Association between hippocampal dose and memory in survivors of childhood or adolescent low-grade glioma: a 10-year neurocognitive longitudinal study.

BACKGROUND: Hippocampal avoidance has been suggested as a strategy to reduce short-term memory decline in adults receiving whole-brain radiation therapy (RT). The purpose of this study was to determine whether the hippocampal dose in children and adolescents undergoing RT for low-grade glioma (LGG) was associated with memory, as measured by verbal recall.
METHODS: Eighty patients aged at least 6 years but less than 21 years with LGG were treated with RT to 54Gy on a phase II protocol. Patients underwent age-appropriate cognitive testing at baseline, 6 months post-treatment, yearly through 5 years post-treatment, year 7 or 8, and year 10 post-treatment. Random coefficient models were used to estimate the longitudinal trends in cognitive assessment scores.
RESULTS: Median neurocognitive follow-up was 9.8 years. There was a significant decline in short-delay recall (slope=-0.01 standard deviation [SD]/year, P<0.001), total recall (slope=-0.09 SD/year, P=0.005) and long-delay recall (slope=-0.01 SD/year, P =0.002). On multivariate regression, after accounting for hydrocephalus, decline in short-delay recall was associated with the volume of right (slope=-0.001 SD/year, P=0.019) or left hippocampus (slope=-0.001 SD/year, P=0.025) receiving 40Gy (V40Gy). On univariate regression, decline in total recall was only associated with right hippocampal dosimetry (V40Gy slope=-0.002, P=0.025). In children <12 years, on univariate regression, decline in long-delay recall was only associated with right (V40Gy slope=-0.002, P=0.013) and left (V40Gy slope=-0.002, P=0.014) hippocampal dosimetry.
CONCLUSION: In this 10-year longitudinal study, greater hippocampal dose was associated with a greater decline in delayed recall. Such findings might be informative for radiation therapy planning, warranting prospective evaluation.