Radt-35. change in hippocampal volume as a function of radiation dose: results from a prospective trial with standardized imaging and morphometric evaluation

Abstract PURPOSE/OBJECTIVES MRIs in pediatric and adult brain tumor patients (Age< 35) were prospectively collected at baseline and during follow-up to measure volumetric changes in multiple brain substructures with neurocognitive, laboratory, and quality-of-life assessments. In this planned interim analysis, we model early outcomes for change in hippocampal volume at 6 months following radiotherapy. MATERIALS AND METHODS As of 5/15/2021, 50 patients enrolled on this prospective study and 41 completed 6-month post-treatment assessments after fractionated intensity-modulated proton therapy. Left and right hippocampus volumes were independently measured on T1 sagittal precontrast MRI at baseline and 6-months after radiotherapy using both automated software and physician-delineated contours. The relationship between mean hippocampus dose and change in volume was assessed by Pearson’s correlation coefficient. A linear mixed-effects model was applied to evaluate other predictors associated with change in hippocampal volume, assuming random effects of subjects. RESULTS Mean hippocampus dose was strongly correlated with change in hippocampal volume at 6 months following radiotherapy (r=−0.727, 95% CI [-0.820,-0.596], p< 0.001). Changes in hippocampal volumes over time were similar between software and physician contours. Hippocampal volume was significantly reduced for mean doses ≥10 Gy (mean Δ -10.8% ± 5.5%, p< 0.001), while no significant volume change was observed with mean doses < 10 Gy (mean Δ +0.7% ± 3.9%). In the mixed-effects model, only mean hippocampus dose was significantly associated with hippocampal volume change (p< 0.001). The final model predicted a -3.4% change in hippocampal volume for every 10 Gy increase in mean dose. CONCLUSIONS Change in hippocampal volume was correlated with hippocampus mean dose at 6 months following radiotherapy. Future analyses will assess volume change in the hippocampus and other brain substructures over time as a function of radiation dose and correlate with measured neurocognitive and other effects.