The Prognostic Role of Blood Inflammatory Biomarkers and EGFR Mutation Status in Stage IIIA/N2 Non-Small Cell Lung Cancer Patients Treated With Trimodality Therapy.

Hui Yang,Bingxu Li,Ling Yuan,Shenglei Li,Kunlun Wang,Yan Li

doi:10.3389/fonc.2021.707041

Abstract

ObjectivesVarious blood inflammatory biomarkers were associated with treatment response and prognosis of non-small cell lung cancer (NSCLC) in previous studies. In this study, we retrospectively evaluated the prognostic role of pretreatment blood inflammatory biomarkers and epidermal growth factor receptor (EGFR) mutation status in stage IIIA/N2 NSCLC patients with trimodality therapy.MethodsCompletely resected stage IIIA/N2 NSCLC patients with adjuvant chemotherapy and postoperative radiotherapy (PORT) were assessed in this study. Cutoff values of blood inflammatory factors were calculated by the R package SurvivalROC of R software. SPSS Statistics software was used for survival analyses. Kaplan-Meier survival curve and log-rank test were used to compare the survival difference between every two groups. Univariate and multivariate analyses of predictive factors were performed by Cox proportional hazards regression model.ResultsThe univariate analysis showed that T stage (p=0.007), EGFR mutation status (p=0.043), lymphocyte-to-monocyte ratio (LMR) (p=0.067), and systemic immune-inflammation index (SII) (p=0.043) were significant prognostic factors of disease-free survival (DFS). In the multivariate analysis, T2 (HR=0. 885, 95% CI: 0.059-0.583, p=0.004), EGFR mutation-positive (HR=0.108, 95% CI: 0.023-0.498, p=0.004) and elevated pretreatment SII (HR=0.181, 95%CI: 0.046-0.709, p=0.014) were independently related to shorter DFS. High pretreatment neutrophil counts (HR=0.113, p=0.019) and high systemic inflammation response index (SIRI) (HR=0.123, p=0.025) were correlated with worse overall survival (OS) by the univariate analysis. In the multivariate analysis, only high pretreatment SIRI was an independent predictor for poorer OS (HR=0.025, 95% CI: 0.001-0.467, p=0.014).ConclusionsIn conclusion, we identified that high pretreatment SII and SIRI were unfavorable prognostic factors in stage IIIA/N2 NSCLC patients treated with surgery, adjuvant chemotherapy and PORT. Patients with high pretreatment SII, high pretreatment SIRI, T2, and EGFR mutation-positive may need more forceful adjuvant treatment. Further prospective studies with large-scale are needed to validate our results and identify the proper cut-off values and optimum adjuvant treatment for distinct patient population.

Highlights

Among the most common cancers, lung cancer ranks first in cancer-associated death worldwide [1]
The inclusion criteria were: stage IIIA/N2 according to the 8th edition of the American Joint Committee on Cancer (AJCC) cancer staging system; completely resected; no neoadjuvant therapy; received four cycles of postoperative chemotherapy and radiotherapy after surgery; no history of other malignant tumors
Median disease-free survival (DFS) was 38.7 months and median overall survival time (OS) was 52.7 months in all patients

Summary

Introduction

Among the most common cancers, lung cancer ranks first in cancer-associated death worldwide [1]. More than 80% of lung cancer patients are non-small cell lung cancer (NSCLC), and 15% of them were diagnosed as stage IIIA [2]. Stage IIIA NSCLC patients have heterogeneous clinical features and prognoses. Stage IIIA/N2 NSCLC patients were always the hotspot of study and require multidisciplinary treatment approaches. Definitive chemoradiotherapy (CRT) followed by maintenance durvalumab was preferred according to the PACIFIC Trial [3]. Surgery followed by adjuvant chemotherapy with or without postoperative radiotherapy (PORT) was recommended by the National Comprehensive cancer network (NCCN)

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