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

Neuro Oncol. 2019 Sep 6;21(9):1175-1183. doi: 10.1093/neuonc/noz068.

Abstract

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 was associated with memory, as measured by verbal recall.

Methods: Eighty patients aged at least 6 years but less than 21 years with low-grade glioma were treated with RT to 54 Gy on a phase II protocol. Patients underwent age-appropriate cognitive testing at baseline, 6 months posttreatment, yearly through 5 years posttreatment, year 7 or 8, and year 10 posttreatment. 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/y, P = 0.005), and long-delay recall (slope = -0.01 SD/y, 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/y, P = 0.019) or left hippocampus (slope = -0.001 SD/y, P = 0.025) receiving 40 Gy (V40 Gy). On univariate regression, decline in total recall was only associated with right hippocampal dosimetry (V40 Gy slope = -0.002, P = 0.025). In children <12 years, on univariate regression, decline in long-delay recall was only associated with right (V40 Gy slope = -0.002, P = 0.013) and left (V40 Gy 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.

Keywords: hippocampus; memory; pediatric low-grade glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Astrocytoma / radiotherapy
  • Brain Neoplasms / radiotherapy*
  • Brain Stem Neoplasms / radiotherapy
  • Child
  • Female
  • Ganglioglioma / radiotherapy
  • Glioma / radiotherapy*
  • Hippocampus / radiation effects*
  • Humans
  • Hypothalamic Neoplasms / radiotherapy
  • Longitudinal Studies
  • Male
  • Memory Disorders*
  • Mental Recall / radiation effects*
  • Organs at Risk
  • Radiometry
  • Radiotherapy Dosage*
  • Thalamus
  • Visual Pathways
  • Young Adult