Novel Approaches of Chemoradiotherapy in Unresectable Stage IIIA and Stage IIIB Non-Small Cell Lung Cancer

Abstract

Abstract Learning Objectives: After completing this course, the reader will be able to: Describe the current status of phase II trials with novel agents in order to distinguish the role of phase III trials in determining the role of novel agents.Describe target therapy in stage III non-small cell lung cancer and discuss the status of personalized medicine in stage III disease.State the current standard for thoracic radiation therapy and the current status of hypofractionated, adaptive radiotherapy and proton therapy and evaluate the recent radiation therapy oncology group (RTOG) 0617 trial. CME This article is available for continuing medical education credit at CME.TheOncologist.com Approximately one third of patients with non-small cell lung cancer have unresectable stage IIIA or stage IIIB disease, and appropriate patients are candidates for chemoradiotherapy with curative intent. The optimal treatment paradigm is currently undefined. Concurrent chemoradiotherapy, compared with sequential chemotherapy and thoracic radiation therapy (TRT), results in superior overall survival outcomes as a result of better locoregional control. Recent trials have revealed efficacy for newer chemotherapy combinations similar to that of older chemotherapy combinations with concurrent TRT and a lower rate of some toxicities. Ongoing phase III trials will determine the roles of cisplatin and pemetrexed concurrent with TRT in patients with nonsquamous histology, cetuximab, and the L-BLP25 vaccine. It is unlikely that bevacizumab will have a role in stage III disease because of its toxicity. Erlotinib, gefitinib, and crizotinib have not been evaluated in stage III patients selected based on molecular characteristics. The preliminary results of a phase III trial that compared conventionally fractionated standard-dose TRT (60 Gy) with high-dose TRT (74 Gy) revealed an inferior survival outcome among patients assigned to the high-dose arm. Hyperfractionation was investigated previously with promising results, but adoption has been limited because of logistical considerations. More recent trials have investigated hypofractionated TRT in chemoradiotherapy. Advances in tumor targeting and radiation treatment planning have made this approach more feasible and reduced the risk for normal tissue toxicity. Adaptive radiotherapy uses changes in tumor volume to adjust the TRT treatment plan during therapy, and trials using this strategy are ongoing. Ongoing trials with proton therapy will provide initial efficacy and safety data.