Summary: A large retrospective study of over 75,000 adults found that moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of developing malignant brain tumors. Within three to five years after a moderate or severe TBI, about 0.6% of patients developed malignant brain tumors—higher than the rate observed in people without TBI or those with mild TBI. Mild TBIs, such as concussions, were not linked to an elevated tumor risk in this analysis. While these findings do not prove causation, they emphasize the need for long-term clinical vigilance for people who sustain serious brain injuries.
Researchers emphasize that TBI should be considered a chronic condition with potential long-term consequences. This study reinforces the importance of ongoing monitoring and follow-up care for survivors of moderate and severe TBI.
Key Facts
- Increased risk: Moderate-to-severe TBI was associated with a higher likelihood of subsequent malignant brain tumors.
- Mild TBI: Concussions and other mild TBIs were not associated with increased tumor risk in this cohort.
- Clinical implication: Findings support long-term surveillance of patients who experience moderate or severe TBI.
Source: Mass General Brigham
Overview
A team led by investigators at Mass General Brigham analyzed electronic health record data spanning 2000–2024 to examine whether a history of traumatic brain injury is associated with later development of malignant brain tumors. The study cohort included 151,358 adults from a major academic health system: 75,679 patients with documented TBI (categorized as mild or moderate-to-severe) and an age- and sex-matched control group of 75,679 patients without TBI. Results were published in JAMA Network Open.
Saef Izzy, MD, co-senior and corresponding author and head of the Immunology of CNS Injury Program at Brigham and Women’s Hospital, described the findings as concerning and said they underscore a need to shift clinical focus from short-term recovery to long-term surveillance for people with significant TBI.
The study categorized injuries as mild (including concussions) or moderate to severe and included a wide range of causes such as car crashes and falls. Among the 14,944 patients with moderate-to-severe TBI, 87 individuals (0.6%) developed malignant brain tumors within 3–5 years following injury. That prevalence exceeded the rate observed in both the control group and the mild TBI group, each of which had a 0.4% prevalence. In statistical analysis, moderate-to-severe TBI was associated with a higher hazard of malignant brain tumor (HR 1.67; 95% CI, 1.31–2.12). When combined with data from two other academic centers in a meta-analysis, the association persisted (HR 1.57; 95% CI, 1.26–1.95).
The study was designed to detect an association rather than to prove a causal link. The authors note that establishing causality and uncovering biological mechanisms will require additional translational research, including imaging and pathological studies that could explore whether tumor location corresponds to the site of prior injury.
This work builds on earlier Mass General Brigham studies linking TBI to a range of long-term health issues, including psychiatric, neurological, and cardiovascular conditions. The current results extend those concerns to malignant brain tumor risk specifically in civilian populations, addressing conflicting results from prior studies.
The research team collaborated with investigators at Northwestern University, the University of California San Francisco, the University of Texas Health Science Center, and the University of Missouri. To limit bias, the investigators excluded individuals with prior brain tumors, benign brain tumors, or known tumor risk factors such as prior therapeutic radiation, using standardized ICD-9 and ICD-10 diagnostic codes.
Lead author Sandro Marini, MD, noted that although the relative risk increase is meaningful, the absolute risk remains low. Even so, because malignant brain tumors are often severe and detected at later stages, closer monitoring of patients after moderate-to-severe TBI may allow earlier detection and intervention.
Authorship: In addition to Sandro Marini and Saef Izzy, Mass General Brigham authors include Joshua D. Bernstock, Ahmad Mashlah, Jakob Gerstl, and E. Antonio Chiocca. Additional contributors 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: Joshua D. Bernstock reports equity positions in Treovir Inc. and UpFront Diagnostics and advisory roles with Centile Bioscience, QV Bioelectronics, and NeuroX1. Sharat Israni reports NIH grant support and a 2023 Stepping Strong Innovator Award.
Funding: Saef Izzy received support from NIH/NINDS (K08NS123503-04), multiple Department of Defense awards, and a Stepping Strong Breakthrough Award. Geoffrey Manley’s contributions were supported in part by NIH/NINDS and Department of Defense grants related to TRACK-TBI studies.
About this TBI and brain cancer research news
Author: Brandon Chase
Source: Mass General Brigham
Contact: Brandon Chase – Mass General
Original Research: Open access. Title: “Traumatic Brain Injury and Risk of Malignant Brain Tumors” by Saef Izzy et al., JAMA Network Open. DOI and journal citation available in the published article.
Abstract
Traumatic Brain Injury and Risk of Malignant Brain Tumors
Importance: A 2024 study of veterans reported an increased risk of brain tumors after TBI, but civilian studies have produced mixed results. This investigation examines the association between civilian TBI history and subsequent malignant brain tumor risk.
Objective: To determine whether a history of TBI in US adult civilians is associated with higher risk of developing malignant brain tumors.
Design, Setting, and Participants: Retrospective cohort analysis using electronic health records from Mass General Brigham from January 1, 2000, to January 1, 2024. Adult patients (>18 years) with documented mild or moderate-to-severe TBI were compared with age- and sex-matched controls without TBI. Results were compared and meta-analyzed with data from two other tertiary academic centers.
Exposure: TBI categorized as mild or moderate-to-severe.
Main Outcomes and Measures: Development of malignant brain tumor identified by ICD-9 and ICD-10 codes. Cox proportional hazards models assessed associations between TBI severity and tumor development, with meta-analysis across contributing centers.
Results: The Mass General Brigham cohort included 151,358 adults (75,679 with TBI, 75,679 controls). Among those with TBI, 60,735 had mild injuries and 14,944 had moderate-to-severe injuries. Median follow-up was 7.2 years. Malignant brain tumor prevalence was 0.6% in the moderate-to-severe group versus 0.4% in controls and the mild TBI group. Moderate-to-severe TBI was associated with increased risk (HR 1.67; 95% CI, 1.31–2.12), and the association remained in meta-analysis with data from other centers (HR 1.57; 95% CI, 1.26–1.95).
Conclusions and Relevance: In this large civilian cohort study, a history of moderate-to-severe TBI was associated with an increased risk of subsequent malignant brain tumors. The finding persisted across geographically diverse datasets. Further research is necessary to clarify mechanisms and to guide strategies for targeted monitoring and early detection in patients with significant TBI.