Efficacy and Safety of Intraventricule Pemetrexed Disodium Administered Via Ommaya Reservoir

Inclusion Criteria:

1. confirmed pathologic diagnosis (histologic type of non-squamous non-small cell lungcancer in the primary lesion or metastatic lesion) with definitely genetic testingresults (EGFR/ALK/ROS1);
2. In accordance with the CSCO Guidelines for the Diagnosis and Management of CentralNervous System Tumors, and the EANO-ESMO diagnostic criteria: a diagnosis of type Imeningeal metastatic carcinoma is made when cerebrospinal fluid cytology testingreveals anisocytosis (3 consecutive tests are required if the cerebrospinal fluidcytology testing is initially negative for the patient) (one study showed that thespecificity of anisocytosis in diagnosing meningeal metastases in patients with solidtumors was 100%) or meningeal lesions Biopsy confirms the diagnosis. (Type IIA-Cmeningeal metastases: negative or atypical cerebrospinal fluid cytology, MRI showinglinear or/and nodular meningeal enhancement^ with typical clinical symptoms*).

• MRI: at least 1.5T; demonstrates sulcal, smear, or linear ventricularenhancement, cranial nerve root enhancement or nodular meningeal enhancement, orcauda equina spinal enhancement; control enhancement T1-weighted sequences andFlair sequences; nodularity is defined as foci of ≥ 5x10mm enhancement; sequencesof choice: cranial planar enhancement + T2Flair (enhancement) or and total spinalplanar enhancement (when suspicion of spinal involvement); 3D T1 enhancement (involved cranial nerves - optional); cerebrospinal fluid flow imaging (functional or anatomic).
• Typical clinical manifestations: headache, nausea, vomiting; epilepsy;mental changes, gait difficulties; cranial nerve damage (diplopia, visualabnormalities, hearing abnormalities, facial nerve palsy, difficultychewing, difficulty swallowing, choking, etc.); neurogenic signs (caudaequina symptoms, mainly perineal numbness, tingling, defecation andurination disturbances, weakness or incomplete paralysis of both lowerlimbs); sensorimotor defects of the limbs; cervical back Radicular pain; becareful to differentiate from signs and symptoms of brain parenchymalmetastases, extracranial disease, treatment-related adverse effects, andnon-tumor comorbidities.

3. Based on the guideline-driven first-line choice of TKI agents forgene-positive patients, enrolment would therefore require: failure of atleast three generations of EGFR-TKIs for patients with EGFR mutations;failure of at least second-generation ALK inhibitors for ALK mutations; andfailure of at least one ROS1 inhibitor for ROS1 mutations.
4. No contraindication to Ommaya capsule implantation. 5. Female subjectswho are capable of becoming pregnant must agree to use reliablecontraception throughout the trial; male subjects whose female partner iscapable of becoming pregnant must agree to use reliable contraceptionthroughout the trial.
5. patients must sign an informed consent form and must be willing and ableto comply with visits, treatment regimens, laboratory tests and otherrequirements as specified in the study protocol

Exclusion Criteria:

1. HBsAg-positive patients may be enrolled, but patients with higher than normal viralcopy number or HBcAb-positive patients should receive effective anti-HBV treatmentuntil 6 months after the end of the trial. HCV RNA carriers may be enrolled, but needto receive effective anti-HCV treatment throughout the trial, and continue to receiveeffective anti-HCV treatment until 6 months after the end of the trial.
2. human immunodeficiency virus (HIV) infection.
3. significant extracranial lesion progression or extensive extracranial lesions causingsevere symptoms that cannot be effectively treated.
4. patients with extreme emaciation or cachexia.
5. Extensive parenchymal brain lesions with severe symptoms that cannot be effectivelytreated.
6. patients with other malignant tumors that are currently undergoing treatment.
7. have received or will receive a live vaccine within 30 days prior to signing theinformed consent form.
8. other conditions that, in the judgment of the investigator, may affect subject safetyor trial compliance, including symptomatic heart failure, unstable angina, myocardialinfarction, active infections (including tuberculosis infections) requiring systemictherapy; or severe organ dysfunction, with creatinine clearance <45 ml/min calculatedfrom glomerular filtration rate by the Cockcroft-Gault formula or by the Tc99m-DPTAserum clearance method; an absolute neutrophil count <0.5 x 109/L; a platelet count <25 x 109/L, or in patients with severe active visceral bleeding; or severe Abnormalliver function (bilirubin greater than 3.0 times upper limit of normal; AST and ALTgreater than 5.0 times upper limit of normal).
9. patients with known hypersensitivity to pemetrexed with a history of serious adversereactions, and patients with potentially life-threatening conditions for reuse.
10. pregnant or lactating women.