Summary: A large study of more than 75,000 people has found that moderate-to-severe traumatic brain injury (TBI) is linked to an increased risk of malignant brain tumors. Within 3–5 years of injury, 0.6% of patients with significant TBIs developed tumors—higher than those without TBI.
In contrast, mild TBIs, such as concussions, did not show an elevated risk. While the findings do not establish causation, they highlight the importance of long-term vigilance and monitoring for people with serious TBIs.
Key Facts
- Higher Risk: Moderate-to-severe TBI patients were more likely to develop malignant brain tumors.
- Mild TBI: Concussions and mild TBIs were not linked to increased tumor risk.
- Clinical Impact: Findings underscore the need for long-term monitoring of TBI survivors.
Source: Mass General
New research led by investigators at Mass General Brigham suggests a link between a history of traumatic brain injury (TBI) and risk of developing a malignant brain tumor.
By evaluating data from 2000-2024 of more than 75,000 people with a history of mild, moderate or severe TBI, the team found the risk of developing a malignant brain tumor was significantly higher compared to people without a history of TBI.
The results were published in JAMA Network Open.
“I see these results as alarming,” said co-senior author and corresponding author Saef Izzy, MD, FNCS, FAAN, a neurologist and head of the Immunology of CNS Injury Program at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system.
“Our work over the past five 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.
“Alongside our earlier findings linking TBI and cardiovascular disease, this underscores the importance of long-term monitoring for anyone with a history of TBI.”
The team divided the severity of TBI between mild, moderate and severe, with participants suffering from incidents ranging from car accidents to falls.
In the two categories of moderate and severe, 0.6% of people (87 out of 14,944) developed brain tumors within 3-to-5 years after the TBI, which was a higher percentage than controls. Mild cases of TBI, such as those caused by concussions, were not associated with an increased risk of tumor.
The aim of the study was not to establish a cause-and-effect link between moderate-to-severe TBI and malignant tumors, but rather to explore whether an association exists. Determining causality and understanding the underlying mechanisms will require a dedicated translational study in the future.
The team collaborated 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.
A previous study showed veterans of the Iraq and Afghanistan wars who suffered TBI experienced an increased risk of brain tumors, but previous studies on civilian populations showed conflicting results.
The researchers used an international disease classifying system known as ICD codes to exclude anyone in the study with a history of brain tumor, benign tumors, and risk factors such as radiation exposure.
Previous neurotrauma studies from Mass General Brigham have looked at patients with a history of TBI and found an association with the emergence of anxiety, depression, and other psychiatric, neurological, and cardiovascular diseases, but the current study focuses on malignant tumor development.
Future imaging studies could draw a connection between the location of the TBI and where tumors developed in the brains of participants. The team would like to further study patients with repeated injuries, such as falls.
“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,” said lead author Sandro Marini, MD, a neurologist at Mass General Brigham. “Now, we’ve opened the door to monitor TBI patients more closely.”
Authorship: In addition to Marini and Izzy, Mass General Brigham authors include Joshua D. Bernstock, Ahmad Mashlah, Jakob Gerstl, and E. Antonio Chiocca. Additional authors include Amr R. Alwakeal, Hunter Mills, Muhammad T. Hassan, Farid Radmanesh, Gundolf Schenk, Sharat Israni, Rachel Grashow, Cathra Halabi, Anthony DiGiorgio, Stephen T. Magill, Geoffrey T. Manley, and Ross Zafonte.
Disclosures: Bernstock has an equity position in Treovir Inc., an oHSV clinical stage company and UpFront Diagnostics. Bernstock is also on the Centile Bioscience, QV Bioelectronics and NeuroX1 boards of scientific advisors. SI reports a grant from the US National Institutes of Health (grant number 5K08NS123503-02) and 2023 Stepping Strong Innovator Awards.
Funding: Izzy is supported by several grants from National Institute of Neurological Disorders and Stroke (K08NS123503-04), Department of Defense (SC240188, W911NF2310276, and HT9425-24-1-0635), and a Stepping Strong Breakthrough Award from the Gillian Reny Stepping Strong Center for Trauma Innovation (Izzy). Manley was supported by grant U01NS086090 from the National Institute of Neurological Disorders and Stroke TRACK-TBI study, grant W81XWH-18-2-0042 from the US Department of Defense TRACK-TBI Precision Medicine project, and grant W81XWH-15-9-0001 from the US Department of Defense/Medical Technology Enterprise Consort.
About this TBI and brain cancer research news
Author: Brandon Chase
Source: Mass General
Contact: Brandon Chase – Mass General
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Traumatic Brain Injury and Risk of Malignant Brain Tumors” by Saef Izzy et al. JAMA Network Open
Abstract
Traumatic Brain Injury and Risk of Malignant Brain Tumors
Importance
A 2024 US study reported that veterans of the Iraq and Afghanistan wars affected by traumatic brain injury (TBI) had an increased risk of developing brain tumors. However, studies among civilians have shown conflicting results and have not replicated the association between TBI and brain tumor risk.
Objective
To examine whether history of TBI in US adult civilians is associated with a risk of subsequent development of malignant brain tumors.
Design, Setting, and Participants
This retrospective cohort study used data from a tertiary academic medical center (Mass General Brigham [MGB]) patient data registry encompassing January 1, 2000, to January 1, 2024. Adult patients (aged >18 years) with mild TBI or moderate to severe TBI (exposure group) were compared with an age- and sex-matched group without a history of TBI (control group). The MGB data were compared across the same time span with data from 2 other tertiary academic medical centers (University of California [UC] Health Data Warehouse and Northwestern Medicine).
Exposure
TBI, which was categorized by severity as mild or moderate to severe.
Main Outcomes and Measures
The primary outcome was development of malignant brain tumor based on International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) diagnostic codes in the patient data registry of each cohort. Cox proportional hazards regression analysis was used to determine whether TBI was associated with brain tumor development. The MGB results were then meta-analyzed with the UC Health and Northwestern Medicine data.
Results
The MGB cohort included 151 358 adults: 75 679 control participants (51.8% female; median age, 56 years [IQR, 39-71 years]) and 75 679 civilians with TBI.
Of the civilians with TBI (median age, 56 years [IQR, 39-74 years]), 60 735 had mild TBI (54.7% female; median age, 54 years [IQR, 37-73 years]) and 14 944 had moderate to severe TBI (42.1% female; median age, 64 years [IQR, 47-79 years]). The median follow-up duration for the MGB cohort was 7.2 years (IQR, 4.1-10.1 years). Malignant brain tumor prevalence was 0.6% in the moderate to severe TBI group vs 0.4% in the control and mild TBI groups.
The moderate to severe TBI group had a higher risk of developing malignant brain tumors (hazard ratio [HR], 1.67 [95% CI, 1.31-2.12]) compared with the mild TBI group (HR, 0.99 [95% CI, 0.83-1.18]). The risk persisted when meta-analyzed with data from the other 2 centers (HR, 1.57 [95% CI, 1.26-1.95]).
Conclusions and Relevance
In this cohort study of US adult civilians, a history of moderate to severe TBI was associated with risk of developing malignant brain tumors. This association was confirmed in a meta-analysis with geographically diverse sites across the US. Additional research is needed to clarify the mechanism through which TBI increases the risk of developing brain tumors.
