Abstract
94 Background: Patients with malignant glioma often develop increased enhancement in the tumor bed after chemoradiation (CRT). Current imaging techniques cannot distinguish if these changes are due to recurrent disease or treatment-related brain injury (TRBI). Serum biomarkers could help noninvasively make this distinction. Brain-specific proteins have been used as markers of the severity of other brain injuries including stroke, hypoxia, and traumatic brain injury. We hypothesized that similar changes could be observed following brain CRT and could provide preliminary data supporting biomarker development for TRBI. Methods: Patients receiving concurrent radiation and temozolomide (TMZ) for malignant glioma were eligible. The study was approved by the institutional review board. Informed consent was obtained from all patients. Serum is sampled before CRT, in the last week of CRT, and at 1 month, 6 mos, and 1 year after CRT. Neurologic exams, cognitive testing, and imaging are performed at the same intervals. Serum samples were tested for glial fibrillary acidic protein (GFAP), neurogranin, ICAM-5, B-syn-nuclein, and brain-derived neurotrophic factor (BDNF). Samples were measured in duplicate using an electrochemiluminescent immunoassay. Results: Data are available for the first 7 patients enrolled in this study. All of the tested markers except GFAP were measurable at baseline and all other time points. None of the markers were consistently elevated during the last week of CRT or at any other time point during follow-up. Three patients had resection of suspected recurrent disease. Two had recurrent tumor and 1 had no evidence of disease. No correlation was apparent with the findings at surgery and serum levels of GFAP, neurogranin, ICAM-5, B-synuclein, or BDNF. Conclusions: This study describes a mechanism for identifying a serum protein marker of TRBI. Preliminary results did not identify elevations in any of the selected markers immediately after CRT when signs of TRBI should be apparent or at other points in the clinical course. Testing of additional serum markers is needed to identify a biomarker of TRBI which would provide valuable information for managing high-grade glioma patients.
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