2600 - Evaluating Serum CXCL Levels as Potential Biomarkers in Glioblastoma: Observed Alteration with Concurrent Chemoirradiation in Upfront Management

J. Shephard, S. Jagasia, E. Tasci, T. Joyce, S. Chappidi, T. Cooley-Zgela, M. Sproull, M. Mackey, K. A. Camphausen, and A. V. Krauze; Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD

Purpose/Objective(s): Glioblastoma (GBM) is characterized by poor survival outcomes and high rates of recurrence due to rapid proliferation and treatment resistance. The CXCL family of chemokines has been implicated in multiple aspects of GBM biology, including angiogenesis and tumor progression. There is a pressing need to identify clinically relevant, easily measurable biomarkers to further the understanding of treatment response. CXCL levels in GBM patients before and after chemoirradiation therapy (CRT) were analyzed for alteration in serum and relationship to clinical and radiation therapy (RT) data. Materials/

Methods: Serum samples from 109 patients with pathologically proven GBM (diagnosed 2005-2023) were collected before and after the completion of CRT and analyzed using the Somalogic 7k proteomic panel. 21 members of the CXCL family were identified, 14 of which were unique. CXCL levels were linked to clinical and RT data. Statistical analyses (Wilcoxon test, Spearman r correlation, Kaplan Meier) were performed to explore alterations following treatment and associations with clinical features, overall survival (OS), and progression free survival (PFS).
Results: Eight unique CXCLs were found to be significantly altered with CRT: CXCL2 (p=0.0002), CXCL3 (p<0.0001), CXCL5 (p<0.0001), CXCL6 (p=0.023), CXCL10 (p<0.0001), CXCL11 (p<0.0001), CXCL13 (p=0.014), and CXCL16 (p<0.0001). CXCL2, 3, 5, 6, and 11 decreased while CXCL10, 13, and 16 increased in response to CRT. Statistically significant interactions were noted between chemokines and between clinical variables. CXCL1, 2, 3, 5, and 6 were strongly directly correlated with each other (p<0.05) and were weakly inversely correlated with age (CXCL1, 2, 3). CXCL16 alteration following CRT was inversely correlated with the alteration of CXCL1, 2, 3, 6, and 13 while being directly correlated with the alteration of CXCL8 and 10 (p<0.05). OS and PFS were strongly associated with age, MGMT status, and GTVT1 (p<0.05). CXCL16 was associated with MGMT status with MGMT methylated patients exhibiting more significant increases in serum CXCL16 (p=0.026) pre vs. post CRT. Elevated CXCL16 was associated with improved OS (p=0.031) (median OS 27 months increased levels vs. 18 months for lower or decreased levels) but was not associated with PFS. Pre CRT CXCL5 had the strongest direct correlation with GTVT1 (p=0.005) and GTVT2 (p=0.008) while pre CRT CXCL13 was directly correlated with GTVT2 only (p=0.006); however, neither was associated with OS or PFS.
Conclusion: Several members of the CXCL family are measurable in serum and significantly altered in response to CRT in GBM patients. The directionality of these changes and further analysis with clinical and RT data could enhance the understanding of molecular signaling pathways relevant to the GBM response to CRT. Association of CXCL16 with MGMT status may indicate potential for these molecules to be employed as biomarkers in GBM.