A Meta-Analysis of Thoracic Radiotherapy for Small-Cell Lung Cancer

In spite of 16 randomized trials conducted during the past 15 years, the effect of thoracic radiotherapy on the survival of patients with limited small-cell lung cancer remains controversial. The majority of these trials did not have enough statistical power to detect a difference in survival of 5 to 10 percent at five years. This meta-analysis was designed to evaluate the hypothesis that thoracic radiotherapy contributes to a moderate increase in overall survival in limited small-cell lung cancer. We collected individual data on all patients enrolled before December 1988 in randomized trials comparing chemotherapy alone with chemotherapy combined with thoracic radiotherapy. Trials that included only patients with extensive disease were excluded. The meta-analysis included 13 trials and 2140 patients with limited disease. A total of 433 patients with extensive disease were excluded. Overall, 1862 of 2103 patients who could be evaluated died; the median follow-up period for the surviving patients was 43 months. The relative risk of death in the combined-therapy group as compared with the chemotherapy group was 0.86 (95 percent confidence interval, 0.78 to 0.94; P = 0.001), corresponding to a 14 percent reduction in the mortality rate. The benefit in terms of overall survival at three years (±SD) was 5.4±1.4 percent. Indirect comparison of early with late radiotherapy and of sequential with non-sequential radiotherapy did not reveal any optimal time for treatment. There was a trend toward a larger reduction in mortality among younger patients: the relative risk of death in the combined-therapy as compared with the chemotherapy group ranged from 0.72 for patients less than 55 years old (95 percent confidence interval, 0.56 to 0.93) to 1.07 (0.70 to 1.64) for patients over 70. Thoracic radiotherapy moderately improves survival in patients with limited small-cell lung cancer who are treated with combination chemotherapy. Identification of the optimal combination of chemotherapy and radiotherapy will require further trials. (N Engl J Med 1992; 327:1618–24.), THE role of thoracic radiotherapy in the management of limited small-cell lung cancer remains controversial. Most investigators agree that it decreases the risk of thoracic recurrence significantly, but no agreement has been reached concerning its possible effect on survival.¹ Sixteen randomized trials have been conducted in the past 15 years, with inconsistent results (Appendix 2); thus, the controversy persists. If the heterogeneity of the patients studied is assumed not to be too great, there are three main possible explanations for the inconsistency: (1) that technical factors such as the radiation dose, tissue volume treated, drug administered, and timing of radiotherapy…