The goal of this clinical trial is to learn if a combined treatment approach can treat glioblastoma (GBM) with ventricular invasion or meningeal metastasis in adults. The main questions it aims to answer are:

Does the combined treatment of radical radiotherapy, the Stupp regimen (oral temozolomide), and intrathecal injection of thiotepa improve progression-free survival compared to standard treatment alone?

Does the combined treatment improve overall survival compared to standard treatment alone?

Participants will:

• Undergo maximal surgical resection of the tumor；
• Receive radical radiotherapy；
• Take oral temozolomide according to the Stupp regimen；
• Receive intrathecal injections of thiotepa。

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults, with a dismal prognosis despite standard treatment. The standard treatment for GBM, which includes surgery, radiotherapy, and chemotherapy with temozolomide (known as the Stupp regimen), has remained largely unchanged for over two decades. Patients with GBM who have tumor invasion of the brain ventricles or meningeal metastasis face an even worse prognosis, with significantly shorter progression-free survival and overall survival compared to patients without these complications. The blood-brain barrier poses a significant challenge to effective chemotherapy delivery, limiting the efficacy of systemic treatments for central nervous system tumors. Intrathecal chemotherapy administration represents a promising strategy to overcome this barrier by directly delivering chemotherapeutic agents into the cerebrospinal fluid, potentially improving tumor control and survival outcomes in patients at high risk for intraventricular dissemination.

Inclusion Criteria:

• Aged 18 - 75, any gender.
• Newly diagnosed WHO grade 4 brain tumor with at least one evaluable lesion, imaging suggesting ventricular or meningeal invasion.
• History of intraoperative intraventricular or cisternal opening.
• Malignant cells found in cerebrospinal fluid pre-radiotherapy.
• ECOG score 0 - 2, expected survival≥3 months.
• Stable neurological symptoms for over 7 days.
• Neutrophil count≥1.5×10⁹/L, hemoglobin≥90 g/L, platelet count≥75×10⁹/L.
• PT/INR and PTT≤1.5×upper limit of normal.
• Total bilirubin≤1.5×upper limit of normal, AST and ALT≤1.5×upper limit of normal, albumin≥30 g/L, creatinine≤2×upper limit of normal, calculated or 24-hour urine creatinine clearance rate≥50 mL/min.
• Agree to effective contraception from first to 3 months after last dose.

Exclusion Criteria:

• Pregnant or breastfeeding women.
• Active infection within 7 days before starting study drug requiring IV antibiotics or therapeutic warfarin.
• Other malignancies in past 5 years.
• HIV/AIDS history; past immunodeficiency, or active autoimmune disease needing systemic treatment.
• Severe medical, neurological, or psychiatric conditions preventing full adherence to study treatment or assessments.
• Ventricular drainage tube rupture or inability to undergo lumbar puncture.
• Uncontrolled chronic diseases like diabetes, CHF, liver cirrhosis, or CKD.