Clinical, molecular, and treatment-related predictors of survival in IDH-mutant grade 4 astrocytoma: a single-center cohort study

Aims: Astrocytoma, IDH-mutant, CNS WHO grade 4 represents a biologically distinct subgroup of high-grade gliomas characterized by more favorable outcomes than IDH-wild-type glioblastoma. However, despite the uniform application of glioblastoma-based treatment paradigms, substantial heterogeneity in survival persists, and the clinical, molecular, and treatment-related determinants of outcomes in this entity remain incompletely defined. Methods: We conducted a retrospective single-center cohort study of adult patients with histologically and molecularly confirmed IDH-mutant grade 4 astrocytomas treated between 2013 and 2024. Clinical, surgical, molecular, and treatment related variables were analyzed for associations with OS and PFS. Survival outcomes were estimated using the Kaplan–Meier method, and prognostic factors were evaluated using univariate and multivariate Cox proportional hazards models. To avoid immortal time bias, adjuvant temozolomide duration was not included in the primary multivariable analyses. Results: A total of 46 patients were included, with a median follow-up of 19.7 months. The median OS and PFS were 26.0 months (95% CI, 21.4–30.6) and 17.7 months (95% CI, 15.8–19.6), respectively. In multivariable analyses, ECOG performance status, Ki-67 proliferation index, and MGMT promoter methylation status emerged as independent predictors of OS, whereas performance status, extent of surgical resection, and MGMT promoter methylation independently predicted PFS. Completion of 12 cycles of adjuvant temozolomide was associated with improved survival in univariate analyses but was interpreted cautiously due to its time-dependent nature. Conclusion: Survival heterogeneity in IDH-mutant grade 4 astrocytomas reflects the combined influence of tumor biology and host-related factors, rather than the molecular subtype alone. Integrating functional performance, proliferative activity, and MGMT promoter status may enhance risk stratification and inform individualized clinical decision-making for this distinct glioma subtype.