Abstract
Objective: To evaluate group differences in social adjustment
in survivors of pediatric ALL compared to survivor siblings, and
controls; identify disease-related predictors of social adjustment in
survivors; and explore whether executive functioning explained
differences in social adjustment across groups and between
disease-related predictors. Methods: Survivors of pediatric ALL
(n =38, average age at diagnosis=4.27 years [SD =1.97];
average time off treatment=4.83 years [SD =1.52]), one sibling
(if available, n=20), and one parent from each family were recruited
from a long-term survivor clinic. Healthy age- and sex-matched controls
(n =38) and one parent from each family were recruited from the
community. Parents completed the Behavioral Assessment System for
Children, Parent Rating Scale (BASC-3) Social Withdrawal subscale as a
measure of social adjustment and the Behavior Rating Inventory of
Executive Functions (BRIEF-2) as a measure of executive function for
each of their children. Results: Parents reported that
survivors had significantly worse social adjustment compared to controls
(b =6.34, p =.004), but not survivor siblings. Among
survivors, greater time off treatment (b =2.06, p =.058) and
poorer executive functioning (b =0.42, p =.006) were
associated with worse social adjustment. Executive function did not
mediate differences in social withdrawal between survivors and controls
or the relationship between time off treatment and social withdrawal
among survivors. Conclusions: Survivors of pediatric ALL
presenting to follow-up programs should be screened for difficulties
with social adjustment. Future research should examine treatment- and
non-treatment-related factors contributing to poorer social outcomes.
Keywords: ALL, Late effects, Pediatric oncology, Psychology,
Psychosocial
Social Adjustment in Survivors of Pediatric ALL
Pediatric ALL is a major medical success story. Advances in treatment
for ALL have resulted in one of the most impressive increases in cancer
survival over the last 35 years, from 60% in 1975 to approximately
80-90% today in North America.1 The number of
survivors is growing rapidly. Given the dramatically improved survival
rates, efforts were made in the early 1990’s to reduce the toxicity of
treatment to the central nervous system (CNS) in ALL. Modern treatments
for pediatric ALL rely less on cranial radiation therapy (CRT) for CNS
prophylaxis and instead focus on intermediate or high dose intravenous
methotrexate and intrathecal chemotherapies, intended to maximize CNS
drug exposure while reducing systemic drug toxicity.2ALL is one of few pediatric cancers to receive both intravenous
methotrexate and intrathecal chemotherapy. Despite efforts to reduce CNS
toxicity, negative effects of these therapies on the developing brain
persist.3-5
Survivors of pediatric ALL experience difficulties with social
adjustment.6-8 Social adjustment is defined as the
extent to which children attain socially desirable and developmentally
appropriate goals.9 The social adjustment difficulties
that have been reported in the literature for survivors of pediatric ALL
include being more withdrawn, socially isolated, lonely, and bullied
compared to their siblings and classmates.8,10Survivors of ALL have been found to engage in less than half the number
of social activities than their peers.8,10-12 As
adults, survivors of ALL are much less likely to marry or live
independently compared to their siblings.6,13-16 Tied
to these enduring social difficulties, adult survivors of pediatric ALL
are 1.7 times more likely to report mental health problems compared to
their siblings, placing a significant burden on our health, economic,
and social welfare systems.15 The majority of studies
describing these specific social outcomes, however, involved patients
treated with older protocols from the late 1970s through the mid-1980s
that included CRT. Moreover, many of these studies reported the outcomes
of long-term survivors of ALL. We do not yet know what effect modern
therapies, which include higher doses of intravenous methotrexate and
intrathecal chemotherapies, have on social adjustment, particularly in
the early survivorship period (e.g., 2-7 years post treatment).
CNS-directed chemotherapies impair cognitive-executive
processes.17-21 Despite the effort to reduce toxicity
to the developing brain by eliminating CRT, treatment with methotrexate
and intrathecal chemotherapy alone has been linked to the presence of
cognitive deficits in 40-60% of survivors of
ALL.3,19-21 Cognitive deficits experienced by
survivors include difficulties with tasks related to processing speed,
attention, working memory, and executive function. Consistent with the
Social Competence Model developed by Yeates and
colleagues,9 these same cognitive processes may play a
role in social adjustment. The ‘Social Competence Model’ is a
theoretical framework examining correlates of social adjustment in
children with acquired brain injuries.9 This model
takes a multilevel approach to understanding social competence,
distinguishing among three key levels: 1) social adjustment; 2) social
interaction; and 3) social information processing, comprised of
social-cognitive and cognitive-executive function and assumes
significant associations among these levels. Indeed, attention has been
found to be uniquely associated with social adjustment in survivors of
pediatric ALL relative to other known demographic- and treatment-related
risk factors.22 The social competence model has been
validated in research examining social outcomes among a variety of
pediatric brain disorders, including traumatic brain injury
(TBI),23,24 stroke,25epilepsy,26 and survivors of pediatric brain
tumor.27 The contribution of cognitive-executive
processes to social adjustment in survivors of ALL requires further
investigation.
Thus, the specific aims of this study were to evaluate: 1) potential
group differences in social adjustment across three groups of children
(survivors of ALL, survivor siblings, age- and sex-matched controls); 2)
disease-related factors (age at diagnosis, time off treatment) and
executive functioning as predictors of social adjustment in survivors;
3) whether executive functioning mediates the differences in social
adjustment across groups that were identified in the first aim (i.e.,
executive functioning as a mediator of the relationship between group
and social adjustment); and 4) whether executive functioning mediates
the relationship between the disease-related predictors (that were
identified in the second aim) and social adjustment in survivors (i.e.,
executive functioning as a mediator of the relationship between
disease-related predictors and social adjustment). We hypothesized that
survivors of ALL would demonstrate significantly more social adjustment
difficulties compared to their siblings and controls and that
disease-related predictors of social adjustment would include diagnostic
risk status with survivors diagnosed with high-risk disease being more
likely to report social adjustment difficulties. Finally, we
hypothesized that executive functioning would explain the differences in
social adjustment across groups and disease-related predictors.