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.