The results of a retrospective cohort study published in JAMA Network Open revealed an association between having a history of moderate to severe traumatic brain injury (TBI) and the risk of developing malignant brain tumors in adult civilians from the United States. Marini et al confirmed the relationship in a meta-analysis that included geographically diverse sites across the country.
“A 2024 U.S. study reported that veterans of the Iraq and Afghanistan wars affected by [TBI] had an increased risk of developing brain tumors,” the investigators remarked. “However,” they added, “studies among civilians have shown conflicting results….” Their abovementioned findings from the present analysis suggested that “additional evaluation and monitoring may be warranted for adult civilians with [TBI] to detect the potential development of malignant brain tumors.”
Study Details
The researchers focused on data from a tertiary academic medical center (Mass General Brigham) patient data registry. Data on nonveterans with TBI were compared with date from an unaffected age- and sex-matched group (both n = 75,679). Of those with TBI, 60,735 and 14,944 had mild and moderate-to-severe cases, respectively. Follow-up data for the Mass General Brigham cohort were provided for a median of 7.2 years.
The investigators identified malignant brain tumor development as the primary outcome. Cox proportional hazards regression analysis was conducted to assess the association between TBI and the risk of developing brain tumors. Results from Mass General Brigham were then the focus of a meta-analysis with findings from two other tertiary academic medical centers (University of California Health Data Warehouse and Northwestern Medicine).
Malignant Brain Tumor Development
In the Mass General Brigham cohort, malignant brain tumors were reported in 0.6% of patients with moderate-to-severe TBI and 0.4% of both the control group and those with mild cases. Compared with patients who had mild TBI (hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.83–1.18), those with moderate-to-severe TBI (HR = 1.67, 95% CI = 1.31–2.12) were found to have a higher risk of developing malignant brain tumors. The observed risk appeared consistent in a meta-analysis with data from the other two centers (HR = 1.57, 95% CI = 1.26–1.95).
The investigators concluded: “This analysis leveraged, to our knowledge, the largest cohort of nonveterans with TBI and identified an association between TBI and malignant brain tumor development in adults that may have gone undetected in previous smaller studies. These findings prompt studies aimed at answering whether specific screening programs for brain tumors should be implemented following TBI. Future studies should clarify whether TBI increases risk directly, indirectly, or via other spurious confounding associations.”
Saef Izzy, MD, of Harvard Medical School, Boston, is the corresponding author of the JAMA Network Open article.
Disclosure: The study was funded by the National Institutes of Health and a Stepping Strong Breakthrough Award from the Gillian Reny Stepping Strong Center for Trauma Innovation. For full disclosures of the study authors, visit jamanetwork.com.
