A meta-analysis of the timing of chest irradiation in the combined modality treatment of limited-stage small cell lung cancer

The objective of this study was to determine whether initial combined chemoradiation results in superior 1-, 2-, and 3-year survivals in the treatment of limited-stage small cell lung cancer versus sequential or split-course therapy. Using a prospective meta-analysis protocol outlining study inclusion criteria, literature search strategy, and statistical procedures, data from all available randomized controlled trials addressing the above-noted objective were pooled using a fixed effects model (Peto). Results were expressed as summary odds ratios (ORp), and statistical tests for data heterogeneity were performed prior to calculation of ORps. Odds ratios greater than 1.0 favored the experimental arm versus control (i.e., early chest irradiation). If statistical heterogeneity was demonstrated, sensitivity analyses were performed by previously described methods to evaluate possible sources of heterogeneity across the included studies. Pooling data from eight randomized controlled trials enrolling over 1,500 patients showed that early integration of chest radiotherapy with systemic chemotherapy increases overall survival by 34%-216%, depending on the end point of interest. Etoposide (E) plus cisplatin (P) in conjunction with chest irradiation appears to offer the greatest increase in survival versus delayed or split-course radiation therapy and non-EP-containing drug schedules. The available randomized trial data support early concurrent chest radiotherapy and systemic chemotherapy in the form of E and P in the management of limited-stage small cell lung cancer.