Background: Circulating tumor DNA (ctDNA) has clinical utility in monitoring treatment response and in the detection of disease recurrence in breast and colorectal cancer1,2. The aim of this study was to explore the role of ctDNA in the management of patients with esophageal cancer (EC).

Methods:Blood samples and tumor biopsies were collected from 79 patients after diagnosis of EC. In patients planned for surgery, blood samples were taken before and after neoadjuvant treatment, and during the surveillance period. Blood and biopsy tissue samples were analysed for mutations using a custom targeted amplicon-based approach to cover mutational foci across 9 of the most commonly mutated genes in EC.

Results:Somatic mutations in treatment-naïve EC tumor biopsies were detected in 71 out of 79 (90%) patients. Out of these 71 cases, 23 (32%) had detectable tumor-informed ctDNA in their plasma. The majority (90%) of patients who were ctDNA positive had either locally advanced or metastatic disease. For node negative locally advanced patients treated with curative intent, positive ctDNA status at diagnosis is a poor prognostic marker (HR 11.71; 1.16 - 118.80; p=0.037). In blood samples taken before and following neoadjuvant therapy (NAT), reversal of a ctDNA positive status after NAT was associated with an excellent response to treatment. In patients who had serial plasma samples taken during surveillance, detection of ctDNA was associated with inferior disease specific survival (HR 4.36; 1.07 - 17.88; p = 0.04).

Discussion:This study demonstrates that ctDNA may have clinical utility in the management of patients with EC by providing additional prognostic information at pre-treatment staging. In the absence of a widely accepted paradigm for surveillance after curative-intent treatment, assessment of ctDNA in post treatment blood samples may lead to the detection of early recurrent disease.

1. Dawson, S.-J. et al. Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer. New Engl J Medicine 368, 1199-1209 (2013).2. Tie, J. et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med 8, 346ra92 (2016).

Citation Format: Carlos Suhady Cabalag, Michael Yates, Mariana B. Corrales, Paul Yeh, Stephen Q. Wong, Bonnie Zhang, Kenji M. Fujihara, Lynn Chong, Michael Hii, Sarah-Jane Dawson, Wayne A. Phillips, Cuong P. Duong, Nicholas J. Clemons. Utility of circulating tumor DNA in esophageal cancer: A potential prognostic biomarker in tumor staging, monitoring of treatment response and detection of recurrent disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 539.