A multidimensional deep ensemble learning model predicts pathological response and outcomes in esophageal squamous...

Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy remains standard for locally advanced esophageal squamous cell carcinoma (ESCC). However, accurately predicting pathological complete response (pCR) and treatment outcomes remains challenging. This study aimed to develop and validate a multidimensional deep ensemble learning model (DELRN) using pretreatment CT imaging to predict pCR and stratify prognostic risk in ESCC patients undergoing nCRT.

In this multicenter, retrospective cohort study, 485 ESCC patients were enrolled from four hospitals (May 2009-August 2023, December 2017-September 2021, May 2014-September 2019, and March 2013-July 2019). Patients were divided into a discovery cohort (n = 194), an internal cohort (n = 49), and three external validation cohorts (n = 242). A multidimensional deep ensemble learning model (DELRN) integrating radiomics and 3D convolutional neural networks was developed based on pretreatment CT images to predict pCR and clinical outcomes. The model's performance was evaluated by discrimination, calibration, and clinical utility. Kaplan-Meier analysis assessed overall survival (OS) and disease-free survival (DFS) at two follow-up centers.

The DELRN model demonstrated robust predictive performance for pCR across the discovery, internal, and external validation cohorts, with area under the curve (AUC) values of 0.943 (95 % CI: 0.912-0.973), 0.796 (95 % CI: 0.661-0.930), 0.767 (95 % CI: 0.646-0.887), 0.829 (95 % CI: 0.715-0.942), and 0.782 (95 % CI: 0.664-0.900), respectively, surpassing single-domain radiomics or deep learning models. DELRN effectively stratified patients into high-risk and low-risk groups for OS (log-rank P = 0.018 and 0.0053) and DFS (log-rank P = 0.00042 and 0.035). Multivariate analysis confirmed DELRN as an independent prognostic factor for OS and DFS.

The DELRN model demonstrated promising clinical potential as an effective, non-invasive tool for predicting nCRT response and treatment outcome in ESCC patients, enabling personalized treatment strategies and improving clinical decision-making with future prospective multicenter validation.