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With modern therapies and supportive care, survival of childhood cancer has increased considerably. Patients who have survived cancers involving the central nervous system or who have received therapy toxic to the developing brain are at risk of long-term neurocognitive sequelae. Negative outcomes are observed most frequently in survivors of acute lymphoblastic leukemia and brain tumors. The Children's Oncology Group Long-term Follow-up Guidelines Task Force on Neurocognitive/Behavioral Complications After Childhood Cancer has generated risk-based, exposure-related guidelines designed to direct the follow-up care of survivors of pediatric malignancies based on a comprehensive literature review and expert opinion. This article expands on these guidelines by reviewing the risk factors for the development of neurocognitive sequelae and describing the expected pattern of these disabilities. We herein present recommendations for the screening and management of neurocognitive late effects and outline important areas of school and legal advocacy for survivors with disabilities. Finally, we list resources that can guide patients, their parents, and their medical caregivers as they face the long-term neurocognitive consequences of cancer therapy.

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Childhood cancer survivors are at risk for development of subsequent neoplasms of the central nervous system (CNS). Better understanding of the rates, risk factors for and outcomes of subsequent neoplasms of the CNS among survivors of childhood cancer may lead to the development of more informed screening guidelines. Two independent investigators independently performed a systematic search of studies from the MEDLINE and EMBASE databases (1966 – 2012) for studies examining subsequent neoplasms of the CNS among childhood cancer survivors. Articles were selected to answer 3 questions: What is the risk of CNS tumors following radiation to the cranium for a pediatric cancer as compared with the general population? What are the outcomes in children with subsequent neoplasms of the CNS who have been treated with CNS directed radiation for a pediatric cancer? Are outcomes of subsequent neoplasms different from primary neoplasms of the same histology? Our search identified 72 reports, of which 18 publications were included in this review. These studies reported that childhood cancer survivors have an 8.1 – 52.3 times higher incidence of subsequent CNS neoplasms compared with the general population. Nearly all cancer survivors who developed a CNS neoplasm had been exposed to cranial radiation; some studies demonstrate a correlation between radiation dose and risk of subsequent CNS tumors. Five year survival rates for subsequent high-grade gliomas and meningiomas range from 0 – 19.5% and 73 – 100%, respectively, which are similar to those observed in patients with primary gliomas or meningiomas. The quality of evidence was limited by variation in study design, heterogeneity of details regarding treatment and outcomes, limited follow-up and relatively small sample sizes. We concluded that survivors of childhood cancer who were treated with cranial radiation therapy have an elevated risk for subsequent CNS neoplasms. The current literature is insufficient to comment about the potential harms and benefits of routine screening for subsequent CNS neoplasms.

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