Neoadjuvant SBRT then sintilimab with chemotherapy for N3-positive locally advanced NSCLC

Inclusion Criteria:

1. Voluntary Participation: The patient volunteers to participate and signs a written informed consent form.
2. Pathology and Staging: Cytologically or histologically confirmed, previously untreated non-small cell lung cancer (NSCLC) with contralateral mediastinal lymph node involvement (N3), classified as stage IIIB or IIIC according to the 9th edition of the International Association for the Study of Lung Cancer (IASLC) staging manual. Baseline staging must be performed with either PET/CT or a combination of contrast-enhanced CT of chest/abdomen + bone scan + brain MRI.
3. Surgical Feasibility: The lung lesion is considered \*\*potentially resectable as evaluated by a multidisciplinary team that includes a thoracic surgeon.
4. Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
5. Adequate Organ Function:

(1) Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (2) Platelet count ≥ 100 x 10\^9/L (3) Hemoglobin \> 9.0 g/dL (4) Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) ≥ 40 mL/min (5) Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤ 3 x ULN (6) Total bilirubin ≤ 1.5 x ULN (7) Forced expiratory volume in 1 second (FEV1) ≥ 1.2 L or \> 40% of predicted value (8) International normalized ratio (INR) and activated partial thromboplastin time (aPTT) within normal limits.

6\. Age: Between 18 and 75 years old.

Exclusion Criteria

1. Autoimmune Disease: Active or suspected autoimmune disease. Exception: Patients with vitiligo, type I diabetes mellitus, or hypothyroidism requiring only hormone replacement therapy (e.g., Hashimoto's thyroiditis) with no signs of active disease may be enrolled.
2. Immunosuppressive Therapy: Requires systemic corticosteroid therapy (\>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to enrollment.
3. Prior Chest Radiotherapy: History of prior radiotherapy to the chest.
4. Active Bleeding: Presence of clinically significant active bleeding prior to treatment.
5. Severe Organ Dysfunction: Severe cardiac, pulmonary, hepatic, or renal dysfunction, hematopoietic system disease, or cachexia, as judged by the investigator to be intolerable to chemo-radiotherapy.
6. Poorly Controlled Diabetes: History of diabetes mellitus for \>10 years with unsatisfactory glycemic control.
7. Interstitial Lung Disease: History of interstitial lung disease or non-infectious pneumonitis.
8. Driver Gene Mutations: NSCLC with known activating EGFR mutations or ALK fusion gene positivity.
9. Other Malignancies:

   Excluded: History of other active malignancies within the past 2 years, except for adequately treated non-melanoma skin cancer or carcinoma in situ (e.g., bladder, gastric, colorectal, endometrial, cervical, melanoma, or breast).

   Exception: Patients with other malignancies who have achieved complete remission for ≥2 years and do not require additional anti-tumor therapy during this study may be enrolled.
10. Compliance/Understanding: Medical, psychological, or physiological conditions that, in the investigator's judgment, prevent the patient from completing the study or understanding the study information.
11. Prior Immune Therapy: Previous treatment with any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other drug targeting T-cell co-stimulation or checkpoint pathways.
12. Active Viral Infection:

(1) Active Hepatitis B (HBsAg positive AND HBV DNA ≥ 2000 IU/mL or 10\^4 copies/mL).

(2) Active Hepatitis C (HCV antibody positive AND HCV RNA above the lower limit of detection).

13\. HIV/AIDS: Known positive test for human immunodeficiency virus (HIV) or diagnosed acquired immunodeficiency syndrome (AIDS).

14\. Allergy: Known history of hypersensitivity to sintilimab, any of the chemotherapy agents used, or any of their excipients.

15\. Pregnancy/Lactation: Pregnant or breastfeeding women. 16. Metastatic Disease: Presence of supraclavicular lymph node metastasis or distant metastasis.