Ivonescimab Plus Short-Course Hypofractionated Radiotherapy as Second-Line Therapy for Esophageal Squamous Cell Carcinoma

Inclusion criteria

• a. Patients with histologically confirmed esophageal squamous cell carcinoma (ESCC) , aged 18-80 years;
• b. Unresectable locally advanced, postoperative recurrent, or metastatic ESCC that has progressed on or is intolerant to first-line systemic therapy. For patients who received definitive concurrent chemoradiotherapy (CCRT) , disease progression during or within 6 months post-treatment is considered first-line treatment failure;
• c. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) . All positive regional lymph nodes are counted as a single lesion, while non-regional metastatic lymph nodes are counted per station;
• d. Adequate major organ function, defined as:

• Hematology:

• Hemoglobin (Hb) ≥ 90 g/L
• White blood cell (WBC) count ≥ 1.5 × 10⁹/L
• Platelet count ≥ 60 × 10⁹/L
• Serum biochemistry:

• Albumin ≥ 25 g/L
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 × ULN
• Serum creatinine ≤ 1.5 × ULN or creatinine clearance (CrCl) ≥ 60 mL/min
• Echocardiography:

Left ventricular ejection fraction (LVEF) ≥ 50% (lower limit of normal)

• e. Eastern Cooperative Oncology Group (ECOG) performance status: 0-2;
• f. Expected survival ≥ 3 months;
• g. Voluntarily enrolled, with signed informed consent, and willing to comply with study protocols and follow-up.

Exclusion criteria

• a. Patients with severe organ dysfunction, uncontrolled acute infection, or significant comorbidities;
• b. Patients with vertebral metastases accompanied by spinal cord compression symptoms;
• c. Patients with esophagotracheal or esophagomediastinal fistulas;
• d. Patients with uncontrolled pleural, pericardial, or pelvic effusions requiring repeated drainage;
• e. Patients with esophageal primary/metastatic lesions invading the heart or great vessels, as assessed by the responsible physician, with a risk of life-threatening hemorrhage;
• f. Patients with esophageal primary/metastatic lesions invading the trachea or bronchi, as assessed by the responsible physician, with a risk of esophagotracheal fistula;
• g. Patients not suitable for short-course hypofractionated radiotherapy, as evaluated by the responsible physician;
• h. Pregnant or lactating women;
• i. Patients with mental disorders, or those with a history of psychotropic drug abuse and unable to quit;
• j. Patients who have participated in other drug clinical trials within the past 4 weeks;
• k. Patients or their families who refuse to participate in the study.