Prognostic Value of Systemic Inflammation Markers and Clinical Factors in Grade 4 Diffuse Glioma: A Multicenter Retrospective Real-World Study.

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.