Stereotactic Radiosurgery Combination With Anlotinib for Limited Brain Metastases With Perilesional Edema in NSCLC

1. Patients voluntarily participate in this study, signed informed consent.
2. Patients pathologically diagnosed as non-small cell lung cancer, with brain metastases and measurable lesions;
3. Patients aged between 18 -80 years; with expected survival time>3 months.
4. Patients with no more than 5 brain metastases

5. Patients with normal organ function within 7 days prior to treatment, the following criteria are met:

   a) blood routine examination criteria : i) hemoglobin (HB) ≥90g/L; ii) absolute neutrophil count (ANC) ≥1.5×10e9/L; iii) platelet (PLT) ≥80×10e9/L; b) biochemical tests meet the following criteria: i) total bilirubin (TBIL) ≤1.5 times of upper limit of normal (ULN); ii) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 ULN, if liver metastasis occurred, ALT and AST ≤5 ULN; iii) serum creatinine (Cr) ≤1.5 ULN or creatinine clearance (CCr) ≥60mL/min;

6. Female patients should agree to use contraceptives during and within 6 months after the study.

Exclusion Criteria:

1. Patients who had previously used antiangiogenic agents within 1 month;
2. Patients with small cell lung cancer (including small cell carcinoma and non-small cell carcinoma mixed lung cancer);
3. Patient with lung squamous cell carcinoma that involved pulmonary hilar, or non-small cell lung cancer with hemoptysis;
4. Patients with cerebral infarction and cerebral hemorrhage;
5. Patients without perilesional edema；
6. Patients with more than grade 2 (NCI-CTCAE v4.0) acute toxicity reaction due to any previous treatment.
7. Patients with factors that affect oral medication (such as cannot swallow, chronic diarrhea and intestinal obstruction, etc.);
8. Patients with visceral dissemination or severe symptoms, which could cause death in short term;
9. Patients with any other severe and/or uncontrolled disease;
10. Patients who received a surgery, a biopsy or a significant traumatic injury within 1 month;
11. Patients with any signs or medical history of bleeding, unhealed wounds, ulcers or fractures, regardless of the severity;
12. Patients underwent artery or venous thrombotic events within 2 months, such as deep vein thrombosis and pulmonary embolism;
13. Patients with a history of psychotropic medicine abuse and cannot quit or have mental disorders;
14. Patients with disease which will severely endanger their security and could not complete this study, according to the judgement of researchers；
15. Patients who still can't tolerate SRS after anlotinib treatment, even after adding mannitol, and have to receive steroid treatment.