Preoperative Clinical Risk Factors in Selecting Patients with Pathological IIIA-N2 Non-Small-Cell Lung Cancer Benefiting from Postoperative Radiation Therapy: A Propensity Score-Matched Analysis

Abstract

Pathological IIIA-N2 Non-small-cell Lung Cancer (pIIIA–N2 NSCLC) is a heterogeneous population and the role of Postoperative Radiotherapy (PORT) after the adjuvant chemotherapy (ACT) in pIIIA–N2 NSCLC has not been well-defined. Not all pIIIA–N2 patients can benefit from PORT. The aim of this study was to identify which subgroup can benefit from PORT after ACT. This study included 886 pIIIA–N2 patients completing radical resection and ACT at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2003 to December 2015. Patients were divided into two groups: Group PORT, comprising of patients that underwent PORT after radical resection and ACT, and Group NON-PORT comprising of a control group of patients who just underwent radical resection and ACT. Propensity score matching (PSM) was used to create patient groups that were balanced across several covariates (n=296 in each group). Accurate clinical lymph node staging is obtained through contrast-enhanced CT and/or PET-CT. Lymph nodes measured in the short axis ≥ 10mm on CT or SUV>2.5 on PET-CT were considered as metastases. Using 3D-CRT/IMRT techniques, PORT was given by 2 Gy per fraction to a total dose of 50 Gy. Outcome measures included overall survival (OS), disease-free survival (DFS), loco-regional recurrence free survival (LRFS), distant metastasis free survival (DMFS) and recurrence. The Kaplan-Meier, Log Rank test, and Cox regression were used for survival analysis and identification of prognostic factors. Statistically significant difference was set at P<0.05. In the overall study cohort, 5-year OS (60.6% vs. 52.2%, P=0.027) and DFS (36.9% vs. 22.4%, P<0.001) rates were significantly higher in Group PORT compared to Group NON-PORT. This data was nearly the same in the matched samples (5-year OS: 60.2% vs. 53.3%, P=0.067; 5-year DFS: 37.2% vs. 22.4%, P<0.001). The overall (P=0.007) and locoregional (P＜ 0.001) recurrence rates in Group PORT were significantly lower than in Group NON-PORT. Multivariate cox analyses in the matched samples revealed that factors independently associated with longer OS were PORT (HR=0.683, 95% CI 0.510-0.916, P=0.011), age<60 years, adenocarcinoma, negative neurovascular invasion. Subgroup analysis indicated that some preoperative clinical factors could predict the population benefiting from PORT after ACT, including preoperative clinical lymph node metastases (P=0.026), smoking index >400 (P=0.023). According to the PSM result, PORT after ACT can significantly improve the 5-year DFS, lower the overall and locoregional recurrence rates in pIIIA–N2 NSCLC patients. In some subgroups PORT can improve the 5-year OS， including preoperative clinical lymph node metastases, smoking index >400.