Inclusion Criteria:
1. Patients voluntarily participate in this study, sign informed consent, and
demonstrate good compliance.
2. Patients with histologically or pathologically confirmed EGFR wild-type and EGFR
mutant non-small cell lung cancer resistant to treatment.
3. The number of brain metastases is ≤ 5, and the patient has at least one assessable
brain metastasis on imaging (RECIST 1.1). Additionally, the patient's physical
condition 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 oral
administration of anlotinib during radiotherapy without intervention regarding
subsequent 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 following
criteria:
1. Hematological examination:
1. Hemoglobin (Hb) ≥ 90g/L (no blood transfusion within 14 days);
2. Absolute neutrophil count (ANC) ≥ 1.5×10^9/L; total white blood cell count ≥
3.5×10^9/L;
3. Platelets (PLT) ≥ 100×10^9/L;
2. 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 or
creatinine clearance rate ≥ 60 ml/min;
3. 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 dose
and with a maximum daily hemoptysis of ≥2.5 mL, as well as other significant
clinically relevant bleeding symptoms or those with a clear bleeding tendency
combined with diseases/history.
2. Patients with diffuse pleural metastases, malignant pericardial effusion, or
diffuse spinal cord involvement.
3. Patients with a history of other malignancies within 5 years (excluding cured
basal cell carcinoma of the skin, prostate intraepithelial neoplasia, and
cervical intraepithelial neoplasia).
4. Current presence of pulmonary pneumonia with CTCAE 5.0 grade ≥ 2.
5. Individuals with various factors that affect oral medication (such as
dysphagia, gastrointestinal resection, chronic diarrhea, and intestinal
obstruction).
6. Evidence of active bleeding, or unexplained persistent decrease in hemoglobin.
Screening/enrollment should be postponed until bleeding stops and the
investigator deems it safe.
7. Within the first 4 weeks before the initial dose, occurrence of any bleeding or
hemorrhagic event ≥ Grade 3 according to CTCAE 5.0 standards; use of
anticoagulants or vitamin K antagonists such as warfarin, heparin, or similar
agents for treatment; under the condition that prothrombin time international
normalized ratio (INR) ≤ 1.5, allowing the use of low-dose warfarin for
prophylactic purposes (≤ 1mg/d), low-dose heparin (≤ 12,000 U/d), or low-dose
aspirin (≤ 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, or
active bleeding from unresected tumors, or conditions judged by the
investigator to potentially cause gastrointestinal bleeding or perforation; or
patients who have undergone major surgeries (excluding vascular access
surgery).
9. Receipt of traditional Chinese medicine listed in the NMPA-approved drug
instructions, which explicitly have indications for anti-tumor and lung cancer
treatment (including compound Bupleurum capsules, Kangai injection, Conlear
capsules/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 the
initial 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, myocardial
infarction within 6 months of the first dose, congestive heart
failure of Grade ≥2, or requiring treatment for arrhythmias
(including QTc ≥480ms);
- Active or uncontrolled severe infections (grade ≥ 2 infection
according to CTCAE 5.0), tuberculosis patients; ④ Known
clinically significant liver disease history, including viral
hepatitis, active HBV infection must be excluded for carriers of
known hepatitis B virus (HBV) through positive HBV DNA (>2500
copies/mL or >500 IU/mL); known HCV infection and positive HCV
RNA (>1×10^3 copies/mL), or other decompensated liver disease,
chronic hepatitis requiring antiviral therapy; ⑤ Positive HIV
test, positive rapid plasma reagin (RPR) test for syphilis; ⑥
Poorly controlled diabetes (fasting blood glucose ≥10mmol/L); ⑦
Urinalysis showing urinary protein ≥++, with confirmed 24-hour
urinary protein quantification >1.0 g;
13.
According to the judgment of the principal investigator, patients with other
factors that may lead to the forced termination of this study, such as other
serious illnesses (including mental illness) requiring combined treatment,
significant laboratory abnormalities, family or social factors affecting
patient safety, or data and sample collection.