Consolidation Radiotherapy vs. Observation in Oligoresidual Advanced Non-Small Cell Lung Cancer After Chemo-Immunotherapy

Inclusion Criteria:

1. Voluntary signed written informed consent and compliance with protocol requirements;

2. Age ≥ 18 years;

3. Expected survival time ≥ 3 months;

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;

5. Histologically or cytologically confirmed advanced non-small cell lung cancer;

6. After receiving 4-6 cycles of first-line platinum-based chemotherapy combined withimmunotherapy, PET-CT evaluation shows no disease progression, with no more than 5lesions not meeting criteria for complete metabolic response, involving no more than 3 organs;

7. All residual lesions can safely receive radiation therapy as assessed by radiationoncologists;

8. Patient can tolerate the radiotherapy process, such as maintaining fixed position;

9. At least one measurable lesion among the oligoresidual lesions according to RECISTv1.1;

10. Agreement to provide archived tumor tissue specimens from primary or metastaticsites, or fresh tissue samples; if unable to provide tumor tissue samples, subjectsmay be enrolled after investigator assessment if meeting other inclusion/exclusioncriteria;

11. Toxicities from previous anti-tumor therapies recovered to ≤ grade 1 per NationalCancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0) (excluding alopecia, fatigue, pigmentation, hypothyroidism stable on hormonereplacement therapy, grade 2 peripheral neuropathy after chemotherapy, andexceptions specified in other inclusion criteria);

12. Laboratory values at screening must meet the following criteria: a) Neutrophils ≥ 1.5×10^9/L b) Platelets ≥ 100×10^9/L c) Hemoglobin ≥ 90g/L (no blood transfusionwithin 14 days) d) Serum Cr ≤ 1×ULN, endogenous creatinine clearance > 50ml/min (Cockcroft-Gault formula) e) AST ≤ 2.5×ULN; ALT ≤ 2.5×ULN; if liver metastasespresent, ALT and AST ≤ 5×ULN f) Total bilirubin ≤ 1.5×ULN (except for Gilbert'ssyndrome subjects, where total bilirubin must be < 51.3μmol/L) g) ThyroidStimulating Hormone (TSH), Free Triiodothyronine (FT3), Free Thyroxine (FT4) allwithin ±10% of normal range.

Exclusion Criteria:

1. Archived tumor tissue, pre-treatment tumor biopsy, or histological examinationshowing evidence of previous small cell or mixed small cell/non-small cellhistology;

2. Previous tissue samples or peripheral blood genetic sequencing reports indicatingEGFR sensitizing mutations, ALK fusion, or other gene variations that should receivestandard first-line targeted therapy; squamous cell carcinoma without genetictesting is presumed negative;

3. Symptomatic brain metastases;

4. Leptomeningeal metastases;

5. Active, known, or suspected autoimmune disease (excluding vitiligo, type I diabetes,residual hypothyroidism due to autoimmune thyroiditis requiring only hormonereplacement therapy, or conditions not expected to recur in the absence of externaltriggers);

6. Active tuberculosis (TB) infection as determined by chest X-ray, sputum examination,and clinical examination. Patients with a history of active pulmonary TB infectionwithin the previous year, even if treated, will be excluded. Patients with a historyof active pulmonary TB infection more than 1 year ago will also be excluded unlesseffective previous anti-TB treatment can be documented;

7. Comorbidities requiring immunosuppressive medication, or requiring systemic or localuse of corticosteroids at immunosuppressive doses;

8. Pregnancy or breastfeeding;

9. Interstitial lung disease with symptomatic manifestations, or that may interferewith the detection or management of suspected drug-related pulmonary toxicity;

10. Positive for human immunodeficiency virus antibody (HIVAb), active hepatitis B virusinfection (HBsAg positive and HBV-DNA > 10^3 copies/ml), or hepatitis C virusinfection (HCV antibody positive and HCV-RNA > lower limit of detection at theresearch center);

11. History of severe neurological or psychiatric disorders, including but not limitedto: dementia, depression, seizures, bipolar disorder, etc.;

12. Receipt of other investigational drugs or treatments within 4 weeks prior to studyrandomization;

13. Use of any Chinese herbal medicines with anti-tumor activity within 2 weeks prior tostudy drug administration;

14. History of other malignancies (excluding non-melanoma skin cancer and the followingin situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma,or breast), unless complete remission was achieved at least 2 years prior to studyenrollment and no additional therapy is required or anticipated during the studyperiod;

15. History of severe cardiac or cerebrovascular disease, e.g., New York HeartAssociation (NYHA) ≥ class 2 heart failure, acute coronary syndrome (such asmyocardial infarction, unstable angina, etc.) within 6 months of screening, acutecerebrovascular disease (such as transient ischemic attack, cerebral infarction,cerebral hemorrhage, etc.) within 6 months of screening;

16. Thromboembolic events requiring therapeutic intervention within 6 months prior toscreening, such as unstable deep vein thrombosis, arterial thrombosis, and pulmonaryembolism; excluding infusion-related thrombosis;

17. Planned vaccination or vaccination with live vaccines within 28 days prior to studyrandomization;

18. Other conditions deemed unsuitable for participation in this clinical trial by theinvestigator due to comorbidities or other circumstances.