2071 - The Role of Tumor-Infiltrating Clonal Hematopoiesis and Frailty in Outcomes for Patients with IDH-Wildtype Glioblastoma

03:00pm - 04:00pm ET

Poster Hall - Exhibit Hall A

Screen: 9

POSTER

Presenter(s)

Homayoun Ghaseminezhad, BS - University of Washington, Seattle, WA

H. Ghaseminezhad^1,2, U. S. Baguda¹, K. Galbraith¹, and S. Hardy^1,3; ¹Department of Radiation Oncology, University of Washington Medical Center, Seattle, WA, ²Loma Linda University School of Medicine, Loma Linda, CA, ³Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY

Purpose/Objective(s):

Tumor-infiltrating clonal hematopoiesis of intermediate potential (TI-CHIP) has been described across solid tumors, but its prevalence in glioblastoma and relationship with clinical frailty and outcomes is not well-described. We evaluated TI-CHIP prevalence and associations with an electronic frailty index (eFI), progression-free survival (PFS), and overall survival (OS) in IDH-wildtype glioblastoma.

Materials/Methods:

We performed a retrospective cohort study of adults =18 years with IDH-wildtype glioblastoma (2019–2025) who underwent a clinically validated 472 gene solid tumor panel. Putative CHIP-associated variants were evaluated and determined by molecular neuropathology at variant allele frequency (VAF) =2% using established gene-specific criteria. Frailty was assessed using an eFI (eFI >/= 0.2 was considered frail). The association between TI-CHIP and eFI was tested using linear and logistic regression. Multivariable Cox regression evaluated TI-CHIP and FI in relation to OS and PFS, adjusting for age at diagnosis, MGMT status, extent of resection, and treatment category.

Results:

Among 119 patients (median age 58), TI-CHIP was present in 23 (19%). TI-CHIP was not associated with eFI (ß=-0.02; p=0.46) or eFI=0.2 (OR=0.95; p=0.93). In adjusted Cox models, TI-CHIP was not associated with OS (HR=0.84, 95%CI 0.39–1.81; p=0.65) or PFS (HR=1.02, 95%CI 0.52–2.01; p=0.96). eFI was not independently associated with OS (HR=3.40; p=0.42) or PFS (HR=6.87; p=0.15). Gross total resection was associated with improved OS (HR=0.44; p=0.022) and PFS (HR=0.54; p=0.043). Combined chemoradiation was associated with improved OS (HR=0.30; p=0.002) and PFS (HR=0.32; p=0.002).

Conclusion:

TI-CHIP was detectable in approximately one-fifth of IDH-wildtype glioblastomas with tumor profiling and was not associated with frailty or survival after adjustment for key clinical covariates. Larger cohorts and paired blood-based confirmation may clarify the clinical and biologic significance of TI-CHIP in glioblastoma.