Moderate-to-Severe TBI Linked to Elevated Risk of Malignant Brain Tumors

A groundbreaking 24-year retrospective cohort study published in JAMA Network Open underscores an important, albeit relatively low, risk: adults experiencing moderate-to-severe traumatic brain injury (TBI) demonstrate a significantly increased risk of developing malignant brain tumors compared to those without TBI or with mild injury.¹ The study, led by Mass General Brigham researchers, is prompting calls for greater long-term vigilance in TBI survivors. As a news release explained, “This is the first large civilian study to show that moderate to severe traumatic brain injury is associated with increased risk of developing malignant brain tumors.”²

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The researchers analyzed data from over 151,000 adults treated across multiple US institutions between 2000 and 2024. Moderate-to-severe TBI was associated with a malignant brain tumor incidence of 0.6%, compared to 0.4% in both the mild TBI and control groups. After adjusting for confounders, moderate-to-severe TBI carried a hazard ratio (HR) of 1.67 (95% CI, 1.31–2.12).² Mild injuries, such as concussions, were not linked to elevated risk.²

Lead author Saef Izzy, MD, MBChB, emphasized the clinical importance: “Although the absolute risk is low, the consequences are devastating. This study highlights the need for clinicians to consider the long-term implications of TBI beyond the immediate recovery period.”²

These findings align with prior observations in veteran populations. Among nearly 1.92 million Iraq and Afghanistan veterans, moderate-to-severe TBI (AHR 1.90; 95% CI, 1.16–3.12) and penetrating TBI (AHR 3.33; 95% CI, 1.71–6.49) were associated with subsequent brain cancer, whereas mild TBI was not.³ A recent peer-reviewed summary also highlighted elevated malignant brain tumor risk in moderate-to-severe TBI cases, calling for intensified monitoring and follow-up.⁴

While ionizing radiation remains the only well-established environmental risk factor for brain tumors, experimental data propose multiple plausible mechanisms arising from TBI. These include chronic neuroinflammation, astrocyte activation, glial scar formation, and metabolic dysregulation—all of which may contribute to neoplastic transformation in susceptible neural tissues.²

“The association we observed suggests that TBIs might leave lasting molecular changes that could predispose brain cells to malignant transformation," senior author Sandro Marini, MD, explained in the news release. "Further translational studies are needed to uncover the exact mechanisms.”²

Pharmacists are in a prime position to support this call for long-term vigilance. They can educate patients with a history of moderate-to-severe TBI about recognizing neurological red flags such as worsening headaches, cognitive decline, or new focal deficits. Additionally, pharmacists can advocate for scheduled neurological follow-up and encourage patients not to dismiss late-appearing symptoms.

Given their accessibility, pharmacists can bridge gaps between hospital discharge and long-term care, reinforcing to patients and caregivers that TBI is not solely an acute event but a condition with potential lifelong consequences. As Izzy noted, “TBI is increasingly being recognized as a chronic condition, not just an isolated injury. Our work adds another reason to monitor these patients long after the injury.”²

The authors acknowledge the study’s observational design, which cannot prove causality, and note the need for more granular research linking injury sites to tumor locations.² Not all data sets have found elevated overall cancer risk, such as a Taiwan population–based study in BMC Cancer that showed no difference between mild and severe TBI groups, underscoring the need for additional tumor-specific analyses.⁵

The accumulating evidence signals that moderate-to-severe TBI, though rendering a modest absolute risk, is associated with a significantly elevated risk of malignant brain tumors. For pharmacists and other healthcare professionals, the implication is clear: integrate long-term neurological vigilance into patient education and care pathways for TBI survivors. As the researchers stated, “This is not about creating fear—it is about ensuring awareness and better follow-up for patients who have already gone through a life-changing injury.”²

REFERENCES

1. Marini S, Alwakeal AR, Mills H, et al. Traumatic Brain Injury and Risk of Malignant Brain Tumors in Civilian Populations. JAMA Netw Open. 2025;8(8):e2528850. doi:10.1001/jamanetworkopen.2025.28850

2. Researchers find link between history of traumatic brain injury and development of malignant brain tumor. EurekAlert! Published August 25, 2025. Accessed September 4, 2025. https://www.eurekalert.org/news-releases/1095550

3. Stewart IJ, Howard JT, Poltavskiy E, et al. Traumatic Brain Injury and Subsequent Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars. JAMA Netw Open. 2024;7(2):e2354588. doi:10.1001/jamanetworkopen.2023.54588

4. Berdugo J. Moderate to severe TBI is associated with elevated malignant brain tumor risk. 2 Minute Medicine. Published September 2025. Accessed September 4, 2025. https://www.2minutemedicine.com/moderate-to-severe-tbi-is-associated-with-elevated-malignant-brain-tumor-risk/

5. Lu CC, Nyam TE, Ho CH, et al. New diagnosis of cancer in mild and moderate/severe traumatic brain injury patients in a 12-year population-based study. BMC Cancer. 2022;22(1):291. Published 2022 Mar 18. doi:10.1186/s12885-022-09416-4