Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy

Abstract

The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol's efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted.

Figure 1. Illustration of circulating tumour cell (CTC) detection protocol.

Figure 2. The correlations among tumour staging, response, surgery, unresectable status and survival.

Panel A demonstrates that initial TNM staging correlates with overall survival (OS). Treatment response after concurrent chemoradiotherapy (CCRT) also correlates with OS (Panel B). Residual tumour with or without surgery is also highly prognostic for OS (Panel C); patients with initial T4b and M1 status are excluded (Panel D).

Figure 3. The number of circulating tumour cells (CTCs) can differentiate oesophageal cancer patients and its impact on survival.

The method of circulating tumour cell (CTC) detection can differentiate healthy individuals from patients with advanced oesophageal cancer with a P value of 0.04 using the Mann-Whitney U test (Panel A). Panels B and C show that patients with a lower pre-treatment CTC number have longer disease-specific progression-free survival or overall survival. Given the CTC status (score zero for CTC number less than 21.0 cells/mL; 1 for CTC number ≥ 21.0 cells/mL) and response after concurrent chemoradiotherapy (CCRT, score zero for complete remission; 1 for partial response; 2 for stable disease, and 3 for progressive disease), the summation of the CTC score and the score of response to CCRT is defined as the circulating tumour cell plus response (CTCR) score, and this score highly correlates with overall survival with a log rank test P value of <0.0001.