [2.096-6.197], p < 0.001) than patients who converted from CTC-high to CTC-low.

Conclusions: Our meta-analysis indicates that CTCs are associated with prognosis in CRC patients treated with chemotherapy. Moreover, CTCs could provide additional prognostic information to tumor radiographic imaging and might be used as a surrogate and novel predictive marker for the response to chemotherapy.

Figure 1

Selection of studies. Flow chart showing the selection process for the included studies.

Figure 2

Risk ratios (RR) summary for correlation of CTCs and tumor response. A: The risk ratio (RR) was summarized for the correlation of tumor response rate with CTCs detection. B: The RR was summarized for the correlation of tumor disease control rate with CTCs detection.

Figure 3

Results for the meta-analysis of overall survival (OS) time. The differences in median OS time based on the combination of CTCs and radiographic imaging, Group 1: patients with CTC-low during chemotherapy and disease control, Group 2: patients with CTC-low during chemotherapy and progression disease (PD), Group 3: patients with CTC-high during chemotherapy and disease control, Group 4: patients with CTC-high during chemotherapy and PD.

Figure 4

The results for the relationship between CTCs conversion and prognosis. A: The estimated odds ratio (OR) was summarized for the correlation of disease control rate with CTCs conversion. B: The estimated hazard ratio (HR) was summarized for progression-free survival (PFS) with CTCs conversion. C: The estimated HR was summarized for overall survival (OS) with CTCs conversion.

Figure 5

Estimated hazard ratios (HR) summary for PFS (A) and OS (B). A: The estimated hazard ratio (HR) was summarized for progression-free survival with CTCs detection. B: The estimated HR was summarized for overall survival with CTCs detection.