Arterial spin labeled perfusion MRI for the assessment of radiation-treated meningiomas.

Purpose: Conventional contrast-enhanced MRI is currently the primary imaging technique used to evaluate radiation treatment response in meningiomas. However, newer perfusion-weighted MRI techniques, such as 3D pseudocontinuous arterial spin labeling (3D pCASL) MRI, capture physiologic information beyond the structural information provided by conventional MRI and may provide additional complementary treatment response information. The purpose of this study is to assess 3D pCASL for the evaluation of radiation-treated meningiomas. Methods: Twenty patients with meningioma treated with surgical resection followed by radiation, or by radiation alone, were included in this retrospective single-institution study. Patients were evaluated with 3D pCASL and conventional contrast-enhanced MRI before and after radiation (median follow up 6.5 months). Maximum pre- and post-radiation ASL normalized cerebral blood flow (ASL-nCBF) was measured within each meningioma and radiation-treated meningioma (or residual resected and radiated meningioma), and the contrast-enhancing area was measured for each meningioma. Wilcoxon signed-rank tests were used to compare pre- and post-radiation ASL-nCBF and pre- and post-radiation area. Results: All treated meningiomas demonstrated decreased ASL-nCBF following radiation (p < 0.001). Meningioma contrast-enhancing area also decreased after radiation (p = 0.008) but only for approximately half of the meningiomas (9), while half (10) remained stable. A larger effect size (Wilcoxon signed-rank effect size) was seen for ASL-nCBF measurements (r = 0.877) compared to contrast-enhanced area measurements (r = 0.597). Conclusions: ASL perfusion may provide complementary treatment response information in radiation-treated meningiomas. This complementary information could aid clinical decision-making and provide an additional endpoint for clinical trials.

Neurocognitive Outcomes in Multiethnic Pediatric Brain Tumor Patients Treated With Proton Versus Photon Radiation.

BACKGROUND: We analyzed post-radiation (RT) neurocognitive outcomes in an ethnically diverse pediatric brain tumor population undergoing photon radiotherapy (XRT) and proton radiotherapy (PRT). PROCEDURE: Post-RT neurocognitive outcomes from 49 pediatric patients (37% Hispanic/Latino) with primary brain tumors were analyzed. Tests included cognitive outcomes, behavioral outcomes, and overall intelligence. For each outcome, proportion of patients with cognitive impairment (scores <1.5 SD) was calculated. The Fisher exact tests compared proportion of patients with impairment and t tests compared T-scores between XRT (n=32) and PRT (n=17) groups. Linear regression assessed associations between radiation modality and outcomes. RESULTS: Median follow-up was 3.2 and 1.8 years in the XRT and PRT groups, respectively. The median RT dose was 54.0 Gy. We found impairment in 16% to 42% of patients across most neurocognitive domains except executive function. There was no difference in scores between XRT and PRT groups. Regression analyses revealed no association of neurocognitive outcomes with radiation modality. Non-Hispanic patients had better Verbal Comprehension Index and General Ability Index scores than Hispanic patients ( P <0.05). CONCLUSIONS: Among pediatric patients with brain tumors receiving RT, all cognitive domains were affected except executive function. Radiation modality was not associated with neurocognitive outcomes. Hispanic patients may be more vulnerable to posttreatment cognitive effects that warrant further study.

Microstructural Cerebellar Injury Independently Associated With Processing Speed in Adult Patients With Primary Brain Tumors: Implications for Cognitive Preservation.

