Purpose/Objectives Following brain radiation therapy (RT), patients often experience memory impairment, which may be partially mediated by damage to the hippocampus. Hippocampal sparing in RT planning is the subject of recent and ongoing clinical trials. Calculating appropriate hippocampal dose constraints would be improved by efficient in vivo measurements of hippocampal damage. In this study we sought to determine whether brain RT was associated with dose-dependent hippocampal atrophy. Materials/Methods Hippocampal volume was measured with MRI in 52 patients who underwent fractionated, partial brain RT for primary brain tumors. Study patients had high-resolution, 3D volumetric MRI prior to and one year post-RT. Images were processed using software with FDA clearance and CE (Conformité Européene) marking for automated measurement of hippocampal volume. Automated results were inspected visually for accuracy. Tumor and surgical changes were censored. Mean hippocampal dose was tested for correlation with hippocampal atrophy one year post-RT. Average hippocampal volume change was also calculated for hippocampi receiving high (>40 Gy) or low (<10 Gy) mean RT dose. A multivariate analysis was conducted with linear mixed-effects modeling to evaluate other potential predictors of hippocampal volume change, including patient (random effect), age, hemisphere, sex, seizure history, and baseline volume. Statistical significance was evaluated at α=0.05. Results Mean hippocampal dose was significantly correlated with hippocampal volume loss (r=−0.24, p=0.03). Mean hippocampal volume was significantly reduced one year after high-dose RT (mean −6%, p=0.009), but not after low-dose RT. In multivariate analysis, both RT dose and patient age were significant predictors of hippocampal atrophy (p<0.01). Conclusions The hippocampus demonstrates radiation dose-dependent atrophy following treatment for brain tumors. Quantitative MRI is a non-invasive imaging technique capable of measuring radiation effects on intracranial structures. This technique could be investigated as a potential biomarker for development of reliable dose constraints for improved cognitive outcomes.

Purpose/Objectives Neurologic deficits after brain radiotherapy (RT) typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We sought to determine whether areas of cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy. Materials/Methods We measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. Study patients had high-resolution, volumetric MRI (T1-weighted; T2 FLAIR) prior to and one year after RT. Semi-automated software was used to segment anatomic regions of the cerebral cortex for each patient. Cortical thickness was measured for each region pre-RT and at one year. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, two primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Linear mixed-effects analyses were used to test all other cortical regions for significant radiation dose-dependent thickness change. Statistical significance was set at α=0.05 using two-tailed tests. Results Cortical atrophy was significantly associated with radiation dose in the entorhinal (p=0.01) and inferior parietal ROIs (p=0.02). In contrast, no significant radiation dose-dependent effect was found in the primary cortex ROIs (pericalcarine and paracentral lobule). In the whole-cortex analysis, 9 regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (p≤0.002). Conclusions Areas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical observations that brain radiation patients develop deficits in domains of memory, executive function, and attention. Correlations of regional cortical atrophy with domain-specific cognitive functioning in prospective trials are warranted.

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in patients 18 years (n Z 13), with 2-year OS of 85.7% vs. 50.0% (HR Z 0.08; 95% CI Z 0.01-0.80; P Z 0.032) and for patients >18 years (n Z 184), with 2-year OS of 95.0% vs. 76.5% (HR Z 0.54; 95% CI Z 0.30-0.97; P Z 0.039), respectively. At 30 months, all patients 18 years who had not received RT had died. Conclusion: PORT appears to improve OS in both pediatric and adult patients with papillary meningioma in this population-based analysis and should therefore be considered in those who present with this rare, aggressive tumor.