Association between metabolic syndrome and glioblastoma post-operative survival time: A retrospective cohort study

Abstract

Background: Glioblastoma (GB) is an aggressive cancer with a poor prognosis. Treatment includes maximal safe surgical resection followed by concomitant chemotherapy and radiotherapy. Systemic metabolic dysregulation, as seen in metabolic syndrome (MetS), may potentiate tumour aggressiveness by promoting an optimal tumour microenvironment. The purpose of this thesis is to characterize the proportion of GB patients with MetS and determine if having MetS is associated with post-operative survival time. Methods: A retrospective cohort study was conducted in 241 GB patients who underwent a tumour resection and/or biopsy at Kingston Health Sciences Centre between April 1st, 2017, and March 31st, 2023. Data were collected via chart review. MetS was identified using established proxy measures, which primarily involve patients past medical and medication history. Survival time was defined as the length of time between date of surgical operation and date of death or censoring. The proportion of patients who met criteria for GB was crudely calculated. Cox proportional hazard models were used to determine if MetS status was associated with survival time for (1) all patients, and (2) patients aged 60 years and older. The age-restricted analysis was performed post-hoc. Results: At the time of surgery, 30% (95% CI [24%, 36%]) of patients met criteria for MetS, with the proportion of patients meeting disease criteria increasing with age. After adjustment with covariates, a statistically significant relationship between MetS and survival time was not found for patients of all ages (HR =0.83, 95% CI [0.60-1.14], p=0.26). In the age-restricted analysis, although statistical significance was not met (HR=0.74, 95% CI [0.53,1.03], p=0.07), replication of this study with a larger, more powerful sample may reveal MetS is associated with a lower HR of death. Conclusion: Contrary to GB cell’s hypothesized ability to harness metabolic dysregulation for more aggressive growth, this study did not find a statistically significant relationship between MetS status and survival time. In patients aged 60 years and older, MetS may be associated with longer survival. This is likely due to the nature of how MetS was identified in this study, rather than a biological mechanism.