Dosimetric predictors for acute esophagitis during radiation therapy for lung cancer: Results of a large statewide observational study

Abstract

Purpose: The purpose of this study is to identify dosimetric variables that best predict for acute esophagitis in patients treated for locally advanced non-small cell lung cancer in a prospectively accrued statewide consortium.

Methods and materials: Patients receiving definitive radiation therapy for stage II-III non-small cell lung cancer within the Michigan Radiation Oncology Quality Consortium were included in the analysis. Dose-volume histogram data were analyzed to determine absolute volumes (cc) receiving doses from 10 to 60 Gy (V10, V20, V30, V40, V50, and V60), as well as maximum dose to 2 cc (D2cc), mean dose (MD), and generalized equivalent uniform dose (gEUD). Logistic regression models were used to characterize the risk of toxicity as a function of dose and other covariates. The ability of each variable to predict esophagitis, individually or in a multivariate model, was quantified by receiver operating characteristic analysis.

Results: There were 533 patients who met study criteria and were included; 437 (81.9%) developed any grade of esophagitis. Significant variables on univariate analysis for grade ≥2 esophagitis were concurrent chemotherapy, V20, V30, V40, V50, V60, MD, D2cc, and gEUD. For grade ≥3 esophagitis, the predictive variables were: V30, V40, V50, V60, MD, D2cc, and gEUD. In multivariable modeling, gEUD was the most significant predictor of both grade ≥2 and grade ≥3 esophagitis. When gEUD was excluded from the model, D2cc was selected as the most predictive variable for grade ≥3 esophagitis. For an estimated risk of grade ≥3 esophagitis of 5%, the threshold values for gEUD and D2cc were 59.3 Gy and 68 Gy, respectively.

Conclusions: In this study, we report the novel finding that gEUD and D2cc, rather than MD, were the most predictive dose metrics for severe esophagitis. To limit the estimated risk of grade ≥3 esophagitis to <5%, thresholds of 59.3 Gy and 68 Gy were identified for gEUD and D2cc, respectively.

Figure 1

Logistic and nonparametric estimates of risk of grade ≥2 (green) and grade ≥3 (black) esophagitis as a function of generalized equivalent uniform dose (gEUD). A horizontal line is drawn at an estimated risk of 5% and intersects the grade ≥3 curve at gEUD = 59.3 Gy. CL, confidence limit.

Figure 2

Logistic and nonparametric estimates of risk of grade ≥2 (green) and grade ≥3 (black) esophagitis as a function of maximum dose of 2cc (D2cc). A horizontal line is drawn at an estimated risk of 5% and intersects the grade ≥3 curve at D2cc = 68 Gy.