Prognostic Value of Systemic Inflammation Markers and Clinical Factors in Grade 4 Diffuse Glioma: A Multicenter...

Background/Objectives: Systemic inflammation contributes to tumor growth and spread. We aimed to evaluate the association of pretreatment inflammatory indices and clinical and laboratory factors with survival in newly diagnosed grade 4 diffuse glioma. Methods: A total of 120 patients diagnosed with grade 4 diffuse glioma at four centers between 2013 and 2026 were analyzed retrospectively. Nine indices derived from complete blood counts were calculated. Overall survival (OS) and progression-free survival (PFS) were analyzed with Kaplan-Meier and multivariable Cox regression. The cut-off for the systemic inflammation response index (SIRI) was determined with maximally selected rank statistics. Ten machine learning models were compared with the Cox model using repeated cross-validation. Results: Median follow-up was 70 months. Median OS was 22.8 months (95% confidence interval [CI] 15.8-26.3) and median PFS was 10.9 months (95% CI 9.1-14.4). In the multivariable model, SIRI > 2.85 was independently associated with OS (hazard ratio [HR] 2.62, 95% CI 1.38-4.96, p = 0.003), and this association persisted in the isocitrate dehydrogenase (IDH)-wildtype subgroup (HR 3.06, 95% CI 1.27-7.39, p = 0.013). Hemoglobin was independently associated with PFS (HR per g/dL 0.84, 95% CI 0.73-0.96, p = 0.011). Smoking was an independent indicator of poor prognosis for both OS (HR 2.02) and PFS (HR 1.73). Ki-67 and tumor size were not associated with survival. Machine learning models did not outperform the Cox model, and their variable importance rankings were consistent with the classical analysis. Conclusions: Pretreatment SIRI, hemoglobin, and smoking were independently associated with survival in grade 4 diffuse glioma. These markers are available from routine tests and may contribute to prognostic assessment.