Background: Induction chemotherapy before surgical resection increases survival compared with surgical resection alone in patients with stage IIIA-N2 non - small-cell lung cancer (NSCLC). We hypothesized that, following a response to induction chemotherapy, surgical resection would be superior to thoracic radiotherapy as locoregional therapy. Methods: Selected patients with histologic or cytologic proven stage IIIA-N2 NSCLC were given three cycles of platinum-based induction chemotherapy. Responding patients were subsequently randomly assigned to surgical resection or radiotherapy. Survival curves were estimated using Kaplan - Meier analyses from time of randomization. Results: Induction chemotherapy resulted in a response rate of 61% (95% confidence interval [CI] = 57% to 65%) among the 579 eligible patients. A total of 167 patients were allocated to resection and 165 to radiotherapy. Of the 154 (92%) patients who underwent surgery, 14% had an exploratory thoracotomy, 50% a radical resection, 42% a pathologic downstaging, and 5% a pathologic complete response; 4% died after surgery. Postoperative radiotherapy was administered to 62 (40%) of patients in the surgery arm. Among the 154 (93%) irradiated patients, overall compliance to the radiotherapy prescription was 55%, and grade 3/4 acute and late esophageal and pulmonary toxic effects occurred in 4% and 7%; one patient died of radiation pneumonitis. Median and 5-year overall survival for patients randomly assigned to resection versus radiotherapy were 16.4 versus 17.5 months and 15.7% versus 14%, respectively (hazard ratio = 1.06, 95% CI = 0.84 to 1.35). Rates of progression-free survival were also similar in both groups. Conclusion: In selected patients with pathologically proven stage IIIA-N2 NSCLC and a response to induction chemotherapy, surgical resection did not improve overall or progression-free survival compared with radiotherapy. In view of its low morbidity and mortality, radiotherapy should be considered the preferred locoregional treatment for these patients.,
National Cancer Institute. Journal (Print)
Erasmus MC: University Medical Center Rotterdam

van Meerbeeck, J., Kramer, G., van Schil, P., Legrand, C., Smit, E., Schramel, F., … Giaccone, G. (2007). Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer. National Cancer Institute. Journal (Print), 99(6), 442–450. doi:10.1093/jnci/djk093