Service members who experienced the worst types of head injuries -- moderate, severe or penetrating traumatic brain injury, or TBI -- are at higher risk for developing brain cancer, researchers at the Uniformed Services University of the Health Sciences and elsewhere have found.
A study published Thursday in JAMA Network Open found veterans with a moderate or severe TBI were at 90% increased risk for developing a subsequent brain malignancy, while those who experienced a penetrating injury had more than three times the risk when compared with those who never suffered a brain injury.
In a piece of good news, mild TBIs -- the most common type of head injury diagnosed in service members -- were not associated with an increased risk of brain cancer, according to the study.
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While brain cancer is uncommon, occurring in less than 1% of the U.S. population, it is a devastating diagnosis with poor outcomes. Just over one-third of those diagnosed with a primary brain cancer tumor survive more than five years, and those with the most common form of brain cancer, glioblastoma, have just a 6% to 22% chance of living five more years, depending on the age of diagnosis, according to the National Brain Tumor Society.
Why some people develop brain cancer remains somewhat of a mystery, although exposure to ionized radiation is strongly associated with malignancies. And according to the study, previous research on the relationship between head injuries and brain cancer conflicted, with some studies suggesting there was a link but others not finding an association.
When Navy Reserve Cmdr. Michael Dore treated two patients with histories of TBI for brain cancer at Naval Medical Center Portsmouth, Virginia, he sought out any relevant data from his alma mater at the Uniformed Services University.
The query led to the recently published research, conducted by researchers at the Bethesda, Maryland-based medical college; the University of Texas San Antonio; Duke University; and elsewhere.
For the retrospective study, "Traumatic Brain Injury and Subsequent Risk of Brain Cancer in Veterans of Iraq and Afghanistan Wars," the researchers examined the data of nearly 2 million veterans, using Defense Department and Department of Veterans Affairs records.
Categorizing traumatic brain injury findings as mild, moderate or severe and penetrating based on billing codes in medical records as well as self-reported loss of consciousness, post-traumatic amnesia or alteration of consciousness, the researchers found that nearly one-quarter of the group had experienced a TBI: 385,848 with a mild TBI; 46,859 categorized as moderate or severe; and 17,173 as penetrating wounds.
In the nearly 1.5 million veterans who never experienced a TBI, 318 persons were diagnosed with brain cancer, or .02%. In the mild TBI cohort, 80 were diagnosed, also .02%. But 17 troops or veterans who had experienced a moderate or severe TBI developed brain cancer, or .04%, and of those with penetrating TBI -- 10 or fewer -- roughly .06% got cancer.
The researchers said the findings may have some utility for general medicine, although given the makeup of the group studied -- a relatively young, mostly male population -- they may not be completely applicable.
Still, with more than 260,000 Americans hospitalized each year for severe traumatic brain injury, according to the Centers for Disease Control and Prevention, the research could contribute to the understanding of the relationship between head injury and cancer, said Air Force Col. Ian Stewart, the study's lead author.
"It is possible that more severe TBI increases risk in the civilian population as well," Stewart said in a statement Thursday.
Previous research has found that a link between TBI and the later development of brain cancer is plausible. Studies have shown that rats who suffered stab wounds to the head were more likely to develop brain tumors -- possibly the result of an inflammatory wound response or other metabolic or cell migration changes.
The main strength of the study, as noted by Stewart and the other researchers, is its sheer size, involving 1.9 million patients, and a time period that spanned more than seven years.
Limitations include the fact that the researchers had access only to the diagnoses recorded in medical records and not the actual lab results, and because the study excluded individuals who had not had a health appointment within the study period, 156 persons who were diagnosed with brain cancer within a year of their traumatic brain injury were excluded.
The study also did not capture persons whose TBIs were diagnosed and treated outside of the DoD or VA health systems, leading the authors to say their findings "are likely a conservative estimate."
Despite the drawbacks, the study provides "meaningful data" that clarifies an association between combat-related brain injury severity and brain cancer risk, according to Dr. Elie Massaad and Ali Kiapour, researchers at Massachusetts General Hospital and Harvard Medical School who were not involved in the study but weighed in with commentary on JAMA Network Open.
"Elucidating potential connections between battlefield trauma and longer-term health outcomes is imperative to inform prevention and care approaches for those who have served," they wrote.
Stewart said that, given the prevalence of TBI in the U.S. military and the poor outcomes of a brain cancer diagnosis, additional research is needed to identify those at risk and develop screening protocols.
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