Summary: An extensive study involving over 75,000 people has linked moderate to severe traumatic brain injury (TBI) to a heightened risk of developing brain tumors. Within three to five years of sustaining a severe TBI, 0.6% of patients were diagnosed with tumors—a rate notably higher than that seen in individuals without a history of TBI.
On the other hand, mild traumatic injuries, such as concussions, did not show any increased risk. Although the results do not demonstrate a causal relationship, they highlight the importance of long-term monitoring and care for people with severe traumatic injuries.
Key data
- High risk: Patients with moderate to severe TBI are at higher risk of developing brain tumors.
- Light LCT: The study found that concussions and other mild head injuries were not linked to a higher risk of developing brain tumors.
- Medical effects: The results emphasize the need for long-term follow-up of TBI survivors.
Source: Mass General
Scientists at Brigham and Women’s Hospital in Massachusetts have discovered an association between a history of traumatic brain injury (TBI) and an elevated risk of developing malignant brain tumors.
The team analyzed data from more than 75,000 people between 2000 and 2024 who had previously suffered mild, moderate or severe traumatic brain injury. The researchers discovered that individuals with a history of brain injury faced a markedly greater risk of developing a brain tumor compared to those with no prior head trauma.
The results are published in JAMA Network Open.
“I find these results alarming,” said co-senior and corresponding author Saif Eazi, MD, FNCS, FAN, neurologist and director of the CNS Injury Immunology Program at Brigham and Women’s Hospital, a founding member of the Mass. General Brigham Health System.
Over the past five years, our research has shown that traumatic brain injury (TBI) should be recognized as a chronic condition—one that can trigger persistent, long-term effects well beyond the initial injury.
The evidence of a possible increased risk of malignant brain tumors now points to the urgency of shifting the focus from short-term rehabilitation to lifelong monitoring.
“Combined with our previous findings linking TBI to cardiovascular disease, this underscores the importance of long-term follow-up for all individuals with a history of TBI.”
Among individuals with moderate or severe traumatic brain injury (TBI), 0.6%—equating to 87 out of 14,944 people—developed brain tumors within three to five years, a rate higher than that observed in the control group. In contrast, mild TBIs, such as those resulting from concussions, showed no association with increased tumor risk.
The researchers emphasized that the study’s purpose was to explore the potential association, not to prove a direct cause-and-effect relationship between moderate to severe TBI and malignant tumors. They note that a dedicated translational study will be essential to confirm causality and uncover the biological mechanisms driving this link.
The study was conducted in partnership with researchers from Northwestern University in Chicago, the University of California, San Francisco, the University of Texas Health Science Center, and the University of Missouri.
While earlier research has found that veterans of the Iraq and Afghanistan wars who experienced traumatic brain injury (TBI) faced a higher risk of developing brain tumors, investigations in civilian populations have produced mixed and sometimes contradictory findings, underscoring the need for large-scale civilian studies like this one.
To ensure accuracy, the researchers applied ICD disease classification codes to exclude participants with pre‑existing risk factors, including prior brain tumors, benign growths, or radiation exposure.
While earlier neurotrauma research at Mass General Brigham linked traumatic brain injury (TBI) to a higher incidence of psychiatric, neurological, and cardiovascular conditions such as anxiety and depression, this investigation specifically examined the potential connection between TBI and malignant brain tumors.
Looking ahead, the team plans to use advanced imaging studies to explore whether the location of a brain injury influences tumor development. They also intend to follow individuals with repeated head injuries, such as those caused by frequent falls, to better understand long‑term risks.
Dr. Sandro Marini, neurologist at Brigham and Massachusetts General Hospital, noted that while traumatic brain injury (TBI) does raise the likelihood of developing tumors, the overall risk is still low. He emphasized, however, that brain tumors are serious and often detected only in advanced stages, making early monitoring crucial. According to Marini, these findings now open the door to more intensive follow‑up care for individuals with a history of TBI.
