Long-Term Effects of Radiation Therapy on Cognitive and Endocrine Function in Children With Leukemia and Brain Tumors

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Abstract
As the number of long-term survivors of childhood cancer has grown, it has become increasingly clear that central nervous system therapy may have serious long-term effects on cognition and endocrine function. These complications have been studied most extensively in children with brain tumors and leukemia. Children with acute lymphoblastic leukemia previously treated with cranial irradiation are at risk for cognitive decline. Chemotherapy-only regimens, which rely on high-dose frequently administered methotrexate, are also associated with producing cognitive dysfunction. Children irradiated for brain tumors are even more vulnerable. Risk factors include perioperative morbidity, young age, large-volume high-dose cranial irradiation, supratentorial location of tumor, moyamoya syndrome, and leukoencephalopathy. Cognitive decline is progressive over at least a decade. The most common radiation-induced endocrinopathies are hypothyroidism and growth hormone deficiency. Treatment effects on growth are multifactorial and include growth hormone deficiency, spinal shortening, precocious puberty, undetected hypothyroidism, and poor nutrition. Fifty percent to 80% of children treated with craniospinal radiation for brain tumors will experience growth failure. In hopes of reducing neurotoxicity, current treatments limit the dose and volume of radiation while adding chemotherapy. Results have not been uniformly positive, however, and may increase toxicity in some cases. The standard of care in 2004 is that children who have been treated for brain tumors and leukemia should be monitored for cognitive and endocrine dysfunction. Until effective nonneurotoxic treatment is identified, long-term effects assessments are essential to maximize the quality of life of survivors of childhood cancer.