Cranial Radiotherapy Plus Chemoimmunotherapy in Untreated Driver-mutation Negative NSCLC With Stable 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 lesionin the brain with a diameter greater than 5mm on thin-section brain MRI;

• Complete baseline assessment of systemic lesions before treatment, includingenhanced brain MRI;

• Informed consent from the patient.

Exclusion Criteria:

• Multiple primary or metastatic tumors (except early skin cancer, cervical carcinomain situ that has been treated radically, with no recurrence or progression for morethan 5 years);

• Severe autoimmune diseases: active inflammatory bowel disease (including Crohn'sdisease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupuserythematosus, autoimmune vasculitis (such as Wegener's granulomatosis), etc.;

• Patients judged by the researcher as unsuitable for brain MRI or stereotactic brainradiotherapy;

• EGFR, ALK, or ROS1 gene mutations;

• Active BMs that could not be controlled by symptomatic treatment, such as mannitoland dexamethasone

• Uncontrolled epilepsy, central nervous system disease, or history of mentaldisorders, judged by the researcher to potentially interfere with the signing of theinformed 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, orother known risk factors for intestinal perforation;

• Patients with active infection, heart failure, myocardial infarction within 6months, unstable angina, or unstable arrhythmia;

• Other uncontrollable diseases or findings from physical examination or clinicalexperiments judged by the researcher to potentially interfere with the results orincrease 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 organtransplantation, allogeneic stem cell transplantation;

• Known HBV, HCV, active pulmonary tuberculosis infection;

• Patients who have received tumor vaccines, or have been vaccinated with othervaccines within 4 weeks before starting treatment (Note: Seasonal influenza vaccinesare usually inactivated vaccines and are allowed, while nasal preparations areusually attenuated live vaccines and are not allowed);

• Concurrent use of other immunomodulators, chemotherapy drugs, drugs in otherclinical studies, and long-term use of corticosteroid treatment are not eligible forinclusion;

• Patients allergic or contraindicated to PD-1/PD-L1 inhibitors or chemotherapy drugs.