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.

Objectives The objectives of this systematic review were to (a) identify supportive‐care (psychosocial/behavioral, pharmacological, complementary, or alternative) interventions that have been evaluated via randomized controlled trials (RCTs) to improve patient‐reported health‐related quality of life (HRQoL) among adults with brain tumors, (b) evaluate the quality of the intervention studies, and (c) evaluate if developed interventions have been efficacious at improving HRQoL, as compared with control conditions in RCTs. Methods This systematic review was conducted using preferred reporting items for systematic reviews and meta‐analyses (PRISMA) guidelines. Four databases were searched for RCTs of supportive‐care interventions for adults with brain tumors, primary or metastatic, that included a patient‐reported HRQoL outcome. Quality of the included studies was assessed using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies. Results Ten RCTs involving 640 patients with either a primary or metastatic brain tumor investigating supportive‐care interventions with a HRQoL outcome were identified. In terms of quality, three of the studies received a “strong” rating, three received a “moderate” rating, and four of the studies received a “weak” rating. Only two of the interventions (ie, a home‐based psychosocial intervention and individualized acupuncture with standard rehabilitation) demonstrated improvements in HRQoL over control conditions. Conclusions HRQoL is of the utmost importance when treating patients with brain tumors. Yet there is a notable paucity of research to inform clinical decisions and evidence‐based practice. More high‐quality studies of interventions aimed at improving HRQoL are needed.

Background and Purpose: Executive function (EF) decline is common after radiation therapy (RT), yet the etiology is unclear. We analyzed the association between longitudinal changes in frontal lobe white matter microstructure and decline in EF following RT in brain tumor patients on a prospective clinical trial.Materials and Methods: Diffusion tensor imaging was obtained on 22 patients with brain tumors prior to RT, as well as 3-and 6-months post-RT, in a prospective, observational trial. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were calculated within the superficial white matter (SWM) of the anterior cingulate (AC) and dorsolateral prefrontal cortex. Measures of cognitive flexibility, verbal fluency, and verbal setshifting were obtained pre-and post-RT. Reliable change indices were calculated to determine significant baseline to 6-month EF changes.Results: Decreases in FA and increases in MD were observed in the caudal AC (CAC) at 3months post-RT. CAC changes were characterized by increased RD bilaterally. From baseline to 6months post-RT, decreased FA and increased MD and RD of the CAC was associated with decline in verbal set-shifting ability, whereas increased MD in the CAC was associated with a decline in cognitive flexibility. Conclusion:White matter underlying the AC may be particularly vulnerable to radiation effects. Early microstructural loss within AC SWM represents an important biomarker for EF decline, and dose reduction in this region may represent a possibility for cognitive preservation for patients receiving radiotherapy.

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