- Mass General Brigham researchers compared data from more than 75,000 adults with TBI to a control group of the same size.
- They studied the patients over 24 years and observed how many developed brain tumors, leaving out any patients with existing risk factors, such as radiation exposure or a history of tumors.
- The study found an increased risk of developing a malignant brain tumor in adults with moderate to severe TBI.
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.
Paper cited: Marini, S. et al. "Traumatic Brain Injury and Risk of Malignant Brain Tumors." JAMA Network Open. DOI: 10.1001/jamanetworkopen.2025.28850
