Sex is an important prognostic factor for glioblastoma but not for nonglioblastoma

Gittleman, Haley; Ostrom, Quinn T.; Waite, Kristin; Hodges, Tiffany R.; Wright, Christina Huang; Wright, James; Rubin, Joshua B.; Berens, Michael E.; Lathia, Justin D.; Connor, James R.; Kruchko, Carol; Sloan, Andrew E.; Barnholtz‐Sloan, Jill S.

doi:10.1093/nop/npz019

Cited by 46 publications

(42 citation statements)

References 38 publications

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“…37 No difference in the Karnofsky performance score at diagnosis was found in another NCDB cohort of glioblastoma or non-glioblastoma patients. 7 Further, no difference was observed regarding healthcare insurance or size of the tumour, type of surgery, or chemotherapy or radiotherapy in non glioblastoma patients. 7 Gender was not identified as a significant factor in a multivariate analysis exploring the association between rates of gross total resection and radiotherapy and racial and socioeconomic disparities among 71 098 meningioma patients in the USA.…”

Section: Sex-specific Differences In Outcomementioning

confidence: 90%

Sex-specific aspects of epidemiology, molecular genetics and outcome: primary brain tumours

Rhun

Weller

2020

ESMO Open

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Recent years have seen a great interest in sex-specific aspects of many diseases, including cancer, in part because of the assumption that females have often not been adequately represented in early drug development and determination of safety, tolerability and efficacy in clinical trials. Brain tumours represent a highly heterogeneous group of neoplastic diseases with strong variation of incidence by age, but partly also by sex. Most gliomas are more common in men whereas meningiomas, the most common primary intracranial tumours, are more common in females. Potential sex-specific genetic risk factors and specific sex biology have been reported in a tumour-specific manner. Several small studies have indicated differences in tolerability and safety of, as well as benefit from, treatment by sex, but no conclusive data have been generated. Exploring sex-specific aspects of neuro-oncology should be studied more systematically and in more depth in order to uncover the biological reasons for known sex differences in this disease.

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Section: Sex-specific Differences In Outcomementioning

confidence: 90%

Sex-specific aspects of epidemiology, molecular genetics and outcome: primary brain tumours

Rhun

Weller

2020

ESMO Open

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“…MGMT promoter methylation is more commonly found in females with GBM, with a subsequent better outcome after treatment with alkylating agent temozolomide (TMZ) [ 12 , 13 , 14 , 15 ]. Interestingly, this prognostic advantage for females is not present in gliomas of lower malignancy grade [ 16 ]. Since MGMT promoter methylation is the most powerful biomarker for response to alkylating agent treatment in GBM at present, these findings have important implications for tailored therapy and need confirmation by further studies [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Sex Disparities in MGMT Promoter Methylation and Survival in Glioblastoma: Further Evidence from Clinical Cohorts

Smits

Łysiak

Magnusson

et al. 2021

JCM

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Introduction: Recent studies suggest an overrepresentation of MGMT promoter methylated tumors in females with IDHwt glioblastoma (GBM) compared to males, with a subsequent better response to alkylating treatment. Methods: To reveal sex-bound associations that may have gone unnoticed in the original analysis, we re-analyzed two previously published clinical cohorts. One was the multicenter Nordic trial of elderly patients with GBM, randomizing patients into three different treatment arms, including 203 cases with known MGMT promoter methylation status. The other was a population-based study of 179 patients with IDHwt GBM, receiving concomittant radiotherapy and chemotherapy with temozolomide. Cohorts were stratified by sex to test the hypothesis that female sex in combination with MGMT promoter methylation constitutes a subgroup with more favorable outcome. Results: There was a significantly larger proportion of MGMT promoter methylation and better outcome for female patients with MGMT promoter methylated tumors. Results were confirmed in 257 TCGA-derived IDHwt GBM with known sex and MGMT status. Conclusions: These results confirm that patient sex in combination with MGMT promoter methylation is a key determinant in GBM to be considered prior to treatment decisions. Our study also illustrates the need for stratification to identify such sex-bound associations.

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“…The bias in glioblastoma (GBM) incidence is approximately 1.6:1 [51]. We expect that if there are adaptations to make in our science to best incorporate common mechanisms underlying sex differences in cancer, they will be most easily identified in a cancer like GBM, that occurs with a mean sex bias in incidence and for which there are data that span the scales of oncology research from the cellular to the patient level [21,35,[52][53][54][55][56][57][58][59]. We conclude with a discussion of the rigorous statistical approaches for studying sex effects in the laboratory and the clinic ( Table 2).…”

mentioning

confidence: 99%

Sex differences in cancer mechanisms

et al. 2020

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We now know that cancer is many different diseases, with great variation even within a single histological subtype. With the current emphasis on developing personalized approaches to cancer treatment, it is astonishing that we have not yet systematically incorporated the biology of sex differences into our paradigms for laboratory and clinical cancer research. While some sex differences in cancer arise through the actions of circulating sex hormones, other sex differences are independent of estrogen, testosterone, or progesterone levels. Instead, these differences are the result of sexual differentiation, a process that involves genetic and epigenetic mechanisms, in addition to acute sex hormone actions. Sexual differentiation begins with fertilization and continues beyond menopause. It affects virtually every body system, resulting in marked sex differences in such areas as growth, lifespan, metabolism, and immunity, all of which can impact on cancer progression, treatment response, and survival. These organismal level differences have correlates at the cellular level, and thus, males and females can fundamentally differ in their protections and vulnerabilities to cancer, from cellular transformation through all stages of progression, spread, and response to treatment. Our goal in this review is to cover some of the robust sex differences that exist in core cancer pathways and to make the case for inclusion of sex as a biological variable in all laboratory and clinical cancer research. We finish with a discussion of lab-and clinic-based experimental design that should be used when testing whether sex matters and the appropriate statistical models to apply in data analysis for rigorous evaluations of potential sex effects. It is our goal to facilitate the evaluation of sex differences in cancer in order to improve outcomes for all patients.

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Sex is an important prognostic factor for glioblastoma but not for nonglioblastoma

Cited by 46 publications

References 38 publications

Sex-specific aspects of epidemiology, molecular genetics and outcome: primary brain tumours

Sex-specific aspects of epidemiology, molecular genetics and outcome: primary brain tumours

Sex Disparities in MGMT Promoter Methylation and Survival in Glioblastoma: Further Evidence from Clinical Cohorts

Sex differences in cancer mechanisms

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