Discussion
The present study examined early psychosocial and executive functioning
outcomes in a large cohort of pediatric brain tumor survivors at an
average of 3.8 years post-PRT. The total sample was not significantly
different than the population norms for psychosocial and executive
functioning at follow-up. Behavior problems, including a lower level of
hyperactivity, aggressive behavior, and conduct problems, were in fact
significantly below normative expectations. This was reflected in the
low rates of impairment for these behaviors. These findings are
consistent with previously reported research.17-19 In
contrast, significantly elevated symptoms of social withdrawal were
observed. These differences were more marked in the younger than in the
older group, although the differences were not statistically
significant. Younger children had significantly more behavior problems
and lower adaptive or “everyday” living skills at follow-up regardless
of treatment with CSI or focal PRT. Prior research has noted greater
neurocognitive difficulty associated with younger age at
treatment12,13,19 as well as greater emotional and
behavioral difficulty.19,40 In this context, the
ependymoma group in this study had more problem behaviors at follow-up,
but this is likely related to age as the ependymoma group was younger
than the other histology groups.
Executive functioning was not significantly different from population
norms, but the total sample did show a higher rate of impairment in
metacognitive executive skills, namely the ability to take initiative,
sustain working memory (e.g., capacity to hold and “work on”
information in mind to complete an activity), and plan and organize
tasks. In contrast, the rate of impairment with behavioral dysregulation
was similar to expected rates and consistent with the lower level of
acting-out behavior that was observed with the BASC. Neither age nor
radiation field were significantly related to executive functioning. In
addition, the time interval between baseline and follow-up was not
significantly related to psychosocial or executive functioning.
Although the total sample had more difficulty with social withdrawal
(e.g., the tendency to evade others to avoid social contact), the
patients’ social skills were within the normal range with a low rate of
impairment, suggesting patients have the skills necessary for
interacting successfully with peers and adults. This finding is
consistent with prior literature on conventional post-radiation outcomes
reflecting greater social withdrawal,14isolation,2,6,21,22 and lower
acceptance,2,23 but the absence of deficits in social
skills as a more primary mechanism of impairment. Social withdrawal was
significantly related to greater problems with metacognitive skills,
namely the ability to take initiative, multi-task, and plan and organize
activities. Prior research has demonstrated a bidirectional relationship
between greater executive dysfunction and greater social
vulnerability38 and reduced quality of
life36,37 reflecting the functional impact of
neurocognitive vulnerability on aspects of social competence. This
relationship between executive dysfunction and social vulnerability is
consistent with a hypothesis that successful social engagement requires
participants to initiate and participate in complex social interactions
involving metacognitive skills. The interrelatedness of aspects of
neurocognitive development and functional social proficiency warrants a
comprehensive approach to intervention.
These findings highlight both the importance of routine screening (e.g.,
rating scales/questionnaires) of pediatric brain tumor survivors for
emerging psychosocial and executive functioning challenges, as well as
the need for targeted proactive interventions, particularly for patients
treated with PRT prior to age 6 years. Such interventions could target
the development of social initiative and participation, independence in
activities of daily living, and metacognitive executive functioning
skills. For example, interventions that provide increased opportunities
for positive social interactions with peers in the context of
adult-facilitated support may minimize social withdrawal and maximize
social initiation and engagement, particularly in younger patients.
Older patients may benefit from explicit instruction or coaching in
executive functioning that teaches them strategies to plan, organize,
set goals, prioritize, multi-task, and be a self-starter and
independently problem solve. Cognitive
remediation,49,50,51 cognitive-behavioral
therapy,52 social skill
programming,53,54 and
psychopharmacology55,56 each have been shown to be
effective for pediatric brain tumor survivors. Methylphenidate may be
beneficial for some patients following PRT as long-term improvements in
both social functioning and internalizing symptoms (e.g., symptoms of
withdrawal, somatic, anxiety/depression) have been
reported.55
While these results contribute to the growing knowledge of psychosocial
and executive functioning outcomes of pediatric brain tumor survivors
treated with PRT, some limitations of the present study should be noted.
One is the relatively short mean time interval to follow-up. Late
effects of radiation therapy have been well
established26 and psychosocial and executive
functioning challenges may emerge later than the mean time interval of
the present study. However, time since PRT was not correlated with
outcome in the present study. Second, the sample was predominantly white
and of relatively high SES, with an estimated median income higher than
that of the United States. Patients represented a diverse mix of SES,
and no relationship was found between estimated household income and
psychosocial and executive functioning outcomes. Finally, the findings
are based only on parent rating scales, which are subject to rater bias
and can reflect parents’ impressions; self-report rating scales were not
included in the analyses for comparison.
In summary, the present study examined psychosocial and executive
functioning outcomes in a large cohort of pediatric brain tumor
survivors treated with PRT. Psychosocial and executive functioning were
within the normal range at follow-up. Younger patients, particularly
those treated with CSI, appeared more vulnerable. These early findings
are encouraging. Future research will examine a longer follow-up
interval to better determine the risk of late effects of PRT, optimally
in a more diverse sample.
Conflict of Interest: No actual or potential conflicts of
interest exist for any author. TY receives in kind research support from
MIM software.
Acknowledgments: The authors thank the MGH Francis Burr Proton
Center pediatric patients and their families for participation in this
study. This project was supported in part by the Federal Share of
program income earned by the Massachusetts General Hospital on C06
CA059267 Proton Therapy Research and Treatment Center to Margaret
Pulsifer and is registered at NCT01180881 ClinicalTrials.gov.