Long-Term Outcomes for Prophylactic Cranial Irradiation vs Observation in Locally Advanced NSCLC


Key Points

  • Prophylactic cranial irradiation was not associated with significantly improved overall survival.
  • Prophylactic cranial irradiation was associated with improved disease-free survival and reduced incidence of brain metastases.

As reported in JAMA Oncology by Sun et al, a long-term update of the phase III NRG Oncology/RTOG 0214 trial has shown that prophylactic cranial irradiation was associated with a reduced incidence of brain metastases and improved disease-free survival—but not overall survival—compared with observation in patients with locally advanced non–small cell lung cancer (NSCLC).

Study Details

In the international trial, 340 patients with stage III NSCLC and no disease progression after therapy were randomly assigned to prophylactic cranial irradiation (n = 163) or observation (n = 177). Randomization was stratified by disease stage (IIIA vs IIIIB), histology, and surgery vs no surgery.

The primary endpoint was overall survival.

Treatment Outcomes

Median follow-up was 2.1 years for all patients and 9.2 years for surviving patients.

Prophylactic cranial irradiation was not associated with a significant overall survival benefit vs observation (hazard ratio [HR] = 0.82, P = .12). Overall survival was 24.7% vs 26.0% at 5 years, and 17.6% vs 13.3% at 10 years. Prophylactic cranial irradiation was associated with significantly improved disease-free survival (HR = 0.76, P = .03); disease-free survival was 19.0% vs 16.1% at 5 years, and 12.6% vs 7.5% at 10 years. Prophylactic cranial irradiation was also associated with reduced risk for brain metastases (HR = 0.43, P = .003); rates of brain metastases at both 5 and 10 years were 16.7% vs 28.3%. Outcomes were similar on multivariate analysis in the entire population—in multivariate analysis among 225 patients who did not initially undergo surgery, prophylactic cranial irradiation was associated with significantly improvement in overall survival (HR = 0.73, P = .04), disease-free survival (HR = 0.70, P = .01), and development of brain metastases (HR = 0.34, P = .002).

The investigators concluded, “In patients with stage III [locally advanced] NSCLC without progression of disease after therapy, prophylactic cranial irradiation decreased the 5- and 10-year rate of [brain metastases] and improved 5- and 10-year [disease-free survival], but did not improve [overall survival].  Although this study did not meet its primary endpoint, the long-term results reveal many important findings that will benefit future trials. Identifying the appropriate patient population and a safe intervention is critical.”

Alexander Sun, MD, of the Department of Radiation Oncology, Princess Margaret Cancer Centre–University Health Network, University of Toronto, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute. The study authors’ full disclosures can be found at

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