Summary: A large-scale study of more than 75,000 participants has found that moderate to severe traumatic brain injuries (TBIs) are associated with an increased risk of malignant brain tumors. Within three to five years of injury, 0.6% of patients with severe TBIs developed tumors, a higher rate than patients without trauma.
In contrast, milder trauma, such as concussion, did not pose a greater risk. While these findings do not prove a cause-and-effect relationship, they do highlight the importance of vigilance and long-term monitoring in people with severe trauma.
Key data
- High risk: Patients with moderate to severe TBI are more likely to develop malignant brain tumors.
- Concussions and mild head injuries are not linked to an increased risk of brain tumors, offering reassurance for patients with minor brain trauma.
- Medical effects: The results highlight the need for long-term follow-up of TBI survivors.
Source: General Mass
A comprehensive study conducted by Brigham and Women’s Hospital in Massachusetts has uncovered a compelling connection between traumatic brain injury (TBI) and the development of malignant brain tumors. The research highlights that individuals with a history of TBI regardless of severity face a notably increased risk of tumor formation compared to those without prior head trauma.
Drawing from health records spanning 24 years and involving over 75,000 participants, the study provides robust evidence that even mild or moderate TBIs may contribute to long-term neurological consequences. These findings underscore the importance of ongoing monitoring and deeper investigation into how brain injuries may influence cancer risk.
The results were published in JAMA Network Open.
“These findings are deeply concerning,” said Dr. Saif Eazi, neurologist and director of the CNS Injury Immunology Program at Brigham and Women’s Hospital, part of the Mass General Brigham Health System”.
The newly discovered link between TBI and malignant brain tumors adds urgency to the need for long-term medical vigilance. Dr. Eazi emphasized that this evidence shifts the focus from temporary treatment to sustained monitoring, especially as these tumors may develop years after the initial injury.
“Combined with our previous findings connecting TBI to cardiovascular disease,” he added, “this underscores the importance of lifelong surveillance for anyone with a history of brain injury. We must rethink how we care for these patients not just in the immediate aftermath, but for decades to come.”
The team categorized the severity of traumatic brain injuries into mild, moderate, and severe, with participants suffering from events ranging from car accidents to falls.
Among individuals with moderate to severe head injuries, 0.6% (87 out of 14,944) developed malignant brain tumors within three to five years post-injury—an incidence notably higher than that observed in the control group. In contrast, mild head injuries, including concussions, showed no significant association with increased tumor risk.
Importantly, the study’s objective was not to prove causation but to explore whether a statistical relationship exists between traumatic brain injury and the development of malignant brain tumors. The findings suggest a need for further investigation into potential biological mechanisms linking the two. A specific translational study will be needed in the future to establish a causal link and understand the underlying mechanisms.
The research team collaborated with experts from Northwestern University, UC San Francisco, the University of Texas Health Science Center, and the University of Missouri to strengthen the study’s scope and rigor. While prior studies have shown elevated brain tumor risks among veterans exposed to combat-related head trauma, findings in civilian populations have been inconsistent—making this new data especially significant.
To ensure accuracy, researchers used ICD codes to exclude individuals with prior brain tumors, benign growths, or known risk factors like radiation exposure. Unlike earlier neurotrauma studies at Mass General Brigham that linked head injuries to psychiatric and cardiovascular disorders, this investigation focused specifically on malignant tumor development.
Looking ahead, the team plans to explore how the location of head trauma may correlate with tumor formation using advanced imaging techniques. They also aim to study patients with repetitive injuries, such as those from frequent falls. “Although the overall risk remains low, brain tumors are devastating and often diagnosed late,” said lead author Dr. Sandro Marini. “This research gives us a chance to monitor head trauma patients more proactively and potentially intervene earlier.”
Authorship: In addition to Marini and Izzi, Mass. General Brigham authors include Joshua D. Burnstock, Ahmed Mashla, Jacob Gristle, and E. Antonio Chiuka. Other authors include Amar R. Al-Walukil, Hunter Mills, Muhammad T. Hassan, Farid Radmanish, Gandolf Schenk, Sharat Asrani, Rachel Grasho, Kethra Halabi, Anthony DiGiorgio, Stephen T. Magill, Jeffrey T. Manley, and Ross Zafonte.
