title: Tumor resection cavity administered iodine-131-labeled antitenascin 81C6 radioimmunotherapy in patients with malignant glioma: neuropathology aspects.
abstract: BACKGROUND
  The neurohistological findings in patients treated with targeted beta emitters such as (131)I are poorly described. We report a histopathologic analysis from patients treated with combined external beam therapy and a brachytherapy consisting of a (131)I-labeled monoclonal antibody (mAb) injected into surgically created resection cavities during brain tumor resections.
  
  
  METHODS
  Directed tissue samples of the cavity walls were obtained because of suspected tumor recurrence from 28 patients. Samples and clinical follow-up were evaluated on all patients (Group A) based on total radiation dose received and a subset of these (n=18; Group B, proximal therapy subset) who had received external beam therapy within <or=3 months of mAb therapy and undergoing 26 biopsies over 37 months. Histologic outcomes were "proliferative glioma," "quiescent glioma" and negative for neoplasm. Statistical analysis was used to assess the casual relation between total absorbed dose ((131)I-mAb+external beam) and histologic diagnosis.
  
  
  RESULTS
  The lesions observed after (131)I-mAb therapy were qualitatively similar to those reported for other types of radiation therapy; however, the high localized dose rate and absorbed doses produced by the short range of (131)I beta particles seem to have resulted in an earlier necrotic reaction in the tumor bed. Among all 28 (Group A) patients, median survival from tissue analysis after mAb therapy depended on histopathology and total radiation absorbed dose. Median survival for patients with tissue classified as proliferative glioma, quiescent glioma and negative for neoplasm were 3.5, 15 and 27.5 months, respectively. Without categorization, total dose was a significant predictor of survival (P<.002) where patients with higher doses had better prognoses. For example, median survival in patients receiving a total radiation dose greater than 86 Gy was 19 months compared with 7 months for those receiving less than 86 Gy.
  
  
  CONCLUSIONS
  Histopathologic analysis correlated with prognosis. Among all patients (Group A) there was a significant correlation between biopsy outcome, survival, and total radiation absorbed dose. Among the Group B proximal therapy patients, the neuropathologic changes were qualitatively similar to those described for external beam therapy and interstitial brachytherapy.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. mclen001@mc.duke.edu
authors.forename: Roger E
authors.initials: RE
authors.lastname: McLendon
authors.forename: Gamal
authors.initials: G
authors.lastname: Akabani
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.forename: Linda
authors.initials: L
authors.lastname: Cleveland
authors.forename: Ilkcan
authors.initials: I
authors.lastname: Cokgor
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: Carol
authors.initials: C
authors.lastname: Wikstrand
authors.forename: Susan T
authors.initials: ST
authors.lastname: Boulton
authors.forename: Allan H
authors.initials: AH
authors.lastname: Friedman
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001253:Astrocytes / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D005260:Female; D005910:Glioma / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D006801:Humans; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009364:Neoplasm Recurrence, Local; D009369:Neoplasms / Q000532:radiotherapy* / Q000601:surgery*; D016499:Radioimmunotherapy / Q000379:methods*; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000627:therapeutic use*; D016019:Survival Analysis; D019063:Tenascin / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D019275:Radiopharmaceuticals; D019063:Tenascin