Hippocampus-Protective Radiotherapy Combined With Osimertinib for Symptomatic Brain Metastases in EGFR-Mutated Lung Cancer

Inclusion Criteria:

* Signed a written informed consent form prior to enrollment;
* Aged 18-75 years;
* Histopathologically confirmed non-small cell lung adenocarcinoma (NSCLC); EGFR gene test confirmed EGFR sensitive mutations, including exon 19 deletion (19del) and exon 21 L858R mutation (verified and confirmed by investigators at the respective study centers);
* Brain metastasis confirmed by contrast-enhanced cranial CT/MRI; the number of brain metastatic lesions requiring local dose escalation is 1-10, with at least one measurable intracranial lesion having a diameter ≥10 mm; the distance between metastatic lesions and important cerebral functional areas meets radiotherapy-related requirements; at least one measurable lesion (per RECIST v1.1 criteria) confirmed by contrast-enhanced extracranial CT/PET-CT;
* Symptomatic brain metastasis;
* ECOG performance status score: 0-2;
* Expected survival time of no less than 12 weeks;
* No prior anti-tumor treatment received for NSCLC;
* Normal function of vital organs, meeting the following requirements (no blood components or cell growth factors administered within 14 days):

A) Routine blood test criteria: Hb ≥100 g/L; ANC ≥1.5×10⁹/L; PLT ≥75×10⁹/L; B) Biochemical test criteria: TBIL ≤1.5×ULN (upper limit of normal); ALT and AST ≤2.5×ULN (for patients with liver metastasis, ALT and AST ≤5×ULN); serum creatinine ≤1.5×ULN, creatinine clearance rate ≥50 ml/min (calculated based on the Cockroft-Gault formula); C) Coagulation function criteria: INR ≤1.5×ULN and APTT ≤1.5×ULN; D) Cardiac color Doppler ultrasound: left ventricular ejection fraction (LVEF) ≥50%;

\- For non-surgically sterilized patients or women of childbearing potential: a medically approved contraceptive method (e.g., intrauterine device, oral contraceptives, or condoms) must be used during the study treatment period and for 3 months after the end of study treatment; non-surgically sterilized women of childbearing potential must have a negative serum or urine HCG test within 7 days prior to study enrollment, and must not be breastfeeding.

All subjects voluntarily participate in the study, with good compliance and willingness to cooperate with safety and overall survival follow-up.

Exclusion Criteria:

* Presence of uncontrollable third space effusion (e.g., pleural effusion, ascites) that cannot be managed with drainage or other interventions;
* Presence of multiple factors impairing oral drug administration and absorption (e.g., inability to swallow, post-gastrointestinal resection, chronic diarrhea, intestinal obstruction, etc.);
* Patients who are known to be pregnant, planning pregnancy, or women of childbearing potential who refuse to adopt effective contraceptive measures throughout the study period;
* Patients with severe concomitant diseases or those deemed ineligible for enrollment by the investigator;
* Patients with meningeal metastasis;
* Participation in other drug clinical trials within 4 weeks prior to enrollment;
* Concurrent receipt of other anti-tumor therapies;
* A known history of psychotropic drug abuse, alcoholism, or drug addiction in the subject;
* Underlying diseases that may interfere with study drugs (e.g., clinically significant electrocardiographic abnormalities, active interstitial lung disease);
* Any other conditions deemed by the investigator to potentially harm the subject or render them unable to meet or comply with the study requirements.