Incidence and predictors of severe acute esophagitis and subsequent esophageal stricture in patients treated with accelerated hyperfractionated chemoradiation for limited-stage small cell lung cancer

Purpose: Clinical and dosimetric predictors of severe (grade 3 or greater) acute esophageal toxicity and subsequent esophageal dilation were explored in patients with limited-stage small cell lung cancer treated with accelerated hyperfractionated chemoradiation. Methods and materials: A total of 130 patients were identified who were treated to 45 Gy in 1.5-Gy twice-daily fractions with concurrent platinum-based chemotherapy between 2000 and 2009. Data on clinical, disease-related, and treatment-related variables were collected. Patients with percutaneous endoscopic gastrostomy tube insertion or intravenous hydration because of poor oral intake were designated as having acute grade 3 esophagitis. Univariate and multivariate analyses that associated treatment characteristics with esophagitis were assessed via logistic regression, and optimal cut points were identified with recursive partitioning analysis. Results: Twenty-five patients developed severe acute esophagitis, at a rate of 26% (18/69) in patients treated with earlier 3-dimensional conformal radiation therapy techniques and 11.5% (7/61) in patients treated with intensity modulated radiation therapy techniques and omission of elective nodal irradiation. The incidence of esophageal stricture was 6% overall (8 of 128 eligible) but 26% (6/23) among those who experienced prior grade 3 acute esophagitis and 2% (2/105) among those with acute esophagitis less than or equal to grade 2. Significant multivariate predictors of acute esophagitis were mean dose and volume of esophagus receiving at least 5% to 35% of the prescribed dose (V₅ to V₄₀). Patients with V₅ ≥ 74% had a 44.4% risk of severe acute esophagitis (12/27) versus 12.6% (13/103) among those with V₅ < 74%. V₄₅ was the only dosimetric predictor for esophageal stricture, with 13.7% of patients in whom V₄₅ was ≥37.5% requiring subsequent dilation. Conclusions: Modern radiation techniques are associated with a lower frequency of severe acute esophagitis than previous paradigms. The proportion of esophagus receiving low- to moderate-range doses (mean, V₅ through V₄₀) predicts acute esophagitis, whereas the proportion of esophagus that receives high doses (V₄₅) predicts the development of esophageal stricture that requires dilation. Patients who develop grade 3 acute esophagitis are at significant risk for subsequent esophageal stricture, whereas those with acute esophagitis of grade 2 or less display minimal risk.