Chemotherapy-induced neurotoxicity in pediatric solid non-CNS tumor patients: An update on current state of research and recommended future directions

Crit Rev Oncol Hematol. 2016 Jul:103:37-48. doi: 10.1016/j.critrevonc.2016.05.001. Epub 2016 May 11.

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.

Keywords: Brain maturation; Chemotherapy; Neurotoxicity; Pediatric oncology; Solid non-CNS tumors.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Brain / drug effects
  • Brain / growth & development
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / immunology
  • Child
  • DNA Damage
  • Disease Models, Animal
  • Humans
  • Oxidative Stress

Substances

  • Antineoplastic Agents