Thoracic radiotherapy for extensive-stage small-cell lung cancer: what is the optimal dose and timing?

Small-cell lung cancer (SCLC) is a neuroendocrine tumor that represents about 12-20% of all lung cancers. Most of the SCLC patients present with extensive-stage (ES) disease. Primary therapy for ES-SCLC is 4-6 cycles of platinum-based chemotherapy (CT) followed by prophylactic cranial irradiation (PCI) in selected cases. Although the response rate to CT is approximately 60-70%, median survival times are very limited. The main problem of ES-SCLC patients after CT is intra-thoracic tumor recurrence since 75% of the patients had persisting intra-thoracic disease after CT, and approximately 90% of the patients had intra-thoracic progressive disease within the first year after diagnosis. Such high rate of intra-thoracic disease progression explains the need of local treatment in selected patients. There are three randomized studies and two meta-analyses evaluating the role of thoracic radiotherapy (TRT) in patients with ES-SCLC who responded to CT. Two of the randomized trials and one of the meta-analyses showed survival benefit of TRT. According to the results of relevant studies, the patients who responded to CT and have intra-thoracic residual disease after CT, who had limited metastatic sites (<= 2), and who have good performance status and limited weight loss have more benefit from TRT. We need novel studies evaluating the optimal dose fractionation schedules, optimal timing of RT, impact of time interval between RT and CT, immunotherapy and RT combinations, and number of CT cycles.