Combined-modality therapy of locally advanced non-small-cell lung cancer

Treatment of patients with unresectable stage IIIA and IIIB non-small-cell lung cancer with conventionally-fractionated radiation therapy (i.e., total doses of 50 to 60 Gy, using one fraction per day), which was standard practice in the 1970s and early 1980s, resulted in good short-term palliation but few long-term survivors. Local control was poor, and the majority of patients also rapidly developed symptomatic metastatic disease outside the chest. In the past 15 years, a number of approaches to improve this situation have been defined in prospective clinical trials. They include radiation therapy with altered fractionation schemes that allow either higher overall doses or shortened treatment times, the use of systemic chemotherapy to address microscopic metastatic disease, and the use of a variety of agents, some but not all with intrinsic cytotoxic activity, to act as radiation sensitizers. These strategies have resulted in modest but significant improvements in local and systemic disease control, but at a cost of increased toxicity, including myelosuppression, esophagitis, and pneumonitis. Further advances in treatment will require better (i.e., more active) cytotoxic agents and better ways of limiting radiation effects to the target volume of tumor.