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

Abstract

Introduction-The neurohistological findings in patients treated with targeted β 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 ≤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 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 post 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 < 0.002) where patients with higher doses had better prognoses. For example, median

Noninvasive Detection of Cardiac Repair After Acute Myocardial Infarction in Rats by 111In Fab Fragment of Monoclonal Antibody Specific for Tenascin-C

“…31) Although we must always be careful about anaphylactic shock against injected antibody, many clinical studies support the beneficial effects of anti-TNC antibody.…”

Molecularly Targeted Therapies for Malignant Gliomas

“…The administration of the mAb against tenascin-C, an extracellular matrix glycoprotein ubiquitously expressed by malignant gliomas, has also been evaluated in clinical trials (49,50). In a nonrandomized, phase II, dose-response clinical trial in patients (n = 33) with primary MGs, 131 I-81C6 (Bradmer Pharmaceuticals, Toronto, Canada), a radiolabeled mAbtargeting tenascin (an extracellular matrix protein present in MGs, but not in normal brain tissue), was injected directly into surgically created resection cavities followed by conventional external-beam radiotherapy and chemotherapy (49).…”

“…Therefore, 131 I-81C6 increased the median survival of GBM patients compared with the standard Stubb regimen (49). Furthermore, histopathological analyses were conducted in patients (n = 28) treated with combined external-beam radiotherapy and a brachytherapy consisting of 131 I-81C6 injected into surgically created resection cavities during brain tumor resections (50). Histological tissue classification outcomes included "proliferative glioma," "quiescent glioma," and "negative for neoplasm".…”

“…Median survival with tissue classified as proliferative glioma, quiescent glioma, and negative for neoplasm were 3.5, 15, and 27.5 months, respectively (50). 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, thus suggesting that the total dose of radiotherapy was a significant predictor of sur-vival (P < 0.002) (50). Therefore, additional clinical trials are warranted to determine the effectiveness of 131 I-81C6 for the treatment of MGs.…”

“…However, interpretation of data from trials, such as those described above, is challenging because of methodological problems, mainly consisting of the small sample sizes enrolled and the open-label study design (48)(49)(50)52).…”