Selinexor, High-dose Methotrexate, and Rituximab Combined With Radiotherapy for Newly Diagnosed, Transplant-ineligible Patients With Central Nervous System Lymphoma: An Open-label, Single-arm, Multicenter Phase II Study

Inclusion Criteria: 1. Age ≥ 18 years, male or female. 2. Histologically confirmed primary CNS lymphoma (PCNSL) or secondary CNS lymphoma (SCNSL) with CNS-only involvement. 3. Ineligible for autologous stem cell transplantation based on clinical assessment or patient refusal. 4. At least one measurable brain lesion ≥1 cm in diameter, or positive cerebrospinal fluid (CSF) cytology/flow cytometry for patients with leptomeningeal disease. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-3. 6. Adequate organ function, including: * Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L * Platelets ≥ 75 × 10⁹/L * Hemoglobin ≥ 80 g/L * Total bilirubin ≤ 1.5 × ULN (or ≤ 3 × ULN if liver involvement) * ALT and AST ≤ 2.5 × ULN (or ≤ 5 × ULN if liver involvement) * Creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula) * INR ≤ 1.5 × ULN; APTT within 10 seconds of normal 7. Estimated life expectancy of ≥ 3 months. 8. Negative serum pregnancy test for women of childbearing potential. 9. Ability to understand and willingness to sign a written informed consent form. Exclusion Criteria: 1. CNS involvement limited to intraocular lymphoma only. 2. Prior systemic therapy for CNS lymphoma. 3. SCNSL with active systemic (non-CNS) disease involvement. 4. Uncontrolled intracranial hypertension. 5. Clinically significant or unstable cardiovascular disease, including: * Myocardial infarction within 6 months * Unstable angina within 3 months * Uncontrolled arrhythmias (e.g., ventricular tachycardia/fibrillation) * Congestive heart failure NYHA class ≥ III * LVEF \< 50% by echocardiography 6. Other severe uncontrolled medical conditions, including active infections requiring systemic therapy. 7. Known active hepatitis B (HBV), hepatitis C (HCV), or HIV infection. 8. Active gastrointestinal dysfunction that interferes with the ability to swallow or absorb oral medication. 9. Prior treatment with selective inhibitor of nuclear export (SINE) compounds, including selinexor. 10. Concurrent malignancy, except for adequately treated basal/squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the cervix, prostate, or breast. 11. Pregnant or breastfeeding women, or subjects unwilling to use medically accepted effective contraception during the study and for 6 months after the last dose. 12. Any condition which, in the investigator's judgment, would make the patient unsuitable for study participation.