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Intensity-modulated radiotherapy reduces esophagitis in palliative NSCLC



Reducing the dose of radiation to the esophagus during palliative radiotherapy for advanced lung cancer significantly reduced the incidence of esophagitis among a small group of patients, according to a new randomized study.

Even though fewer patients experienced esophagitis, the procedure did little to significantly improve quality of life for these patients.

The study, called Palliative Radiation for Advanced Central Lung Tumors with Intentional Avoidance of the Esophagus (PROACTIVE), explored the use of a technique called intensity-modulated radiotherapy (IMRT) to sculpt the radiation dose around the esophagus, reducing its exposure. IMRT is a standard technique to avoid healthy tissue with higher radiation doses in the curative setting, but it hasn’t been explored much in the palliative setting, said investigators led by Alexander V. Louie, MD, PhD, a radiation oncologist at the University of Toronto’s Odette Cancer Centre.

The study included 90 patients (mean age 70 years, 56% female) with stage 3 and 4 non–small cell lung cancer. They were randomized evenly to standard radiotherapy with the esophagus getting the same dose as the tumor, or to esophagus-sparing IMRT (ES-IMRT) with the esophagus exposed to no more than 80% of the prescribed dose.

The overall survival was similar between both groups: 8.6 months for standard therapy and 8.7 months for IMRT. Forty percent of patients received 20 Gy in 5 fractions and the rest 30 Gy in 10 fractions. The reduction in esophagitis with IMRT was most evident in the 30 Gy group.

Only one patient in the esophagus-sparing group developed grade 2 esophagitis versus 11 patients (24%) in the standard radiotherapy group. There were no grade 3 or higher cases. There was also an almost 4-point improvement (54.3 points with ES-IMRT versus 50.5 points) on an esophagus-related quality of life (QOL) measure, which is a subscale of the Functional Assessment of Cancer Therapy: Esophagus questionnaire, but it wasn’t statistically significant (P = 0.06).

“The ES-IMRT technique we describe herein represents a paradigm shift in palliative radiotherapy planning,” the investigators wrote. “This technique holds merit for translation into clinical practice.”

However, in their editorial, Ashley A. Weiner, MD, PhD, and Joel E. Tepper, MD, of the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill, wrote that it is too preliminary to recommend esophagus-sparing IMRT to patients. “In the absence of meeting the primary quality of life end point and without demonstration of adequate symptom palliation, one cannot recommend ES-IMRT as a standard therapy for palliation of thoracic symptoms due to NSCLC,” they wrote.

They said the study raises an important issue: The balance between tumor coverage and sparing healthy tissue when symptom palliation instead of cure is the goal.

Striking the right balance “is challenging and part of the art of radiotherapy” particularly in the palliative setting, where there are many unanswered questions, they said.

Unlike in curative intent scenarios, “the ideal dose to the tumor to provide a maximal palliative benefit is unknown, and perhaps there is no ideal dose,” Dr. Weiner and Dr. Tepper said.

It’s also unclear whether the entire tumor needs to be irradiated to the full dose when the goal is simply to shrink the tumor and relieve symptoms. “Perhaps a lower dose to a portion of the tumor makes sense,” especially when radiation doses for palliation are “somewhat arbitrary,” they said.

Indeed, the portion of the tumor next to the esophagus in the IMRT subjects was necessarily undercovered to achieve the esophagus-sparing effect. “It seems very likely to us that underdosing a small portion of the tumor will have little adverse effect” on palliation, Dr. Weiner and Dr. Tepper wrote.

Also, “if undercovering” the tumor with lower doses “results in adequate tumor reduction for palliation,” they wondered if IMRT – a more expensive and complex technique than standard radiotherapy – is even needed.

The work was funded by the Canadian Cancer Society. Dr. Louie reported payments from AstraZeneca as an advisor and personal fees from Varian Medical Systems and Reflexion, the makers of IMRT technology. The authors of the editorial reported no conflicts of interest.

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