SRT Combined With Anlotinib for the Treatment of Brain Metastases From Non-small Cell Lung Cancer

Inclusion Criteria:

1. Patients voluntarily participate in this study, sign informed consent, anddemonstrate good compliance.

2. Patients with histologically or pathologically confirmed EGFR wild-type and EGFRmutant non-small cell lung cancer resistant to treatment.

3. The number of brain metastases is ≤ 5, and the patient has at least one assessablebrain metastasis on imaging (RECIST 1.1). Additionally, the patient's physicalcondition allows for the completion of stereotactic radiosurgery.

4. Age between 18-80 years, gender unspecified.

5. ECOG performance status of 0 or 1; expected survival of no less than 3 months.

6. Regardless of prior treatment, it is only required that concurrent oraladministration of anlotinib during radiotherapy without intervention regardingsubsequent treatment regimens.

7. Oral administration of anlotinib including, but not limited to, third-line therapy.

8. Good function of major organs, with laboratory test indicators meeting the followingcriteria:

9. Hematological examination:

10. Hemoglobin (Hb) ≥ 90g/L (no blood transfusion within 14 days);

11. Absolute neutrophil count (ANC) ≥ 1.5×10^9/L; total white blood cell count ≥ 3.5×10^9/L;

12. Platelets (PLT) ≥ 100×10^9/L;

13. Blood biochemistry examination: a、Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN for liver metastasis/bone metastasis; ≤ 5 ULN for tumor bone metastasis);b、Total bilirubin (TBIL) ≤ 1.5 × ULN; c、Serum creatinine (Cr) ≤ 1.5×ULN orcreatinine clearance rate ≥ 60 ml/min;

14. Coagulation function examination: Activated partial thromboplastin time (APTT),international normalized ratio (INR), prothrombin time (PT) ≤ 1.5×ULN.

Exclusion Criteria:

1. Squamous cell carcinoma patients (including adenosquamous carcinoma patients)should be excluded under the following conditions: ① Cavitary lung cancer. ② Patients who have had hemoptysis within the last month before the first doseand with a maximum daily hemoptysis of ≥2.5 mL, as well as other significantclinically relevant bleeding symptoms or those with a clear bleeding tendencycombined with diseases/history.

2. Patients with diffuse pleural metastases, malignant pericardial effusion, ordiffuse spinal cord involvement.

3. Patients with a history of other malignancies within 5 years (excluding curedbasal cell carcinoma of the skin, prostate intraepithelial neoplasia, andcervical intraepithelial neoplasia).

4. Current presence of pulmonary pneumonia with CTCAE 5.0 grade ≥ 2.

5. Individuals with various factors that affect oral medication (such asdysphagia, gastrointestinal resection, chronic diarrhea, and intestinalobstruction).

6. Evidence of active bleeding, or unexplained persistent decrease in hemoglobin.Screening/enrollment should be postponed until bleeding stops and theinvestigator deems it safe.

7. Within the first 4 weeks before the initial dose, occurrence of any bleeding orhemorrhagic event ≥ Grade 3 according to CTCAE 5.0 standards; use ofanticoagulants or vitamin K antagonists such as warfarin, heparin, or similaragents for treatment; under the condition that prothrombin time internationalnormalized ratio (INR) ≤ 1.5, allowing the use of low-dose warfarin forprophylactic purposes (≤ 1mg/d), low-dose heparin (≤ 12,000 U/d), or low-doseaspirin (≤ 100mg/d).

8. Within the 4 weeks before the initial dose, the presence of unhealed wounds,fractures, active ulcers of the stomach and duodenum, ulcerative colitis, oractive bleeding from unresected tumors, or conditions judged by theinvestigator to potentially cause gastrointestinal bleeding or perforation; orpatients who have undergone major surgeries (excluding vascular accesssurgery).

9. Receipt of traditional Chinese medicine listed in the NMPA-approved druginstructions, which explicitly have indications for anti-tumor and lung cancertreatment (including compound Bupleurum capsules, Kangai injection, Conlearcapsules/injections, Edaravone injections, Yadanzi oil injections/capsules,Xiaocanping tablets/injections, HuaChanSu capsules), or immune modulating drugs (excluding local use for pleural effusion control) within 2 weeks before theinitial dose.

10. History of organ or hematologic system transplantation.

11. Presence of clinically active diverticulitis, abdominal abscess,gastrointestinal obstruction.

12. Patients with severe and/or uncontrolled diseases, including:

• Patients with poorly controlled blood pressure (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥90mmHg);
• Occurrence of thrombotic events, ischemic stroke, myocardialinfarction within 6 months of the first dose, congestive heartfailure of Grade ≥2, or requiring treatment for arrhythmias (including QTc ≥480ms);
• Active or uncontrolled severe infections (grade ≥ 2 infectionaccording to CTCAE 5.0), tuberculosis patients; ④ Knownclinically significant liver disease history, including viralhepatitis, active HBV infection must be excluded for carriers ofknown hepatitis B virus (HBV) through positive HBV DNA (>2500copies/mL or >500 IU/mL); known HCV infection and positive HCVRNA (>1×10^3 copies/mL), or other decompensated liver disease,chronic hepatitis requiring antiviral therapy; ⑤ Positive HIVtest, positive rapid plasma reagin (RPR) test for syphilis; ⑥Poorly controlled diabetes (fasting blood glucose ≥10mmol/L); ⑦Urinalysis showing urinary protein ≥++, with confirmed 24-hoururinary protein quantification >1.0 g;

13. According to the judgment of the principal investigator, patients with otherfactors that may lead to the forced termination of this study, such as otherserious illnesses (including mental illness) requiring combined treatment,significant laboratory abnormalities, family or social factors affectingpatient safety, or data and sample collection.