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Brief Report
April 8, 2021

Assessment of a Contralateral Esophagus–Sparing Technique in Locally Advanced Lung Cancer Treated With High-Dose Chemoradiation: A Phase 1 Nonrandomized Clinical Trial

Author Affiliations
  • 1Department of Radiation Oncology, Massachusetts General Hospital, Boston
  • 2Department of Medicine, Massachusetts General Hospital, Boston
  • 3Department of Radiation Oncology, Newton-Wellesley Hospital, Newton, Massachusetts
JAMA Oncol. 2021;7(6):910-914. doi:10.1001/jamaoncol.2021.0281
Key Points

Question  How can modern radiation techniques reduce the risk of severe esophagitis (Common Terminology Criteria for Adverse Events grade 3 or higher) in the treatment of locally advanced lung cancers?

Findings  In this phase 1 nonrandomized clinical trial, esophagitis rates were examined among 25 participants with locally advanced non–small cell or small cell lung carcinoma treated with intensity-modulated radiation therapy and concurrent chemotherapy using a novel contralateral esophagus–sparing technique. Despite the delivery of high-dose radiation to 70 Gy and the requirement for gross tumor within 1 cm of the esophagus, no participant developed grade 3 or higher esophagitis.

Meaning  The use of this contralateral esophagus–sparing technique was associated with a reduced risk of severe esophagitis among patients with locally advanced lung cancer receiving high-dose intensity-modulated radiation therapy and may be translated into clinical practice.


Importance  Severe acute esophagitis occurs in up to 20% of patients with locally advanced lung cancer treated with chemoradiation therapy to at least 60 Gy once daily and represents a dose-limiting toxic event associated with poor outcomes.

Objective  To assess whether formalized sparing of the contralateral esophagus (CE) is associated with reduced risk of severe acute esophagitis.

Design, Setting, and Participants  This single-center phase 1 nonrandomized clinical trial assessing an empirical CE-sparing technique enrolled patients from July 2015 to January 2019. In total, 27 patients with locally advanced non–small cell lung carcinoma (with or without solitary brain metastasis) or limited-stage small cell lung carcinoma with gross tumor within 1 cm of the esophagus were eligible.

Interventions  Intensity-modulated radiation therapy to 70 Gy at 2 Gy/fraction concurrent with standard chemotherapy with or without adjuvant durvalumab. The esophageal wall contralateral to gross tumor was contoured as an avoidance structure to guide a steep dose falloff gradient. Target coverage was prioritized over CE sparing, and 99% of internal and planning target volumes had to be covered by 70 Gy and at least 63 Gy, respectively.

Main Outcomes and Measures  The primary end point was the rate of at least grade 3 acute esophagitis as assessed by Common Terminology Criteria for Adverse Events, version 4.

Results  Of 27 patients enrolled, 25 completed chemoradiation therapy. Nineteen patients had non–small cell lung carcinoma, and 6 had small cell lung carcinoma. The median age at diagnosis was 67 years (range, 51-81 years), and 15 patients (60%) were men. Thirteen patients (52%) had stage IIIA cancer, 10 (40%) had stage IIIB cancer, and 2 (8%) had stage IV cancer. The median CE maximum dose was 66 Gy (range, 44-71 Gy); the median volume of CE receiving at least 55 Gy was 1.4 cm3 (range, 0-5.3 cm3), and the median volume of CE receiving at least 45 Gy was 2.7 cm3 (range, 0-9.2 cm3). The median combined percentage of lung receiving at least 20 Gy was 25% (range, 11%-37%). The median follow-up was 33.3 months (range, 11.1-52.2 months). Among the 20 patients who had treatment breaks of 0 to 3 days and were thus evaluable for the primary end point, the rate of at least grade 3 esophagitis was 0%. Other toxic events observed among all 25 patients included 7 (28%) with grade 2 esophagitis, 3 (12%) with at least grade 2 pneumonitis (including 1 with grade 5), and 2 (8%) with at least grade 3 cardiac toxic event (including 1 with grade 5). There was no isolated local tumor failure. The 2-year progression-free survival rate was 57% (95% CI, 33%-75%), and the 2-year overall survival rate was 67% (95% CI, 45%-82%).

Conclusions and Relevance  This phase 1 nonrandomized clinical trial found that the CE-sparing technique was associated with reduced risk of esophagitis among patients treated uniformly with chemoradiation therapy (to 70 Gy), with no grade 3 or higher esophagitis despite tumor within 1 cm of the esophagus. This technique may be translated into clinical practice.

Trial Registration  ClinicalTrials.gov Identifier: NCT02394548

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