Efficacy of SRT as Salvage Therapy in Patients With Brain Oligo-progression of EGFR-mutant Non-small Cell Lung Cancer After Failure of the Third-generation EGFR-TKIs

Inclusion Criteria:

1. Age ≥ 18 and ≤ 75.
2. Life expectancy exceeding 3 months.
3. Histologic or cytologic pathology confirmed non-small cell lung cancer. However,sputum cytology results alone are not acceptable. The cytology results of trachealswabbing, tracheal irrigation fluid and needle aspiration are acceptable.
4. Investigators have confirmed the presence of at least one intracranial measurablelesion according to RECIST 1.1 criteria.
5. Patients with stage IV NSCLC with intracranial metastases at MR baseline.
6. Eastern Oncology Collaborative Group (ECOG) fitness status score of 0 or 1.
7. Genetic testing suggests EGFR driver gene positivity, which can be accompanied byother driver gene positivity.
8. Oligo-progression of intracranial tumors at the most recent evaluation followingtreatment with third- generation TKIs.
9. Good hematopoiesis, defined as an absolute neutrophil count ≥1.5 × 109/L, plateletcount ≥100 ×109/L, blood erythropoietin ≥ 90 g/L [7 days without transfusion orerythropoietin (EPO-dependent).
10. Good liver function, defined as total bilirubin levels ≤ 1.5 times the upper limit ofnormal (ULN); inpatients without hepatic metastases, glutinous rice straw is used as asupplement.
11. Aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times ULN; forpatients with documented liver metastases. AST and ALT levels ≤5 times ULN.
12. Good renal function, defined as serum creatinine ≤ 1.5 times ULN or calculatedcreatinine clearance ≥60 ml/min
13. (Cockcroft-Gault formula); less than 2+ urine protein on routine urinalysis, or 24-hour urine protein quantification <1 g.
14. Good coagulation, defined as an International Standardized Ratio (INR) or ProthrombinTime (PT) ≤ 1.5times ULN; if the subject is receiving anticoagulant therapy, providedthat the PT is within the intended range of use of the anticoagulant.
15. For female subjects of childbearing age, within 3 days prior to receiving the firststudy drug administration (Week 1, Day 1) A negative urine or serum pregnancy test isperformed. If a negative urine pregnancy test cannot be confirmed, a blood pregnancytest may be ordered test.
16. High-performance contraception (i.e., methods with a failure rate of less than 1 percent per year) for both male and female patients if there is a risk of conception.

Exclusion Criteria:

1. NSCLC EGFR driver gene negativity.
2. Patients who cannot be examined by MR.
3. Pathological examination of a mixture of small cell lung cancer components.
4. Currently participating in an interventional clinical research treatment or havereceived another investigational drug within 4 weeks prior to the first administrationof the drug.
5. Use of third-generation TKIs or major surgical procedures within 3 weeks prior to thefirst dose of the drug.
6. Received palliative intracranial radiotherapy prior to first administration.
7. Presence of clinically active diverticulitis, abdominal abscesses, gastrointestinalobstruction.
8. Have received a transplant of a solid organ or blood system.
9. Presence of clinically uncontrollable pleural effusion/abdominal fluid.
10. Known severe allergic reaction (≥ grade 3) to TKIs.
11. Have not sufficiently recovered from toxicity and/or complications from any of theinterventions prior to initiating treatment (i.e. ≤ grade 1 or at baseline, notincluding weakness or hair loss).
12. Diagnosis of other malignancies within 5 years prior to the first dose, withexceptions including radically treated basal cell carcinoma of the skin, squamous cellcarcinoma of the skin, and/or radically resected carcinoma in situ.
13. Active infections that require systemic treatment.
14. The known existence of a mental illness or substance abuse condition that may affectcompliance with the test requirements.
15. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibodypositive).
16. Evidence of a medical history or illness that could interfere with the results of thetrial, prevent the subject from participating throughout the study, abnormal valuesfor treatment or laboratory tests, or other circumstances that, in the opinion of theinvestigator, make enrollment unsuitable.
17. Breastfeeding women.