Integrating Clinical Variables, Radiomics, and Tumor-derived Cell-free DNA for Enhanced Prediction of Resectable Esophageal Adenocarcinoma Outcomes

BACKGROUND: The value of integrating clinical variables, radiomics, and tumor-derived cell-free DNA (cfDNA) for the prediction of survival and response to chemoradiation of resectable esophageal adenocarcinoma (rEAC) patients is not yet known. Our aim was to investigate if radiomics and cfDNA metrics combined with clinical variables can improve personalized predictions. METHODS: A cohort of 111 rEAC patients from two centers treated with neoadjuvant chemoradiotherapy was used for exploratory retrospective analyses. Models combining the clinical variables of the SOURCE survival model with radiomic features and cfDNA, were built using elastic net regression and internally validated using 5-fold cross validation. Model performance for overall survival (OS) and time to progression (TTP) were evaluated with the C-index and the area under the curve (AUC) for pathological complete response (pCR) RESULTS: The best performing baseline models for OS and TTP were based on the combination of SOURCE-cfDNA which reached a C-index of 0.55 and 0.59 compared to 0.44-0.45 with SOURCE alone. The addition of re-staging PET radiomics to SOURCE was the most promising addition for predicting OS (C-index: 0.65) and TTP (C-index: 0.60). Baseline risk-stratification was achieved for OS and TTP by combining SOURCE with radiomics or cfDNA, log-rank p<0.01. The best performing combination model for the prediction of pCR reached an AUC of 0.61 compared to 0.47 with SOURCE variables alone. CONCLUSIONS: The addition of radiomics and cfDNA can improve the performance of an established survival model. External validity needs to be further assessed in future studies together with the optimization of radiomic pipelines.