Radiation to the gut boosts cancer-killing power of immunotherapy in esophageal cancer trial

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Patients voluntarily enroll in this study, sign an informed consent form, and demonstrate good compliance. 2. Age ≥18 years and ≤75 years; both sexes are eligible. 3. ECOG performance status score of 0-1. 4. Pathologically confirmed esophageal squamous cell carcinoma (ESCC) prior to surgery. 5. Thoracic esophageal cancer. 6. 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. 7. No prior history of anti-tumor treatment, including chemotherapy, hormonal therapy, radiotherapy, or immunotherapy. 8. Baseline laboratory requirements (within 7 days prior to enrollment): Hematology: 1. Hb≥90 g/L (no transfusion within 14 days) 2. NEUT ≥1.5×10⁹/L 3. PLT ≥100×10⁹/L 4. WBC≥3×10⁹/L Biochemistry: 1. ALT and AST≤2.5×ULN 2. TBIL≤1.5×ULN 3. 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% 9. 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. 10. No psychological, familial, social, or geographical factors that may impair protocol adherence. 11. Other parameters meet general clinical trial enrollment criteria. 12. The subject or authorized representative has read, fully understands the patient information sheet, and signed the informed consent form. Exclusion Criteria: 1. Patients with distant metastases other than supraclavicular lymph node metastases. 2. Presence or high risk of esophageal perforation. 3. Patients with contraindications to radiotherapy or immune checkpoint inhibitor (ICI) therapy. 4. Patients who previously experienced unacceptable toxicity after receiving ICI therapy. 5. Patients with a history of thoracoabdominal/pelvic radiotherapy within 6 months prior to enrollment. 6. 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). 7. Subjects with active, uncontrolled systemic bacterial, viral, or fungal infections despite optimal treatment. 8. Respiratory depression, airway obstruction, or tissue hypoxia. 9. Severe cardiac disease (i.e., NYHA functional class II or higher). 10. Markedly abnormal liver or kidney function (i.e., indicators \>3 times the upper limit of normal). 11. Active hepatitis B, hepatitis C, HIV, or syphilis. 12. Active brain disease or central nervous system/meningeal metastases with significant symptoms, or impaired decision-making capacity. 13. Hypersensitivity to drugs included in the trial. 14. Drug and/or alcohol abuse. 15. Pregnant or lactating women. 16. Concurrent participation in another therapeutic clinical trial. 17. Major surgical procedure within 30 days prior to enrollment. 18. Use of antibiotics, antifungals, antivirals, or antiparasitics within 4 weeks prior to registration.