Hypofractionated Versus Conventional Chemoradiotherapy Followed by Consolidative Immunotherapy in Locally Advanced NSCLC

Inclusion Criteria:

* Signed and Dated Informed Consent: Written informed consent must be provided prior to any study procedures, with the consent form signed and dated by the participant.
* Age Range: Male or female patients aged 18 to 75 years.
* Diagnosis: Patients must have locally advanced, unresectable (stage III) non-small cell lung cancer (NSCLC), with histological or cytological confirmation of the diagnosis.
* Previous Treatment: Treatment-naïve or previously treated with induction chemotherapy ± immunotherapy.
* Tumor Sample Requirement: Tumor tissue samples must be provided, and they should be sufficient for analysis. The samples must be unstained and archived.
* Driver gene testing: EGFR wild-type, ALK rearrangement-negative.
* Life Expectancy: Patients must have an expected survival of at least 12 weeks.
* Performance Status (PS): The patient's WHO Performance Status (PS) must be 0 or 1.
* Pregnancy Testing: Postmenopausal women, or women who have had a negative urine or serum pregnancy test within 14 days before the study medication (HCG sensitivity ≥ 25 IU/L or equivalent).
* Breastfeeding: Women must not be breastfeeding.
* Women of childbearing potential (WOCBP) must agree to use contraception during the study treatment period and for 5 months after the last dose of the investigational drug (i.e., 30 days \[ovulation cycle\] + approximately 5 half-lives of the study drug).
* Men who have sexual relations with WOCBP must agree to use contraception during the study treatment period and for 7 months after the last dose of the investigational drug (i.e., 90 days \[sperm renewal cycle\] + approximately 5 half-lives of the study drug).
* Males with no sperm production are exempt from contraception requirements. WOCBP who are not sexually active are exempt from contraception but must still undergo pregnancy testing as outlined above.
* Organ and Bone Marrow Function: The following laboratory parameters must be met:

Forced expiratory volume in 1 second (FEV1) ≥ 800 mL Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L Platelets ≥ 100 × 10⁹/L Hemoglobin ≥ 9.0 g/dL Calculated creatinine clearance using the Cockcroft-Gault formula ≥ 50 mL/min Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) AST and ALT ≤ 2.5 × ULN

Exclusion Criteria:

* Patients meeting any of the following criteria should not be enrolled in the study:
* Concurrent participation in another clinical trial, except for observational (non-interventional) studies.
* Histological subtype of mixed small-cell and non-small-cell lung cancer. Use of immunosuppressive drugs within 28 days before treatment, except for intranasal or inhaled corticosteroids at physiological doses or systemic corticosteroids ≤10 mg/day of prednisone or equivalent.
* Major surgery within 4 weeks prior to enrollment (excluding procedures for vascular access).
* History or active autoimmune diseases within the past two years.
* Active or a history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
* History of primary immunodeficiency.
* History of organ transplantation requiring immunosuppressive therapy.
* Average corrected QT interval (QTc) ≥470 ms calculated from three ECG cycles using the Bazett formula.
* Uncontrolled comorbidities, including but not limited to: Persistent or active infections. Symptomatic congestive heart failure. Poorly controlled hypertension. Unstable angina. Cardiac arrhythmias. Active peptic ulcer disease or gastritis. Active bleeding disorders. Hepatitis C or HIV infection. HBsAg-positive patients with HBV DNA \>500 IU/mL. Mental or social conditions that may limit adherence to study requirements or compromise the ability to provide informed consent.
* Known history of tuberculosis.
* Receipt of a live attenuated vaccine within 30 days before study initiation or planned during the study period.
* History of another primary malignancy within the past 5 years, except for adequately treated basal or squamous cell carcinoma of the skin or in situ cervical cancer.
* Pregnancy, breastfeeding, or not using effective contraception (for men and women of reproductive potential).

Patients in the experimental group should not proceed to concurrent chemoradiotherapy if any of the following criteria are met:

* Presence of distant metastases.
* Locoregional progression making definitive concurrent chemoradiotherapy unfeasible due to normal tissue dose constraints (assessed by the radiation oncologist).
* WHO performance status score of 2-4.
* Impaired organ or bone marrow function, including:

Forced expiratory volume in 1 second (FEV1) \<800 mL. Absolute neutrophil count (ANC) \<1.5 × 10⁹/L. Platelets \<100 × 10⁹/L. Hemoglobin \<9.0 g/dL. Creatinine clearance (Cockcroft-Gault formula) \<50 mL/min. Serum bilirubin \>1.5 × upper limit of normal (ULN). AST and ALT \>2.5 × ULN.

\- Patient withdrawal from the study.

Patients should not proceed to consolidation immunotherapy if any of the following criteria are met:

* Disease progression during concurrent chemoradiotherapy.
* Use of immunosuppressive drugs within 28 days before the first dose of tislelizumab, except for physiological doses of intranasal or inhaled corticosteroids or systemic corticosteroids ≤10 mg/day of prednisone or equivalent. Use of corticosteroids to manage chemoradiotherapy-related toxicity is permitted.
* Persistent unresolved CTCAE grade \>2 toxicities from prior chemoradiotherapy.
* Grade ≥2 pneumonitis resulting from prior chemoradiotherapy.
* Any prior grade ≥3 immune-related adverse event (irAE) or unresolved irAE \> grade 1.