Long-term outcome of patients with WHO Grade III and IV gliomas treated by fractionated intracavitary radioimmunotherapy

Abstract

OBJECT The aim in this study was to present long-term results regarding overall survival (OS), adverse effects, and toxicity following fractionated intracavitary radioimmunotherapy (RIT) with iodine-131− or yttrium-90−labeled anti-tenascin monoclonal antibody ( 131 I-mAB or 90 Y-mAB) for the treatment of patients with malignant glioma. METHODS In 55 patients (15 patients with WHO Grade III anaplastic astrocytoma [AA] and 40 patients with WHO Grade IV glioblastoma multiforme [GBM]) following tumor resection and conventional radiotherapy, radioimmunoconjugate was introduced into the postoperative resection cavity. Patients received 5 cycles of 90 Y-mAB (Group A, average dose 18 mCi/cycle), 5 cycles of 131 I-mAB (Group B, average dose 30 mCi/cycle), or 3 cycles of 131 I-mAB (Group C, 50, 40, and 30 mCi). RESULTS Median OS of patients with AA was 77.2 months (95% CI 30.8 to > 120). Five AA patients (33%) are currently alive, with a median observation time of 162.2 months. Median OS of all 40 patients with GBM was 18.9 months (95% CI 15.8–25.3), and median OS was 25.3 months (95% CI18–30) forthose patients treated with the 131 I-mAB. Three GBM patients are currently alive. One-, 2-, and 3-year survival probabilities were 100%, 93.3%, and 66.7%, respectively, for AA patients and 82.5%, 42.5%, and 15.9%, respectively, for GBM patients. Restratification of GBM patients by recursive partitioning analysis (RPA) Classes III, IV, and V produced median OSs of 31.1, 18.9, and 14.5 months, respectively (p = 0.004), which was higher than expected. Multivariate analysis confirmed the role of RPA class, age, and treatment in predicting survival. No Grade 3 or 4 hematological, nephrologic, or hepatic toxic effects were observed; 4 patients developed Grade 3 neurological deficits. Radiological signs of radionecrosis were observed in 6 patients, who were all responding well to steroids. CONCLUSIONS Median OS of GBM and AA patients treated with 131 I-mABs reached 25.3 and 77.2 months, respectively, thus markedly exceeding that of historical controls. Adverse events remained well controllable with the fractionated dosage regimen.