In a small, single-institution phase I trial reported in JAMA Oncology, Kamran et al found that the use of a contralateral esophagus-sparing radiotherapy technique in patients receiving high-dose chemoradiation for locally advanced lung cancer was associated with no cases of grade ≥ 3 esophagitis, despite radiation to tumors within 1 cm of the esophagus.
As stated by the investigators, “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.”
The study enrolled 27 patients with locally advanced non–small cell lung cancer (NSCLC; with or without solitary brain metastasis) or limited-stage small cell lung carcinoma (SCLC) with gross tumor within 1 cm of the esophagus at Massachusetts General Hospital between July 2015 and January 2019. Patients received intensity-modulated radiotherapy to 70 Gy at 2 Gy/fraction with concurrent standard chemotherapy with or without adjuvant durvalumab.
The contralateral esophagus was contoured as an avoidance structure to promote a steep dose falloff across the esophagus. Target coverage was prioritized over contralateral esophagus sparing; 99% of internal and planning target volumes had to be covered by 70 Gy and at least 63 Gy, respectively.
The primary endpoint was the rate of grade ≥ 3 acute esophagitis. To be included in analysis of the primary endpoint, patients had to have received concurrently five or more cycles of weekly carboplatin/paclitaxel or two or more cycles of platinum and pemetrexed or etoposide and to have had at most 3 days of unplanned treatment interruption unrelated to esophagitis.
Of 27 patients enrolled, 25 completed chemoradiation therapy, including 19 with NSCLC and 6 with SCLC. The median contralateral esophagus radiotherapy maximum dose was 66 Gy (range = 44–71 Gy), the median volume receiving ≥ 55 Gy was 1.4 cm3 (range = 0–5.3 cm3), and the median volume receiving ≥ 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%).
Among the 20 eligible patients, the rate of grade ≥ 3 esophagitis was 0%. Five patients were ineligible for analysis due to unplanned treatment breaks ≥ 3 days unrelated to esophagitis.
Toxicity observed among the 25 patients included grade 2 esophagitis in 7 (28%), grade ≥ 2 pneumonitis in 3 (12%; including 1 patient with grade 5 pneumonitis), and grade ≥ 3 cardiac toxicity in 2 (8%; including 1 patient with grade 5 toxicity).
Median follow-up was 33.3 months (range = 11.1–52.2 months). No patients had isolated local tumor failure. At 2 years, progression-free survival was 57% (95% confidence interval [CI] = 33%–75%) and overall survival was 67% (95% CI = 45%–82%).
The investigators concluded, “This phase I nonrandomized clinical trial found that the contralateral esophagus-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.”
Henning Willers, MD, of the Department of Radiation Oncology, Massachusetts General Hospital, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the PAN-MASS Challenge and by the Federal Share of program income earned by Massachusetts General Hospital. For full disclosures of the study authors, visit jamanetwork.com.