Grant Number:	5R01CA239630-04 Interpret this number
Primary Investigator:	Brinkman, Tara
Organization:	St. Jude Children'S Research Hospital
Project Title:	Neurostimulation in Adult Survivors of Childhood Leukemia
Fiscal Year:	2022

ABSTRACT Adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with cranial radiation, intrathecal methotrexate (MTX), or high dose intravenous MTX and/or cytarabine are at risk for neurocognitive morbidities, particularly in the domain of executive function. Deficits in executive function have been associated with reduced educational attainment, employment, emotional functioning, and social functioning in survivors. We have recently identified that higher treatment intensity, as reflected through serum concentration of MTX, is associated with worse executive functioning, increased brain activation in dorsolateral prefrontal regions based on functional MRI, and decreased myelin integrity in frontostrial tracts based on diffusion tensor imaging. This suggests that frontal brain regions may be less efficient in survivors treated with more intense therapies than those treated with less intensive therapy. Therefore, interventions designed to target the dorsolateral region and focus on remediation of executive functioning skills may be particularly beneficial for survivors. Importantly, because most long-term survivors do not reside in close proximity to their primary cancer treatment center, the need for interventions that can be delivered remotely is critical. We recently piloted a two-month trial of remote transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex paired with cognitive training for the treatment of executive dysfunction in a randomly selected sample of 30 adult survivors of childhood ALL (mean age 33 years, SD 7.5 years). Among the 27 survivors eligible for remote stimulation, 25 (93%) completed at least 50% of the home-based sessions, and 22 (81%) completed all prescribed sessions. These data support the safety, acceptability, and feasibility of remote tDCS among long-term survivors. Among the survivors who completed the intervention, we observed significant improvements on a direct measure of executive functioning (working memory: 0.5 SD increase) and self-reported emotional regulation (0.7 SD increase). Now, we propose a randomized placebo-controlled study to examine the efficacy of home-based tDCS + remote cognitive training vs. sham (placebo) + remote cognitive training on symptoms of executive dysfunction in a larger sample of long-term survivors of ALL. We also will examine impact of tDCS and cognitive training on underlying neural networks via brain imaging. Results of this study will lead to the development of subsequent clinical trials to examine optimal treatment intensity and duration as well as dissemination and implementation strategies. This work has the potential to significantly impact current standard of care with a scalable intervention for common symptoms of executive dysfunction in long-term survivors of childhood cancer.





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