Intestinal Low-Dose Radiotherapy Plus Immunochemotherapy for Conversion of Borderline Resectable/Unresectable Esophageal Squamous Cell Carcinoma

Inclusion criteria

• Patients voluntarily enroll in this study, sign an informed consent form, and demonstrate good compliance.
• Age ≥18 years and ≤75 years; both sexes are eligible.
• ECOG performance status score of 0-1.
• Pathologically confirmed esophageal squamous cell carcinoma (ESCC) prior to surgery.
• Thoracic esophageal cancer.
• Unresectable lesions, defined as: T4 stage; marginally resectable T3 stage (invading other organs, e.g., trachea, bronchus, or aorta not ruled out by imaging); presence or absence of unresectable lymph nodes or metastatic lymph nodes invading adjacent organs; presence or absence of supraclavicular lymph node metastasis; or clinically confirmed unresectable disease by the surgeon.
• No prior history of anti-tumor treatment, including chemotherapy, hormonal therapy, radiotherapy, or immunotherapy.
• Baseline laboratory requirements (within 7 days prior to enrollment):

Hematology:

• Hb≥90 g/L (no transfusion within 14 days)
• NEUT ≥1.5×10⁹/L
• PLT ≥100×10⁹/L
• WBC≥3×10⁹/L

Biochemistry:

• ALT and AST≤2.5×ULN
• TBIL≤1.5×ULN
• SCr≤1.5×ULN; or CrCl≥60 mL/min Coagulation: APTT, INR, and PT≤1.5×ULN Thyroid function: TSH≤ULN (if abnormal, FT3/FT4 levels should also be considered; eligible if FT3/FT4 are normal) Echocardiography: LVEF≥50%
• Female subjects need to agree to use contraception during the study and for 6 months post-study; serum pregnancy test negative within 7 days prior to enrollment; non-lactating. Male subjects must agree to use contraception during the study and for 6 months post-study.
• No psychological, familial, social, or geographical factors that may impair protocol adherence.
• Other parameters meet general clinical trial enrollment criteria.
• The subject or authorized representative has read, fully understands the patient information sheet, and signed the informed consent form.

Exclusion criteria

• Patients with distant metastases other than supraclavicular lymph node metastases.
• Presence or high risk of esophageal perforation.
• Patients with contraindications to radiotherapy or immune checkpoint inhibitor (ICI) therapy.
• Patients who previously experienced unacceptable toxicity after receiving ICI therapy.
• Patients with a history of thoracoabdominal/pelvic radiotherapy within 6 months prior to enrollment.
• Adverse reactions from prior anti-tumor treatment have not recovered to CTCAE v5.0 grade≤1 (excluding toxicities deemed by the investigator to pose no safety risk, such as fatigue or alopecia).
• Subjects with active, uncontrolled systemic bacterial, viral, or fungal infections despite optimal treatment.
• Respiratory depression, airway obstruction, or tissue hypoxia.
• Severe cardiac disease (i.e., NYHA functional class II or higher).
• Markedly abnormal liver or kidney function (i.e., indicators >3 times the upper limit of normal).
• Active hepatitis B, hepatitis C, HIV, or syphilis.
• Active brain disease or central nervous system/meningeal metastases with significant symptoms, or impaired decision-making capacity.
• Hypersensitivity to drugs included in the trial.
• Drug and/or alcohol abuse.
• Pregnant or lactating women.
• Concurrent participation in another therapeutic clinical trial.
• Major surgical procedure within 30 days prior to enrollment.
• Use of antibiotics, antifungals, antivirals, or antiparasitics within 4 weeks prior to registration.