Jeff Craven
August 28, 2025
Moderate-to-severe traumatic brain injury (TBI), but not mild TBI, is associated with a significantly higher risk for malignant brain tumor, a new study showed.
In a cohort that included more than 150,000 US adults with and without TBI, researchers found that those with a history of moderate-to-severe TBI were 67% more likely to develop any type of malignant brain tumor than individuals with mild TBI.
Though the overall risk for brain tumors was low, “I see these results as alarming,” Saef Izzy, MD, neurologist and head of the Immunology of CNS Injury Program at Brigham and Women’s Hospital, Boston, stated in a press release.
“Our work over the past 5 years has shown that TBI is a chronic condition with lasting effects. Now, evidence of a potential increased risk of malignant brain tumors adds urgency to shift the focus from short-term recovery to lifelong vigilance.”
The study was published on August 25 in JAMA Network Open.
Role of TBI Severity?
The retrospective cohort study builds on previous research that showed an association between brain tumors and a history of moderate-to-severe TBI in veterans of the Iraq and Afghanistan wars.
The analysis drew on information in the Mass General Brigham patient registry collected between 2000 and 2024 on 75,679 patients with no history of TBI (control individuals), 60,735 patients with a history of mild TBI, and 14,944 patients with moderate-to-severe TBI.
At baseline, patients had similar median ages in the control group and mild TBI group (56 years vs 54 years), while patients with moderate-to-severe TBI tended to be older (64 years).
Patients with TBI also had a longer median follow-up duration (4.6 years vs 4.9 years) and a significantly higher median number of encounters (20 vs 10) than patients in the control group. There were no significant differences in the control group and the TBI groups regarding race and ethnicity.
Overall prevalence of malignant brain tumors was low but was significantly higher among those with moderate-to-severe TBI (0.6%) than those in the control (0.4%) and mild TBI groups (0.4%; P = .001).
After adjusting for factors such as age, sex, race, and ethnicity, the researchers found a significant association between moderate-to-severe TBI and the risk for malignant brain tumors (adjusted hazard ratio [aHR], 1.67; P < .001). There was no association between mild TBI and development of brain tumors.
“Alongside our earlier findings linking TBI and cardiovascular disease, this underscores the importance of long-term monitoring for anyone with a history of TBI,” Izzy added.
Close Monitoring Needed
The researchers also compared the results of the Mass General Brigham cohort with data from 39,403 patients with TBI and 39,403 matched control participants from the University of California Health Data Warehouse and 16,222 patients with TBI and 16,222 matched control participants from the Northwestern Medicine.
For the University of California cohort malignant brain tumors were diagnosed in 0.1% of patients in the control group, 0.2% of the mild TBI group, and 0.1% of those with moderate-to-severe TBI. The analysis of the Northwestern Medicine cohort yielded similar results.
In a meta-analysis that included data from all three centers, the risk of developing malignant brain tumors remained significant for patients with a history of moderate-to-severe TBI (aHR, 1.57; 95% CI, 1.26-1.95).
The researchers were unable to determine malignant tumor type or identify patients with multiple TBIs. They also lacked access to socioeconomic factors such as smoking and alcohol use that might have impacted the results.
The researchers called for additional research into the association between TBI and brain tumors, and whether screening programs for brain tumors in patients with a history of TBI are warranted.
“While there is an increased risk of tumor from TBI, the overall risk remains low. Still, brain tumor is a devasting disease and often gets detected in later stages,” Sandro Marini, MD, lead author and neurologist at Mass General Brigham, Boston, said in the press release. “Now, we’ve opened the door to monitor TBI patients more closely.”
The study was supported by grants from the National Institutes of Health and the Gillian Reny Stepping Strong Center for Trauma Innovation. Izzy and Marini reported having no relevant financial conflicts. Full disclosures are included in the original article.