PURPOSE: The cerebellum's role in posttreatment neurocognitive decline is unexplored. This study investigated associations between cerebellar microstructural integrity using quantitative neuroimaging biomarkers and neurocognition among patients with primary brain tumors receiving partial-brain radiation therapy (RT). METHODS AND MATERIALS: In a prospective trial, 65 patients underwent volumetric brain magnetic resonance imaging, diffusion tensor imaging, and memory, executive function, language, attention, and processing speed (PS) assessment before RT and at 3, 6, and 12 months after RT. Delis-Kaplan Executive Function System-Trail Making (D-KEFS-TM) visual scanning and number and letter sequencing and Wechsler Adult Intelligence Scale, Fourth Edition, coding were used to evaluate PS. The cerebellar cortex and white matter (WM) and supratentorial structures subserving the previously mentioned cognitive domains were autosegmented. Volume was measured within each structure at each time point along with diffusion biomarkers (fractional anisotropy and mean diffusivity) in WM structures. Linear mixed-effects models assessed cerebellar biomarkers as predictors of neurocognitive scores. If associated, cerebellar biomarkers were evaluated as independent predictors of cognitive scores controlling for domain-specific supratentorial biomarkers. RESULTS: Left (P = .04) and right (P < .001) cerebellar WM volume declined significantly over time. Cerebellar biomarkers were not associated with memory, executive function, or language. Smaller left cerebellar cortex volume was associated with worse D-KEFS-TM number (P = .01) and letter (P = .01) sequencing scores. A smaller right cerebellar cortex volume correlated with worse D-KEFS-TM visual scanning (P = .02) and number (P = .03) and letter (P = .02) sequencing scores. Greater right cerebellar WM mean diffusivity, indicating WM injury, was associated with worse D-KEFS-TM visual scanning performance (P = .03). Associations remained significant after controlling for corpus callosum and intrahemispheric WM injury biomarkers. CONCLUSIONS: Injury to the cerebellum as measured with quantitative biomarkers correlates with worse post-RT PS, independent of corpus callosum and intrahemispheric WM damage. Efforts to preserve cerebellar integrity may preserve PS.

Thermal ablation compared to stereotactic body radiation therapy for hepatocellular carcinoma: A multicenter retrospective comparative study.

BACKGROUND AIMS: Early-stage HCC can be treated with thermal ablation or stereotactic body radiation therapy (SBRT). We retrospectively compared local progression, mortality, and toxicity among patients with HCC treated with ablation or SBRT in a multicenter, US cohort. APPROACH RESULTS: We included adult patients with treatment-naïve HCC lesions without vascular invasion treated with thermal ablation or SBRT per individual physician or institutional preference from January 2012 to December 2018. Outcomes included local progression after a 3-month landmark period assessed at the lesion level and overall survival at the patient level. Inverse probability of treatment weighting was used to account for imbalances in treatment groups. The Cox proportional hazard modeling was used to compare progression and overall survival, and logistic regression was used for toxicity. There were 642 patients with 786 lesions (median size: 2.1 cm) treated with ablation or SBRT. In adjusted analyses, SBRT was associated with a reduced risk of local progression compared to ablation (aHR 0.30, 95% CI: 0.15-0.60). However, SBRT-treated patients had an increased risk of liver dysfunction at 3 months (absolute difference 5.5%, aOR 2.31, 95% CI: 1.13-4.73) and death (aHR 2.04, 95% CI: 1.44-2.88, p < 0.0001). CONCLUSIONS: In this multicenter study of patients with HCC, SBRT was associated with a lower risk of local progression compared to thermal ablation but higher all-cause mortality. Survival differences may be attributable to residual confounding, patient selection, or downstream treatments. These retrospective real-world data help guide treatment decisions while demonstrating the need for a prospective clinical trial.

Fine Motor Skill Decline After Brain Radiation Therapy-A Multivariate Normal Tissue Complication Probability Study of a Prospective Trial.

PURPOSE: Brain radiation therapy can impair fine motor skills (FMS). Fine motor skills are essential for activities of daily living, enabling hand-eye coordination for manipulative movements. We developed normal tissue complication probability (NTCP) models for the decline in FMS after fractionated brain radiation therapy (RT). METHODS AND MATERIALS: On a prospective trial, 44 patients with primary brain tumors received fractioned RT; underwent high-resolution volumetric magnetic resonance imaging, diffusion tensor imaging, and comprehensive FMS assessments (Delis-Kaplan Executive Function System Trail Making Test Motor Speed [DKEFS-MS]; and Grooved Pegboard dominant/nondominant hands) at baseline and 6 months postRT. Regions of interest subserving motor function (including cortex, superficial white matter, thalamus, basal ganglia, cerebellum, and white matter tracts) were autosegmented using validated methods and manually verified. Dosimetric and clinical variables were included in multivariate NTCP models using automated bootstrapped logistic regression, least absolute shrinkage and selection operator logistic regression, and random forests with nested cross-validation. RESULTS: Half of the patients showed a decline on grooved pegboard test of nondominant hands, 17 of 42 (40.4%) on grooved pegboard test of -dominant hands, and 11 of 44 (25%) on DKEFS-MS. Automated bootstrapped logistic regression selected a 1-term model including maximum dose to dominant postcentral white matter. The least absolute shrinkage and selection operator logistic regression selected this term and steroid use. The top 5 variables in the random forest were all dosimetric: maximum dose to dominant thalamus, mean dose to dominant caudate, mean and maximum dose to the dominant corticospinal tract, and maximum dose to dominant postcentral white matter. This technique performed best with an area under the curve of 0.69 (95% CI, 0.68-0.70) on nested cross-validation. CONCLUSIONS: We present the first NTCP models for FMS impairment after brain RT. Dose to several supratentorial motor-associated regions of interest correlated with a decline in dominant-hand fine motor dexterity in patients with primary brain tumors in multivariate models, outperforming clinical variables. These data can guide prospective fine motor-sparing strategies for brain RT.

