337 - Independent External Validation of Radiation-Induced Esophagitis Prediction during Chemoradiation Therapy for NSCLC Using RTOG 0617 Trial Data

Purpose/Objective(s):

Radiation-induced esophagitis (RE) is a dose-limiting complication associated with concurrent chemoradiation therapy for Non-Small-Cell Lung Cancer (NSCLC). We hypothesized that dose patterns in the upper-middle (UM) thoracic esophagus are significantly associated with RE of grade = 2 (RE2+) and aimed to externally validate published dosimetric predictors and voxel-based analysis (VBA) findings in a separate NSCLC cohort.

Materials/Methods:

We analyzed RTOG 0617 trial data retrieved from The Cancer Imaging Archive. Patients received concurrent chemotherapy with or without cetuximab and 60- versus 74-Gy radiation doses. The average esophageal dose-volume histograms (DVHs) for patients with and without RE2+ were compared. VBA assessed spatial dose differences between patients with and without RE2+, with dose converted to Biologically Effective Dose (BED) using an alpha-beta ratio of 10 Gy. The generalized linear model (GLM) iwas designed to include BED maps and each non-dosimetric variables selected by a LASSO regularized GLM of RE2+. A non-parametric permutation test of the maximum threshold-free cluster-enhanced statistics accounting for multiple comparisons was performed, the significance p-maps generated and compared to previous VBA results using DICE over volume metrics. External validity of esophageal dosimetric predictors was assessed via discrimination (ROC-AUC) and calibration.

Results:

Among 495 trial patients, 326 met inclusion criteria for analysis. The RE2+ incidence (44%) was consistent with the development cohort. Clinical factors were not significantly associated with RE2+. VBA identified the most significant regions of associations between BED and RE2+ in the UM thoracic esophageal segment, with satisfactory overlap with a prior study (DICE over volume = 0.7). Esophageal and UM thoracic esophageal DVHs showed significant dose separation between patients with and without RE2+ starting at 10 Gy. The relative esophageal volume receiving =55 Gy (V_55Gy) and the UM thoracic esophagus mean dose (D_mean) were both confirmed as good predictors in external validation with comparable discrimination (AUC = 0.67, 95% CI 0.61–0.72). Calibration curves indicated superior risk prediction accuracy for UM thoracic esophagus Dmean (R_adj^2 = 0.8 vs. 0.65).

Conclusion:

This study successfully validated VBA findings on RE in an independent NSCLC cohort, reinforcing the role of the UM thoracic esophagus as a critical region for RE2+ risk. The UM thoracic esophagus Dmean emerged as a robust predictor across diverse treatment techniques and patient characteristics. These findings provide a foundation for clinical implementation of VBA for treatment planning optimization.