Ramesh Rengan

Lung cancer accounts for nearly one-fifth of all cancer deaths worldwide and is the most common cause of cancer-related death in the United States. Outcomes for locally advanced non-small cell lung cancer remain extremely poor with regards to both local control and overall survival. Modest gains in local control were obtained with the incorporation of multimodality treatment, including preoperative chemotherapy followed by surgical resection; combination chemoradiotherapy also improved survival, secondary to improved local control. While the natural progression to trimodality therapy resulted in superior local control, it did not translate to improved overall survival, secondary to increased toxicity. The additional morbidity is likely from radiation toxicity, the minimization of which will be crucial to the future success of trimodality therapy. One strategy to decrease toxicity is to utilize charged particles, such as protons, which deposit a high dose at the Bragg peak with a minimal dose beyond the peak, thereby reducing the dose to distal normal tissues. Trimodality therapy incorporating preoperative proton radiation therapy and chemotherapy, followed by surgery, is currently being evaluated as a potential strategy to achieve improved local control and overall survival in locally advanced non-small cell lung cancer.

Stereotactic body-radiation therapy (SBRT) delivers large doses of radiation with millimeter accuracy.¹ With SBRT, control rates for stage I non–small-cell lung cancer are 90% or greater, and this effectiveness has led to its worldwide adoption in treating patients with inoperable disease.^1,2 Despite technological advances that permit the precision required for SBRT, normal tissues near the tumor receive higher biologic doses of radiation than with standard treatment. Consequently, patients with tumors adjacent to radiation-sensitive structures, such as the large airways, great vessels, heart, phrenic nerves, and spinal cord, may be at an increased risk for severe radiation injury.³ Documenting the extent of the toxic effects on these central structures represents a challenge given the competing risk of death in patients with lung cancer and the extended time required for toxicity to develop.