Introduction
Brain tumors are the most common type of solid tumor in children.1 Radiation treatment is a life-saving intervention that can be associated with neurocognitive, emotional, and behavioral sequalae,2-7 although the use of proton radiation treatment (PRT) has yielded more favorable outcomes due to its dose-sparing properties.8-10 Initial studies examining the outcomes of PRT revealed cognitive and adaptive functioning in the normal range more than 3 years post-treatment;11-13however, psychosocial and executive functioning outcomes have not been comprehensively described.
Psychological functioning following conventional radiation has revealed higher rates of internalizing emotional problems characterized by depression and anxiety.14-16 Rates of externalizing behavior problems (e.g., conduct problems, aggression, defiance) have not been reported at elevated levels,17,18 and, in some cases, rates are lower than the normative mean.19Greater attention problems (an internally experienced symptom) have been reported on parent questionnaires, whereas greater hyperactivity (externally observed behavior) has generally not been reported in this population.17,20 As a whole, pediatric patients treated with radiation tend to experience higher rates of symptoms that are experienced inside one’s mind (internalizing) rather than symptoms that are more readily observed and directed towards other people (externalizing).
Social functioning is also impacted at higher rates following conventional radiation treatment. The most consistent findings are higher rates of social isolation6,21,22 as well as reduced social acceptance2,23 and withdrawal.14 Reduced leadership skills have also been described.2,21 Studies have collectively demonstrated weaknesses in social responsiveness and engagement levels, rather than deficits in social skills themselves.
Executive functions are a group of higher ordered cognitive skills that represent a constellation of behaviors required for task completion and goal-directed behavior.24 Executive functions are mediated by frontal-subcortical-cerebellar white matter circuits which are highly susceptible to injury from radiation treatment,25,26 and disruption of white matter integrity can impact the long-term developmental trajectory of pediatric survivors.
Executive functioning is affected at higher rates following radiation compared to the general population.17,19,22,27,28,29Ecological assessment using parent-report is a valuable method to capture executive functioning abilities in daily contexts.30 The Behavior Rating Inventory of Executive Function (BRIEF) is a widely used, standardized measure that is sensitive to executive functioning difficulty in daily life.31,32 Parent report using the BRIEF has revealed greater levels of executive dysfunction in pediatric brain tumor survivors, particularly in the domain of metacognitive executive skills including working memory, planning/organization, and initiation.16,33,34 Reports of difficulty with behavioral dysregulation are mixed, with some studies citing significantly more difficulty33,35 and others reporting lower rates of behavioral dysregulation.34Reduced problems with inhibition, even relative to healthy controls, have been reported.16,34
Executive dysfunction is associated with reduced quality of life,36,37 greater social deficits,38 and symptoms of depression,16 suggesting a multidirectional effect of cognitive, psychosocial, and behavioral status impacting overall well-being among pediatric patients treated with conventional radiation therapy. Similarly, greater attention problems can have an adverse impact on social functioning39 resulting from an inability to attend to simultaneous stimuli, particularly when there are competing external demands (e.g., group conversations; excess/extraneous noise). The inter-relatedness of cognitive, psychosocial, and behavioral functioning requires comprehensive assessment as each domain directly impacts others. As such, improved cognitive outcomes associated with PRT may contribute to reduced psychosocial and executive functioning sequalae.
Several specific risk factors may lead to adverse outcomes for pediatric brain tumor survivors. Younger age at diagnosis and treatment is a risk factor for greater neurocognitive,12,13,19 emotional, and behavioral19,40 sequalae. The extent of radiation (e.g., craniospinal radiation (CSI) vs. focal) has also been shown to impact cognitive outcomes,12,13,41 including executive functioning.42 Socioeconomic status (SES) can adversely impact functional outcomes in pediatric oncological conditions,43 including pediatric patients diagnosed with brain tumors.44,45 Examination of risk factors is important to determine if these impact outcomes of pediatric survivors treated with PRT.
The goal of the current study was to examine whether pediatric brain tumor survivors treated with PRT had difficulties with psychosocial and executive functioning at follow-up. The study examined demographic, diagnostic (e.g., tumor location), and treatment-related variables to identify those patients at highest risk for adverse outcome. It was anticipated that: 1) psychosocial and executive functioning for the total sample would be within the normal range; 2) problems with behavioral dysregulation and externalizing behaviors (e.g., conduct) would not be seen; 3) patients treated with PRT prior to age 6 years would have greater impairment compared to patients treated after that age; 4) a longer time interval between PRT and follow-up would be associated with greater problems; 5) demographic factors, such as SES, would impact outcomes, and 6) outcomes after PRT would be favorable compared to published outcomes with conventional radiation therapy.