A pilot grant funded in part by the University of Colorado Cancer Center will support a study that will look at factors contributing to extreme obesity in children with a type of benign brain tumor.
The one-year pilot study will be led by Todd Hankinson, MD, a CU Cancer Center member and division head of pediatric neurosurgery in the CU Department of Neurosurgery; and Allison Shapiro, PhD, MPH, assistant professor in the CU Department of Pediatrics.
The CU Cancer Center’s Cancer Prevention and Control (CPC) Program and the Lifecourse Epidemiology of Adiposity & Diabetes (LEAD) Center at the Colorado School of Public Health are providing $50,000 in pilot funding.
Hankinson and Shapiro will explore brain, cognitive, and behavioral contributions to obesity in youth with adamantinomatous craniopharyngioma (ACP), a benign, slow-growing brain tumor that affects children, especially between ages 5 and 14.
Although ACP is relatively uncommon, at roughly 1.9 cases per 1 million patients per year, it accounts for 5% to 10% of all pediatric brain tumors, and it can have a serious impact on young lives.
Shortened lifespans
ACP usually develops near the pituitary gland, behind the eyes. As the tumor grows, it can put pressure on important structures, leading to varied problems such as weight gain, impaired vision, sleep and memory problems, stunted growth, delayed puberty, headaches, and nausea.
Hankinson, whose lab focuses on ACP research, says it is “associated with the lowest quality of life scores of any pediatric brain tumor and with significantly shortened lifespan relative to otherwise healthy people.” He says treatment for years has focused on surgery with or without radiation therapy, but clinical research has shown that the tumors tend to return after treatment.
According to Shapiro and Hankinson, over half of children with ACP develop severe obesity, putting them at significant risk of metabolic and cardiovascular disease, which may contribute to lower life expectancy.
ACP growth “has a significant impact on hormone function, on vision and on a brain structure called the hypothalamus, which is really critical to a lot of basic maintenance functions of the body, things like feeling full when you eat, and how you metabolize calories, and even sleep and memory,” Hankinson says.
Poorly understood
Structural damage to the hypothalamus has long been known to be associated with higher rates of obesity among children with ACP, but how that process works is poorly understood.
“What we don’t know,” Shapiro says, “is how that potential structural damage, either from the tumor itself or from treatment, is influencing eating behaviors that may include disinhibition of eating – meaning you can't control your eating, it’s never enough – or even cognitive dysfunction that could contribute to eating behaviors.”
The study will be conducted at Children’s Hospital Colorado, which is a magnet hospital for treatment of ACP. Hankinson, Shapiro, and their colleagues will compare three groups: ACP-affected children with obesity, ACP children without obesity, and children with typical obesity without a tumor. “We’ll start with a small group of kids who are being identified at Children's Hospital, and we'll see if they’re interested in being a part of the study,” Shapiro says.
The research team will explore the ways in which the groups are neurologically different. They’ll also test the relationship between hypothalamic damage and its ability to connect with other parts of the brain that affect eating behavior. And they’ll investigate differences in cognitive function related to hypothalamic damage.
Eating patterns observed
As part of the study, participants will undergo a structural MRI scan to measure their hypothalamus and a functional MRI scan to assess connectivity to other parts of the brain after the participants consume a sugary drink. They’ll be asked how they feel when they eat and what they crave. Participants’ eating patterns will be observed at the Children’s Eating Laboratory, which has an observation room. And their cognitive domains – such as attention, memory, and ability to shift focus – will be tested.
Hankinson and Shapiro hope that preliminary data generated by the study will inform plans for a larger, comprehensive investigation of how brain, cognitive, and behavioral factors contribute to obesity in youth with ACP.
They say further study – possibly involving other research centers – could point to better weight-management interventions, involving cognitive training, behavioral approaches, and pharmaceutical treatments.
“There are preliminary trials out there of medications that are meant to address this type of hypothalamic dysfunction,” Hankinson says. “The mechanisms of those drugs may not be completely understood in the context of this patient population, and so this may be an opportunity to provide some useful data in terms of how to approach the use of those drugs in these patients.”
Shapiro and Hankinson will be working on the project with a team that includes two other CU Department of Pediatrics faculty members: Christina Chambers, MD, assistant professor of pediatric endocrinology, and Greta Wilkening, PsyD, PhD, professor of pediatric neurology.
Image at top: A digitally reconstructed magnetic resonance image of a patient with an adamantinomatous craniopharyngioma (ACP) tumor in the brain, shown in bright red, located behind the eyes (green) and pushing on the optic nerves. Image courtesy Todd Hankinson, MD.
