Sex Differences in Glioblastoma—Findings from the Swedish National Quality Registry for Primary Brain Tumors between 1999–2018

Abstract

Sex disparities in glioblastoma (GBM) have received increasing attention. Sex-related differences for several molecular markers have been reported, which could impact on clinical factors and outcomes. We therefore analyzed data on all patients with GBM reported to the Swedish National Quality Registry for Primary Brain Tumors, according to sex, with a focus on prognostic factors and survival. All glioma patients registered during 20 years, from 1 January 1999 until 31 December 2018, with SNOMED codes 94403, 94413, and 94423, were analyzed. Chi2-test, log-rank test, and Kaplan–Meier analyses were performed. We identified 5243 patients, of which 2083 were females and 3160 males, resulting in a ratio of 1:1.5. We found sex related differences, with women having diagnostic surgery at a significantly higher age (p = 0.001). Women were also reported to have a worse preoperative performance status (PPS) (<0.001). There was no gender difference for the type of surgery performed. For women with radical surgery, overall survival was slightly better than for men (p = 0.045). The time period did not influence survival, neither for 1999–2005 nor 2006–2018, after temozolomide treatment was introduced (p = 0.35 and 0.10, respectively). In the multivariate analysis including sex, age, surgery, and PPS, a survival advantage was noted for women, but this was not clinically relevant (HR = 0.92, p = 0.006). For patients with GBM; sex-related differences in clinical factors could be identified in a population-based cohort. In this dataset, for survival, the only advantage noted was for women who had undergone radical surgery, although this was clinically almost negligible.

Clinical management and survival outcomes of patients with different molecular subtypes of diffuse gliomas in China (2011–2017): a multicenter retrospective study from CGGA

“…Interestingly, sex was also significantly associated with patient survival in specific molecular groups in our cohort, e.g., GBM-IDHwt. To our knowledge, this study is the first to reveal the prognostic role of sex in a Chinese cohort, although similar results have been reported in Western cohorts 56 – 59 . Several explanations have been suggested, including hormone rhythms, lifestyle, psychological status, and genetic inheritance 60 , 61 , and women appear to have a stronger protective response against DGs.…”

The Next Frontier in Health Disparities—A Closer Look at Exploring Sex Differences in Glioma Data and Omics Analysis, from Bench to Bedside and Back

“…However, similar to retrospective studies in larger trials, there are limited reports on gender differences [ 45 , 46 , 47 , 48 ]. Nonetheless, some large retrospective cohorts did identify sex-specific differences of note ( Table 3 ) [ 6 , 7 , 10 , 49 ]. This leads to further examination of data embedded in large-scale data sets, as discussed in the following section.…”

“…For women with radical surgery, overall survival was improved. However, a survival advantage for women was no longer statistically significant in multivariate analysis, including of sex, age, surgery, and performance status [ 10 ]. Intersectionality with age is revealed in several studies, including in a recent analysis of brainstem tumors from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2018 [ 6 ], which revealed that, in younger patients, females had a higher age-adjusted mortality rate compared to males, with the reverse trend noted in older patients.…”

“…In the context of glioma, several papers have explored biological factors and sex-dependent differences between men and women and implications related to histology, sex hormones [ 8 , 9 ], pregnancy, menstruation, menopause, and oral contraceptives. There is, however, an ongoing lack of in-depth understanding of the physiology and metabolism that underpins sex differences in glioma, with data just emerging [ 3 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. These biological differences can result in differences in the clinical outcomes of novel interventions.…”

Cost Matrix of Molecular Pathology in Glioma—Towards AI-Driven Rational Molecular Testing and Precision Care for the Future

“…There is also reported intersectionality between age and gender and between these clinical features and molecular markers with GFAP, EMA, MGMT, P53, NeuN, Oligo2, EGFR, VEGF, IDH1, Ki-67, PR, CD3, H3K27M, TS, and 1p/19q status included in the age group classification by Lin et al 2020 [ 55 ]. Gender-related prognosis differences and associated molecular features support connections to outcomes [ 57 , 58 ]. Molecular differences associated with gender were reported for XIST, PUDP, ZFX, JPX, KDM6A, and TSIX in females and PRKY, RPS4Y2, PCDH11Y, EIF1AY, RPS4Y1, and ZFY in males when the analysis was carried out on GBM and LGG [ 58 ].…”