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.

A pilot randomized controlled trial to improve sleep and fatigue in children with central nervous system tumors hospitalized for high‐dose chemotherapy

“…Central nervous system (CNS) cancers are the most frequently occurring solid tumors in children and most common cause of cancer deaths among children 0 to 14 years of age . Despite improvements in survival, morbidity remains high . Sleep disturbances are frequently reported during treatment and survivorship .…”

Pediatric oncology provider perspectives and practices: Supporting patients and families in schooling after cancer diagnosis

“…The pediatric oncologist plays an important role in assuring optimal outcomes for the children they treat, including outcomes associated with neurocognitive function. A number of CNS‐directed treatments are both necessary and unavoidable to ensure the improving survival rates of many pediatric cancers . Supporting and educating families about neurocognitive impacts of therapy is an important component of childhood cancer care .…”

“…A number of CNS-directed treatments are both necessary and unavoidable to ensure the improving survival rates of many pediatric cancers. 10 Supporting and educating families about neurocognitive impacts of therapy is an important component of childhood cancer care. 11 However, a recent study reported that approximately half of parents do not recall receiving information about cognitive impacts from their oncology treatment team and nearly half felt unprepared for their child's return to school.…”

Cognitive Deficits and Altered Functional Brain Network Organization in Pediatric Brain Tumor Patients

“…With advances in treatment options, overall survival for pediatric brain tumors has significantly improved and the majority of patients become long-term survivors (Gajjar et al, 1997;Merchant et al, 2009;Packer et al, 2006). The presence of a Central Nervous System tumor increases the risk of cognitive impairment, with 20-50% of patients exhibiting such impairment at the time of diagnosis (Krull et al, 2018). In addition to experiencing cognitive deficits from the presence of the tumor, survivors of childhood brain tumors can develop sequelae from their diagnosis and from tumor directed therapies, such as surgery, chemotherapy, and radiotherapy.…”