Prophylactic Cranial Irradiation for Patients With Locally Advanced Non–Small-Cell Lung Cancer

Prophylactic cranial irradiation (PCI) in patients with locally advanced non-small-cell lung cancer (NSCLC) remains an area of controversy. Dr. Gore has provided a review of the literature, including randomized and nonrandomized studies and, in particular, the ongoing Radiation Therapy Oncology Group trial (RTOG 0214), which is randomizing NSCLC patients to PCI or observation. Locally Advanced NSCLC
Patients with locally advanced NSCLC are most commonly treated with a combination of chemotherapy and radiation therapy as well as possible surgical resection. In addition to locoregional relapse, the brain continues to be a frequent site of failure with long-term follow-up (15% to 30% as first site of failure and 21% to 54% overall central nervous system [CNS] failure rate).[1,2] As the incidence of adenocarcinomas continues to rise, so will the rate of CNS failures. Multiple studies show that with longer survival rates, the rate of CNS metastases increases. Treatment strategies that reduce the risk of CNS metastases are, therefore, needed to optimize the outcome of multimodality therapy in locally advanced NSCLC patients. Small-Cell Lung Cancer
In small-cell lung cancer, the use of PCI for the prevention of CNS metastases is more widely accepted. Multiple trials and a meta-analysis demonstrate that PCI administered to patients with a complete response to induction therapy significantly reduces the risk of brain metastases and offers an improvement in absolute overall survival (5.4% at 3 years).[3] Despite multiple randomized studies in locally advanced NSCLC showing a decreased or delayed incidence of brain metastasis with the use of PCI, no survival benefit has been proven. Limiting factors include short survival rates, inadequate locoregional treatment, ineffective systemic therapy, possible reseeding of the CNS, and a lack of statistical power. Conclusions
The results of RTOG 0214 will be crucial in addressing these issues. This trial will include patients with stage IIIA/IIIB NSCLC who have completed definitive locoregional and systemic therapy, with or without surgery, and have achieved a complete or partial response, or stable disease. Patients are stratified by stage, histology, and therapy and then randomized to PCI at 2 Gy per fraction to a total of 30 Gy or observation. This study is powered to detect a survival benefit with a target sample size of over 1,000 patients. Moreover, it will address the possible impact on neuropsychological function and quality of life, which have never been adequately assessed in this patient population.