PURPOSE We sought to characterize the genomic landscape of gastroesophageal adenocarcinoma (GEA) using next-generation sequencing (NGS) of circulating cell-free DNA (cfDNA), compare the genomic profile to tissue NGS, and determine the association of circulating tumor DNA (ctDNA) detection with clinical outcomes. METHODS In this prospective biospecimen-collection study (2017-2022), cfDNA was analyzed using a clinically validated 129-gene tumor-informed NGS assay Memorial Sloan Kettering-Analysis of Circulating cfDNA to Evaluate Somatic Status (MSK-ACCESS); tissue-NGS was performed using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. RESULTS In total, 169 patients with GEA underwent baseline molecular profiling of cfDNA; 93 had localized disease, 55 had untreated metastatic disease, and 21 had progressive metastatic disease. The frequency of the most common alterations was similar between platforms, although copy-number alterations were detected less frequently in plasma than in tissue (10% v 40%; P < .001). Matched-tumor NGS was conducted in 154 patients (91%). Baseline ctDNA detection and on-treatment clearance were associated with improved overall survival and recurrence-free survival in patients with localized disease and progression-free survival in patients with metastatic disease. Baseline ctDNA detection was a stronger predictor of overall survival than American Joint Committee on Cancer (AJCC) clinical stage and positively predicted lymph node metastasis in 87% of cases. Trends in variant allele fractions correlated with pathologic responses to neoadjuvant therapy more closely than fluorodeoxyglucose-positron emission tomography standard uptake values. Persistence or resurgence of ctDNA was associated with worse survival and forecasted recurrent disease a median of 7 months sooner than imaging. CONCLUSION cfDNA analysis using MSK-ACCESS in patients with GEA is a valuable adjunctive clinical tool that enhances molecular profiling, prognostication, treatment response assessment, and detection of recurrent disease in conjunction with tissue NGS, imaging, and AJCC clinical staging criteria.
Cytryn et al. (2026) studied this question.