Disclosures: Dr. Joshua Bernstock holds equity interests in Treovir Inc., a clinical-stage company focused on herpes simplex virus (HSV) therapies, and UpFront Diagnostics, a firm specializing in diagnostic technologies. Bernstock also serves on the scientific advisory boards of Centile Bioscience, QV Bioelectronics, and NeuroX1. SI announced that it has received grants from the U.S. National Institutes of Health.
Funding Acknowledgments:
Dr. Saef Izzy’s work received funding from several key institutions, including the National Institute of Neurological Disorders and Stroke (grant K08NS123503-04), the U.S. Department of Defense (grants SC240188, W911NF2310276, and HT9425-24-1-0635), and the Stepping Strong Center for Trauma Innovation, supporting his ongoing research into the long-term impacts of traumatic brain injury.
Dr. Geoffrey Manley was funded by the NINDS TRACK-TBI Study Grant (U01NS086090), the Department of Defense TRACK-TBI Precision Medicine Project Grant (W81XWH-18-2-0042), and the Department of Defense Medical Technology Enterprise Consortium Grant (W81-XWH-0505-01)
Abstract
Head trauma and brain tumor risk
Importance
A 2024 U.S. study published in JAMA Network Open revealed that veterans of the Iraq and Afghanistan wars who experienced moderate, severe, or penetrating traumatic brain injuries (TBIs) had a significantly higher risk of developing malignant brain tumors. The research, based on data from over 1.9 million veterans, found that while mild TBIs were not linked to increased cancer risk, more severe injuries were associated with up to a threefold rise in brain tumor incidence.
In contrast, studies conducted in civilian populations have produced mixed results, with many failing to replicate this association. These discrepancies may stem from differences in injury severity, environmental exposures, or long-term monitoring practices between military and civilian groups.
Objective
The aim was to determine whether a history of head trauma in adult US citizens was associated with the risk of subsequent development of malignant brain tumors.
Design, framework and participants
This retrospective cohort study analyzed patient registry data from Mass General Brigham (MGB), a leading tertiary academic medical center, spanning January 1, 2000, to January 1, 2024. The extensive dataset enabled researchers to examine long-term trends and associations between traumatic brain injury and malignant brain tumor development across a diverse patient population.
Adult patients (> 18 years) with mild or moderate to severe TBI were compared with a gender-neutral control group (TBI) without a history of TBI. The MGB data were compared with data from two other tertiary academic medical centers (University of California [UC] Health Data Warehouse and Northwestern Medicine) during the same period.
Key findings and actions
The primary endpoint in each patient registry was the development of a malignant brain tumor according to diagnostic codes from the International Classification of Diseases (ICD-9, 9th and 10th revisions). Cox proportional hazards regression analysis was used to determine whether head trauma (TBI) was associated with the development of brain tumors.
Results
The MGB group included 151,358 adults: 75,679 control participants (51.8% female; median age 56 years [IQR 39–71 years]) and 75,679 civilians with traumatic brain injury.
Among the general population studied with traumatic brain injury (TBI), the median age was 56 years (interquartile range [IQR] 39–74 years). Of these, 60,735 individuals had mild TBI—54.7% were women, with a median age of 54 years (IQR 37–73). In contrast, 14,944 had moderate to severe TBI, with 42.1% women and a notably younger median age range of 9–17 years, reflecting a distinct demographic profile for more severe injuries.
The median follow-up for the MGB cohort was 7.2 years (IQR 4.1–10.1 years). The prevalence of malignant brain tumors was 0.6% in the moderate to severe TBI group, compared with 0.4% in the control and mild TBI groups.
The risk of developing malignant brain tumors (hazard ratio [HR] 1.67 [95% CI 1.31–2.12]) was higher in the moderate-to-severe TBI group than in the mild TBI group (HR 0.99 [95% CI 0.83–1.18]). This risk persisted in a meta-analysis that also included data from two other centers (HR 1.57 [95% CI 1.26–1.95]).
Conclusion and relevance
A major U.S. cohort study has identified a strong correlation between moderate to severe traumatic brain injury (TBI) and an increased likelihood of developing malignant brain tumors. This association was not only evident in the primary dataset but also reinforced by a meta-analysis that pooled findings from several academic medical centers across different regions of the country.
While the findings underscore the importance of long-term monitoring for individuals with a history of traumatic brain injury (TBI), the biological mechanisms driving this increased risk remain unclear. Researchers emphasize the need for future studies to explore how head trauma may trigger or accelerate tumor development, potentially through chronic inflammation, immune dysregulation, or structural brain changes.
