S1124
Clinical – Upper GI
ESTRO 2026
Digital Poster Highlight 4905
Spared Lung Volume as a Novel Predictor of Postoperative Respiratory Failure in Esophageal Cancer Yuting Liu 1 , Gilles Defraene 1 , Pieter Populaire 1,2 , Radhe Mohan 3 , Steven Lin 4 , Karin Haustermans 1,2 1 Department of Oncology, KU Leuven, Leuven, Belgium. 2 Department of Radiation Oncology, UZ Leuven, Leuven, Belgium. 3 Department of Radiation Physics, MD Anderson Cancer Center, Houston, USA. 4 Department of Thoracic Radiation Oncology, MD Anderson Cancer Center, Houston, USA Purpose/Objective: Severe postoperative complications after neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy substantially increase hospital costs1. Identifying esophageal cancer (EC) patients at high radiation-induced risk for severe complications, specifically postoperative respiratory failure, could improve individual treatment outcomes and reduce costs. This study aimed to develop and externally validate a normal tissue complication probability (NTCP) model for postoperative respiratory failure in EC. Material/Methods: Individual patients with locally advanced EC treated with nCRT followed by surgery were extracted from prospectively recorded databases at two centers. The model development cohort included 115 patients treated with IMRT from a European center. The external validation cohort comprised 410 patients from a US center including 134 treated with proton therapy. Respiratory failure was defined as Clavien- Dindo grade ≥ Ⅳ a within 90 days after esophagectomy. Patient- and disease-characteristics and dosimetric variables for heart and lungs were evaluated. In addition to conventional dose-volume histogram metrics, total and spared lung volumes were similarly analyzed per 5 Gy dose levels. A multivariable logistic regression NTCP model was developed using LASSO and repeated cross-validation for feature selection. Features with a selection frequency ≥ 60% were included. Comparative logistic regression models were fitted using mean lung dose (MLD) and lung effective dose (Deff)2. The volume parameter n for Deffwas estimated using maximum likelihood analysis. Model performance was assessed using AUC and calibration plot. Results: The incidence of respiratory failure was 11.30% (n=13) in the development cohort and 2.93% (n=12) in the validation cohort. Absolute lung volume spared from 15 Gy (LungVS15a) was the only feature selected by LASSO for final model inclusion.The resulting LungVS15a-based NTCP model demonstrated good
Conclusion: Patients with severe RIL during neoadjuvant CRT do not seem to benefit from adjuvant nivolumab for esophageal cancer. The DFS and OS benefit of adjuvant nivolumab appears confined to patients without severe RIL. How this relates to PD-L1-status is under investigation. This hypothesis-generating study indicates RIL might serve as predictive biomarker for nivolumab benefit in esophageal cancer. References: 1. Damen PJJ, Peters M, Hobbs B, Chen Y, Titt U, Nout R, Mohan R, Lin SH, van Rossum PSN. Defining the Optimal Radiation-induced Lymphopenia Metric to Discern Its Survival Impact in Esophageal Cancer. Int J Radiat Oncol Biol Phys. 2025 May 1;122(1):31-42. doi: 10.1016/j.ijrobp.2024.12.014. Epub 2025 Jan 2. PMID: 39755214; PMCID: PMC12278156. Keywords: esophageal cancer; lymphopenia; nivolumab
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