Phase III, Multicenter, Randomized Controlled Clinical Study of Three-Dimensional Radiotherapy for Primary Tumors in Non-Oligometastatic Stage IV Non-Small Cell Lung Cancer

Inclusion Criteria:

1. Pathologically or cytologically confirmed stage IV NSCLC \[9th edition, 2024\];
2. Non-oligometastatic disease (number of metastatic lesions \> 5, regardless of the number of organs involved); patients with brain metastases must be conscious; the number of lung metastases must not affect lung function and allow for possible primary tumor radiotherapy;
3. Treatment-naïve (no prior antitumor therapy); or disease control after 1-3 months of monotherapy with TKI, ALK inhibitor/ROS inhibitor; or disease control after 4-6 cycles of chemotherapy combined with immunotherapy;
4. Age 18-80 years, ECOG 0-2 or KPS ≥70; no contraindications to radiotherapy, EGFR-TKI, ALK/ROS1 inhibitors, chemotherapy, or immunotherapy;
5. No major organ dysfunction, or laboratory test results must meet the following criteria: Hematology , cardiac function, liver function , and renal function within normal ranges according to respective laboratory standards. Pulmonary function : FEV1 \>50%, mild to moderate impairment of lung function.
6. Signed informed consent before treatment (for radiotherapy, chemotherapy, immunotherapy, and targeted drug therapy);
7. Good patient compliance with the treatment and follow-up.

Exclusion Criteria:

1. Stage I-III NSCLC, oligometastasis (number of metastatic lesions ≤ 5), Stage IV NSCLC with malignant serous cavity effusion, or KPS ≤ 60;
2. Patients with extensive liver metastases or lung metastases that have severely impaired liver or lung function;
3. Patients with uncontrolled hypertension, diabetes, unstable angina, history of myocardial infarction, symptomatic congestive heart failure within the past 12 months, or uncontrolled arrhythmia; clinically diagnosed valvular heart disease; active bacterial, fungal, or viral infections; mental disorders; severe pulmonary dysfunction;
4. Pregnant or lactating patients;
5. Patients with a history of other active malignant tumors prior to enrollment, except for non-small cell lung cancer; excluding non-melanoma skin basal cell carcinoma, cervical carcinoma in situ, and cured early-stage prostate cancer;
6. Patients with allergic constitution or known/suspected allergy to any investigational drugs without alternative medications;
7. Patients with poor compliance; Patients deemed unsuitable for participation in this trial by the investigator.