Esophageal-sparing intensity-modulated radiotherapy (ES-IMRT) significantly reduced esophagitis but did not improve esophageal quality of life (QOL) in patients with advanced non-small cell lung cancer (NSCLC), according to research published in JAMA Oncology.

In the phase 3 PROACTIVE study ( Identifier: NCT02752126), researchers sought to determine whether ES-IMRT decreases the risk of radiation-associated esophageal toxic effects compared with standard radiotherapy (RT) in patients with advanced NSCLC.

The study enrolled 90 patients with stage III/IV NSCLC. The median age at randomization was 72 years, and 56% of patients were women. Most patients had stage IV disease (71%), and a majority had an Eastern Cooperative Oncology Group performance status of 0 to 1 (72%).

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Patients were stratified by intended-dose prescription (20 Gy in 5 fractions vs 30 Gy in 10 fractions), with RT dose selection at the discretion of the treating radiation oncologist. In all, 40% of patients received 20 Gy, and 60% received 30 Gy.

After they were stratified by RT dose, patients were randomly assigned 1:1 to receive ES-IMRT or standard palliative thoracic RT. In the standard RT arm, the mean esophagus dose administered was 10.2 Gy, and the maximum esophagus dose was 25.3 Gy. In the ES-IMRT arm, the mean esophagus dose was 9.8 Gy, and the maximum esophagus dose was 23.8 Gy.

The primary outcome was esophageal QOL 2 weeks after receiving RT, as measured by the esophageal cancer subscale (ECS) of the Functional Assessment of Cancer Therapy questionnaire.

There was no significant difference in esophageal QOL between the study arms. The mean 2-week ECS score was 50.5 in the standard RT arm and 54.3 in the ES-IMRT arm (P =.06).

However, the incidence of grade 2 or higher esophagitis was 24% in the standard RT arm and 2% in the ES-IMRT arm (P =.002). In a post hoc subgroup analysis, the researchers noted a significant reduction in esophagitis in patients receiving 30 Gy (30% vs 0%; P =.004) but not 20 Gy (17% vs 6%; P =.60).

The 1-year overall survival (OS) was similar between the arms. The median OS was 8.6 months in the standard RT arm and 8.7 months in the ES-IMRT arm (P =.62).

On multivariate analysis, prior chemotherapy (odds ratio [OR], 9.3; P =.02) and standard RT (OR, 16.8; P =.012) were predictive of symptomatic esophagitis.

“ES-IMRT may be an option for patients in whom reduction of esophageal toxic events is important,” the researchers concluded. “This technique holds merit for translation into clinical practice.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Louie AV, Granton PV, Fairchild A, et al. Palliative radiation for advanced central lung tumors with intentional avoidance of the esophagus (PROACTIVE): A phase 3 randomized clinical trial. JAMA Oncol. Published online February 24, 2022. doi:10.1001/jamaoncol.2021.7664