Genome‐wide and panel‐based cell‐free DNA characterization of patients with resectable esophageal adenocarcinoma

Circulating tumor DNA (ctDNA) holds promise in resectable esophageal adenocarcinoma (EAC) to predict patient outcome but is not yet sensitive enough to be clinically applicable. Our aim was to combine ctDNA mutation data with shallow whole‐genome sequencing (sWGS)‐derived copy number tumor fraction estimates (ichorCNA) to improve pathological response and survival prediction in EAC. In total, 111 stage II/III EAC patients with baseline ( n = 111), post‐neoadjuvant chemoradiotherapy (nCRT) ( n = 68), and pre‐surgery ( n = 92) plasma samples were used for ctDNA characterization. sWGS ( 1% or ichorCNA > 3%) were associated with a high risk of disease progression [HR = 2.23 (95% CI 1.22–4.07), p = 0.007]. The non‐clearance of a baseline variant or ichorCNA > 3% in pre‐surgery samples was related to early progression [HR = 4.58 (95% CI 2.22–9.46), p