Circulating Tumor DNA Dynamic Changes in Esophageal Squamous Cell Carcinoma Receiving Immunochemotherapy

ABSTRACT Background Immune checkpoint inhibitors have revolutionized the treatment strategy of esophageal squamous cell carcinoma (ESCC). The value of ctDNA dynamic changes in ESCC patients treated with immunochemotherapy was not clear. Methods A retrospective analysis was performed to analyze the association of ctDNA dynamic changes with the treatment efficacy of immunochemotherapy in patients with locally advanced, metastatic, or recurrent ESCC and who received immunochemotherapy at the Department of Medical Oncology, National Cancer Center from June 2023 to December 2024. Tumor mutation burden (TMB) and PD‐L1 expression of tumor tissue were also explored. Results 57 patients with paired ctDNA at baseline and during treatment were analyzed. We found that patients with negative ctDNA during treatment demonstrated a higher tumor regression rate (96.8% vs. 73.1%; p = 0.018) and a higher cCR rate (45.2% vs. 15.4%; p = 0.022). Additionally, patients with continuously negative ctDNA ( p = 0.033) or experienced ctDNA clearance during treatment ( p = 0.043) had a higher cCR rate compared to those with persistently positive ctDNA. Moreover, among patients with TP53 mutations at baseline, those with TP53 mutations cleared during treatment showed a higher tumor regression rate (88.9% vs. 54.5%; p = 0.031) and cCR rate (33.3% vs. 0%; p = 0.038) compared to patients with persistent TP53 mutations. No correlation was observed between TMB and treatment efficacy, while a higher cCR rate was observed in patients with PD‐L1 CPS ≥ 15 (63.6% vs. 24.4%; p = 0.027). Conclusions ctDNA dynamic changes demonstrated potential predictive value for the efficacy of immunochemotherapy in patients with ESCC. Further exploration through larger‐scale studies is necessary.