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 cerebrospinal fluid 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 histopathological diagnosis or a combination of cytopathology and imaging, and failure of standard treatment;
4. Efficacy of extracranial lesions SD;
5. Patients with no contraindications to craniocranial radiotherapy were judged by radiotherapy 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 biomarker testing;
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 the following 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 creatinine clearance (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 3 times the upper normal limit, and transaminase should not be higher than 5 times the upper normal limit);
10. The fertile women agreed to use contraception during the study period and for 6 months after the study ended; Patients who tested negative for a serum or urine pregnancy test within 7 days prior to joining the study and were not breastfed; Men who agreed to use contraception during the study period and for 6 months after the study 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 cell transplantation;
6. Other systemic malignancies within the last 5 years;
7. Allergy to any test drug;
8. Uncontrolled epilepsy, neurological failure, or severe treatment-related neurological impairment, uncontrollable psychosis, and other conditions deemed unsuitable for inclusion by the investigator;
9. Pregnant and lactating women, subjects with reproductive capacity are unwilling to take effective contraceptive measures.