Role of radiation therapy in the management of stage Ⅲ non-small cell lung cancers： current status and controversies

The treatment of stage Ⅲ non-small cell lung cancer （NSCLC） consisting of the heterogeneous stage subsets remains a challenge. Overall, it has been gradually recognized that radiation therapy （RT） plays a crucial role in the management of stage Ⅲ NSCLC. One superior sulcus tumors are the subset for which the trimodality treatments are clearly preferred. One subset of stage Ⅲ NSCLC has a minimal disease burden with microscopic pN2 disease or with discrete pN2 involvement identified preoperatively, thus technically could undergo a surgical resection. For the incidentally found pN2 disease after complete surgery （ⅢA-1, ⅢA-2）, the value of postoperative radiotherapy （PORT） has been recognized by a reassessment based on new data. However, doubt persists regarding how to define the clinical target volume for PORT. For the discrete pN2 involvement identified preoperatively （a selected part of ⅢA-3）, induction chemoradiation therapy （CRT） before surgery may yield a survival advantage, although the phase Ⅲ randomized trials in this issue are not conclusive. The other major subset of stage Ⅲ NSCLC is the infiltrative stage Ⅲ NSCLC with N2 or N3 nodal disease （ⅢA-3, ⅢA-4, and ⅢB）, for which concurrent CRT is considered as the current standard of care. The potential role of radiation dose escalation/acceleration has been proposed; however, the optimal dose fractionation remains an important unresolved question. Additionally, the role of prophylac- tic cranial irradiation for stage Ⅲ patients with high risk of brain metastasis is worth of further assessment. Moreover, how to integrate molecular targeted therapy with RT, as well as whether they had a role in stage Ⅲ diseases, are other controversies actively under study in ongoing trials. This review specifically describes the updated role of RT in multimodal approach to treat stage Ⅲ NSCLC and the controversies regarding these results in various situations.