Tumor resection cavity administered iodine-131-labeled antitenascin 81C6 radioimmunotherapy in patients with malignant glioma: neuropathology aspects

McLendon, Roger E.; Akabani, Gamal; Friedman, Henry S.; Reardon, David A.; Cleveland, Linda; Cokgor, Ilkcan; Herndon, James E.; Wikstrand, Carol; Boulton, Susan T.; Friedman, Allan H.; Bigner, Darell D.; Zalutsky, Michael R.

doi:10.1016/j.nucmedbio.2007.01.009

« Previous Next »Nuclear Medicine and Biology
Volume 34, Issue 4 , Pages 405-413, May 2007

Tumor resection cavity administered iodine-131-labeled antitenascin 81C6 radioimmunotherapy in patients with malignant glioma: neuropathology aspects

Roger E. McLendon
- Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
- Corresponding author. Tel.: +1 919 684 6940; fax: +1 919 681 7634.
Gamal Akabani
- Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA
Henry S. Friedman
- Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA
David A. Reardon
- Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
Linda Cleveland
- Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
Ilkcan Cokgor
- Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA
James E. Herndon II
- Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC 27710, USA
Carol Wikstrand
- Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
Susan T. Boulton
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
Allan H. Friedman
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
Darell D. Bigner
- Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
Michael R. Zalutsky
- Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA

Received 25 October 2006; received in revised form 24 January 2007; accepted 29 January 2007. published online 02 April 2007.

Abstract

Introduction

The neurohistological findings in patients treated with targeted β emitters such as ¹³¹I are poorly described. We report a histopathologic analysis from patients treated with combined external beam therapy and a brachytherapy consisting of a ¹³¹I-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 ≤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 (¹³¹I-mAb+external beam) and histologic diagnosis.

Results

The lesions observed after ¹³¹I-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 ¹³¹I β 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.

Keywords: Radioimmunotherapy, Neuropathology, ¹³¹I, Brain tumor, Monoclonal antibody, Radiation therapy