Therapeutic Advances in Local-Regional Therapy for Stage III Non-Small-Cell Lung Cancer: Evolving Role of Dose-Escalated Conformal (3-Dimensional) Radiation Therapy

Lung cancer is the leading cause of cancer-related death among men and women in the United States. Approximately 80%–85% of lung cancer cases are non-small-cell lung cancer, and approximately 30%–40% of these patients have unresectable stage IIIA/B disease at diagnosis. The standard of care for locally advanced disease in patients with a good performance status consists of combined modality therapy, chemotherapy and radiation therapy (RT). Despite improved survival with combined modality therapy, local-regional recurrences and the development of distant metastases are still problematic. The radiation dose of 60 Gy for inoperable stage III non–small-cell lung cancer, established by Radiation Therapy Oncology Group trials 7301 and 7302, has remained the standard until the present time. More recently, trials suggest that local-regional control can be improved with RT dose escalation, improved tumor targeting (eg, 3-dimensional planning and intensity-modulated RT), and altered RT fractionation. Improvements in local-regional control could translate into an overall survival benefit. This article reviews the rationale for aggressive therapy and techniques to improve local disease control. It also provides an overview of trials that utilize such techniques, with a focus on efficacy, toxicity, and overall survival. Further well-designed clinical trials that examine RT dose escalation, improved tumor targeting, altered fractionation, and incorporation of biologic agents are crucial for progress in this disease.