PROJECT SUMMARY/ABSTRACT Survivors of pediatric brain tumors often experience significant problems with social connectedness during youth that have lasting effects as adults (e.g., reduced rates of marriage). However, the factors contributing to these difficulties are unclear and little is known about how domains of social connectedness influence health- related quality of life (HRQL) and psychological well-being over time in survivors of pediatric brain cancer. Further, intervention efforts to address these issues have been limited by a lack of research on the underlying risk and mechanistic factors of social connectedness. Candidate risk and mechanistic factors include age at diagnosis, treatment, and treatment-related morbidities across many domains (e.g., cognitive, neurologic, endocrine, metabolic). Additionally, brain cancer treatments disrupt neurodevelopmental processes that are essential to social behavior, such as brain connectivity, face processing, and social attention. Establishing the importance of social connectedness to overall health and the mechanistic processes contributing to social connectedness impairments in pediatric brain cancer survivors is important in order to develop appropriate interventions. The broad objectives of this proposal are to compare domains of social connectedness among survivors of malignant brain tumors to survivors of non-malignant brain tumors, evaluate the influence of social connectedness on HQRL and psychological well-being among survivors, and to evaluate risk and mechanistic factors for the trajectory of social connectedness. We propose an innovative study of youth treated for medulloblastoma (MB), cerebellar pilocytic astrocytoma (PA) or craniopharyngioma (CP) (N = 180; ages 8-16) using a 2-year accelerated longitudinal design with annual visits with cohorts stratified by time since diagnosis. Clinical differences between groups (e.g., malignant/non-malignant, use of craniospinal irradiation) allow for tests of their unique impacts on social connectedness and for identification of potential intervention targets. Participants will be recruited from the Children's Hospital of Philadelphia. At each study visit, participants will complete measures of social connectedness, HRQL, and psychological well-being, as well as assessments of body composition, neuroendocrine function, hearing, brain connectivity (e.g., MRI), social information processing (SIP) and social behavior. Neuroimaging markers of interest include structural connectivity, resting state functional connectivity, and functional connectivity in the social brain during social processing tasks. We hypothesize that social connectedness, and thus HRQL and psychological well-being, are uniquely impacted in MB survivors, and that risk (e.g., CSI) and mechanistic factors (e.g., hearing, social behavior) affect social connectedness over time. We expect to establish deficits in social connectedness as a notable late effect in survivors of medulloblastoma with significant impact on HRQL and well-being and to identify mechanisms of social connectedness. By identifying the mechanisms underlying social connectedness, we can then develop interventions that target key mechanistic factors and improve social connectedness, health, and well-being.

PROJECT NARRATIVE Pediatric brain cancer survivors are at increased risk for poor social connectedness, diminished health-related quality of life and reduced psychological well-being, though the associations between these factors and the underlying mechanisms impacting the trajectory of social connectedness are poorly understood. The proposed project will use an accelerated longitudinal design to compare the social connectedness and well-being among survivors of malignant and non-malignant brain tumors, determine the influence of social connectedness on health and well-being, and evaluate risk and mechanistic factors for social connectedness. Findings from this project will significantly advance our understanding of the importance of social connectedness in pediatric brain cancer survivorship and inform the development of effective interventions that target mechanistic factors.