Background/Aim: Although locally advanced esophageal squamous cell carcinoma (ESCC) can be controlled and survival can be prolonged by neoadjuvant chemoradiotherapy (NCRT) followed by surgery (trimodal therapy), some patients still develop early recurrence and die of cancer even after such intensive therapy. The present study aimed to determine the factors associated with early recurrence and cancer death for patients with ESCC treated by trimodal therapy. Patients and Methods: We evaluated risk factors for recurrence within 6 months, as well as cancer death within 1 year based on data from 141 patients with ESCC who underwent NCRT followed by curative esophagectomy. Results: The carcinoembryonic antigen level before treatment, postoperative complications, pathology after neo-adjuvant therapy (ypT, ypN), lymphatic invasion, venous invasion and pathological response of the primary tumor were significant factors in a comparison of patients with and without early recurrence. Multivariate analysis subsequently selected ypN [ypN, 0/1 vs. 2/3; hazard ratio (HR)=4.13, 95% confidence interval (CI)=1.25-13.66; p=0.02] as an independent covariate for early recurrence. Postoperative complications, ypT, ypN, poorer tumor differentiation, lymphatic invasion and venous invasion were significant factors in a comparison of patients with and without early cancer death. Multivariate analysis subsequently selected postoperative complications of grade ≥3b (vs. <3b) defined according to the Clavien–Dindo classification (HR=5.9, 95% CI=1.53-23.47; p=0.01) and venous invasion (vs. without: HR=4.80, 95% CI=1.21-19.14; p=0.03) as independent covariates for early cancer death. Conclusion: Further reduction of postoperative complications are needed after NCRT for patients with ESCC. Meticulous surveillance and postoperative adjuvant therapy should be considered for patients with risk factors for early recurrence and cancer death.

Purpose: Various blood cell parameters have been identified as predictive markers of tumor responses and the survival of patients with cancer treated with immune checkpoint inhibitors. The purpose of this study is to assess the ability of various blood cell parameters to predict therapeutic effects and survival in patients with esophageal squamous cell carcinoma (ESCC) treated with nivolumab monotherapy. Patients and Methods: We evaluated neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and lymphocyte-to-monocyte (LMR) ratios as predictive markers of patients’ survival and effects of nivolumab monotherapy after one or more prior chemotherapies for unresectable advanced or recurrent ESCC. Results: The objective response and disease control rates were 20.3% and 47.5%, respectively. The LMRs before, and 14 and 28 days after nivolumab initiation were significantly higher in patients with complete response (CR)/partial response (PR)/stable disease (SD) than those with progressive disease (PD). The NLRs at 14 and 28 days after nivolumab initiation were significantly lower in patients with CR/PR/SD than with PD. The optimal cutoffs for these parameters significantly discriminated patients with CR/PR/SD and PD. Univariate and multivariate analyses identified pretreatment NLRs as a significant independent factor for progression-free and overall survival (hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.07– 1.32, and HR 1.23, 95% CI: 1.11– 1.37, respectively; p ≤ 0.001 for both). Conclusion: The pretreatment LMRs, and NLR and LMR at 14 and 28 days after starting nivolumab monotherapy were significantly associated with the clinical therapeutic effect. The pretreatment NLR was significantly associated with patients’ survival. These blood cell parameters before and during the early days of nivolumab monotherapy can help to identify patients with ESCC who would most likely benefit from nivolumab monotherapy.