Sex-Based Differences in Outcomes for Glioblastoma Patients Treated with Hypofractionated Chemoradiotherapy

Elucidation of prognostic factors is key to personalizing management approach for patients with glioblastoma (GBM). In patients who are treated with conventionally fractionated radiotherapy (cvRT), sex and other demographic variables (e.g., income level) were recently found to predict for treatment outcomes. However, it is unknown whether these factors predict for outcomes in elderly or poor performance status patients who receive hypofractionated RT (hyRT). In this study, we assess the association of clinical and non-clinical factors to outcomes in GBM patients treated with hyRT concurrent with temozolomide (TMZ).

The records of 61 adult patients with newly diagnosed GBM consecutively treated at our institution with post-operative hyRT (4005 cGy in 15 daily fractions) and TMZ were retrospectively analyzed. Established clinical variables as well as key demographic variables were compared using chi-squared tests. Kaplan-Meier analyses were used to compare overall survival (OS) and progression-free survival (PFS) between clinical and demographic subgroups. Multivariate modeling was performed using Cox proportional hazards regression.

Female and male patients composed 44.3% and 55.7% of the study population, respectively, and did not differ significantly in their clinical or tumor characteristics. Most patients were 65 years or older (85.2%), and over half resided in middle/high-income regions (55.7%) and were privately insured (55.7%). On an univariate analysis, female sex was associated with shorter OS (median 10.0 months vs. 13.3 months in males, p = 0.0224) and PFS (median 3.00 months vs. 4.60 months in males, p = 0.0134). Female sex remained significantly associated with inferior outcomes on multivariate analysis. Income level, type of insurance and marital status were not significantly associated with treatment outcomes.

Our study is the first to report sex differences in GBM outcomes following hyRT-TMZ. Contrary to responses following cvRT-TMZ, females appear to have inferior outcomes after hyRT-TMZ versus males. Further investigation is warranted to define the optimal treatment approach for sex subgroups in GBM.