5323 Harry Hines Boulevard
Dallas, Texas 75390
05/25/2011

Brain tumors are the second most common form of cancer during childhood. Brain tumors account for 16.6% of all cancers diagnosed among children younger than 15 years. In the United States, an estimated 2200 children and adolescents are diagnosed with a brain tumor annually. With current five-year survival rates of 73.3% for children with brain tumors, the majority of these will become long-term survivors. Survivors may be at increased risk for specific late effects, including: neurocognitive deficits, endocrine deficiencies, growth failure, and stroke.

Literature suggests that cranial radiation portends an increased risk for early development of cardiovascular risk factors, insulin resistance, and the metabolic syndrome. In adults, metabolic syndrome is known to be associated with premature heart disease, type 2 diabetes mellitus, and cardiovascular mortality. The core features of metabolic syndrome include lipid disorder, elevated blood pressure, central obesity, and insulin resistance. These late effects can have dramatic effect on quality of life and life expectancy. Cardiovascular disease can be the result of direct cardiovascular damage caused by cancer treatment or of accelerated atherosclerosis related to cancer treatment. Metabolic syndrome may represent the connection between childhood cancer survivorship and increased long-term risk of cardiovascular disease, particularly in brain tumor survivors.

Few studies have attempted to further characterize the specific components of cancer diagnosis and therapy associated with increased cardiovascular risk and metabolic syndrome. Only one study has evaluated pediatric brain tumor survivors for these late effects. This group examined fifty-two pediatric and young adult survivors of brain tumors for cardiovascular risk factors and metabolic syndrome. Their study evaluated laboratory markers and DXA scanning for fat mass and percentage, then compared their subjects to published norms for age/gender. They found that survivors of childhood brain tumors are, as a group, more overweight/obese, and have more dyslipidemia, metabolic syndrome, hypertension, and hyperuricemia. Specific risk factors included cranial radiation, hypothalamic/hypophyseal damage, growth hormone deficiency, and/or impaired mobility. The authors note, however, their small and heterogenous patient population.

This case control study will be the first of its kind to evaluate a significant population of radiated brain tumor survivors for cardiovascular risk factors, insulin resistance, and metabolic syndrome. It will also be the first to evaluate the biomarkers leptin, adiponectin and ghrelin in this population, and to compare results to current diagnostic criteria for insulin resistance and metabolic syndrome.

We hypothesize that childhood brain tumor survivors treated with radiation are at increased risk for metabolic syndrome compared with survivors treated without radiation. Current guidelines for long term follow-up of cancer survivors recommend yearly physical exams, to include height, weight, and BMI measurements. If patients have received greater than 18Gy cranial radiation, the recommendation is for screening labs with fasting glucose and lipid evaluation every two years. These recommendations are based on data in survivors of bone marrow transplantation and leukemia who received radiation as part of their therapy. We hope to provide definitive evidence of increased cardiometabolic risk in survivors of brain tumors, and demonstrate the need for more aggressive follow-up and interventions in this population. Such interventions could include diet modification, physical activity regimens, and medical treatment of insulin resistance, high blood pressure, and cholesterol disorders