Session Item

Radiation doses to the hippocampus have been linked to neurocognitive outcomes in primary brain tumors and brain metastasis treated with radiotherapy (RT). Hippocampus has extensive neural connections to the surrounding structures, including the amygdala and parahippocampal gyrus (PG), which are known to play a crucial role in emotional response and memory encoding. However, clinical data is lacking on the impact of RT doses on these structures, which led to the current study investigating the effect of doses on memory functions.

Adults (>18 years) with pituitary adenoma receiving intensity-modulated radiotherapy RT (45Gy/25fractions/5weeks) were accrued on a phase 2 prospective study. No definitive dose-constraints were applied to the hippocampus, amygdala, or PG, although as low as reasonably achievable (ALARA) principle was followed. The amygdala and PG on the left and right sides were drawn on T1-weighted 3D-FSPGR (slice thickness 1 mm) based on the consensus of two neuroradiologists. Dose parameters were extracted for the individual volumes. A dedicated neuropsychologist performed the memory evaluation using Wechsler Memory Scale, pre-RT, at 6 &18 months post-RT. We evaluated the 18-month scores, and a drop > 5% was considered clinically relevant. Shapiro-Wilk test was used for normality of data. Independent t-test and Mann-Whitney tests were done to correlate memory quotient (MQ) with sub-volume dosimetric data. A p-value of <0.05 was considered statistically significant. 

Nineteen patients were analyzed for dose correlation with memory function. Nine patients had a drop of >5% from the baseline. Of the four structure sets from both sides, only the dose-parameters from the left amygdala had a significant correlation with the memory outcomes at 18 months. The mean values of doses to the left amygdala for the two outcome groups (>5% vs ≤ 5% drop) were: mean dose 37.8 Gy vs 31.2 Gy (p=0.05), D30 40.1 Gy vs 33.3 Gy (p=0.04), D40 39.1 Gy vs 32.1 Gy (p=0.04), and D60 37.0 Gy vs 29.8 Gy (p=0.04).

This is the first exploratory clinical study to demonstrate that the dose to the left amygdala correlated with memory outcomes. This study provides further opportunities to explore the dose-volume parameters of the amygdala and definitive constraints can be used along with the hippocampus to preserve memory function following RT.