This is clinical trial evaluating the safety and efficacy of radiotherapy combined with immunotherapy and chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC) and liver metastases.

All eligible patients will receive liver-directed radiotherapy, followed by PD-1/PD-L1 inhibitors plus chemotherapy. The systemic therapy is initiated concurrently with radiotherapy. PD-1/PD-L1 inhibitors and chemotherapeutic agents (such as Etoposide, Nab-paclitaxel, Irinotecan, or Lurbinectedin) are administered intravenously every 3 weeks according to their approved product information. The treatment regimen consists of an initial concurrent phase of radiotherapy, immunotherapy, and chemotherapy, followed by a maintenance phase with PD-1/PD-L1 inhibitors alone until disease progression or for up to 24 months.Main Objective and Endpoint:

The primary objective is to evaluate the objective response rate (ORR) and safety of the combination therapy. The primary endpoint is the ORR, defined as the proportion of subjects achieving a complete response (CR) or partial response (PR) based on RECIST v1.1 criteria, as determined by the investigator.

Inclusion Criteria:

1. Aged 18 to 75 years, with an ECOG Performance Status of 0-2.
2. Histologically confirmed stage IV non-small cell lung cancer (NSCLC) or extensive-stage small cell lung cancer, with radiologically confirmed liver metastases (at least one measurable lesion with the longest diameter ≥ 1 cm).
3. Prior failure (due to progression or intolerance) to platinum-based doublet chemotherapy and PD-1/PD-L1 inhibitor therapy.
4. Adequate liver function reserve (Child-Pugh class A or B, ALT/AST ≤ 5 × ULN, total bilirubin ≤ 1.5 × ULN).
5. Life expectancy of at least 3 months.
6. Normal function of major organs and no severe dysfunction of the hematopoietic, cardiac, pulmonary, hepatic, renal, or bone marrow systems, or immunodeficiency diseases.
7. Within one week prior to enrollment, bone marrow and organ function meet the following criteria:Hemoglobin ≥ 80 g/L, neutrophil count ≥ 1.5 × 10⁹/L, and platelet count ≥ 70 × 10⁹/L. Renal function: Serum creatinine ≤ 1.5 × ULN, and endogenous creatinine clearance rate ≥ 55 ml/min.Liver function: Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN (if liver metastases are present, total bilirubin ≤ 3 × ULN and transaminases ≤ 5 × ULN are acceptable).
8. Voluntarily participates and provides written informed consent.
9. Good compliance and willingness to adhere to the study visit schedule and other protocol requirements.
10. Willingness to provide blood and tissue samples for biomarker testing.
11. Judged by the radiation oncologist to have no contraindications to liver radiotherapy. Patients who agree to receive immunotherapy, chemotherapy, and radiotherapy.
12. For patients of childbearing potential: agreement to use effective contraception during the study period and for at least 6 months after the last study treatment; negative serum or urine pregnancy test within 7 days prior to study entry; and not breastfeeding. Male patients with partners of childbearing potential must agree to use effective contraception during the study and for 6 months after the last dose.

Exclusion Criteria:

1. Presence of any active autoimmune disease or a history of autoimmune diseases (such as interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism [may be included if controlled with hormone replacement therapy]); prior liver radiotherapy or liver transplantation; history of liver cirrhosis (Fibroscan ≥ F3), portal hypertension, or hepatic encephalopathy.
2. Congenital or acquired immunodeficiency, such as Human Immunodeficiency Virus (HIV) infection, active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (positive HCV antibody and HCV RNA above the lower limit of detection of the assay), or co-infection with both hepatitis B and C.
3. Uncontrolled or significant cardiac disease, including: (a) NYHA Class II or higher heart failure; (b) Unstable angina; (c) Myocardial infarction within the past 1 year; (d) Patients with clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention.
4. Severe infection or serious comorbidities within 4 weeks prior to the first dose of study treatment.
5. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
6. History of other primary malignancies within the past 5 years.
7. Known allergy to any of the trial drugs or their excipients.
8. Pregnant or lactating women, or subjects of childbearing potential unwilling to use effective contraception during the study period.
9. Patients with Child-Pugh class B or C liver insufficiency.
10. Any other contraindication as determined by the investigator to preclude participation in the study.