Examining the role of circulating tumor DNA in gastroesophageal cancers treated with curative intent.

Abstract

437 Background: Circulating tumor DNA (ctDNA) is an emerging biomarker that, when positive, suggests the presence of viable disease. The clinical significance of detectable ctDNA is not fully elucidated in oncology practice. We performed a retrospective analysis of patients with gastroesophageal (GE) cancers who underwent curative-intent treatment and had clinically ordered tumor-informed ctDNA testing with the Signatera assay. We aim to better understand the role of ctDNA testing in the detection of molecular residual disease (MRD) and recurrence. Methods: Patients with locally advanced/metastatic GE cancers who underwent curative-intent treatment and had ctDNA testing between 2022 and 2025 were retrospectively reviewed in the electronic medical record. Of these 54 patients, 17 were identified as having ctDNA assays performed during at least one the following time periods: up to 60 days after neoadjuvant or definitive chemoradiation, up to 90 days after surgical resection, up to 60 days after adjuvant chemotherapy, and/or during the subsequent 2-year surveillance period after completion of curative-intent treatment. The remaining 37 patients did not have testing during these time periods and were excluded. Clinical variables regarding treatments received and oncologic outcomes were descriptively summarized. Results: All 17 cases were adenocarcinoma; with primary tumors in the esophagus (10), GE junction (1), and stomach (6). Treatment consisted of: 10/17 (59%) perioperative chemotherapy and surgical resection; 4/17 (24%) perioperative chemotherapy, neoadjuvant chemoradiation, and surgical resection; 2/17 (11%) neoadjuvant chemoradiation and surgical resection; 1/17 (6%) chemoradiation only. CtDNA results were extracted at the following timepoints: only during the 90-day postoperative period for 5 patients, only during the 60-day post-adjuvant chemotherapy period for 1 patient, only during the 2-year surveillance period for 5 patients, and across a combination of these time periods for 6 patients. A total of 10 patients had ctDNA testing in the 90-day postoperative period, and 4 were positive. All 4 of these had rapid radiographic progression (range 0-4 months from positive result). The remaining 6 patients had negative ctDNA results in the 90-day postoperative period, and only 1 of these developed recurrence. 1 patient had positive ctDNA testing after adjuvant chemotherapy and had radiographic recurrence within 3 months. The patient who received definitive chemoradiation had 4 negative ctDNA assays in the 2-year surveillance period. Conclusions: Initial ctDNA results in GE cancers suggest that ctDNA may be a useful biomarker for assessing response to definitive therapy. Next steps in this project include assessment of ctDNA in patients with GE cancers prior to treatment, and serial testing thereafter to improve understanding of ctDNA as a biomarker in GE cancers.