Purpose
The value of integrating clinical variables, radiomics, and tumor-derived cell-free DNA (cfDNA) for the prediction of survival and response to chemoradiation of patients with resectable esophageal adenocarcinoma is not yet known. Our aim was to investigate if radiomics and cfDNA metrics combined with clinical variables can improve personalized predictions.

Methods and Materials
A cohort of 111 patients with resectable esophageal adenocarcinoma from 2 centers treated with neoadjuvant chemoradiation therapy 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 for pathologic complete response.

Results
The best-performing baseline models for OS and TTP were based on the combination of SOURCE-cfDNA that reached a C-index of 0.55 and 0.59 compared with 0.44 to 0.45 with SOURCE alone. The addition of restaging positron emission tomography 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 < .01. The best-performing combination model for the prediction of pathologic complete response reached an area under the curve of 0.61 compared with 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.