Chapter Closed on Higher-Dose Radiation for Late Lung Cancer

Zosia Chustecka

May 16, 2013

The results that have emerged from a study of advanced (stage  3) lung cancer are the opposite of what was expected. It was hoped that a radiation dose higher than the standard dose would improve outcomes; surprisingly, outcomes were significantly worse.

The final results of the large phase 3 RTOG 0617 trial will be presented at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO), but the top-line findings were reported at a presscast held in advance of the meeting. Previous RTOG 0617 results were presented in 2011.

This is a critical study in the field of radiation oncology. Dr. Sandra Swain

"This is a critical study in the field of radiation oncology," said outgoing ASCO president Sandra Swain MD, FACP, from the Washington Cancer Institute, Washington, DC.

"After a decade of research, we can finally close the chapter on the high-dose vs standard-dose debate in lung cancer," she said.

Results Were Surprising

The RTOG 0617 trial involved 464 patients with stage III nonsmall-cell lung cancer (NSCLC), and compared high-dose (74 Gy) with standard-dose (60 Gy) radiation. All patients also received chemotherapy with paclitaxel and carboplatin.

This same trial also randomized patients to receive the targeted agent cetuximab (Erbitux), but those results are not yet available.

After an interim analysis showed that high-dose radiation is not superior to standard-dose radiation, that study group was discontinued.

The results were a surprise. "We had expected at the outset that high-dose radiotherapy would lead to better outcomes," said lead author Jeffrey Bradley, MD, from the Washington School of Medicine in St. Louis, Missouri.

However, all the outcomes were better with the standard dose, and all the differences between the 2 doses were statistically significant.

Table. Outcomes With Standard- and High-Dose Radiation

Outcome Standard Dose (60 Gy) High Dose (74 Gy)
Median survival, months 28.7 19.5
Estimated 18-month overall survival, % 66.9 53.9
Local recurrence rates, % 25.1 34.3
Distant recurrence rates, % 35.3 44.0
Treatment-related deaths, n 2 10


"We were pleased to discover that the less-intense treatment led to better control of cancer progression and spread, and even to improved overall survival," Dr. Bradley noted.

He reported that the survival rates in both groups were higher than had been seen previously, but the difference between the 2 groups was statistically significant. Patients in the high-dose group had a 56% greater risk for death than those in the standard-dose group, and a 37% greater risk for local progression.

The survival advantage with the standard dose is "independent of the cetuximab question," Dr. Bradley noted.

Why the high dose came out worse is not clear, he said during the presscast. "Conventional thinking is that if you can give more radiation, you can kill the tumor better and prolong survival."

It is possible that the high dose increased radiation to the heart, extended therapy, or caused unreported toxicity, or it could be a combination of these factors, he said.

The adverse events reported for the 2 doses were similar. The only significant difference was a slightly higher rate of physician-reported esophagitis in the high-dose group (21% vs 7%).

The main message from this study is that 60 Gy remains the standard dose for radiation administered concurrent with chemotherapy for stage III NSCLC, Dr. Bradley concluded.

The radiation techniques used in this study were designed to deliver the radiation precisely to the lung tumor, so you would expect that the outcome with the higher dose would be better. However, these results now put an end to that idea, Dr. Swain said.

This study was supported by grants from the National Cancer Institute and Eli Lilly.

2013 Annual Meeting of the American Society of Clinical Oncology: Abstract 7501. To be presented June 4, 2013.


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