Cranial Irradiation Reduces Long-term Risk for Brain Metastasis in NSCLC

Long-term results from a clinical trial of patients with locally advanced non–small-cell lung cancer (NSCLC) yielded important findings regarding prophylactic cranial irradiation (PCI), which will benefit future studies (JAMA Oncol. 2019 Mar 14. Epub ahead of print).

“[Rates of brain metastasis are high in patients with locally advanced NSCLC], approaching rates seen in small cell lung cancer, where…PCI…is standard of care,” explained lead investigator Alexander Sun, MD, Department of Radiation Oncology, Princess Margaret Cancer Centre–University Health Network, University of Toronto, Ontario, Canada, and colleagues.

PCI decreases brain metastases in this patient population, but a survival advantage has yet to be demonstrated.

Thus, to determine whether PCI improves survival in patients with locally advanced NSCLC, Dr Sun and colleagues conducted the phase 3 Radiation Therapy Oncology Group (RTOG) 0214 clinical trial.

RTOG 0214 included a total of 340 patients (mean age, 61 years), 213 of whom were men and 127 of whom were women, with stage III NSCLC from 291 institutions in the United States, Canada, and abroad. Patients were stratified by stage (IIIA vs IIIB), histologic characteristics (nonsquamous vs squamous), and therapy (no surgery vs surgery) before being randomized to undergo PCI or observation.

The primary end point of the study was overall survival (OS), and secondary end points included disease-free survival (DFS) and brain metastasis.

All patients in the study were followed-up with for a median of 2.1 years; this time was increased to 9.2 years for living patients.

Ultimately, OS was not found to be significantly better with PCI versus observation (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.63-1.06; P = .12; 5- and 10-year rates, 24.7% and 17.6% vs 26.0% and 13.3%, respectively). However, the rates of DFS (HR, 0.76; 95% CI, 0.59-0.97; P = .03; 5- and 10-year rates, 19.0% and 12.6% vs 16.1% and 7.5% for PCI vs observation) and brain metastasis (HR, 0.43; 95% CI, 0.24-0.77; P = .003; 5- and 10-year rates, 16.7% vs 28.3% for PCI vs observation) were significantly different.

Patients who received PCI were 57% less likely to have brain metastasis than those who underwent observation. In addition, rates of brain metastasis were higher among patients aged <60 years and with nonsquamous disease than among those aged ≥60 years and with squamous disease.

According to a multivariable analysis, PCI was associated with reduced rates of brain metastasis and improved DFS, but not with improved OS. In the nonsurgical arm, however, PCI effectively prolonged OS, DFS, and brain metastasis.

“In patients with stage III LA [locally advanced]-NSCLC without progression of disease after therapy, PCI decreased the 5- and 10-year rate of BM [brain metastasis] and improved 5- and 10-year DFS, but did not improve OS,” Dr Sun and colleagues concluded.

“Although this study did not meet its primary end point, the long-term results reveal many important findings that will benefit future trials. Identifying the appropriate patient population and a safe intervention is critical,” they added.—Hina Khaliq