Dose-Dependent Atrophy in Bilateral Amygdalae and Nuclei After Brain Radiation Therapy and Its Association With Mood and Memory Outcomes on a Longitudinal Clinical Trial.

PURPOSE: Amygdalae are bilateral, almond-shaped structures located anterior to the hippocampi, critical to limbic system functions of emotional processing and memory consolidation. The amygdalae are heterogeneous, composed of multiple nuclei with distinct structural and functional properties. We prospectively assessed associations between longitudinal changes in amygdala morphometry, including component nuclei, and functional outcomes in patients with primary brain tumors receiving radiation therapy (RT). METHODS AND MATERIALS: On a prospective longitudinal trial, 63 patients underwent high-resolution volumetric brain magnetic resonance imaging and testing for mood (Beck Depression Inventory and Beck Anxiety Inventory), memory (Brief Visuospatial Memory Test-Revised [BVMT] Total Recall and Delayed Recall; Hopkins Verbal Learning Test-Revised [HVLT] Total Recall and Delayed Recall), and health-related quality-of-life outcomes (Functional Assessment of Cancer Therapy-Brain Social/Family Well-Being and Emotional Well-Being) at baseline and 3, 6, and 12 months after RT. Amygdalae, including 8 nuclei, were autosegmented bilaterally using validated techniques. Linear mixed-effects models assessed longitudinal change in amygdalae and nuclei volumes and associations with dose and outcomes. Wilcoxon rank sum tests compared amygdala volume change between patient groups with worse and more stable outcomes at each time point. RESULTS: Atrophy was found in the right amygdala at 6 months (P = .001) and the left amygdala at 12 months (P = .046). A higher dose was associated with atrophy of the left amygdala (P = .013) at 12 months. The right amygdala showed dose-dependent atrophy at 6 months (P = .016) and 12 months (P = .001). Worse BVMT-Total, HVLT-Total, and HVLT-Delayed performance was associated with smaller left lateral (P = .014, P = .004, and P = .007, respectively) and left basal (P = .034, P = .016, and P = .026, respectively) nuclei volumes. Increased anxiety at 6 months was associated with greater combined (P = .031) and right (P = .007) amygdala atrophy. Greater left amygdala atrophy (P = .038) was noted in patients with decreased emotional well-being at 12 months. CONCLUSIONS: Bilateral amygdalae and nuclei undergo time- and dose-dependent atrophy after brain RT. Atrophy in amygdalae and specific nuclei was associated with poorer memory, mood, and emotional well-being. Amygdalae-sparing treatment planning may preserve neurocognitive and neuropsychiatric outcomes in this population.

Comparison of first-line radiosurgery for small-cell and non-small cell lung cancer brain metastases (CROSS-FIRE).

INTRODUCTION: Historical reservations regarding stereotactic radiosurgery (SRS) for small-cell lung cancer (SCLC) brain metastases include concerns for short-interval and diffuse central nervous system (CNS) progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small cell lung cancer (NSCLC) where SRS is well established. METHODS: Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000 to 2022 were retrospectively collected (n = 892 SCLC, n = 4785 NSCLC). Data from the prospective Japanese Leksell Gamma Knife Society (JLGK0901) clinical trial of first-line SRS were analyzed as a comparison cohort (n = 98 SCLC, n = 814 NSCLC). Overall survival (OS) and CNS progression were analyzed using Cox proportional hazard and Fine-Gray models, respectively, with multivariable adjustment for cofactors including age, sex, performance status, year, extracranial disease status, and brain metastasis number and volume. Mutation-stratified analyses were performed in propensity score-matched retrospective cohorts of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive NSCLC, mutation-negative NSCLC, and SCLC. RESULTS: OS was superior for patients with NSCLC compared to SCLC in the retrospective dataset (median OS = 10.5 vs 8.6 months; P < .001) and in the JLGK0901 dataset. Hazard estimates for first CNS progression favoring NSCLC were similar in both datasets but reached statistical significance in the retrospective dataset only (multivariable hazard ratio = 0.82, 95% confidence interval = 0.73 to 0.92, P = .001). In the propensity score-matched cohorts, there were continued OS advantages for NSCLC patients (median OS = 23.7 [EGFR and ALK positive NSCLC] vs 13.6 [mutation-negative NSCLC] vs 10.4 months [SCLC], pairwise P values < 0.001), but no statistically significant differences in CNS progression were observed in the matched cohorts. Neurological mortality and number of lesions at CNS progression were similar for NSCLC and SCLC patients. Leptomeningeal progression was increased in patients with NSCLC compared to SCLC in the retrospective dataset only (multivariable hazard ratio = 1.61, 95% confidence interval = 1.14 to 2.26, P = .007). CONCLUSIONS: After SRS, SCLC histology was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC patients overall but was similar in patients matched on baseline factors. SCLC was not associated with increased neurological mortality, number of lesions at CNS progression, or leptomeningeal progression compared to NSCLC. These findings may better inform clinical expectations and individualized decision making regarding SRS for SCLC patients.

