No Survival Advantage for High-Dose Radiation Versus Standard-Dose Radiation in Stage III NSCLC

Jeffrey D. Bradley, MD

High-dose radiation was no better than standard-dose radiation given concurrently with chemotherapy in extending survival of patients with advanced unresectable non-small cell lung cancer (NSCLC), according to interim results of a phase III trial. The results of the trial (RTOG 0617) were presented at the 2011 annual meeting of the American Society for Radiation Oncology (ASTRO) in Miami Beach, Florida. Overall survival was 74% in the high-dose group and 81% in the standard-dose group; median survival was 20 months versus 21.7 months, respectively.

“This was the first study in 30 years to see if a higher dose of radiation would have a survival benefit, and radiation techniques have improved significantly over that time,” said Jeffrey D. Bradley, MD, Washington University in St. Louis, Missouri. “There was no benefit for 74 Gy over 60 Gy, and the 74-Gy-dose arms were closed in June 2011. The 60-Gy dose should remain the accepted standard,” he stated.

The ongoing phase III trial plans to enroll 500 patients with stage III NSCLC; at the time of the interim analysis, enrollment was up to 423 patients. Patients were randomized to 4 arms: standard-dose radiation (60 Gy) plus chemotherapy (paclitaxel/ carboplatin) and cetuximab; standard-dose radiation with chemotherapy and no cetuximab; high-dose radiation (74 Gy) with chemotherapy plus cetuximab; and high-dose radiation with chemotherapy and no cetuximab. The second question the study is exploring is whether cetuximab provides added benefit over radiation and chemotherapy in this setting. That part of the trial is still open.

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This was the first study in 30 years to see if a higher dose of radiation would have a survival benefit, and radiation techniques have improved significantly over that time. ”

—Jeffrey D. Bradley, MD

Baseline characteristics were similar among groups; more than 50% were men, and median age was 64 years. Median follow-up on the 423 enrolled patients is 9.1 months. After 90 events, the high-dose group crossed the futility boundary. Deaths have been due primarily to disease progression. Ten grade 5 treatment-related adverse events were reported; 8 on the high-dose arm and 5 on the standard-dose arm. Two deaths occurred from radiation pneumonitis in each arm. No significant difference in treatment-related toxicity was reported among the radiotherapy arms.

According to multivariate analysis, factors that contributed to worse survival were radiation dose, nonsquamous histology, and smaller tumor volume.

Speculating on why high-dose radiation did not improve survival, Bradley said that distant metastases pose a significant challenge in patients with lung cancer, and that radiation addresses local control, but not systemic control.