Early versus late chest radiotherapy for limited stage small cell lung cancer

Background It is standard clinical practice to combine chemotherapy and chest radiotherapy in treating patients with limited-stage small cell lung cancer. However, the best way to integrate both modalities is unclear. Objectives To establish the most effective way of combining chest radiotherapy with chemotherapy for patients with limited-stage small cell lung cancer in order to improve long-term survival. Search strategy The electronic databases MEDLINE, EMBASE, Cancerlit and the Cochrane Central Register of Controlled Trials ( CENTRAL), reference lists, handsearching of journals and conference proceedings, and discussion with experts were used to identify potentially eligible trials, published and unpublished. Selection criteria Randomised controlled clinical trials comparing different timing of chest radiotherapy in patients with limited-stage small cell lung cancer. Data collection and analysis Seven randomised trials were reviewed. There were differences in the timing and the overall treatment time of chest radiotherapy, the overall treatment time of, and the type of chemotherapy used. Main results No significant differences in the 2-year and the 5-year survival were found, whether chest radiotherapy was delivered within 30 days after the start of chemotherapy or later. When the only study that delivered chest radiotherapy during cycles of non-platinum chemotherapy was excluded, a trend for the 5-year survival was observed (RR: 0.93, p=0.07) in favour of early radiation, but not for the 2-year survival. Survival at 5 years, but not at 2 years, was significantly better for those having early chest radiotherapy delivered in an overall treatment time of less than 30 days compared with a longer treatment time (RR: 0.90, p=0.006). These results, however, should be interpreted with caution because the largest trial has follow-up data at three years, but not later. It remains to be seen what the effect of longer follow up will be for 5-year survival rates. Local tumour control was not significantly different between early and late chest radiotherapy. The incidence of severe pneumonitis or severe oesophagitis was not significantly different for early versus late thoracic radiotherapy. However, a trend for a higher chance to develop pneumonitis when early chest radiotherapy was delivered during non-platinum based chemotherapy was observed. Authors' conclusions At present, it is uncertain whether the timing of chest radiotherapy as such is important for survival. The optimal integration of chemotherapy and chest radiotherapy in patients with limited-stage small cell lung cancer is unknown. Therefore, further research is needed to establish the most effective combination of radiotherapy and chemotherapy in this disease.