Zosia Chustecka

October 23, 2015

SAN ANTONIO — New results from one of the largest clinical trials ever carried out in non-small cell lung cancer (NSCLC) could "fundamentally change the way we deliver radiation therapy" for locally advanced disease, says Stephen Chun, MD, from the Department of Radiation Oncology at the University of Texas MD Anderson Cancer Center in Houston.

Dr Chun was speaking here at the American Society for Radiation Oncology (ASTRO) 57th Annual Meeting. The new findings show that intensity-modulated radiotherapy (IMRT) was associated with fewer adverse events, including severe pneumonitis, than was standard three-dimensional (3D) conformal radiotherapy (CRT), he said.

"IMRT should be routinely considered for locally advanced NSCLC patients," Dr Chun concluded.

"We predict that the new findings will change practice practices," he commented at a press briefing, explaining that insurance companies do not yet cover IMRT use in lung cancer, although it is covered for prostate, head and neck, and brain cancer. "Their argument has been lack of data," he said, adding that IMRT is more expensive because it is more complex as a result of configuring. He hopes that insurance companies will now be convinced by the new data.

The data come from the RTOG 0617 trial, a phase 3 study that has already shown that higher-dose radiotherapy was not better than low-dose (results presented in 2013). Now, Dr Chun and colleagues have conducted a secondary analysis of the data, focusing on the two different forms of radiotherapy used, in a total of 482 patients.

In this trial, the choice of radiotherapy was left to the physician's discretion; about 47% of patients received IMRT and the rest had standard CRT, Dr Chun told Medscape Medical News.

Because this aspect of the trial not randomized, the IMRT group had larger and more advanced-stage tumors (stage 3B tumors in 38.6% vs 30.3% of patients in the CRT group). Despite this, the patients in the IMRT group had fewer problems.

Patients in the IMRT group had a significantly lower occurrence of severe pneumonitis (defined as lung inflammation that required oxygen, steroids, or mechanical ventilation and/or led to death). The rate was 3.5% compared with 7.9% in the CRT group (P = .046).

Dr Chun noted that the protective effect of IMRT for pneumonitis persisted in multivariate analysis (hazard ratio [HR], 0.44; P=.0653) and was particularly pronounced in large tumors that were bigger than the median size of 460 mL (HR, 0.22; P = .02).

IMRT also significantly reduced radiation doses delivered to the heart, which was highly associated with patient survival. Larger heart radiation volume (V40) was associated with worse overall survival (HR, 1.013; P < .001), and the heart V40 was significantly lower in patients treated with IMRT, Dr Chun noted.

In addition, patients treated with IMRT were more likely to complete high-dose consolidative chemotherapy than patients treated with CRT (37% vs 29%; P = .05).

"By reducing severe and life-threatening pneumonitis, IMRT can improve patients' quality of life, reduce hospital/intensive care unit admissions, and decrease supplemental oxygen use," Dr Chun said in a statement. "In our study, it seemed that IMRT might also facilitate patients being able to tolerate higher doses of consolidative chemotherapy, which are standard after radiation."

Approached for comment on the study, Henning Willers, MD, PhD, radiation oncologist at the Massachusetts General Hospital Cancer Center in Boston, Massachusetts, welcomed the new data, which support what he has been seeing in clinical practice. The difference with IMRT is clear in patients "so much that in my mind it's a no-brainer that IMRT is better," he told Medscape Medical News. As well as the reduction in severe pneumonitis reported by the trialists, he says that in practice he has seen a dramatic reduction in severe esophagitis: "It is completely eliminated with IMRT," he said, whereas with CRT about 11% to 20% of patients develop grade 3 esophagitis and require feeding tubes.

Insurance companies have opposed covering IMRT for lung cancer, especially Blue Cross and Blue Shield, because of the lack of data to support it, he said. These new data come from a prospective, well-designed clinical trial, he said. Although the choice of radiotherapy was not randomized, and so there may be some institutional bias there, the results clearly show that IMRT is associated with fewer adverse events.

This may be the best data that will be available, he added. Dr Willers said that he cannot see another trial that would randomize between IMRT and CRT being conducted now because clinicians would be unwilling to put their patients in the CRT group, having seen in practice the improved toxicity with IMRT.

The RTOG 0617 study was supported by grants from the National Cancer Institute (NCI) and Bristol-Myers Squibb and Eli Lilly and Company.

American Society for Radiation Oncology (ASTRO) 57th Annual Meeting. Abstract 2 presented October 18, 2015.


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