Predictive role of circulating tumor DNA for locally advanced esophageal squamous cell carcinoma before surgery.

476 Background: A precise preoperative tumor monitoring method that reflects tumor burden during neoadjuvant treatment is required to guide individualized perioperative treatment strategies for esophageal squamous cell carcinoma (ESCC). This study examined the clinical significance of preoperative circulating tumor DNA (ctDNA) in the plasma of patients undergoing neoadjuvant chemotherapy (NAC) followed by esophagectomy. Methods: Plasma samples were collected longitudinally for ctDNA analysis as well as genomic DNA from primary lesions from patients with histologically confirmed ESCC who received neoadjuvant chemotherapy (NAC) followed by subtotal esophagectomy. Next-generation sequencing was used to identify mutations in both the plasma and primary tumors. We evaluated the relation ship between ctDNA alterations and recurrence in patients with locally advanced ESCC. Results: Pretreatment samples from 25 patients (100%) showed the same mutations in both ctDNA and primary tumors; therefore, they were classified as ctDNA-positive before treatment. In the cohort of 25 patients analyzed, those who tested positive for ctDNA after NAC had a significantly higher risk of recurrence; the 36-month recurrence-free survival rates were 92% for ctDNA-negative patients and 8% for ctDNA-positive patients (p < 0.001). Conclusions: Preoperative ctDNA status may be a promising prognostic biomarker that can be assessed before surgery in patients with ESCC who received NAC. Expanded cohort validation will allow for more personalized multidisciplinary treatment approaches for ESCC tailored to ctDNA analysis.