INSP-07. Improving cognitive outcomes for children treated for cancer: moving beyond the cure

With improved survival rates, increasing numbers of childhood cancer survivors are living with long-term cognitive deficits that negatively impact their ability to attain important life milestones. Our collaborative research program has focused on characterizing cognitive outcomes associated with specific treatment modalities to inform modifications in front-line therapy. This line of investigation has demonstrated the negative cognitive impact of high radiation dose/large treatment volume, posterior fossa syndrome, treatment-related ototoxicity, and lower socioeconomic status (SES). Research-informed, treatment approaches under investigation include proton radiotherapy and hippocampal sparing irradiation, molecularly based risk-adapted therapy, surgical approaches with reduced risk of injury, and on-therapy otoprotectants, as well as identification of modifiable factors that are driving the protective effects of higher SES. Our research also strives to improve specification of cognitive deficits following treatment, at the behavioral and neural systems level, to identify targets for intervention. Study findings have revealed disease- and treatment- related alterations in neural systems supporting attention, working memory, and executive functions, as well as genetic factors that increase risk for cognitive late effects. We are now using sophisticated connectivity brain mapping with enhanced sensitivity to behaviorally-relevant changes in brain organization and sensitivity to intervention-based neuroplasticity to guide cognitive intervention development. A primary research focus moving forward is development of empirically validated interventions that prevent or mitigate cognitive late effects among childhood cancer survivors. Our studies have demonstrated the efficacy of stimulant medications, computerized cognitive training, and aerobic exercise for children treated for cancer, as well as the limitations to these approaches. Current investigations include use of neuroprotectant agents during radiotherapy, combining multiple interventions, interventions tailored to children undergoing treatment in infancy, and the use of virtual reality to increase intervention engagement. Our ultimate benchmark of success is ensuring children are not only cured of cancer but also experience a high quality of life.