IMGP-02. A Prospective Trial Identifying Functional Neuroimaging Biomarkers of Impaired Neurocognition and Quality of Life After Proton Beam Radiotherapy (PBRT) for Treatment of Brain Tumors in Pediatric Patients

BACKGROUND Radiotherapy (RT) is integral for treating pediatric brain tumors but can cause neurotoxicity. This prospective study characterized neurocognition in pediatric patients undergoing PBRT using cognitive resting state networks (RSNs). METHODS Patients aged 6-25y with brain tumors planned for cranial PBRT and age-, sex-, and handedness-matched healthy controls (HCs) underwent resting state functional connectivity (FC) MRI and neurocognitive assessments (NIH Toolbox, PROMIS QoL Questionnaire) at 3-5 months post-PBRT. FC and interconnectivity of each RSN (default mode [DMN], dorsal attention [DAN], executive central [ECN], salience [SN]), and between network interactions were compared between patients vs. HC. One-sample t-tests assessed average RSN-specific FC. Group-level analysis compared patients vs. HC for all RSNs using paired t-tests (q=0.05). RESULTS 14 patients (ages 6-9y [n=5, 3M], 10-13y [n=2, 0M], 14-17y [n=3, 3M], 18-25y [n=4, 3M]) with matched HCs were analyzed. Most had medulloblastoma (n=3), craniopharyngioma (n=2), ependymoma (n=2), or germinoma (n=2). Median RT dose was 54Gy (range 18-60). Most had college (or higher) educated parents (n=21). FC was reduced in SN and the posterior cingulate cortex (PCC) and dorsomedial frontal cortex of DMN (p<0.01). The normal anti-correlation relationship between DMN and SN was disrupted in patients. RSNs had reduced local efficiency (p<0.05). DMN (in PCC), ECN (in left lateral prefrontal cortex), and SN (in anterior cingulate cortex, left and right anterior insula) showed reduced clustering coefficients, average path length, and degree (p<0.05). Patients performed worse in attention/executive function, working and episodic memory, and processing speed (p<0.05), and general neurocognitive functioning (p=0.02). For quality of life (QoL), patients had worse self-reported anxiety and social participation (p=0.03). CONCLUSIONS On this prospective study, pediatric patients had significant disruption in several RSNs after PBRT, notably disrupting the interplay between SN and DMN known to be critical in neurocognitive control. Patients also had impaired neurocognition and QoL, warranting further investigation for mitigation.