Induction chemoradiotherapy is not superior to induction chemotherapy alone in patients with stage IIIA(N2) non-small cell lung cancer: A systematic review and meta-analysis

Background: The optimal treatment strategy for patients with stage IIIA(N2) non-small cell lung cancer (NSCLC) is uncertain. We performed a systematic review and meta-analysis to test the hypothesis that the addition of radiotherapy to induction chemotherapy prior to surgical resection does not improve survival compared to induction chemotherapy alone. Methods: A systematic review and meta-analysis were performed by searching English articles in PubMed and the Cochrane Database over the years 1990-2010. Additional studies were identified by searching bibliographies of published review articles on lung cancer. All studies of stage IIIA(N2) NSCLC that reported outcomes on both patients treated with induction chemotherapy alone and patients treated with induction chemoradiotherapy were included in the overall systematic review. In addition, randomized controlled studies comparing induction chemotherapy and induction chemoradiotherapy that reported survival data were considered for use in the meta-analysis. The number of patients in each treatment group, survival data, and hazard ratios were extracted from each study. Results: The initial database search yielded review 3276 potential studies, 205 of which were screened based on the inclusion and exclusion criteria. Six studies eligible for analysis were found, including 1 randomized control trial, 1 phase II study, 2 retrospective reviews, and 2 published abstracts of randomized controlled trials (Table). None of the studies demonstrated a survival benefit to adding radiation therapy to induction chemotherapy versus chemotherapy alone. There was inadequate survival data available to perform a meta-analysis specifically on stage IIIA(N2) patients. A meta-analysis was performed on randomized controlled trials (N=336 patients) with available survival data on stage III patients, which showed no benefit of the addition of radiation to induction chemotherapy (odds ratio 0.88, 95% confidence interval 0.56-1.36, P=0.55). (Table Presented) a includes all stage III patients b arm B. Arm C not chosen given lack of survival data c overall survival of both groups, which was not significantly different between groups Conclusion: The use of radiation therapy in induction regimens for stage IIIA(N2) NSCLC is not supported by published evidence. Given the potential disadvantages of adding RT preoperatively, clinicians should consider using this treatment strategy only in the context of a clinical trial to allow better assessment of its effectiveness.