2261 - Peripheral Immune Profiles at 6-12 Weeks Post-Radiation, IDH Status, and MGMT Status or Other Clinical Characteristics in GBM Patients Treated with Chemoradiation
Presenter(s)
S. Workman1, A. Li1, Y. Tarui2, S. Pokala3, I. C. Liu1, L. G. Ross4, L. Sloan5, K. J. Redmond6, R. Agyekum1, and L. R. Kleinberg1; 1Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 2Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 3Department of Molecular and Cellular Biology, Johns Hopkins University, Baltimore, MD, 4Department of Radiology, Johns Hopkins University, Baltimore, MD, 5University of Minnesota: Department of Radiation Oncology, Minneapolis, MN, 6Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD
Purpose/Objective(s): We aimed to characterize systemic immune state at 6–12 weeks post-treatment in glioblastoma using a composite immune score derived from lymphocytes, monocytes, and neutrophils, and to evaluate associations with molecular and clinical characteristics.
Materials/Methods: We retrospectively analyzed 314 patients treated with conventionally fractionated radiotherapy with available blood counts at 6–12 weeks post-treatment. We included patients with a diagnosis of Glioblastoma per the WHO 2007 CNS classification. An equally weighted immune score (lymphocytes - monocytes - neutrophils) was constructed to represent adaptive-to-myeloid immune balance and standardized to the baseline distribution using z-transformation, allowing post-treatment values to be interpreted as standardized deviations from pretreatment immune composition. Associations of immune score and individual components with IDH status, MGMT status, age, gender, PTV volume, and total dose were assessed using t-tests, OLS regression, and Pearson correlation.
Results: IDH-mutant patients (n = 15) had higher lymphocyte counts (mean 1.31 ×10?/L) compared with wild-type patients (n=235, mean 0.95 ×10?/L; mean difference 0.37, 95% CI -0.76 to 0.02; p = 0.009; Cohen’s d = 0.70). Monocyte counts were slightly lower in mutants (0.45 ×10?/L vs 0.52 ×10?/L; mean difference -0.07, 95% CI -0.002 to 0.15; p = 0.22; Cohen’s d = 0.33). Neutrophil counts were significantly reduced in mutants (3.43 ×10?/L vs 4.91 ×10?/L; mean difference -1.48, 95% CI 0.55 to 2.41; p = 0.003; Cohen’s d = 0.56). The composite equally weighted immune score was significantly higher in IDH-mutant patients (mean 1.13 vs -0.10), with a mean difference of 1.23 (95% CI 0.50–1.95; p = 0.002), corresponding to a large effect size (Cohen’s d = 0.90). Other clinical variables, including gender, total dose, PTV volume, MGMT status, and age, were not significantly associated with the composite immune score despite showing trends in some individual components.
Conclusion:
In this cohort, IDH-mutant patients demonstrated a distinct systemic immune profile characterized by higher circulating lymphocyte counts, lower neutrophil counts, and significantly elevated composite immune scores 6-12 weeks after treatment compared to IDH-wildtype patients. These differences were not explained by other clinical variables including age, gender, MGMT status, radiation dose, or treatment volume. This observed shift toward relative lymphocyte predominance in IDH-mutant disease may reflect intrinsic biological differences in tumor metabolism and host-tumor immune interactions that influence systemic immune composition. These findings support the presence of genotype-associated differences in circulating immune balance and warrant validation in independent cohorts.