Authorship: In addition to Marini and Izzi, “Mass. General Brigham” is written by Joshua D. Burnstock, Ahmed Mashla, Jacob Gristle, and E. Antonio Chiuka. Other writers include Amar R. Al-Walukiel, 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: Bernstock holds interests in Treovir Inc., a clinical‑stage company developing treatments for oHSV, as well as UpFront Diagnostics. He also serves on the boards of Centile Bioscience, QV Bioelectronics, and NeuroX1.
In addition, SI reports receiving funding from the U.S. National Institutes of Health (Grant No. 5K08NS123503‑02) and the 2023 Stepping Strong Innovation Awards.
Funding: Izzy has received multiple grants from the National Institute of Neurological Disorders and Stroke (K08NS123503‑04), the U.S. Department of Defense (SC240188, W911NF2310276, and HT9425‑24‑1‑0635), and the Stepping Strong Center for Trauma Innovation.
Manley’s research has been supported by the NINDS TRACK‑TBI Study Grant (U01NS086090), the U.S. Department of Defense TRACK‑TBI Precision Medicine Project Grant (W81XWH‑18‑2‑0042), and the U.S. Department of Defense/Medical Business Technology Grant (W81XWH‑15‑9‑0001).
Abstract
Recent large‑scale research has found a clear association between moderate to severe traumatic brain injury (TBI) and an elevated risk of malignant brain tumors in civilian populations
Importance
A 2024 U.S. study reported that veterans of the Iraq and Afghanistan wars who sustained a traumatic brain injury (TBI) faced a higher likelihood of developing brain tumors. In contrast, research involving civilian populations has produced inconsistent findings, with no definitive evidence yet confirming a connection between TBI and brain tumor risk.
Objective
The aim was to investigate whether a history of TBI in adult US citizens is associated with the risk of subsequent development of malignant brain tumors.
Design, Setting, and Participants
This retrospective cohort study analyzed patient registry data from Mass General Brigham (MGB) spanning January 1, 2000, to January 1, 2024. It included adults aged 18 and older with either mild or moderate to severe traumatic brain injury (TBI), comparing them to a control group of adults with no history of brain injury.
To strengthen the findings, the MGB dataset was also compared with records from two other major U.S. tertiary academic medical centers the University of California (UC) Health Data Warehouse and Northwestern Medicine covering the same time frame. This multi‑center approach allowed for broader validation and reduced the likelihood that results were specific to a single institution.
Exposure
LCT, which was classified as mild or moderate to severe.
Main Outcomes and Measures
The primary outcome was the development of a malignant brain tumor, based on the diagnostic codes from the International Classification of Diseases (ICD-9) and the Tenth Revision (ICD-10) in each patient’s data. A Cox proportional hazards regression analysis was used to determine whether traumatic brain injury (TBI) was associated with the development of brain tumors. MGB outcomes were meta-analyzed using data from UC Health and Northwestern Medicine.
Results
The MGB cohort consisted of 151,358 adults: 75,679 controls (51.8% female; median age 56 years [IQR 39–71 years]) and 75,679 civilians with TBI.
Among the citizens with TBI (median age 56 years [IQR: 39-74 years]), 60,735 had mild TBI (54.7% women; median age 54 years [IQR: 37-73 years]) and 14,944 had moderate to severe TBI (42.1% women; median age 47 years [IQR: 7-7 years]). The median follow-up duration 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 group and mild TBI group.
The risk of developing malignant brain tumors (hazard ratio [HR] 1.67 [95% CI 1.31-2.12]) in the moderate-to-severe TBI group was higher than in the mild TBI group (HR 0.99 [95% CI 0.83-1.18]). This risk persisted after meta-analysis of data from two other centers (HR 1.57 [95% CI 1.26-1.95]).
Conclusion and relevance
In this U.S. cohort study, adults with a history of moderate to severe traumatic brain injury (TBI) were found to have a significantly higher risk of developing malignant brain tumors. A meta‑analysis combining data from multiple, geographically diverse medical centers across the country confirmed this association. The authors note that further research is essential to uncover the biological mechanisms linking TBI to tumor development and to determine whether the relationship is causal.
