Sex-based survival differences in IDH-wildtype glioblastoma: Results from a retrospective cohort study

A female survival benefit has been described for glioblastoma patients. Recent studies report that the effect of 0⁶-methylguanine-DNA-methyltransferase gene promoter (MGMTp) methylation is only present in female patients. We retrospectively studied sex-based survival, including MGMTp-methylation, in a cohort of 159 uniformly treated isocitrate dehydrogenase wildtype (IDHwt) patients. All patients were treated with temozolomide-based chemoradiotherapy after surgery. Kaplan-Meier survival curves and Cox regression models were used to evaluate overall survival. The study included 59 female (37.1%) and 100 male patients (62.9%). There were no statistically significant differences between sexes concerning demographic, surgical or radiological characteristics. Female patients harbored MGMTp-methylated tumors in 45.8% of cases and males in 33% (P = 0.129). Median overall survival was 13.4 months for men and women alike. After adjustment of survival for age, Karnofsky Performance Score, extent of resection and MGMTp-methylation, sex did not have a significant survival impact. However, MGMTp-methylation proved to be an independent beneficial prognosticator for both sexes, contradicting earlier reports. Several sex-based molecular subtypes of glioblastoma with different response to current treatment may exist explaining conflicting survival results in different patient cohorts. Further research on sex-based differences in IDHwt glioblastoma patients is needed.