Low-Dose Radiotherapy in Patients With Advanced Esophageal Squamous Cell Carcinoma Resistant to First-Line Chemotherapy Combined With Immunotherapy

Inclusion Criteria:

* Age≥18 years old;
* ECOG score 0-1;
* Histologically or cytologically confirmed esophageal squamous cell carcinoma that is locally advanced (unresectable) or metastatic (AJCC/TNM 8th edition).
* Progression during or after one prior systemic first-line regimen that contained both a platinum-based chemotherapy and a PD-1/PD-L1 inhibitor (progression must be documented radiologically or clinically). Patients who received neoadjuvant/adjuvant therapy containing a PD-1/PD-L1 inhibitor are considered first-line failures if progression/recurrence occurs during or within 6 months after completion of that therapy.
* At least one measurable lesion per RECIST 1.1 within 4 weeks before enrollment. NOTE: a previously irradiated lesion cannot serve as a target lesion unless clear progression after radiotherapy is documented.
* Life expectancy ≥ 3 months.
* Adequate organ function within 1 week before enrollment:

  * Hematologic: Hb ≥ 80 g/L; WBC ≥ 3.0 × 10⁹/L or ANC ≥ 1.5 × 10⁹/L; platelets ≥ 100 × 10⁹/L.
  * Hepatic: total bilirubin ≤ 1.5 × ULN (direct bilirubin ≤ ULN if total \> 1.5 × ULN); ALT/AST ≤ 2.5 × ULN.
  * Renal: serum creatinine \< 1.5 × ULN or creatinine clearance ≥ 50 mL/min; BUN ≤ 200 mg/L; albumin ≥ 30 g/L.
* Ability to understand and provide written informed consent.

Exclusion Criteria:

* Active autoimmune disease (e.g., inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, vasculitis).
* Symptomatic interstitial lung disease or active infectious/non-infectious pneumonitis.
* Tumor invasion into adjacent organs (aorta or trachea) with high risk of bleeding or fistula; prior esophageal stent placement.
* Other malignancies within the past 2 years (except adequately treated basal-cell carcinoma, cervical carcinoma in situ, etc.).
* Active infection, heart failure, myocardial infarction within 6 months, unstable angina, or uncontrolled arrhythmia.
* Any condition that, in the investigator's opinion, could interfere with study results or increase patient risk.
* Mixed small-cell histology.
* Pregnant or breastfeeding women.
* Congenital or acquired immunodeficiency, HIV infection, prior organ or allogeneic stem-cell transplantation.
* Active HBV, HCV, or tuberculosis infection.
* Prior tumor vaccine or any live vaccine within 4 weeks (inactivated influenza vaccine is allowed).
* Concurrent use of other immunosuppressive agents, chemotherapy, investigational drugs, or chronic corticosteroids.
* Psychiatric illness, substance abuse, or social issues that could compromise compliance.
* Prior intolerance, hypersensitivity, or contraindication to PD-1/PD-L1 inhibitors or chemotherapy components.