Integrating Surgery and Radiotherapy Following Tislelizumab-based Conversion Therapy in N3-Stage III NSCLC

Exclusion Criteria

• •1. Diagnosed with Pancoast tumor;
• •2. Pathologically confirmed large cell neuroendocrine carcinoma (LCNEC);
• •3. Primary tumor or metastatic lymph nodes infiltrating major vessels/aorta, trachea, esophagus, heart, etc.;
• •4. Any of the following prior treatments: ① Previous lung surgery; ② Prior systemic chemotherapy, immunotherapy, targeted therapy, or any other anti-tumor treatment for lung cancer; ③ Known presence of epidermal growth factor receptor (EGFR) mutations, ALK rearrangements, ROS1 rearrangements, BRAF V600 mutations, RET rearrangements, MET exon 14 skipping mutations, NTRK1/2/3 rearrangements, or other sensitive mutations; ④ Prior radiotherapy to the lungs; ⑤ Major surgery within 14 days prior to first dose or within 28 days if not fully recovered from toxicity and/or complications; ⑥ Use of traditional Chinese medicine with anti-tumor effects is allowed if discontinued at least 2 weeks before study drug administration and used for no more than 7 days;
• •5. Diagnosis of other malignancies within the last 5 years, except for completely resected basal cell or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or breast carcinoma in situ;
• •6. Active autoimmune disease or history of autoimmune disease that may recur \[excluding patients with well-controlled type 1 diabetes, hypothyroidism (if controlled by hormone replacement therapy alone), celiac disease, non-systemic dermatological conditions (e.g., vitiligo, psoriasis, alopecia), or any other disease not expected to recur without external triggers\];
• •7. Conditions requiring systemic corticosteroid therapy (\> 10 mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days prior to first dose \[patients currently or previously using any of the following steroid regimens are eligible: adrenal replacement steroids (prednisone ≤ 10 mg/day or equivalent), minimal systemic absorption of local, ocular, intra-articular, intranasal, and inhaled corticosteroids, short-term (≤ 7 days) use of corticosteroids for prophylaxis or treatment of non-autoimmune conditions\];
• •8. Uncontrolled diabetes or laboratory abnormalities (\> Grade 1) in potassium, sodium, or corrected calcium despite standard medical management within 14 days prior to first dose;
• •9. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence within 2 weeks after intervention);
• •10. History of interstitial lung disease or active interstitial lung disease, pneumonitis (non-infectious), or uncontrolled pulmonary conditions (e.g., pulmonary fibrosis, acute interstitial lung disease);
• •11. Fever ≥ 38°C within 7 days prior to first dose, significant active infection, active tuberculosis, or active fungal, bacterial, or viral infections requiring systemic treatment \[chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection patients receiving antiviral therapy are allowed\];
• •12. Untreated chronic hepatitis B or chronic HBV carriers with HBV DNA \> 500 IU/mL (or \> 2500 copies/mL) \[inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B patients (HBV DNA \< 500 IU/mL or \< 2500 copies/mL) are eligible. Patients with detectable HBsAg or HBV DNA should be managed according to guidelines\];
• •13. Active HCV infection \[patients with negative HCV antibody tests or positive HCV antibody but negative HCV RNA tests are eligible. Only patients with positive HCV antibody tests will undergo HCV RNA testing\];
• •14. Known history of HIV infection;
• •15. Prior allogeneic stem cell transplantation or organ transplantation;
• •16. Any cardiovascular risk factors: ① Cardiac chest pain within 28 days prior to first dose; ② Pulmonary embolism within 28 days prior to first dose; ③ Acute myocardial infarction within 6 months prior to first dose; ④ NYHA Class III or IV heart failure within 6 months prior to first dose; ⑤ ≥ Grade 2 ventricular arrhythmia within 6 months prior to first dose; ⑥ Cerebrovascular accident within 6 months prior to first dose; ⑦ Uncontrolled hypertension (≥ CTCAE Grade 3) despite medication within 28 days prior to first dose; ⑧ Syncope or seizure within 28 days prior to first dose; ⑨ Left ventricular ejection fraction (LVEF) ≤ 40% \[patients with coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF between 40% and 50% must receive optimized stable treatment as per their physician's advice, consulting a cardiologist if necessary\];
• •17. History of severe hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins;
• •18. Allergy to pemetrexed, its excipients, cisplatin/carboplatin, albumin-bound paclitaxel, or other platinum compounds; contraindications to cisplatin such as hearing impairment;
• •19. Severe or uncontrolled systemic diseases, unstable or uncompensated respiratory, hepatic, or renal diseases;
• •20. Insufficient bone marrow reserve or organ function, meeting any of the following laboratory limits (without corrective treatment within one week prior to blood draw): ① Absolute neutrophil count \< 1.5 × 10\^9/L; ② Platelet count \< 90 × 10\^9/L; ③ Hemoglobin \< 90 g/L (\< 9 g/dL); ④ Alanine aminotransferase \> 2.5 × ULN; ⑤ Aspartate aminotransferase \> 2.5 × ULN; ⑥ Total bilirubin \> 1.5 × ULN (Gilbert syndrome allowed); ⑦ Creatinine \> 1.5 × ULN (confirmation of creatinine clearance required); ⑧ Serum albumin (ALB) \< 25 g/L; ⑨ INR or aPTT \> 1.5 × ULN for patients not on anticoagulant therapy;
• •21. Any immunotherapy (e.g., interleukins, interferons, thymosin, etc.) or experimental treatment within 14 days or 5 half-lives (whichever is longer) prior to first dose;
• •22. Live vaccines or live-attenuated vaccines within 28 days prior to first dose \[seasonal influenza vaccines are generally inactivated and allowed; intranasal vaccines are live and not allowed\];
• •23. Underlying diseases (including laboratory abnormalities), alcohol or drug abuse, or dependence that could interfere with study treatment administration, toxicity assessment, adverse event interpretation, or reduce compliance with the study protocol;
• •24. Concurrent participation in another therapeutic clinical trial \[concurrent participation in observational or non-interventional studies is allowed\];
• •25. Pregnant, lactating, or planning to become pregnant during the study period;
• •26. Participants judged by the investigator to have poor compliance with study procedures and requirements due to a history of neurological or psychiatric disorders (including epilepsy or dementia), current mental health conditions, etc.;
• •27. Participants deemed by the investigator to have any condition that endangers safety or interferes with study assessments.