Safety and Efficacy of Whole Brain LDRT+ICI+Intrathecal Chemotherapy in Refractory Meningeal Metastasis of Lung Cancer

Inclusion Criteria:

1. ≥ 18 years old and ≤ 75 years old;

2. Patients with a definite diagnosis of leptomeningeal metastasis by cerebrospinalfluid cytology, or patients with clinical diagnosis combined with tumor history,neuroimaging, clinical manifestations, cerebrospinal fluid examination, etc.;

3. Patients with a clear history of lung carcinoma, including histopathologicaldiagnosis or a combination of cytopathology and imaging, and failure of standardtreatment;

4. Efficacy of extracranial lesions SD;

5. Patients with no contraindications to craniocranial radiotherapy were judged byradiotherapy doctors. Subjects who agree to receive immunotherapy, Lumbar puncture,intrathecal chemotherapy, and radiotherapy;

6. Expected survival ≥3 months, PS score ≤3;

7. Agree to provide cerebrospinal fluid, blood and tissue samples for biomarkertesting;

8. The main organs function normally, no serious blood, heart, lung, liver, kidney,bone marrow and other functional abnormalities and immune deficiency diseases;

9. One week before enrollment, bone marrow and liver and kidney function met thefollowing criteria:

① Hemoglobin ≥80 g/L, neutrophils ≥1.5×10^9/L and platelets ≥70×10^9/L;

② Renal function: Cr≤ULN (upper limit of normal) × 1.5, endogenous creatinineclearance (Ccr)≥55 ml/min; Liver function: total bilirubin ≤ULN × 1.5; ALT, AST≤ULN × 2.5; (In case of liver metastasis, total bilirubin should not be higher than 3times the upper normal limit, and transaminase should not be higher than 5 times theupper normal limit);

10. The fertile women agreed to use contraception during the study period and for 6months after the study ended; Patients who tested negative for a serum or urinepregnancy test within 7 days prior to joining the study and were not breastfed; Menwho agreed to use contraception during the study period and for 6 months after thestudy ended

Exclusion Criteria:

1. Active autoimmune disease or history of autoimmune diseases;

2. Congenital or acquired immunodeficiency;

3. Uncontrolled cardiac clinical symptoms or diseases;

4. Severe infection or severe comorbidities, such as bleeding peptic ulcer, ileus,heart failure, renal failure, or poorly controlled diabetes;

5. History of allogeneic organ transplantation or allogeneic hematopoietic stem celltransplantation;

6. Other systemic malignancies within the last 5 years;

7. Allergy to any test drug;

8. Uncontrolled epilepsy, neurological failure, or severe treatment-relatedneurological impairment, uncontrollable psychosis, and other conditions deemedunsuitable for inclusion by the investigator;

9. Pregnant and lactating women, subjects with reproductive capacity are unwilling totake effective contraceptive measures.