Cranial Radiotherapy Plus Chemoimmunotherapy in Untreated Driver-mutation Negative NSCLC With Active Brain Metastasis

Inclusion Criteria:

* Age ≥ 18 years;
* KPS score ≥ 70;
* Negative genetic testing for common driver genes including EGFR, ALK, ROS-1;
* Pathologically confirmed non-small cell lung cancer;
* Clinical stage IV (AJCC, 8th edition, 2017);
* Diagnosed with brain metastasis at the time of diagnosis, with at least one lesion in the brain with a diameter greater than 5mm on thin-section brain MRI;
* Active BMs that could not be controlled by symptomatic treatment, such as mannitol and dexamethasone
* Complete baseline assessment of systemic lesions before treatment, including enhanced brain MRI;
* Informed consent from the patient.

Exclusion Criteria:

* Multiple primary or metastatic tumors (except early skin cancer, cervical carcinoma in situ that has been treated radically, with no recurrence or progression for more than 5 years);
* Severe autoimmune diseases: active inflammatory bowel disease (including Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (such as Wegener's granulomatosis), etc.;
* Patients judged by the researcher as unsuitable for brain MRI or stereotactic brain radiotherapy;
* EGFR, ALK, or ROS1 gene mutations;
* Uncontrolled epilepsy, central nervous system disease, or history of mental disorders, judged by the researcher to potentially interfere with the signing of the informed consent form or affect patient compliance;
* Symptomatic interstitial lung disease or active infection/non-infectious pneumonia;
* Patients with risk factors for intestinal perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal cancer, or other known risk factors for intestinal perforation;
* Patients with active infection, heart failure, myocardial infarction within 6 months, unstable angina, or unstable arrhythmia;
* Other uncontrollable diseases or findings from physical examination or clinical experiments judged by the researcher to potentially interfere with the results or increase the risk of treatment complications for the patient;
* Mixed with small cell lung cancer components;
* Pregnant or lactating women;
* Congenital or acquired immunodeficiency diseases including HIV, or history of organ transplantation, allogeneic stem cell transplantation;
* Known HBV, HCV, active pulmonary tuberculosis infection;
* Patients who have received tumor vaccines, or have been vaccinated with other vaccines within 4 weeks before starting treatment (Note: Seasonal influenza vaccines are usually inactivated vaccines and are allowed, while nasal preparations are usually attenuated live vaccines and are not allowed);
* Concurrent use of other immunomodulators, chemotherapy drugs, drugs in other clinical studies, and long-term use of corticosteroid treatment are not eligible for inclusion;
* Patients allergic or contraindicated to PD-1/PD-L1 inhibitors or chemotherapy drugs.