Neurocognitive Outcomes and Interventions in Long-Term Survivors of Childhood Cancer

Abstract

Recent research has demonstrated that survivors of childhood cancer are at risk for a myriad of late effects that affect physical and mental quality of life. We discuss the patterns and prevalence of neurocognitive problems commonly experienced by survivors of CNS tumors and acute lymphoblastic leukemia, the two most commonly researched cancer diagnoses. Research documenting the direct effects of tumor location and treatment type and intensity is presented, and patient characteristics that moderate outcomes (eg, age at diagnosis and sex) are discussed. Potential biologic mechanisms of neurotoxic treatment exposures, such as cranial irradiation and intrathecal and high-dose antimetabolite chemotherapy, are reviewed. Genetic, brain imaging, and neurochemical biomarkers of neurocognitive impairment are discussed. Long-term survivors of childhood cancer are also at risk for physical morbidity (eg, cardiac, pulmonary, endocrine) and problems with health behaviors (eg, sleep); research is reviewed that demonstrates these health problems contribute to neurocognitive impairment in survivors with or without exposure to neurotoxic therapies. We conclude this review with a discussion of literature supporting specific interventions that may be beneficial in the treatment of survivors who already experience neurocognitive impairment, as well as in the prevention of impairment manifestation.

Fig 1.

Model of biobehavioral impact of cancer and cancer therapy on brain development and neurocognitive outcomes in long-term survivors of childhood cancer.

Fig 2.

(A) Survivors of childhood acute lymphoblastic leukemia demonstrate a profile of both higher (warm colors) and lower (cool colors) white matter connectivity compared with healthy controls (color bar indicates T score). (B) Connectivity seems to have an optimal range with respect to cognitive function.