1. Carlson, Robert H.

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SAN ANTONIO-Intensity-modulated radiation therapy (IMRT) is increasingly being used for locally advanced non-small cell lung cancer (NSCLC) as a way to improve target coverage and reduce toxicity. But outcomes of IMRT versus 3D-conformal radiation therapy (3D-CRT) for NSCLC have not been previously studied in a large prospective cooperative group clinical trial.

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Now, however, data presented here at the American Society for Radiation Oncology Annual Meeting from a secondary analysis of the NRG/RTOG 0617 trial comparing IMRT versus 3-D CRT in patients with stage III NSCLC showed that patients in the IMRT arm had 44 percent fewer cases of severe pneumonitis (Abstract 3767). IMRT also significantly reduced radiation doses delivered to the heart, and patients treated with IMRT were more likely to complete high-dose chemotherapy.


The original NRG/RTOG 0617 study was a large, multi-institutional Phase III, randomized clinical trial of patients with locally advanced NSCLC conducted between 2007 and 2011. It compared a high dose of 74 Gy with a standard dose of 60 Gy. All patients received concurrent chemotherapy consisting of carboplatin/paclitaxel and were randomized to be treated with or without cetuximab. Of the 482 patients treated with radiotherapy, 47 percent were treated with IMRT and 53 percent received 3-D CRT.


'Deck Stacked against IMRT'

The lead author of the new study, Stephen Chun, MD, a fellow in the Department of Radiation Oncology at the University of Texas MD Anderson Cancer Center, said the "deck was stacked against IMRT" in the earlier study: "The original trial design was not randomized for radiation technique, and in fact the IMRT group had larger and more advanced-stage tumors."


In the IMRT group, about 39 percent of patients had stage IIIB tumors, versus 30 percent of the 3-D CRT group.


Protective Effect

"Even though IMRT patients had more advanced tumors, our secondary analysis showed that they had a lower occurrence of severe pneumonitis," Chun said. Severe pneumonitis was defined as lung inflammation requiring oxygen, steroids, or mechanical ventilation, and/or that led to death. IMRT patients had a 3.5 percent rate of grade-3+ pneumonitis compared with 7.9 percent of 3-D CRT patients.


"The protective effect of IMRT for pneumonitis persisted in multivariate analysis, and was particularly pronounced in large tumors that were bigger than the median size of 460 mL."


IMRT also significantly reduced the radiation doses delivered to the heart, which were highly associated with survival. Larger heart radiation volume (V40) was associated with a worse overall survival, and the heart V40 was significantly lower in patients treated with IMRT, Chun noted.


Additionally, patients treated with IMRT were more likely to complete high-dose chemotherapy.


"These findings may fundamentally change the way we deliver radiation therapy for locally advanced lung cancer," Chun said.


Anticipated Change in Practice Patterns

He said he believed that the approximate 50/50 mix in RTOG 0617 between IMRT and 3D-conformal radiotherapy use reflects practice patterns across the country, but that he anticipates that this secondary study would change practice patterns in favor of more use of IMRT for selected patients.


Asked for his perspective, Benjamin Movsas, MD, Chairman of Radiation Oncology at Henry Ford Hospital in Detroit and the co-moderator of the session where the study was presented, agreed: "It has the potential to change practice."


He noted that the study showed a benefit for IMRT in patients who had larger-volume tumors. "That makes a lot of sense to me, because those are the more complex situations for which one would imagine that more sophisticated technology would have a tangible benefit. In those situations it makes sense to consider and evaluate the role of IMRT."


Movsas said that if a patient has a small tumor and the plan for using the 3-D conformal radiation looks just as good as the IMRT plan, that it would make sense to use the more cost-effective 3D-conformal radiation. But in NRG/RTOG 0617, in which the choice of radiotherapy modality was left up to the radiation oncologist, IMRT was chosen for the more complex, larger-volume situations: "I think the same lesson would apply in the community as well," he said.


Movsas cited a study he led that was also based on data from RTOG 0617, showing IMRT to be associated with a relative benefit in quality of life. That study (Movsas et al: Int J Rad Oncol 2013;87:S1-S2), based on patient reports, showed that clinically meaningful declines in quality of life were significantly reduced with the use of IMRT compared with use of 3D-conformal radiation.


"Many studies have shown that quality of life is a much more sensitive indicator of what's really happening than when you simply just look at toxicities," he said.


Movsas said Chun's report on clinical toxicity in RTOG 0617 mirrors the results he found from the patient-reported data: "They actually support each other, which is good."