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.