Contemporary Postoperative Radiation Therapy Improves the Survival of Patients with Resected Pathological IIIA-N2 Non–small Cell Lung Cancer Treated With Adjuvant Chemotherapy

Abstract

For pIIIA–N2 non-small cell lung cancer (NSCLC) after complete resection followed by adjuvant chemotherapy (ACT), the effect of PORT on survival may be counterbalanced by severe toxicities induced by suboptimal RT techniques. Our study is to evaluate the effect of contemporary PORT using 3D-CRT/IMRT techniques on survival of patients with resected pIIIA–N2 NSCLC treated with ACT. Between Jan. 2006 and Mar. 2015, patients with pIIIA–N2 NSCLC after complete resection followed by ACT in our single institution were retrospectively analyzed. Using 3D-CRT/IMRT techniques, PORT was given by 2 Gy per fraction to a total dose of 50 Gy. The effect of PORT on overall survival (OS) and disease free survival (DFS) was evaluated with Kaplan-Meier method and log-rank test. The impact of PORT on loco-regional recurrence free survival (LRFS) and distant metastasis free survival (DMFS) was also analyzed. Statistically significant difference was set as p<0.05. Overall, 545 consecutive patients were enrolled, including 187 (34.3%) in the PORT group and 358 (65.7%) in the non-PORT group. The characteristics were comparable between the two groups except that the patients with less positive lymph nodes were more prevalent in the PORT group. The median follow-up time for survival patients was 37.4 months. The median survival time of whole group was 60.0 months. PORT significantly improved the OS (p=0.003). The median survival time was 56.1 months in the non-PORT group and not reached in the PORT group. The 3- and 5-year OS rates were 76.5%, and 65.7%, respectively in the PORT group and were 67.1%, and 47.8%, respectively in the non-PORT group. The differences of the DFS, LRFS and DMFS between the two groups were all statistically significant (p=0.001, p=0.001, and p=0.006, respectively). The 3-, and 5-year DFS rates were 41.4%, and 33.6% in the PORT group and 33.8%, and 19.5% in the non-PORT group, respectively. The 3-, and 5-year LRFS rates were 68.2%, and 51.9% in the PORT group and 58.1%, and 36.9% in the non-PORT group, respectively. The 3-, and 5-year DMFS rates were 45.7%, and 37.7% in the PORT group and 40.0%, and 23.6% in the non-PORT group, respectively. Multivariate analyses also showed that PORT was significantly associated with longer OS (HR=0.640, 95% CI: 0.432-0.947; p=0.025). The other independent prognostic factors included age≤60 year (HR=0.563, 95% CI: 0.420-0.754; p=0.000) and the number of positive nodes ≤4 (HR=0.564, 95% CI: 0.421-0.756; p=0.000). In the PORT group, IMRT was used in 145 patients (75.9%) and 3D-CRT was used in 46 patients (24.1%). Up to the last follow up, none irradiation toxicity-related deaths were observed. Based on our study, postoperative 3D-CRT/IMRT is safe and can significantly improve the survival of patients with pIIIA–N2 NSCLC treated with surgery followed by ACT. A prospective randomized multicenter clinical trial is ongoing to evaluate the definitive role of PORT using contemporary techniques.