Abstract

PurposeThis study aimed to evaluate the prognostic value of circulating tumor cells (CTCs) in advanced colorectal cancer (CRC) patients during chemotherapy course.MethodsFrom January 2016 to September 2017, the clinicopathological variables, such as gender, age, tumor location, tumor de-differentiation, depth of invasion, lymphatic invasion, distant metastasis, TNM stage, CTCs enumeration during 2-6 cycles of chemotherapy, and serum carcinoembryonic antigen (CEA) level during the same period, of 121 newly acquired and histopathologically confirmed CRC patients were collected from the Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine. All patients were followed up for survival until the end of November 2018. Statistical analysis focused on the associations between CTCs counts and clinicopathological variables. Overall survival (OS) and progression-free survival (PFS) among different prognostic factors were calculated using the Kaplan–Meier method, and the differences between the survival curves were compared by using the log-rank test. Factors of prognostic significance were investigated with the multivariate Cox regression analysis.ResultsHere, 71 of 121 patients were CTC-positive, in which CTC-positive rate was positively correlated with the depth of invasion, lymphatic invasion, distant metastasis, TNM stage, and serum CEA level (P < 0.05 for all). However, no significant difference was found between CTC-positive and other clinicopathological variables (P > 0.05 for all), such as gender, age, tumor location, and tumor de-differentiation. CTCs counts gradually increased with the advancement of depth of invasion (P = 0.002), lymphatic invasion (P = 0.004), distant metastasis (P = 0.007), TNM stage (P = 0.001), serum CEA level (P = 0.001), and decreased tumor de-differentiation (P = 0.011). Furthermore, the Kaplan–Meier survival curves showed that patients with CTC-positive had a significantly unfavorable PFS (14 vs. 23 months, P = 0.001) and OS (18 vs. 25 months, P = 0.003). The multivariate Cox regression analyses revealed that the presence of CTCs during chemotherapy was an independent factor for unfavorable PFS (hazard ratio (HR) 2.682, P = 0.017, 95% confidence interval (CI) 1.193–6.029) and OS (HR 2.790, P = 0.048, 95% CI 1.010–7.705) in advanced CRC patients.ConclusionsThis study provided an evidence that the presence of CTCs may be valuable for predicting survival outcome, and CTCs was associated with unfavorable survival in advanced CRC patients during chemotherapy.

Highlights

  • Colorectal cancer (CRC) is the third most common tumor in men and women worldwide [1]

  • Tremendous efforts at diagnosis and treatment have been made for advanced CRC patients, several patients benefit from chemotherapy to some extent

  • Overall survival (OS) is currently approaching 30 months for the patients treated with the combination of cytotoxic chemotherapy and biologic agents, targeting angiogenesis and the epidermal growth factor receptor (EGFR), which inhibit signal transduction pathways [4,5,6,7]

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Summary

Introduction

Colorectal cancer (CRC) is the third most common tumor in men and women worldwide [1]. Due to the lack of effective methods for early diagnosis, in which 15–20% of patients with CRC were diagnosed with liver metastasis at the first time of diagnosis, and the remaining 60% would have recurrence or metastasis during subsequent treatment [2]. These poor outcomes are associated with the fact that the majority of patients are diagnosed at advanced stage (III/IV stage), with distant. Approximately 28–44% of patients are ineffective to the firstline treatment with doublet chemotherapy plus either cetuximab or bevacizumab, and about 50% of these patients have postoperative recurrence or distant metastasis [8]. There is of great importance to develop a more accurate method to identify patients with poor prognosis or with rapid disease progression, in which identification of more reliable predictive biomarkers to chemotherapy make them to be directed towards the most effective treatment for clinical precise management of CRC [10]

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