Abstract / Summary
Background and Objectives: Clinical outcomes remain markedly heterogeneous in glioblastoma, isocitrate dehydrogenase (IDH)-wildtype, despite contemporary molecular classification and established clinicopathological risk factors. We investigated whether the pretreatment lactate dehydrogenase-to-albumin ratio (LAR), an accessible circulating index integrating systemic disease- and host-related information, provides complementary prognostic information. Materials and Methods: We retrospectively evaluated 134 patients with glioblastoma, IDH-wildtype, central nervous system (CNS) World Health Organization (WHO) grade 4. An exploratory, cohort-specific LAR threshold was derived for 12-month overall survival (OS) and retained without re-optimization across subsequent analyses. Associations with OS and progression-free survival (PFS) were evaluated using Cox regression, and incremental prognostic performance was assessed against a baseline clinicopathological model. Temporal and continuous associations with survival, internal model validation, and the relationship between LAR and treatment response during adjuvant temozolomide therapy were also examined. Results: The cohort-derived LAR threshold was 5.718. High pretreatment LAR was associated with shorter median OS (5.5 vs. 16.0 months) and PFS (5.2 vs. 10.6 months; both p < 0.001) and remained independently associated with OS (adjusted hazard ratio [HR], 4.51; 95% CI, 2.84–7.18) and PFS (adjusted HR, 3.60; 95% CI, 2.33–5.56). Adding LAR to the clinicopathological model increased Harrell’s C-index from 0.699 to 0.760 for OS and from 0.690 to 0.759 for PFS (both likelihood ratios, p < 0.001), with optimism-corrected C-indices of 0.743 and 0.742, respectively. Prognostic discrimination and adjusted effect estimates were greatest early in the follow-up period and attenuated over time, whereas continuous LAR showed nonlinear associations with both endpoints. Among the 104 patients who received adjuvant temozolomide, a high LAR was independently associated with progressive disease (adjusted odds ratio, 3.72; 95% CI, 1.28–10.81). Conclusions: Pretreatment LAR identified patients with IDH-wildtype glioblastoma who experienced poorer survival, and the prognostic effect was concentrated predominantly in the early disease course. Its incremental contribution beyond conventional clinicopathological characteristics supports the further evaluation of LAR as an accessible component of baseline risk characterization. However, independent external validation is required before clinical application.