Preoperative clinical risk factors in selecting patients with pathological IIIA-N2 non-small-cell lung cancer benefiting from postoperative radiotherapy

Abstract

Objective Pathological Ⅲ A-N2 non-small-cell lung cancer (p Ⅲ A-N2 NSCLC) is a heterogeneous population, and the role of postoperative radiotherapy(PORT) after the adjuvant chemotherapy (ACT) in pⅢA-N2 NSCLC remains ambiguous. Not all pⅢA-N2 patients can benefit from PORT. This study was performed to identify the subgroup that can benefit from PORT after ACT. Methods This study included 804 pⅢ A-N2 NSCLC patients completing radical resection and ACT from January 2006 to December 2015. The patients were divided into two groups: PORT group, patients who underwent PORT after radical resection and ACT; and NON-PORT group, control group of patients who only underwent radical resection and ACT. The PORT and NON-PORT groups consisted of 276 and 528 patients, respectively. Accurate clinical lymph node staging was obtained through contrast-enhanced CT and/or PET/CT. Lymph nodes measured in the short axis≥10 mm on CT or SUV>2.5 on PET/CT were considered as metastases. Using 3-dimensional conformal radiation therapy or intensity modulated radiation therapy techniques, PORT was administered at 1.8-2.2 Gy per fraction to a prescription dose to the planning target volume of 50-60 Gy. Outcome measures included overall survival(OS), disease-free survival (DFS), locoregional recurrence-free survival(LRFS), and distant metastasis-free survival(DMFS). Kaplan-Meier, Log Rank test, and Cox regression were used to analyze survival data and identify prognostic factors. Statistically significant difference was set to P<0.05. Results Median follow-up time was 32.07 months. The 2-year and 5-year OS of the patients in the entire cohort were 82.1% and 54.5%, respectively. The median values of the DFS, LRFS, and DMFS were 19.84, 120.31, and 30.52 months, respectively. In the overall study cohort, the median values of the OS(97.31 months vs. 64.10 months, χ2=5.253, P=0.022), DFS (25.76 months vs. 17.97 months, χ2=18.397, P<0.001), LRFS(120.31 months vs. 101.03 months, χ2=15.358, P<0.001) and DMFS(36.83 months vs. 28.49 months, χ2=6.434, P=0.011) were significantly higher in the PORT group than in the NON-PORT group. Univariate analysis showed that the adverse prognostic factors which significantly affected OS were: male, age≥60 years, advanced preoperative T staging, preoperative N1-N2, non-squamous carcinoma and non-adenocarcinoma, 1-2 chemotherapy cycles and NON-PORT. Multivariate Cox analyses revealed that factors independently associated with longer OS were PORT(HR=0.754, 95%CI=0.584-0.973, P=0.03), female, age <60 years, preoperative clinical N0, clinic stage Ⅰ-Ⅱ, adenocarcinoma, or squamous carcinoma. Subgroup analysis indicated that several preoperative clinical factors could predict the population that would benefit from PORT after ACT. These factors included male(HR=0.697, 95%CI= 0.513-0.947, P=0.021), smoking patient (HR=0.648, 95%CI=0.464-0.905, P=0.011), preoperative clinical N1-N2(HR=0.640, 95%CI=0.465-0.881, P=0.006), clinic stage Ⅲ(HR=0.688, 95%CI= 0.484-0.980, P=0.038), and adenocarcinoma(HR=0.726, 95%CI=0.527-0.999, P=0.049). Conclusions PORT after ACT could significantly improve the 5-year OS, DFS, LRFS, and DMFS in pⅢA-N2 NSCLC patients. Moreover, PORT could improve the 5-year OS of the subgroups with the following characteristics: male, smoking patient, preoperative clinical N1-N2, clinic stage Ⅲ, and adenocarcinoma. Key words: Carcinoma, non-small-cell lung; Radiotherapy; Chemotherapy; Therapeutic evaluation