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CHICAGO -- Boosting the dose of radiation therapy in stage III non-small cell lung cancer (NSCLC) actually compromises outcomes and cuts survival, a randomized trial showed.

Overall survival was 56% higher with standard 60 Gy radiation than with a 74 Gy dose (median 28.7 versus 19.5 months, P=0.0007), Jeffrey D. Bradley, MD, of the Washington University School of Medicine in St. Louis, Mo., and colleagues found.

Local control, which usually refers to local recurrence, favored the conventional arm as well, they reported at a telephone press briefing in advance of their presentation here at the American Society of Clinical Oncology meeting, similar to an interim analysis of the trial in 2011.

Action Points Note that this study was published as an abstract to be presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.

Boosting the dose of radiation therapy in stage III non-small cell lung cancer (NSCLC) actually compromises outcomes and reduces survival.

Point out that the trial didn't yield clues regarding why less radiation was more effective in NSCLC since physician-reported side effects recorded in the trial didn't appear to account for the difference, nor did protocol deviations.

After a decade of research, it's time to close the book on high-dose radiation in lung cancer therapy, ASCO President Sandra M. Swain, MD, of Georgetown University in Washington, D.C., commented at the briefing.

While the trial results were surprising, they "really should put an end to higher-dose treatment, given the better outcomes in the standard dose arm," she said, although noting that the findings wouldn't generalize broadly to early stage cancer.

The conventional thinking was that more radiation would more effectively kill the tumor and improve outcomes, as suggested in prior phase II studies, Bradley explained.

"That's why you do a phase III trial," he said.

However, the trial didn't yield clues as to why less was more in NSCLC.

Physician-reported side effects recorded in the trial didn't appear to account for the difference, nor did protocol deviations, Bradley noted.

The only significant difference in adverse events between arms was esophagitis, with rates of 21% versus 7% in the high- and standard-dose groups, respectively. There were numerically more deaths from toxicity in the high-dose group, although the difference didn't rise to statistical significance.

"Possible explanations are increased heart dose, extended therapy duration, unreported toxicities, possible too-tight margins in the high-dose arms, or a combination of these factors," Bradley suggested.

Unmeasured side effects, particularly to the heart, are top candidates, he told reporters, noting that left ventricular ejection fraction as an indicator of cardiac damage wasn't routinely monitored.

The Radiation Therapy Oncology Group (RTOG) 0617 trial included 464 patients with newly-diagnosed unresectable Stage III A or B NSCLC.

They were randomized in a two-by-two factorial design to a 60 or 74 Gy dose of 3-D conformal or intensity-modulated radiation and cetuximab (Erbitux) or none atop the concurrent and consolidation chemotherapy with carboplatin and paclitaxel (Taxol) all patients got.

Patients were stratified by the radiation therapy technique, Zubrod performance status, and histology.

The 18-month rate of survival was 67% with standard radiation versus 54% with the high dose.

Local failure likewise came in at 34% versus 25%, respectively, for a 37% relative difference that was significant at P=0.0319.

The results were independent of cetuximab, although results from the cetuximab versus none comparison in the trial are expected to come out in 2014, Bradley noted.