Limited-stage small-cell lung cancer: the current status of combined-modality therapy.

Limited-stage (LS) small-cell lung cancer (SCLC) remains a therapeutic challenge to medical and radiation oncologists. The treatment of LS-SCLC has evolved significantly over the last two decades with combined-modality therapy now the standard of care. The addition of thoracic radiotherapy (TRT) to standard chemotherapy has led to improvements in long-term survival in this population. However, many questions remain about the optimal way to deliver chemoradiotherapy. In a landmark trial, twice-daily TRT to a dose of 45 Gy increased 5-year survival by 10% compared with once-daily TRT administered to the same dose. This suggests that more intensive TRT regimens may lead to further survival gains, assuming they can be delivered safely in this setting. Strategies currently under investigation include higher total daily doses delivered once daily or novel concurrent boost techniques allowing more intensive treatments over shorter periods of time. Several trials and meta-analyses have evaluated the timing of TRT with chemotherapy, with the weight of evidence suggesting that early and concurrent TRT with chemotherapy is optimal. Novel cytotoxic chemotherapy combinations have failed thus far to provide an advantage over standard etoposide-cisplatin combinations. Prophylactic cranial irradiation in near or complete responders to induction chemoradiotherapy has also been shown to improve long-term survival rates. LS-SCLC has been a model cancer in terms of the potential benefit of combined chemoradiotherapy strategies in improving patient outcomes.