Brain Cancer Mortality following Traumatic Brain Injury (TBI): A TBI Model Systems Study

Introduction: Growing evidence suggests traumatic brain injury (TBI) may be a risk factor for subsequent brain cancer. We aimed to compare brain cancer mortality rates between persons with TBI and the general population. Methods: Retrospective cohort study of 20,211 individuals with TBI admitted for inpatient rehabilitation following acute hospitalization who enrolled in the TBI Model Systems (TBIMS) National Database (1987-2024). Brain cancer cases were identified by underlying or contributing cause of death on death certificate. Standardized mortality ratios (SMRs) compared to an age, sex, race, and calendar-year matched general population were calculated using the National Institute for Occupational Safety and Health LTASR R package. Secondary analyses explored brain cancer risk factors. Results: Of the 4,297 decedents, 18 died of brain cancer, reflecting a higher rate than the general population (SMR=1.75; 95%CI:1.04-2.77). Significantly higher brain cancer mortality was observed among participants with gunshot wound (GSW) related TBI (SMR=14.29; 95%CI:2.95-41.75), mild TBI (mTBI; SMR=3.88; 95%CI:1.06-9.94), but not moderate-to-severe TBI (SMR=1.52; 95%CI:0.83-2.54). Conclusion: Individuals who sustained a TBI had a 1.75-fold higher likelihood of brain cancer death than the general population. Further analyses observed increased brain cancer mortality risk among those with GSW-related TBI and mTBI. Together, these results may inform targets for early prevention and support further investigation of the causal pathophysiology underlying TBI-related brain cancer mortality.