Abstract 4992: Baseline and alteration in pre vs post standard of care management serum-derived inflammatory markers are associated with radiation treatment volumes and patient outcomes in patients with GBM in a large-scale proteomic panel
Authors: Sarisha V. Jagasia, Thomas Joyce, Shreya Chappidi, Erdal Tasci, Theresa Cooley Zgela, Megan Mackey, Mary Sproull, Kevin Camphausen, Andra V. Krauze
Journal: Cancer Research (2024)

Abstract Glioblastomas (GBM) are the most aggressive central nervous system tumors with near universal recurrence following resection and chemoradiation (CRT). Inflammation plays a multifaceted role in GBM development and progression through disruption of the brain barrier, immunosuppression, angiogenesis, and release of inflammatory mediators. Previously established serum inflammatory markers (IM) have been studied in baseline measures obtained prior to surgical resection, making it difficult to establish patterns for potential treatment-induced alteration of IM. We tested the hypothesis that serum-derived IM measured post-resection, prior to and following completion of CRT, may be related to residual tumor burden and response to treatment. IM was analyzed in serum collected pre and post-CRT from 82 individuals with a pathologic confirmed diagnosis of GBM using aptamer-based SOMAScan® proteomic assay. Clinical variables were collected or derived from electronic health records and included RT (radiation therapy) gross tumor volumes GTVT1 (enhancing tumor volume on T1 gadolinium MRI pre CRT), GTVT2 ( T2 FLAIR tumor volume on MRI pre CRT), the volume receiving the higher prescribed RT dose (60Gy) (PTVHD) and lower dose (46Gy) (PTVLD), and outcomes (overall survival (OS), progression-free survival (PFS)). Cox regression analyses were performed with pre and post IM levels significant associations (p&amp;lt;0.05) were identified. GTVT1 and PTVHD correlated positively with pre-CRT Fibrinogen level and negatively with alteration in CD23. GTVT2 and PTVLD correlated negatively with Kininogen alteration (p&amp;lt;0.05 for all). GTVT1 correlated positively with pre IL-6 level. PTVLD correlated negatively with pre TNFb level and PTVHD with CD14 alteration. High alteration in Albumin and a2-HS glycoprotein, lower pre HLA-G and pre IL-6, high pre IgE, pre PD-1 and pre TNF-b and lower altered TNF-b were all associated with longer OS (p&amp;lt;0.05). Accounting for age, tumor volumes and RT volumes, fibrinogen was the most prevalent signal associated with outcomes, the pre CRT level associated with OS (HR: 0.66, p: 0.04) and pre, post, and alteration significant for PFS (pre (HR : 0.60, p : 0.01), post (HR: 1.6, p: 0.01), alt (HR : 1.52 , p &amp;lt; 0.005). SAA pre CRT level was associated with OS (HR : 1.46, p: 0.02) and its alteration with PFS (HR : 1.62, p : 0.02 ). Additional IM alterations associated with OS CRP (HR: 0.57, p: 0.01), PD-1 (HR : 3.52, p , 0.005) and PFS, post CRT IL-10 level (HR : 0.04 , p : 0.02). GTVT1/PTVHD, GTVT2/PTVLD have distinct IM correlates in serum. Serum IM are associated with OS ad PFS and tumor volumes. Potential associations of previously literature-described inflammatory markers including Fibrinogen, SAA, IL-6, TNF-b and PD-1, were identified and are undergoing further analysis. Citation Format: Sarisha V. Jagasia, Thomas Joyce, Shreya Chappidi, Erdal Tasci, Theresa Cooley Zgela, Megan Mackey, Mary Sproull, Kevin Camphausen, Andra V. Krauze. Baseline and alteration in pre vs post standard of care management serum-derived inflammatory markers are associated with radiation treatment volumes and patient outcomes in patients with GBM in a large-scale proteomic panel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4992.