The relationship between radiation dose and bevacizumab-related imaging abnormality in patients with brain tumors: A voxel-wise normal tissue complication probability (NTCP) analysis.

PURPOSE: Bevacizumab-related imaging abnormality (BRIA), appearing as areas of restricted diffusion on magnetic resonance imaging (MRI) and representing atypical coagulative necrosis pathologically, has been observed in patients with brain tumors receiving radiotherapy and bevacizumab. We investigated the role of cumulative radiation dose in BRIA development in a voxel-wise analysis. METHODS: Patients (n = 18) with BRIA were identified. All had high-grade gliomas or brain metastases treated with radiotherapy and bevacizumab. Areas of BRIA were segmented semi-automatically on diffusion-weighted MRI with apparent diffusion coefficient (ADC) images. To avoid confounding by possible tumor, hypoperfusion was confirmed with perfusion imaging. ADC images and radiation dose maps were co-registered to a high-resolution T1-weighted MRI and registration accuracy was verified. Voxel-wise normal tissue complication probability analyses were performed using a logistic model analyzing the relationship between cumulative voxel equivalent total dose in 2 Gy fractions (EQD2) and BRIA development at each voxel. Confidence intervals for regression model predictions were estimated with bootstrapping. RESULTS: Among 18 patients, 39 brain tumors were treated. Patients received a median of 4.5 cycles of bevacizumab and 1-4 radiation courses prior to BRIA appearance. Most (64%) treated tumors overlapped with areas of BRIA. The median proportion of each BRIA region of interest volume overlapping with tumor was 98%. We found a dose-dependent association between cumulative voxel EQD2 and the relative probability of BRIA (ß0 = -5.1, ß1 = 0.03 Gy-1, γ = 1.3). CONCLUSIONS: BRIA is likely a radiation dose-dependent phenomenon in patients with brain tumors receiving bevacizumab and radiotherapy. The combination of radiation effects and tumor microenvironmental factors in potentiating BRIA in this population should be further investigated.

Neurocognitive considerations in the treatment of meningioma with radiation therapy: applications for quantitative neuroimaging and precision radiation medicine.

This article focuses on the role of radiotherapy in the management of meningioma, in the definitive and adjuvant setting and across the spectrum of meningioma grade. Treatment paradigms, informed by clinical evidence, are discussed. Notably, we focus on the impact of radiotherapy on normal brain tissues and neurocognitive function, particularly the dose-dependent changes in white matter and cerebral cortex thickness. Novel imaging techniques have allowed the identification of microstructural changes to eloquent white matter, cortex, and subcortical regions as biomarkers for understanding RT-induced changes in cognitive functioning. Deficits in multiple domains including attention, memory, language and executive function can become more pronounced following radiation. Longitudinal assessment with imaging and neurocognitive testing pre- and post-radiation have allowed correlation between dose to specific regions of the brain and decline in associated domains of neurocognitive function. These findings suggest incorporation of areas at higher risk for neurocognitive sequelae into precision radiation planning. Volumetric arc therapy, advanced planning with cortical sparing, proton therapy and stereotactic radiosurgery are reviewed as options for delivering therapeutic dose to target volumes while minimizing risk to adjacent sensitive regions. The treatment of meningioma is an evolving area, with improving outcomes for higher grade disease in modern trials, where care must be taken to maximize both disease control as well as quality of life for patients.

Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides updated evidence-based recommendations addressing recent developments in the management of patients with brain metastases, including advanced radiation therapy techniques such as stereotactic radiosurgery (SRS) and hippocampal avoidance whole brain radiation therapy and the emergence of systemic therapies with central nervous system activity. METHODS: The American Society for Radiation Oncology convened a task force to address 4 key questions focused on the radiotherapeutic management of intact and resected brain metastases from nonhematologic solid tumors. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality. Recommendations were created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: Strong recommendations are made for SRS for patients with limited brain metastases and Eastern Cooperative Oncology Group performance status 0 to 2. Multidisciplinary discussion with neurosurgery is conditionally recommended to consider surgical resection for all tumors causing mass effect and/or that are greater than 4 cm. For patients with symptomatic brain metastases, upfront local therapy is strongly recommended. For patients with asymptomatic brain metastases eligible for central nervous system-active systemic therapy, multidisciplinary and patient-centered decision-making to determine whether local therapy may be safely deferred is conditionally recommended. For patients with resected brain metastases, SRS is strongly recommended to improve local control. For patients with favorable prognosis and brain metastases receiving whole brain radiation therapy, hippocampal avoidance and memantine are strongly recommended. For patients with poor prognosis, early introduction of palliative care for symptom management and caregiver support are strongly recommended. CONCLUSIONS: The task force has proposed recommendations to inform best clinical practices on the use of radiation therapy for brain metastases with strong emphasis on multidisciplinary care.

Post-treatment neuroendocrine outcomes among pediatric brain tumor patients: Is there a difference between proton and photon therapy?

Purpose: Pediatric brain tumor patients are vulnerable to radiotherapy (RT) sequelae including endocrinopathies. We compared post-RT neuroendocrine outcomes between pediatric brain tumor patients receiving photons (XRT) versus protons (PRT). Methods: Using a prospectively maintained single-institution database, we analyzed 112 pediatric primary brain tumor patients (80 XRT, 32 PRT) from 1996 to 2019. Patient/treatment characteristics and endocrinopathy diagnoses (growth hormone deficiency [GHD], sex hormone deficiency [SHD], hypothyroidism, and requirement of hormone replacement [HRT]) were obtained via chart review. Univariable/multivariable logistic regression identified neuroendocrine outcome predictors. Time-adjusted propensity score models accounted for treatment type. Craniospinal irradiation (CSI) patients were evaluated as a sub-cohort. Results: Median follow-up was 6.3 and 4.4 years for XRT and PRT patients respectively. Medulloblastoma was the most common histology (38%). Half of patients (44% in XRT, 60% in PRT) received CSI. Common endocrinopathies were GHD (26% XRT, 38% PRT) and hypothyroidism (29% XRT, 19% PRT). CSI cohort PRT patients had lower odds of hypothyroidism (OR 0.16, 95% CI[0.02-0.87], p = 0.045) on multivariable regression and propensity score analyses. There were no significant differences in endocrinopathies in the overall cohort and in the odds of GHD or HRT within the CSI cohort. SHD developed in 17.1% of the XRT CSI group but did not occur in the PRT CSI group. Conclusion: Endocrinopathies were common among pediatric brain tumor survivors. Among CSI patients, PRT was associated with lower risk of hypothyroidism, and potentially associated with lower incidence of SHD. Future studies should involve collaborative registries to explore the survivorship benefits of PRT.

Automated segmentation of multiparametric magnetic resonance images for cerebral AVM radiosurgery planning: a deep learning approach.

Stereotactic radiosurgery planning for cerebral arteriovenous malformations (AVM) is complicated by the variability in appearance of an AVM nidus across different imaging modalities. We developed a deep learning approach to automatically segment cerebrovascular-anatomical maps from multiple high-resolution magnetic resonance imaging/angiography (MRI/MRA) sequences in AVM patients, with the goal of facilitating target delineation. Twenty-three AVM patients who were evaluated for radiosurgery and underwent multi-parametric MRI/MRA were included. A hybrid semi-automated and manual approach was used to label MRI/MRAs with arteries, veins, brain parenchyma, cerebral spinal fluid (CSF), and embolized vessels. Next, these labels were used to train a convolutional neural network to perform this task. Imaging from 17 patients (6362 image slices) was used for training, and 6 patients (1224 slices) for validation. Performance was evaluated by Dice Similarity Coefficient (DSC). Classification performance was good for arteries, veins, brain parenchyma, and CSF, with DSCs of 0.86, 0.91, 0.98, and 0.91, respectively in the validation image set. Performance was lower for embolized vessels, with a DSC of 0.75. This demonstrates the proof of principle that accurate, high-resolution cerebrovascular-anatomical maps can be generated from multiparametric MRI/MRA. Clinical validation of their utility in radiosurgery planning is warranted.

