Impact of Sex Differences and Tumor Location on Survival Outcomes in Glioblastoma Patients Receiving Standard of Care

abstract: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults and is linked to poor survival in affected patients due to its invasive and aggressive nature. The potential role of sexual dimorphism in GBM outcomes has long been overlooked. Notably, males and females differ in tumor behavior across many cancers1, which may be attributable to differences in genetic makeup and physiology, and in GBM there is a difference in incidence rate between males and females. The aim of the study was to investigate sex differences in GBM patients and compare median survival outcomes (OS) and progression-free survival outcomes (PFS) between sexes based on tumor location, laterality, age, tumor volume, and extent of resection. Patients who received standard-of-care (Stupp protocol) consisting of surgical intervention, concomitant chemoradiation, and 6 cycles of adjuvant temozolomide (TMZ) were included in this study to investigate sex differences in tumor characteristics (n = 216; males: n = 129, females: n = 87). Pre-surgical MRIs, specifically T1Gd sequences, were analyzed to determine tumor laterality and location. The patient cohort was divided into two groups indicating the extent of resection (EOR) they received: Gross Total Resection (GTR) and Subtotal Resection (STR). Additionally, the patient cohort was split into three age groups (Group I: 18-29, Group II: 30-49, and Group III: >50). Analyses were done using independent t-test and Cox proportional hazard modeling to determine which variables affect patient survival. The log-rank test was utilized to compare differences in survival rate in Kaplan-Meier analysis. Overall, our results suggest that female patients receiving standard-of-care may have a better prognosis than male patients. There was a significant difference in OS and PFS in females showing an increase in survival. Additionally, survival was significantly different between sexes following resection, with female patients receiving STR or GTR having longer OS and PFS than males. The difference in median OS between sexes is more pronounced among younger patients. Among five different brain locations, female patients who possess a frontal lobe tumor may live longer than male patients. The apparent difference in OS for patients living >1000 days in the Kaplan-Meier plot warrants further investigation in a larger cohort. Following tumor resection, female patients with a frontal lobe tumor may survive longer in comparison to male patients. Comparing brain hemispheres, patients who possessed a tumor on the left may survive longer. Investigating tumor location and tumor laterality, our results suggests that female patients with a left frontal lobe tumor show a significant survival advantage in comparison to females who possess a right frontal lobe tumor