2898 - Prospective Longitudinal Study of Quality of Life, Brain Substructure Atrophy, and Neurocognitive Outcomes in Children Following Proton Therapy for Brain Tumors

K. Von Werne¹, C. Rojas¹, N. Martinez Green¹, R. Hamilton², Y. Odia³, A. Kudryashev¹, M. B. Currier², and M. D. Hall¹; ¹Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, ²Department of Supportive Care Medicine, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, ³Department of Neuro-Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL

Purpose/Objective(s): To prospectively evaluate health-related quality of life (QOL) in pediatric/young adult brain tumor patients before and after intensity-modulated proton therapy (IMPT) and their relationship to neurocognitive scores and radiation dose to brain substructures after two years of follow-up. Materials/

Methods: Sixty brain tumor patients (age <35 years) enrolled and received IMPT at a single institution on a prospective trial (NCT03972514). MRIs, neurocognitive testing, and QOL assessments were collected at baseline and yearly during follow-up. Brain substructure volumes (hippocampus, amygdala) were segmented using 3D, high-resolution, pre-contrast T1 MRI. Neurocognitive testing included assessments of memory, total/delayed recall, processing speed, and executive function. Patients and/or proxies completed the Neuro-QOL pediatric assessments for fatigue, anxiety, depression, cognitive function, and adaptive behavior/emotional functioning tests. Correlations between QOL, neurocognitive testing, brain substructure atrophy, radiation dose, and clinical data were examined.
Results: Increased mean dose to the hippocampus and amygdala were associated with reduced verbal memory and visual memory/total recall scores, respectively, by two years after IMPT (p<0.01 for both comparisons). Greater atrophy developed in both substructures as a function of increasing mean dose (p<0.001 for both comparisons). No significant associations were identified between adaptive behavior/emotional functioning/QOL scores and the measured neurocognitive domains, radiation dose, or atrophy of the hippocampus/amygdala. Patients treated with chemotherapy and/or craniospinal irradiation (CSI) demonstrated worse emotional functioning, anxiety, and fatigue scores compared to patients who received focal IMPT alone (p<0.01 for all comparisons). Anxiety, fatigue, and emotional functioning scores were higher at baseline and following treatment in patients who received focal IMPT. These metrics were lower and remained depressed longer in patients who received CSI. Anxiety scores increased significantly after patients developed new medical findings during follow-up, including radiation-induced contrast enhancement, vascular complications, and tumor recurrence.
Conclusion: Radiation dose-dependent atrophy was observed in the hippocampus and amygdala, and higher mean doses to these substructures were associated with lower scores across certain neurocognitive domains two years following IMPT. Anxiety, emotional functioning, and other QOL scores were not correlated with either neurocognitive outcomes or radiation dose to the hippocampus or amygdala 2 years following IMPT. QOL scores for patients treated with focal IMPT were significantly higher than patients treated with CSI.