The role of plasma GFAP as a biomarker for glioblastoma.

Abstract

2095 Background: Magnetic resonance imaging (MRI) of the brain primarily assesses blood brain barrier (BBB) dysfunction which provides indirect information regarding tumor size. The limitations of MRI have become evident with the use of temozolomide (pseudo-progression) and VEGF based therapies (pseudo-response). As a result, a blood-based marker to assess tumor burden is increasingly important. Previous studies suggested that plasma glial fibrillary acidic protein (GFAP) levels are sensitive and specific for glioblastoma (GBM). This pilot study examines the utility of GFAP as a biomarker in pre- and post-operative gliomas. Methods: Plasma samples were collected in patients pre-operatively (N=34) and 24-48 hours post-operatively (N=24) for what was post-operatively confirmed to be newly diagnosed glioma. Plasma GFAP was detected using an electrochemiluminescent immunoassay with a detection threshold of >0.04ng/ml. Presence or absence of contrast enhancement (CE) on the pre-op MRI was compared with the pre-op plasma GFAP level using Fisher’s exact test. Results: The histologic, radiographic, and detection rates and pre- and post-op plasma GFAP levels are presented below. Higher grade tumors more often had CE on MRI than lower grade tumors (p=0.002). Plasma GFAP was detectable in 80% of patients with CE and 21% without CE (p=0.001). Conclusions: Higher grade tumors had more CE and higher plasma GFAP levels pre-operatively. However, post-operative GFAP levels dramatically increased in patients with lower grade gliomas that previously had undetectable levels. These data strongly suggest that GFAP is not a specific biomarker for GBM or an accurate measure of tumor burden. In addition, injury to the brain or BBB from surgery results in striking elevations of plasma GFAP independent of histologic grade or prior contrast enhancement. Histologic findings Contrast enhancement pre-op GFAP detectable pre-op GFAP levels pre-op median (range) GFAP detectable post-op GFAP levels post-op median (range) Grade 4 (n=9) 89% 100% 0.09 (0.07-0.15) 100% 0.07 (0.04-0.32) (N=5) Grade 3 (n=11) 55% 36% 0 (0-0.58) 100% 1.18 (0.11-4.56) (N=8) Grade 2 (n=14) 7% 21% 0 (0-0.22) 91% 0.38 (0.05-9.65) (N=11)