Stage III non-small cell lung cancer (NSCLC) patients treated with surgery and/or radiation therapy have a significantly reduced risk of developing brain metastases if they also receive prophylactic cranial irradiation (PCI); however, this study did not show an improvement in overall survival with PCI, according to research presented at the 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology. This symposium is sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), the International Association for the Study of Lung Cancer (IASLC) and The University of Chicago.
Patients with non-small cell lung cancer that has not spread outside the chest have a high incidence of brain metastases after receiving treatment for their primary cancer. Radiation to the brain has been proven to decrease the chance of cancer spreading to the brain and to improve overall survival in small cell lung cancer, but its benefits to NSCLC patients are unproven.
Researchers in this study examined 340 stage III NSCLC patients who had received surgery and/or radiation therapy with or without chemotherapy. Patients were randomly assigned to receive PCI or to not receive the additional treatment (observational arm). After a median follow-up time of 24.2 months for all patients and 58.6 months for living patients, the rates of overall survival for the PCI arm versus the observational arm were 26.1 percent versus 24.6 percent, respectively. However, the rate of brain metastases for the PCI arm was much lower at 17.3 percent versus 26.8 percent for the observational arm.
“This is important confirmatory information regarding the effectiveness of brain radiation in decreasing the rate of brain failures. Unfortunately this study was very difficult to enroll patients on and ultimately did not accrue enough patients to answer the primary question-Does PCI improve overall survival in patients with locally advanced NSCLC?,” said Elizabeth Gore, MD, lead author of the study and a professor of radiation oncology at the Medical College of Wisconsin in Milwaukee. “I’d like to emphasize the need for participation in clinical trials. This is particularly important in lung cancer, which is understudied despite being the leading cause of cancer death in the United States.”
The abstract, “Phase III Comparison of Prophylactic Cranial Irradiation Versus Observation in Patients with Locally Advanced Non-small-cell Lung Cancer: Updated Analysis of RTOG 0214,” was presented during the Plenary Session at 12:30 p.m., Central time on September 7, 2012.
Phase III Comparison of Prophylactic Cranial Irradiation Versus Observation in Patients with Locally Advanced Non-small-cell Lung Cancer: Updated Analysis of RTOG 0214
E. M. Gore1, R. Paulus2, S. Wong1, A. Sun3, G. Videtic4, S. Dutta5, M. Suntharalingam6, Y. Chen7, L. E. Gaspar8, H. Choy9, 1Medical College of Wisconsin, Milwaukee, 2Radiation Therapy Oncology Group, Philadelphia, 3Princess Margaret Hospital-University Health Network, Toronto, Ontario, Canada, 4Cleveland Clinic Foundation, Cleveland, 5Michigan Cancer Research Consortium, Ann Arbor, Mich., 6University of Maryland, Baltimore, 7University of Rochester, Rochester, N.Y., 8University of Colorado, Aurora, Colo., 9UT Southwestern, Dallas.
Purpose/Objective(s): To determine if prophylactic cranial irradiation (PCI) improves survival in locally advanced non-small-cell lung cancer (LA-NSCLC). This is an updated 5-year analysis.
Materials/Methods: Patients with stage III NSCLC without disease progression after treatment with surgery and/or radiation therapy (RT) with or without chemotherapy were eligible. Participants were stratified by stage (IIIA v IIIB), histology (nonsquamous v squamous), and therapy (surgery v none) and were randomly assigned to PCI or observation. PCI was delivered to 30 Gy in 15 fractions. The primary end point of the study was overall survival (OS). Secondary end points were disease-free survival (DFS), neurocognitive function (NCF), and quality of life. Kaplan-Meier and log-rank analyses were used for OS and DFS. The incidence of brain metastasis (BM) was evaluated with the logistic regression model.
Results: A total 356 patients were enrolled with 340 eligible for analysis. The median follow-up time was 24.2 months for all patients and 58.6 months for living patients. The 5-year OS (P = .57; 26.1% v 24.6% for PCI v observation) and 5-year DFS (P = .13; 18.5% v 14.9% for PCI v observation) were not significantly different. The 5-year rates of BM were significantly different (P = .009; 17.3% v 26.8% for PCI v observation). Of the patients who failed, 10% of patients on the PCI arm and 23% of patients on the observation arm experienced failure in the brain initially. Brain metastases were the only component of first failure in 9.1% and 21.5% of patients with and without PCI.. On multivariate analysis PCI is significantly associated with decreased BM. Non-squamous histology was associated with increased risk of BM. The overall rate of BM in this trial was insufficient for reliable subset analyses by histology.
Conclusions: In patients with stage III disease without progression of disease after therapy, PCI decreased the 5- year rate of BM but did not improve OS or DFS. This study confirms the effectiveness of PCI for prevention of brain failures. Further information is needed to determine which patient subset could derive a survival benefit from PCI.
Author Disclosure Block: E.M. Gore: None. R. Paulus: None. S. Wong: None. A. Sun: None. G. Videtic: None. S. Dutta: None. M. Suntharalingam: None. Y. Chen: None. L.E. Gaspar: None. H. Choy: None.