Apatinib Combined With Radiotherapy in Patient With BM From Drive Gene Negative NSCLC

1. Age 18-75 years old, male or female, signed informed consent;

2. The primary lesion is confirmed by histopathology. The patient with brain metastases confirmed by histopathology or imaging confirmed the brain metastases. All patients with non-small cell lung cancer brain metastases should be recommended for EGFR mutation and ALK gene rearrangement assay，exclusion of patients with NSCLC brain metastases with positive EGFR-sensitive mutations and ALK gene rearrangement detection for TKI treatment; After multidisciplinary consultation and evaluation, patients with single or local multiple metastatic tumors with well-controlled primary lesions, who have the economic ability and are willing to undergo surgery for brain metastatic tumors were excluded.

3. Observable imaging data such as CT, MRI, etc., have measurable lesions as defined by RECIST 1.1 (R09-0262);

4. ECOG PS score: 0-2;

5. Hemogram index: RBC≥3.0×1012/L, WBC≥3.5×109/L, ANC≥1.5×109/L, PLT≥100×109/L, Hb≥90g/L

6. the expected survival time ≥ 3 months

7. Renal function: Cr≤1.2×UNL (upper limit of normal value);

8. Liver function: total bilirubin ≤ 1.5 × UNL; ALT, AST ≤ 1.5 × UNL

1. . Allergies, known to be hypersensitive to any excipients in the study drug. ;

2. . Patients with recurrent brain metastases have previously received brain radiation therapy

3. . Patients with high fever and acute infection;

4. . Patients with active, progressive bleeding or a significant bleeding tendency in the primary lesion;

5. . Participated in any clinical trial of research drugs within 4 weeks prior to enrollment

6. . Diarrhea is the main symptom of the important or newly diagnosed acute gastrointestinal diseases, such as Crohn's disease, malabsorption or any cause of CTC ≥ 2 grade diarrhea.

7. . Current clinically relevant cardiovascular disease or medical history, such as refractory hypertension, NYHA grade 3 congestive heart failure, unstable angina or poorly controlled arrhythmias. Myocardial infarction occurred 6 months before randomization.

8. . Absolute neutrophil count <1000/mm3;

9. . Platelet count <50000/mm3;

10. . According to the investigator's point of view, any other serious disease or organ system dysfunction that may affect patient safety or interfere with the safety assessment of the test drug, such as proteinuria (CTCAE4.0-≥3), severe liver and kidney dysfunction (CTCAE4.0-≥3), hand-foot syndrome (CTCAE4.0-≥3) and so on.

11. . There are ulcers, intestinal perforations, and intestinal obstruction.

12. . Pregnant and lactating women

13. . Suspected or indeed have a history of alcohol and drug abuse