title: Long-term outcome of patients with WHO Grade III and IV gliomas treated by fractionated intracavitary radioimmunotherapy.
abstract: OBJECTIVE
  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.
authors.affiliation: Departments of 1 Neurosurgery.
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Reulen
authors.affiliation: Nuclear Medicine;
authors.forename: Gabriele
authors.initials: G
authors.lastname: Poepperl
authors.affiliation: Departments of 1 Neurosurgery.
authors.forename: Claudia
authors.initials: C
authors.lastname: Goetz
authors.affiliation: Nuclear Medicine;
authors.forename: Franz Joseph
authors.initials: FJ
authors.lastname: Gildehaus
authors.affiliation: Munich Cancer Registry, Institute of Medical Informatics, Biometry, and Epidemiology, and.
authors.forename: Michael
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Nuclear Medicine;
authors.forename: Klaus
authors.initials: K
authors.lastname: Tatsch
authors.affiliation: Department of Neuropathology, University of Bonn, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.affiliation: Department of Neuropathology, Ludwig Maximilian University Munich, Klinikum Grosshadern, Munich; and.
authors.forename: Theo
authors.initials: T
authors.lastname: Kraus
authors.affiliation: Departments of 1 Neurosurgery.
authors.forename: Walter
authors.initials: W
authors.lastname: Rachinger
mesh_terms: D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D016499:Radioimmunotherapy / Q000379:methods*; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
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