Abstract

BackgroundThe neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) have been used to predict therapeutic response in different tumors. However, no assessments of their usefulness have been performed in esophageal squamous cell carcinoma (ESCC) patients receiving anti‑PD‑1 combined with neoadjuvant chemotherapy.MethodsThe respective data of 64 ESCC patients receiving anti‑PD‑1 combined with neoadjuvant chemotherapy were analyzed. Whether NLR, LMR, PLR, and SII at baseline and post-treatment might predict pathological response to anti‑PD‑1 plus neoadjuvant chemotherapy, and cutoff values of these parameters were all determined by ROC curve analysis.ResultsNLR (cutoff = 3.173, AUC = 0.644, 95% CI 0.500–0.788, P = 0.124, sensitivity = 1.000, specificity = 0.373), LMR (cutoff = 1.622, AUC = 0.631, 95% CI 0.477–0.784, P = 0.161, sensitivity = 0.917, specificity = 0.137), PLR (cutoff = 71.108, AUC = 0.712, 95% CI 0.575–0.849, P = 0.023, sensitivity = 1.000, specificity = 0.059), and SII at baseline (cutoff = 559.266, AUC = 0.681, 95% CI 0.533–0.830, P = 0.052, sensitivity = 0.373, specificity = 1.000) seemed to be a useful predictor for distinguishing responders from non-responders. Combining NLR with SII at baseline (AUC = 0.729, 95% CI 0.600–0.858, P = 0.014, sensitivity = 0.917, specificity = 0.510), LMR and SII at baseline (AUC = 0.735, 95% CI 0.609–0.861, P = 0.012, sensitivity = 1.000 specificity = 0.471), PLR and SII at baseline (AUC = 0.716, 95% CI 0.584–0.847, P = 0.021, sensitivity = 1.000 specificity = 0.431), and LMR and PLR at post-treatment in the third period (AUC = 0.761, 95% CI 0.605–0.917, P = 0.010, sensitivity = 0.800, specificity = 0.696) might slightly increase the prediction ability to determine patients who have response or no response. Finally, combining LMR at baseline, SII at post-treatment in the second period with PLR at post-treatment in the third period could be considered a better predictor for discriminating responders and non-responders than single or dual biomarkers (AUC = 0.879, 95% CI 0.788–0.969, P = 0.0001, sensitivity = 0.909, specificity = 0.800).ConclusionsThe models we constructed allowed for the accurate and efficient stratification of ESCC patients receiving anti-PD-1 plus chemotherapy and are easily applicable for clinical practice at no additional cost.

Highlights

  • Esophageal carcinoma (EC) is one of the most common malignancies and the sixth leading cause of cancer deaths worldwide, with an overall 5-year survival rate ranging from 0 to 10% [1, 2]

  • The NCT02395705 trial showed that the pathological complete response rate of the neoadjuvant chemotherapy (NCT) group was only 10.2% [9], esophageal squamous cell carcinoma (ESCC) patients receiving NCT showed poor survival, and over 20% of patients relapsed for locally advanced ESCC [10]

  • It is worth mentioning that a recent phase I study of JCOG1804E (FRONTiER Trial, NCT03914443) was conducted to evaluate the safety of nivolumab as a human monoclonal antibody targeting PD-1 in combination with chemotherapy of CDDP+ 5-FU (CF) or Docetaxel (DTX) + CF (DCF) as neoadjuvant therapy and could provide a new promising neoadjuvant therapy regimen for patients with locally advanced EC [11]

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Summary

Introduction

Esophageal carcinoma (EC) is one of the most common malignancies and the sixth leading cause of cancer deaths worldwide, with an overall 5-year survival rate ranging from 0 to 10% [1, 2]. A preclinical study suggested that an immune checkpoint inhibitor (ICI) as a neoadjuvant obtained better efficacy than that of an adjuvant [12] This is consistent with other studies reporting that nivolumab monotherapy showed a pCR of 43% in patients with resectable non-small-cell lung cancer [13], though the rate was 20% in lung cancer patients with metastatic disease when nivolumab was considered as an adjuvant [14]. In patients with ESCC who received anti-PD-1 antibody combined with neoadjuvant chemotherapy, no studies have estimated the predictive role of hematologic parameters such as NLR, PLR, lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) that are easier to access by physicians. No assessments of their usefulness have been performed in esophageal squamous cell carcinoma (ESCC) patients receiving anti‐PD‐1 combined with neoadjuvant chemotherapy

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