Postoperative radiotherapy is associated with better survival in non-small cell lung cancer with involved N2 lymph nodes: results of an analysis of the National Cancer Data Base

Abstract

Introduction: Use of postoperative radiotherapy (PORT) in non-small-cell lung cancer remains controversial. Limited data indicate that PORT may benefit patients with involved N2 nodes. This study evaluates this hypothesis in a large retrospective cohort treated with chemotherapy and contemporary radiation techniques.

Methods: The National Cancer Data Base was queried for patients diagnosed 2004-2006 with resected non-small-cell lung cancer and pathologically involved N2 (pN2) nodes also treated with chemotherapy. Multivariable Cox proportional hazards model was used to assess factors associated with overall survival (OS). Inverse probability of treatment weighting (IPTW) using the propensity score was used to reduce selection bias. OS was compared between patients treated with versus without PORT using the adjusted Kaplan-Meier estimator and weighted log-rank test based on IPTW.

Results: Two thousand and one hundred and fifteen patients were eligible for analysis. 918 (43.4%) received PORT, 1197 (56.6%) did not. PORT was associated with better OS (median survival time 42 months with PORT versus 38 months without, p = 0.048). This effect was significant in multivariable and IPTW Cox models (hazard ratio: 0.87, 95% confidence interval: 0.78-0.98, p = 0.026, and hazard ratio: 0.89, 95% confidence interval: 0.79-1.00, p = 0.046, respectively). No interaction was seen between the effects of PORT and number of involved lymph nodes (p = 0.615).

Conclusions: PORT was associated with better survival for patients with pN2 nodes also treated with chemotherapy. No interaction was seen between benefit of PORT and number of involved nodes. These findings reinforce the benefit of PORT for N2 disease in modern practice using the largest, most recent cohort of chemotherapy-treated pN2 patients to date.

Figure 1

Adjusted Kaplan-Meier Survival Estimates and Weighted Log Rank Test

Figure 2

Representative “Beam’s Eye View” from a single anterior-posterior field from a modern course of postoperative radiotherapy (A) and out-of-date postoperative radiotherapy (B) for a patient with a completely-resected right upper lobe tumor found to have involved N2 nodes. The borders for the field on the right (B) were derived from the specifications of the Medical Research Council (MRC) Lung Cancer Working Party randomized trial of postoperative radiotherapy, a trial included in the PORT meta-analysis. The MRC study mandated coverage of the entire mediastinum, bilateral hila, bronchial stump, and, in the case of an upper lobe tumor, the bilateral supraclavicular fossae. These field specifications resulted in significantly higher volumes of normal heart and lung in the treatment field than what is currently acceptable. Additionally, with older radiotherapy equipment (such as Cobalt-60 units), less penetrating, lower energy beams were used, which resulted in higher superficial dose relative to the dose at the desired target depth. This created significant dose inhomogeneity with the highest dose level deposited in uninvolved lung, chest wall, and heart. Contoured normal structures seen in this figure are the lungs (purple), the heart (pink), and the esophagus (orange).