Hippocampal dose volume histogram predicts Hopkins Verbal Learning Test scores after brain irradiation

Radiation-induced cognitive decline is relatively common after treatment for primary and metastatic brain tumors; however, identifying dosimetric parameters that are predictive of radiation-induced cognitive decline is difficult due to the heterogeneity of patient characteristics. The memory function is especially susceptible to radiation effects after treatment. The objective of this study is to correlate volumetric radiation doses received by critical neuroanatomic structures to post-radiation therapy (RT) memory impairment.

Between 2008 and 2011, 53 patients with primary brain malignancies were treated with conventionally fractionated RT in prospectively accrued clinical trials performed at our institution. Dose-volume histogram analysis was performed for the hippocampus, parahippocampus, amygdala, and fusiform gyrus. Hopkins Verbal Learning Test-Revised scores were obtained at least 6 months after RT. Impairment was defined as an immediate recall score ≤15. For each anatomic region, serial regression was performed to correlate volume receiving a given dose (V_D(Gy)) with memory impairment.

Hippocampal V_53.4Gy to V_60.9Gy significantly predicted post-RT memory impairment (P < .05). Within this range, the hippocampal V_55Gy was the most significant predictor (P = .004). Hippocampal V_55Gy of 0%, 25%, and 50% was associated with tumor-induced impairment rates of 14.9% (95% confidence interval [CI], 7.2%-28.7%), 45.9% (95% CI, 24.7%-68.6%), and 80.6% (95% CI, 39.2%-96.4%), respectively.

The hippocampal V_55Gy is a significant predictor for impairment, and a limiting dose below 55 Gy may minimize radiation-induced cognitive impairment.