Esophageal squamous cell carcinoma (ESCC) continues to exhibit high incidence and mortality rates in China, with the majority of patients diagnosed at middle to advanced stages. Concurrent chemoradiotherapy (CCRT) is the standard treatment for unresectable locally advanced ESCC. The 5-year survival rate for advanced esophageal cancer remains below 20%. Immunotherapy has demonstrated definitive efficacy and a favorable toxicity profile in advanced ESCC, and preliminary results of its combination with radiotherapy have been reported. Induction immunochemotherapy followed by concurrent chemoradiotherapy represents a feasible combined treatment strategy. However, optimal biomarkers to identify patients who would benefit from this approach are still lacking. Circulating tumor DNA (ctDNA) status can accurately guide treatment implementation and predict tumor progression. Studies have shown that ctDNA changes precede imaging evidence of recurrence or metastasis, and ctDNA detection can sensitively predict tumor progression and prognosis. Therefore, it is necessary to dynamically monitor ctDNA changes throughout the course of induction immunochemotherapy followed by radical concurrent chemoradiotherapy in esophageal cancer and explore its correlation with prognosis.

Inclusion Criteria:

• All subjects must sign an informed consent form before initiating any study-related procedures;
• All patients must be aged ≥18 years and ≤75 years;
• Histologically or cytologically confirmed esophageal cancer (squamous cell carcinoma);
• Clinical stage II-IVa, assessed by a surgeon as inoperable, or patient refusal of surgery;
• No prior radiotherapy, chemotherapy, immunotherapy, or biotherapy for esophageal cancer;
• ECOG performance status of 0-1;
• Laboratory test values within the following limits before the first dose of the investigational drug:
• Hematology: WBC ≥3.0×10⁹/L; ANC ≥1.5×10⁹/L; PLT ≥70×10⁹/L; HGB ≥9.0 g/dL;
• Liver function: AST ≤2.5×ULN; ALT ≤2.5×ULN;
• Renal function: Cr ≤1.5×ULN or CrCl ≥40 mL/min;
• Coagulation: INR ≤1.5, APTT ≤1.5×ULN;
• Other: Lipase ≤1.5×ULN, unless clinically/radiographically insignificant if lipase >1.5×ULN.

Exclusion Criteria:

• Insufficient tissue/blood sample available before treatment as required for the study;
• Patient refusal to undergo dynamic ctDNA testing;
• The primary esophageal lesion is in close proximity to the tracheobronchial tree or major blood vessels, with an investigator-assessed high risk of perforation or major hemorrhage;
• History of malignancies other than esophageal carcinoma within the past 5 years (except for curatively treated localized tumors such as carcinoma in situ of the cervix, basal cell carcinoma, or localized prostate cancer);
• History of gastrointestinal bleeding within the past 6 months, or coagulopathy at enrollment, or current thrombolytic or anticoagulant therapy indicating a high risk of bleeding;
• Severe cardiovascular or cerebrovascular diseases;
• History of interstitial lung disease or active pneumonia/tuberculosis;
• Severe allergic reactions to paclitaxel/cisplatin or any monoclonal antibody;
• Any other condition deemed inappropriate for participation in this study as judged by the investigator.

The results of the study were inconclusive.