title: Chemotherapy-induced neurotoxicity in pediatric solid non-CNS tumor patients: An update on current state of research and recommended future directions.
abstract: Neurocognitive sequelae are known to be induced by cranial radiotherapy and central-nervous-system-directed chemotherapy in childhood Acute Lymphoblastic Leukemia (ALL) and brain tumor patients. However, less evidence exists for solid non-CNS-tumor patients. To get a better understanding of the potential neurotoxic mechanisms of non-CNS-directed chemotherapy during childhood, we performed a comprehensive literature review of this topic. Here, we provide an overview of preclinical and clinical studies investigating neurotoxicity associated with chemotherapy in the treatment of pediatric solid non-CNS tumors. Research to date suggests that chemotherapy has deleterious biological and psychological effects, with animal studies demonstrating histological evidence for neurotoxic effects of specific agents and human studies demonstrating acute neurotoxicity. Although the existing literature suggests potential neurotoxicity throughout neurodevelopment, research into the long-term neurocognitive sequelae in survivors of non-CNS cancers remains limited. Therefore, we stress the critical need for neurodevelopmental focused research in children who are treated for solid non-CNS tumors, since they are at risk for potential neurocognitive impairment.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital Leuven, Leuven, Belgium; Department of Radiology, University Hospital Leuven, Leuven, Belgium. Electronic address: charlotte.sleurs@kuleuven.be.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Sleurs
authors.affiliation: Department of Radiology, University Hospital Leuven, Leuven, Belgium.
authors.forename: Sabine
authors.initials: S
authors.lastname: Deprez
authors.affiliation: Department of Radiology, University Hospital Leuven, Leuven, Belgium.
authors.forename: Louise
authors.initials: L
authors.lastname: Emsell
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital Leuven, Leuven, Belgium; Department of Child & Adolescent Psychiatry, University Hospital Leuven, Leuven, Belgium.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Lemiere
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital Leuven, Leuven, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Uyttebroeck
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000276:immunology; D002648:Child; D004249:DNA Damage; D004195:Disease Models, Animal; D006801:Humans; D018384:Oxidative Stress
chemical_list: D000970:Antineoplastic Agents
keywords: Brain maturation; Chemotherapy; Neurotoxicity; Pediatric oncology; Solid non-CNS tumors