Discussion
The present study examines psychosocial and executive functioning outcomes in a large cohort of pediatric brain tumor survivors at an average of 3.84 years post-PRT. Mean scores were not significantly different from normative expectation for psychosocial and executive functioning at follow-up. However, rates of impairment in social withdrawal, activities of daily living, and metacognitive executive functioning skills were markedly higher than would be expected in the general population. These results are largely consistent with the growing body of literature among pediatric brain tumor survivors post-PRT that report sample means in the normal range for many aspects of emotional and behavioral functioning whereas problems are often reported at a higher level with social and executive functioning.14
Favorably, the current findings revealed significantly less behavior problems (hyperactivity, aggression) compared to normative expectations consistent with previous studies.20-22 Problems with depression or anxiety were not identified, an important finding with regard to quality of life. However, a relatively large proportion of patients (12.5%) was rated as having problems with somatization and were viewed by their parents as having more physical complaints/discomforts; 42-43 not surprising given the complex medical history of brain tumor survivors.
A large proportion of survivors were rated as having impairment in social withdrawal (≈18%) (a tendency to evade others to avoid social contact) 42-43 although their social skills were within the normal range with a low rate of impairment, suggesting survivors 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,17 isolation,2,6,23,25and lower acceptance,2,26 but lacking deficits in social cognition skills (knowledge about how to appropriately interact). Reduced prosocial skills (complimenting others, offering help) were observed in a post-PRT study14 reflecting the need for further exploration of this specific aspect of socialization.
The higher rate of challenges with activities of daily living (15%) is consistent with prior research that identified greater adaptive skills impairment among a more homogenous sample of youth 5 years post-PRT, particularly in the domains of practical and social skills.12 While the mean for our total sample did not exceed normative expectation, the rate of impairment in activities of daily living and the recent finding in the literature warrant continued attention to the development of these skills. Metacognitive executive functioning was the area of greatest concern reported by parents in this study, consistent with the literature.19,34-35Significantly more survivors were rated as having problems with aspects of metacognitive executive functioning skills (up to 25%), which includes 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.
Previous research has indicated an association between problems with psychosocial and executive functioning and time interval following PRT.14,46 However, this finding was surprisingly not revealed in this sample. In fact, most demographic and treatment-related factors examined did not significantly impact psychosocial and executive functioning outcomes in this sample, including gender, race, SES, tumor location, radiation field, history of surgery, or chemotherapy. While some studies have identified relationships between PRT treatment variables (hydrocephalus, time since treatment) and social outcomes,14 these patterns are not universal.
Age at baseline and histology were the only factors that had significant relationships with outcomes; younger ages at baseline and those diagnosed with ependymoma (youngest histology group at baseline) had more behavior problems and older ages at baseline had more problems with adaptive skills at follow-up. Prior research has noted greater emotional and behavioral difficulty associated with younger age at treatment..22,37 For older ages, the inability to meet increasing expectations to carry out tasks with greater independence with advancing age may reflect the high rate of metacognitive executive challenges found in this sample.
Psychosocial and executive functioning outcomes should be understood in the context of various environmental and situational factors (extended absences from school, reduced opportunities for peer interactions, development of everyday living skills). The impact of tumor-related symptoms prior to diagnosis (e.g., tailored treatment interventions, premorbid developmental and genetic patterns) also need to be considered. Similarly, the major role of parents and health care professionals during their treatment course may contribute to deviations in typical developmental trajectories that may not be accounted for by late effects alone. Taken together, these factors may contribute to, but do not fully account for,27 the disruption of normal development of psychosocial and executive functioning.
These findings highlight both the importance of routine targeted screening (rating scales/questionnaires) for emerging challenges in psychosocial and executive functioning in pediatric brain tumor survivors treated with PRT, as well as the need for targeted proactive interventions. Such interventions could target the development of social initiative and participation, independence in adaptive skills, 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 appropriate for age may minimize social withdrawal and maximize social initiation and engagement. Patients may benefit from explicit instruction or coaching in executive functioning that teaches them age-appropriate strategies to plan, organize, set goals, prioritize, multi-task, and be a self-starter and independently problem solve. Cognitive remediation,47-49 cognitive-behavioral therapy,46 social skill programming,50-51 and psychopharmacology52-53 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 withdrawal have been reported.52
A strength of the current study is the large cohort of pediatric brain tumor survivors in the sample. While these results contribute to the growing knowledge of psychosocial and executive functioning outcomes of pediatric brain tumor survivors treated with PRT, several limitations of the present study should be noted. First, the cross-sectional study design precludes direct analysis of change over time. Longitudinal studies are needed to examine change in order to identify the emergence and trajectory of psychosocial and executive functioning challenges and to guide targeted screening and proactive intervention efforts. Second, the mean follow-up time interval in this study is relatively short. Late effects of radiation therapy have been well established29 and psychosocial and executive functioning challenges may emerge later than the mean time interval observed. However, the time interval since PRT and follow-up was not correlated with the primary outcome measures in the present study. Third, the sample was predominantly White and of relatively high SES, with an estimated median income higher than that of the United States. This homogenous profile may not be representative of patients who receive similar treatment at other medical centers and the results need to viewed in this context. In addition, patients who received follow-up assessment may have parents with greater concerns regarding their child’s outcome, possibly resulting in a sample that is not representative of all pediatric brain tumor survivors. Finally, the current findings are based only on parent rating scales, which are subject to rater bias and can reflect parents’ impressions.
In summary, although psychosocial and executive functioning were, on average, in the normal range in this large cohort of pediatric brain tumor survivors, significant problems were found with social withdrawal, activities of daily living, and metacognitive executive functioning skills. However, no significant problems were evident with depression, anxiety, inattention, hyperactivity, conduct, behavioral dysregulation or overall adaptive skills. Age at baseline was related to problem behaviors and adaptive skills: Younger patients tended to have problem behaviors at follow-up whereas older patients struggled with independent adaptive or everyday living skills. Neither time interval since PRT nor radiation field were related to outcome. Future research will examine a longer follow-up interval to better determine the risk of late effects of PRT.
Conflict of Interest: No actual or potential conflicts of interest exist for any author. Torunn Yock 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.