Cancer Res Treat.  2022 Oct;54(4):1017-1029. 10.4143/crt.2021.1007.

The Role of Neutrophil-to-Lymphocyte Ratio in Predicting Pathological Response for Resectable Non–Small Cell Lung Cancer Treated with Neoadjuvant Chemotherapy Combined with PD-1 Checkpoint Inhibitors

• Sun X
• Feng Y
• Zhang B
• Huang W
• Zhao X
• Zhang H
• Yue D
• Wang C

• KMID: 2534181
• DOI: http://doi.org/10.4143/crt.2021.1007

Abstract

Purpose
The aim of our study was to investigate the value of baseline and preoperative neutrophil-to-lymphocyte ratio (NLR) in predicting the pathological response and disease-free survival (DFS) of neoadjuvant chemotherapy alone or combined with programmed cell death-1 (PD-1) checkpoint inhibitors in patients with resectable non‒small cell lung cancer (NSCLC).
Materials and Methods
Resectable NSCLC patients who underwent neoadjuvant chemotherapy alone or combined with PD-1 checkpoint inhibitors between January 2018 and January 2020 were included. Peripheral venous blood samples of the patients were collected within 3 days prior to the first neoadjuvant treatment and within 3 days prior to surgery.
Results
A total of 79 patients in neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group and 89 patients in neoadjuvant chemotherapy alone group were included. Thirty-five point four percent of the patients achieved pathological complete response (pCR) in neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group, whereas only 9.0% reached pCR in the group of neoadjuvant chemotherapy. High NLR level were correlated with poor pathological response and DFS in neoadjuvant chemotherapy or combined with PD-1 checkpoint inhibitors group. Multivariate analysis revealed that baseline NLR could independently predict pathological response and DFS in the neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group.
Conclusion
High NLR level were correlated with poor pathological response and shorter DFS in patients with NSCLC undergoing neoadjuvant chemotherapy or combined with PD-1 checkpoint inhibitors. Meanwhile, baseline NLR could independently predict response to pathological response and DFS, revealing its potential as a screening tool in NSCLC patients who received neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors.

Keyword

Non/small cell lung neoplasm; Neutrophil-lymphocyte ratio; PD-1 checkpoint inhibitors; Neoadjuvant chemotherapy; Pathological response

Figure

• 

  Fig. 1 Receiver operating characteristic curve identified the cutoff point of neutrophil-to-lymphocyte ratio (NLR). (A) Baseline and preoperative NLR for predicting pathological complete response (pCR) were 1.96 (area under the curve [AUC], 0.679; sensitivity, 0.86; specificity, 0.50] and 1.89 (AUC, 0.657; sensitivity, 0.60; specificity, 0.75) in neoadjuvant chemotherapy combined with immunotherapy group. (B) Baseline and preoperative NLR for predicting major pathologic response (MPR) were 2.05 (AUC, 0.664; sensitivity, 0.829; specificity, 0.500) and 1.93 (AUC, 0.594; sensitivity, 0.575; specificity, 0.684) in neoadjuvant chemotherapy combined with immunotherapy group. (C) Baseline and preoperative NLR for predicting pCR were 1.01 (AUC, 0.433; sensitivity, 0.97; specificity, 0.25) and 1.43 (AUC, 0.516; sensitivity, 0.61; specificity, 0.63) in neoadjuvant chemotherapy alone group. (D) Preoperative NLR for predicting MPR were 1.01 (AUC, 0.422; sensitivity, 0.968; specificity, 0.154) and 1.43 (AUC, 0.615; sensitivity, 0.694; specificity, 0.615) in neoadjuvant chemotherapy alone group.

• 

  Fig. 2 The correlations between baseline and preoperative neutrophil-to-lymphocyte ratio (NLR) and pathological responses. (A–D) Neoadjuvant chemotherapy combined with programmed death-1 (PD-1) checkpoint inhibitors group. (A) The difference of baseline NLR between pathological complete response (pCR; mean±standard deviation, 2.39±1.19) and non-pCR (3.60±2.27) patients (p=0.009). (B) The difference of preoperative NLR between pCR (2.33±3.84) and non-pCR (2.32±1.30) patients (p=0.022). (C) The difference of baseline NLR between major pathologic response (MPR; 2.76±2.15) and non-MPR (3.55±1.86) patients (p=0.012). (D) The difference of preoperative NLR between MPR (2.35±3.33) and non-MPR (2.30±1.33) patients (p=0.154). (E–H) Neoadjuvant chemotherapy alone group. (E) The difference of baseline NLR between pCR (3.98±4.56) and non-pCR (2.48±1.11) patients (p=0.537). (F) the difference of preoperative NLR between pCR (2.50±2.04) and non-pCR (2.29±2.21) patients (p=0.880). (G) The difference of baseline NLR between MPR (3.52±3.60) and non-MPR (2.45±1.12) patients (p=0.378). (H) The difference of preoperative NLR between MPR (2.03±1.72) and non-MPR (2.36±2.26) patients (p=0.187).

• 

  Fig. 3 Kaplan-Meier analysis of disease-free survival in relation to neutrophil-to-lymphocyte ratio (NLR). Kaplan-Meier curves for disease-free survival (DFS). (A) DFS curve of patients with baseline NLR in neoadjuvant chemotherapy combined with programmed death-1 (PD-1) checkpoint inhibitors group (p=0.001). (B) DFS curve of patients with preoperative NLR in neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group (p=0.011). (C) DFS curve of patients with baseline NLR in neoadjuvant chemotherapy alone group (p=0.004). (D) DFS curve of patients with preoperative NLR in neoadjuvant chemotherapy alone group (p=0.001).

Reference

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