Monocytic resilience during chemoradiotherapy is independently associated with survival in IDH-Wildtype glioblastoma.

Abstract

Purpose: Routine blood counts may capture treatment-related host immune perturbation in glioblastoma, but most studies rely on static pretreatment values. We investigated whether the intra-individual preservation of circulating monocytes during chemoradiotherapy provides prognostic information beyond established clinical factors and other hematologic trajectories.

Methods: We retrospectively analyzed adults with histologically confirmed IDH-wildtype glioblastoma treated with radiotherapy and concurrent temozolomide. Absolute monocyte counts obtained before and at the end of chemoradiotherapy were used to define monocytic resilience as log2(post-treatment/pre-treatment monocyte ratio). Overall survival (OS) was the primary endpoint. Cox models adjusted for MGMT promoter methylation, gross total resection, Karnofsky Performance Status, and age. The ratio was analyzed continuously for primary inference. A post/pre ratio of 0.75 was additionally evaluated as an exploratory, clinically interpretable threshold for two-group Kaplan-Meier visualization and sensitivity analysis.

Results: Among 127 patients, 115 had complete monocyte trajectories and OS data. The primary adjusted model included 102 patients and 86 deaths. The continuous monocyte post/pre ratio was independently associated with OS (HR 0.53 per doubling, 95% CI 0.37-0.76; p = 0.00051). Using the exploratory 0.75 threshold, 52 patients had low resilience (< 0.75) and 63 had preserved resilience (≥ 0.75), with median OS of 10.2 and 17.3 months, respectively (log-rank p = 0.00064). Preserved resilience was associated with lower mortality in univariable Cox analysis (HR 0.50, 95% CI 0.34-0.75; p = 0.00080). Bootstrap resampling showed that outcome-optimized cut-points clustered around this region (median 0.74; IQR 0.70-0.81), although the threshold remains exploratory and requires external validation.

Conclusions: Preservation or recovery of circulating monocytes during chemoradiotherapy was associated with a favorable host-response phenotype in IDH-wildtype glioblastoma. This dynamic signal remained associated with survival after adjustment for established clinical factors, baseline monocyte burden, lymphocyte change, systemic inflammatory imbalance, and measured corticosteroid exposure. External prospective validation, medication-level confounder assessment, and immune phenotyping are required before clinical use.