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

## TL;DR

This study finds that female glioblastoma patients treated with short-course chemoradiotherapy have worse outcomes than males, which is the opposite of what is seen with standard treatment.

## Contribution

First study to show sex-based outcome differences in glioblastoma patients treated with hypofractionated chemoradiotherapy.

## Key findings

- Female sex was associated with shorter overall and progression-free survival in patients receiving hypofractionated chemoradiotherapy.
- These findings contradict previous reports where females had better outcomes with standard chemoradiotherapy.
- Income level, insurance type, and marital status were not significantly linked to treatment outcomes.

## Abstract

Glioblastoma is a fatal brain tumor treated with surgery and chemoradiotherapy. In addition to known clinical and tumor related factors, certain demographic factors like sex, insurance status and income level have been recently reported to prognosticate for outcomes in patients receiving standard long-course chemoradiotherapy. However, it is not known whether these demographic factors prognosticate in patients who receive short-course chemoradiotherapy, an abbreviated treatment alternative reserved for elderly or low functional status patients. Identifying prognostic factors is important for refining personalized management approaches for this critically ill population. In this study, we investigate the role of demographic factors in patients receiving short-course chemoradiotherapy and find that female sex predicts for shorter time to tumor recurrence and death. These findings are first-in-kind and are contrary to what has been reported in patients who receive long-course chemoradiotherapy, highlighting the need to further investigate the impact of sex on response to different treatment regimens in glioblastoma.

Background/Objective: 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). Methods: 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. Results: 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. Conclusion: 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.