Definitive chemoradiation for the treatment of locally advanced non-small-cell lung cancer

A third of patients with newly diagnosed non-small-cell lung cancer (NSCLC) have locally advanced disease not amenable for curative resection. Addition of chemotherapy to thoracic radiation improves survival in patients with locally advanced NSCLC when compared with thoracic radiation alone. Over the past two decades, we have made slow but steady progress in improving the outcomes of therapy in this subset of patients. This review summarizes the past two decades of research and outlines the direction we need to pursue to significantly enhance the outcomes. The widespread use of positron emission tomography (identifying those with occult distant metastatic disease and sparing them combined-modality therapy), improved radiation techniques, and better supportive care resulting in improved chemotherapy delivery have resulted in improved outcomes. There is considerable interest in studying the role of higher doses of thoracic radiation (74 Gy) in this disease, and this is the subject of an ongoing intergroup study. Despite some recent setbacks, molecularly targeted therapies need to be studied carefully in combination with chemoradiotherapy. There is an urgent need to develop regimens that incorporate chemotherapy agents that can be administered at doses that are systemically active and yet tolerable.