Combined-modality treatment of leptomeningeal gliomatosis

Leptomeningeal gliomatosis (LG) is a clinically uncommon metastatic complication of high-grade gliomas (HGGs), for which there is no consensus regarding treatment. The goal of this study was to determine the toxicity and response rate of combined-modality therapy for the treatment of patients with HGGs and LG.

Eighteen patients (10 men and 8 women), ranging in age from 28 to 70 years (median, 38 yr), with clinically, neuroradiologically, and cytologically documented LG received intraventricular chemotherapy. Tumor histological types included anaplastic astrocytoma (10 patients) and glioblastoma multiforme (8 patients). Concurrent radiotherapy (11 patients) or systemic chemotherapy (13 patients) was administered as clinically indicated. Methotrexate was administered initially, and treatment was continued for patients in stable or improved condition. For patients who experienced progression, cytosine arabinoside was administered as second-line therapy, followed by N,N',N"-triethylenethiophosphoramide as third-line therapy. Patients underwent bimonthly evaluations with cerebrospinal fluid cytological assessments and neurological examinations.

Four to 13 cycles (median, 5 cycles) of intraventricular chemotherapy were administered. Toxicity included aseptic meningitis (12 patients), radiation-induced enteritis (2 patients), and myelosuppression of Grade II or less (4 patients). No patient required hospitalization or transfusions, and no treatment-related deaths occurred. Partial responses were observed for 6 patients, and 12 patients demonstrated progressive disease. The median duration of response was 3 months (range, 2-4 mo). Survival times after the initiation of intraventricular chemotherapy ranged from 2 to 8 months (median, 3.5 mo). The cause of death was progressive LG (14 patients), combined LG and HGG (3 patients), and HGG (1 patient).

For this small cohort of patients, combined-modality therapy had modest toxicity but minimal palliative efficacy. For the majority of patients with LG, supportive care should be considered.