OA03-RF01.08. Clinical Significance of Circulating Tumor DNA Dynamics in Patients With Esophageal Squamous Cell Carcinoma

Abstract

Abstract Topic Esophageal Cancer: New Diagnostic Modalities (Including PET, PET-CT, New Tracers) Background In the perioperative management of esophageal squamous cell carcinoma (ESCC), the accuracy of conventional modalities such as computed tomography and esophagogastroduodenoscopy remains unsatisfactory for predicting recurrence. While circulating tumor DNA (ctDNA) has recently emerged as a promising biomarker for assessing minimal residual disease (MRD) across various malignancies, clinical reports in resectable advanced ESCC are limited. This study aimed to investigate the clinical significance of longitudinal perioperative ctDNA monitoring. Methods This study included patients with resectable advanced ESCC who underwent neoadjuvant chemotherapy (NAC) followed by subtotal esophagectomy between December 2019 and October 2023. For each case, genomic DNA was extracted from primary tumor specimens obtained endoscopically before the initiation of NAC. Furthermore, serial plasma samples for ctDNA analysis were collected at three longitudinal time points: pre-NAC, post-NAC, and one month postoperatively (1POM). While tissue specimens were analyzed using next-generation sequencing (NGS), plasma samples were profiled using targeted NGS-based panels covering either 77 or 17 cancer-related genes. ctDNA status was determined using a tumor-informed approach. Patients were stratified into five groups based on ctDNA dynamics (pre-NAC/post-NAC/1POM): Persistently negative (---), Sustained clearance (+--), Postoperative clearance (++-), Persistently positive (+++), and Transient clearance (+-+). The association between these dynamics and recurrence-free survival (RFS) was evaluated. Results Among the eligible patients, 27 cases with available ctDNA results at all three longitudinal time points (pre-NAC, post-NAC, and 1POM) were analyzed. The median age was 70 years. NAC regimens consisted of DCF (n=12), CF (n=10), FLOT (n=4), and others (n=1). The distribution of clinical stages I/II/III/IVA/IVB(#104) was 2, 10, 14, 0, and 1, respectively. Regarding histological response, Grades 0/1a/1b/2/3 were observed in 2, 13, 4, 7, and 1 cases, respectively. Analysis of ctDNA dynamics revealed significant prognostic stratification; the 3-year RFS rates were 100% in the Persistently negative group (---) and 90.9% in the Sustained clearance group (+--). In contrast, survival was significantly worse in the remaining groups: 22.2% for Postoperative clearance (++-), 17.1% for Persistently positive (+++), and 0% for Transient clearance (+-+). Maintaining ctDNA negativity through the 1POM time point was associated with a significantly prolonged RFS (p < 0.001). Conclusion ctDNA dynamics may serve as a valuable biomarker in patients with resectable ESCC. Longitudinal monitoring of ctDNA transitions through one month postoperatively could potentially facilitate the implementation of more individualized multidisciplinary treatment approaches.