Prospective Longitudinal Assessment of Health-related Quality of Life in Patients With Brain Metastases Undergoing Radiation Therapy.

OBJECTIVE: We conducted a prospective clinical trial of patients receiving radiation (RT) for brain metastases to identify clinical predictors of pre-RT and post-RT health-related quality of life (hrQoL). MATERIALS AND METHODS: Patients with brain metastases completed overall (European Organisation for Research and Treatment of Cancer QLQ C15-PAL) and brain tumor-specific (QLQ-BN20) hrQoL assessments pre-RT (n=127) and 1 (n=56) and 3 (n=45) months post-RT. Linear and proportional-odds models analyzed patient, disease, and treatment predictors of baseline, 1-, and 3-month hrQoL scores. Generalized estimating equations and repeated measures proportional-odds models assessed predictors of longitudinal hrQoL scores. RESULTS: Most patients underwent stereotactic radiosurgery (SRS) (69.3%) and had non-small-cell lung (36.0%) metastases. Compared with SRS, receipt of whole brain RT was associated with a higher odds of appetite loss (baseline P=0.04, 1 mo P=0.02) and greater motor dysfunction (baseline P=0.01, 1 mo P=0.003, 3 mo P=0.02). Receipt of systemic therapy was associated with better emotional functioning after RT (1 mo P=0.03, 3 mo P=0.01). Compared with patients with breast cancer, patients with melanoma had higher odds of better global hrQoL (P=0.01) and less pain (P=0.048), while patients with lung cancer reported lower physical function (P=0.048) 3 months post-RT. Nonmarried patients had greater odds of higher global hrQoL (1 mo P=0.01), while male patients had lower odds of reporting more hair loss (baseline P=0.03, 3 mo P=0.045). Patients 60 years and above had lower odds of more drowsiness (P=0.04) and pain (P=0.049) over time. CONCLUSIONS: Patients receiving SRS versus whole brain RT and systemic therapy reported better posttreatment hrQoL. In addition, melanoma metastases, nonmarried, male, and older patients with reported better hrQoL in various as well as domains after intracranial RT.

Quality of Life Is Independently Associated With Neurocognitive Function in Patients With Brain Tumors: Analysis of a Prospective Clinical Trial.

PURPOSE: We conducted the first prospective longitudinal study examining the independent association between patient-reported health-related quality of life (hrQoL) (physical, social/family, emotional, functional, and brain cancer-specific) and neurocognitive function (NCF), while controlling for mood symptoms in patients with primary brain tumors. METHODS AND MATERIALS: Patients with primary brain tumors (n = 59) receiving brain radiation therapy underwent hrQOL (Functional Assessment of Cancer Therapy-Brain), mood (Beck Depression and Anxiety Inventories), and neurocognitive evaluation at baseline and 3, 6, and 12 months postradiation therapy in a prospective clinical trial. Neurocognitive assessments measured attention/processing speed, memory, and executive function, including the Delis-Kaplan Executive Function System Verbal Fluency, Hopkins Verbal Learning Test Revised (HVLT-R), and Brief Visuospatial Memory Test. Subjects underwent neurocognitive, mood, and hrQoL assessments in the same testing session. Multivariable linear mixed-effects models assessed associations between hrQOL and NCF over time, controlling for patient, tumor, and treatment characteristics as well as timepoint-specific patient-reported mood (ie, anxiety and depression symptoms). P values were adjusted for multiple comparisons. RESULTS: Higher physical hrQoL was associated with better verbal memory (HVLT-R Total Recall, P = .047), and higher functional hrQoL was associated with better executive function (Delis-Kaplan Executive Function System Verbal Fluency Switching Total, P = .009) and verbal memory (HVLT-R Delayed Recall, P = .006). Higher brain tumor-specific hrQoL was associated with better verbal and nonverbal memory (HVLT-R Total, P = .004 and Delayed Recall, P = .030; Brief Visuospatial Memory Test Total, P = .049 and Delayed Recall, P = .049). There was no association between social/family or emotional hrQoL and NCF after controlling for mood. CONCLUSIONS: Higher physical, functional, and brain tumor-specific hrQoL were associated with better executive function and memory among patients with primary brain tumors. Physical and functional impairments are correlated with cognitive performance. Interventions to maximize quality of life after treatment may influence neurocognition and vice versa.