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.