A contralateral esophagus–sparing technique (CEST) was associated with a reduced risk of severe acute esophagitis in patients with locally advanced lung cancer who were treated with chemoradiation therapy up to 70 Gy, with no grade 3 or higher esophagitis, according to a study published in JAMA Oncology.

The single-center, phase 1, nonrandomized clinical trial (ClinicalTrials.gov Identifier: NCT02394548) enrolled patients from July 2015 to January 2019. Eligible participants were aged 18 years or older with histologically confirmed locally advanced non–small cell lung cancer (NSCLC), with or without solitary brain metastasis,      or limited-stage small cell lung cancer (LS-SCLC) with a gross primary or nodal tumor within 1 cm of the esophagus.

CEST spares the esophageal wall contralateral to gross disease and involves contouring the contralateral esophagus as an avoidance structure to guide a steep dose falloff gradient across the esophagus.

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Participants received standard-of-care chemoradiation therapy to 70 Gy at 2 Gy/fraction with or without adjuvant durvalumab for NSCLC. The rate of at least grade 3 acute esophagitis according to the Common Terminology Criteria for Adverse Events version 4 was the primary end point.

In the cohort, the median age at diagnosis was 67 years (range: 51-81 years), and 15 of the study patients were men; 19 patients had NSCLC, and 6 had SCLC. A total of 24 of the participants had a dose of 70 Gy, and the median contralateral esophagus (CE) maximum dose was 66 Gy (range, 44-71 Gy). In addition, 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 that received at least 20 Gy was 25% (range: 11%-37%).

Among the 20 patients who were eligible for the primary end point analysis, the rate of grade 3 or higher esophagitis was 0% (95% CI, 0-16). Grade 2 esophagitis was observed in 24% to 28% of patients, based on the scoring criteria and number of participants who were analyzed. Cardiopulmonary events, fatigue, and dermatitis were other common toxic events.

Of      the full cohort, 3 patients (12%) had grade 2 or higher pneumonitis, and 2 (8%) patients had grade 3 or higher cardiac toxic events. In addition, 2 grade 5 events were observed: 1 participant had fatal pneumonitis, and 1 with pre     existing congestive heart failure died shortly after radiation therapy.

Among the surviving patients, the median follow-up was 33.3 months (range: 11.1-52.2 months). 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 ).

Study limitations included the single-institution design and small sample size. Also, the investigators used multicriteria optimization, which is not widely available.

“Our data suggest that near-normal esophageal function may be maintained by preserving the function of approximately half of the esophageal cross section (ie, by converting the esophagus from a serial organ to a parallel organ),” the study authors concluded.

Disclosures: Several study  authors declared affiliations with the pharmaceutical      industry     . Please see the original reference for a full list of authors’ disclosures.


Kamran SC, Yeap BY, Ulysse CA, et al. Assessment of a contralateral esophagus–sparing technique in locally advanced lung cancer treated with high-dose chemoradiation: a phase 1 nonrandomized clinical trial. JAMA Oncol. Published online April 8, 2021. doi: 10.1001/jamaoncol.2021.0281