Using Genomics Feature Selection Method in Radiomics Pipeline Improves Prognostication Performance in Locally Advanced Esophageal Squamous Cell Carcinoma—A Pilot Study

Xie, Chen-Yi; Hu, Yi-Huai; Ho, Joshua Wing-Kei; Han, Lu-Jun; Yang, Hong; Wen, Jing; Lam, Ka-On; Wong, Ian Yu-Hong; Law, Simon Ying-Kit; Chiu, Keith Wan-Hang; Fu, Jian-Hua; Vardhanabhuti, Varut

SIMPLE SUMMARY: Prognosis for patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains poor mainly due to late diagnosis and limited curative treatment options. Neoadjuvant chemoradiotherapy (nCRT) plus surgery is considered the standard of care for patients with locally advanced ESCC. Currently, predicting prognosis remains a challenging task. Quantitative imaging radiomics analysis has shown promising results, but these methods are traditionally data-intensive, requiring a large sample size, and are not necessarily based on the underlying biology. Feature selection based on genomics is proposed in this work, leveraging differentially expressed genes to reduce the number of radiomic features allowing for the creation of a CT-based radiomic model using the genomics-based feature selection method. The established radiomic signature was prognostic for patients’ long-term survival. The radiomic nomogram could provide a valuable prediction for individualized long-term survival. ABSTRACT: Purpose: To evaluate the prognostic value of baseline and restaging CT-based radiomics with features associated with gene expression in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiation (nCRT) plus surgery. Methods: We enrolled 106 ESCC patients receiving nCRT from two institutions. Gene expression profiles of 28 patients in the training set were used to detect differentially expressed (DE) genes between patients with and without relapse. Radiomic features that were correlated to DE genes were selected, followed by additional machine learning selection. A radiomic nomogram for disease-free survival (DFS) prediction incorporating the radiomic signature and prognostic clinical characteristics was established for DFS estimation and validated. Results: The radiomic signature with DE genes feature selection achieved better performance for DFS prediction than without. The nomogram incorporating the radiomic signature and lymph nodal status significantly stratified patients into high and low-risk groups for DFS (p < 0.001). The areas under the curve (AUCs) for predicting 5-year DFS were 0.912 in the training set, 0.852 in the internal test set, 0.769 in the external test set. Conclusions: Genomics association was useful for radiomic feature selection. The established radiomic signature was prognostic for DFS. The radiomic nomogram could provide a valuable prediction for individualized long-term survival.