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

J Neurosurg. 2015 Sep;123(3):760-70. doi: 10.3171/2014.12.JNS142168. Epub 2015 Jul 3.


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.

Keywords: AA = anaplastic astrocytoma; ALA = 5-aminolevulinic acid; CTC = Common Toxicity Criteria; GBM = glioblastoma multiforme; HR = hazard ratio; I-131−Labeled anti-tenascin mAB; IDH1 = isocitrate dehydrogenase; KPS = Karnofsky Performance Scale; MGMT = O6-methylguanine-DNA methyltransferase; OS = overall survival; RC = resection cavity; RIT = radioimmunotherapy; RPA = recursive partitioning analysis; RTOG = Radiation Therapy Oncology Group; anaplastic astrocytoma; glioblastoma; mAB = monoclonal antibody; oncology; radioimmunoconjugate; radioimmunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Astrocytoma / mortality
  • Astrocytoma / pathology
  • Astrocytoma / radiotherapy*
  • Astrocytoma / surgery
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy*
  • Brain Neoplasms / surgery
  • Combined Modality Therapy
  • Female
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Glioblastoma / radiotherapy*
  • Glioblastoma / surgery
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prognosis
  • Radioimmunotherapy / methods*
  • Survival Rate
  • Treatment Outcome
  • Young Adult