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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.

Introduction Historical reservations regarding radiosurgery (SRS) for small-cell-lung-cancer (SCLC) brain metastases (BrM) include concerns for short-interval/diffuse 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 2000-2022 were retrospectively collected (N=892-SCLC/N=4,785-NSCLC). Data from the prospective JLGK0901 SRS trial were analyzed as a comparison cohort (N=98-SCLC/N=794-NSCLC). OS and CNS-progression were analyzed using Cox-Proportional-Hazard and Fine-Gray models, respectively, with multivariable (MV) adjustment (including age/sex/performance-status/year/extracranial disease/BrM-number/BrM-volume). Mutation-stratified analyses were performed in propensity score-matched (PSM) retrospective cohorts of EGFR/ALK-positive-NSCLC, mutation-negative-NSCLC, and SCLC. Results OS was superior with NSCLC over SCLC in the retrospective dataset (median-OS, 10.5 vs 8.6 months, MV-p Conclusion After SRS, SCLC was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC overall but was similar in patients matched on baseline characteristics. Neurological mortality, lesions at CNS-progression, and leptomeningeal-progression were comparable. These findings may better inform clinical decision-making for SCLC patients.

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.

Gliomas are the most common primary brain cancer, yet are extraordinarily challenging to treat as they can be aggressive and infiltrative, locally recurrent, and resistant to standard treatments. Furthermore, the treatments themselves, including radiation therapy, can affect patients’ neurocognitive function and quality of life. Non-invasive imaging is standard of care for primary brain tumors, including diagnosis, treatment planning, and monitoring for treatment response. This article will explore the ways in which advanced imaging has and will continue to transform radiation treatment for patients with gliomas, with a focus on cognitive preservation and novel biomarkers, as well as precision radiotherapy and treatment adaptation. Advances in novel imaging techniques continue to push the field forward, to more precisely guided treatment planning, radiation dose escalation, measurement of therapeutic response, and understanding of radiation-associated injury. High-grade gliomas represent the most common primary brain tumors, yet are extraordinarily challenging to treat as they can be aggressive and locally recurrent. In addition, the brain is responsible for critical neurocognitive processing, so tumor and treatment effects on these functions can be devastating for patients and their quality of life. Clinical trials and clinical care have moved towards maximizing not only patient survival and local control but also the preservation of neurocognition and quality of life. Radiotherapy (RT) is indispensable in the management of gliomas, yet the majority of patients who survive longer than 6 months will experience a decline in neurocognitive function. Advances in novel imaging techniques continue to push the field forward, to more precisely guided treatment planning, radiation dose escalation, measurement of therapeutic response, and understanding of radiation-associated injury. This article will explore the ways in which advanced imaging has and will continue to transform radiation treatment for patients with gliomas, with a focus on cognitive preservation and novel biomarkers, as well as precision radiotherapy and treatment adaptation. As novel imaging technologies are leveraged to enable precision radiation therapy for HGG, so too can these technologies be employed as potential in vivo biomarkers of cognitive toxicity, paving the way for individualized interventions to preserve function. Specifically, cortical thickness, white matter integrity, and hippocampal volume represent in vivo imaging biomarkers and tools for individualized, precision RT.

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.

Purpose The corpus callosum (CC) and intrahemispheric white matter tracts (IHWM) subserve critical aspects of attention and processing speed. We analyzed imaging biomarkers of microstructural injury within these regions and association with attention and processing speed performance before and after radiation therapy in primary brain tumor patients. Methods and Materials In a prospective clinical trial, 44 primary brain tumor patients underwent cognitive testing and magnetic resonance imaging/diffusion-weighted imaging at baseline (pre-radiation therapy) and 3-, 6-, and 12-months post-radiation therapy. CC (subregions, total) and IHWM tracts (left/right without CC, total) were autosegmented; tumor, tumor bed, and edema were censored. Biomarkers included volume changes (cm3), mean diffusivity ([MD]; higher values indicate white matter injury), fractional anisotropy ([FA]; lower values indicate white matter injury). Reliable-change indices measured changes in attention (Weschler Adult Intelligence Scale [WAIS-IV] digits-forward; Delis-Kaplan Executive Function System Trail Making [D-KEFS-TM] visual-scanning), and processing speed (WAIS-IV coding; D-KEFS-TM number-sequencing, letter-sequencing), accounting for practice effects. Linear mixed-effects models evaluated associations between mean radiation dose and biomarkers (volume, MD, FA) and imaging biomarkers and neurocognitive performance. Statistics were corrected for multiple comparisons. Results Processing speed declined at 6 months following radiation therapy (number sequencing, letter sequencing; P Conclusions The CC demonstrated radiation dose-dependent atrophy and WM injury. Microstructural injury within the CC and IHWM was associated with attention and processing speed decline after radiation therapy. These areas represent possible avoidance regions for preservation of attention and processing speed.

PURPOSE: The corpus callosum (CC) and intrahemispheric white matter tracts (IHWM) subserve critical aspects of attention and processing speed. We analyzed imaging biomarkers of microstructural injury within these regions and association with attention and processing speed performance before and after radiation therapy in primary brain tumor patients. METHODS AND MATERIALS: In a prospective clinical trial, 44 primary brain tumor patients underwent cognitive testing and magnetic resonance imaging/diffusion-weighted imaging at baseline (pre-radiation therapy) and 3-, 6-, and 12-months post-radiation therapy. CC (subregions, total) and IHWM tracts (left/right without CC, total) were autosegmented; tumor, tumor bed, and edema were censored. Biomarkers included volume changes (cm(3)), mean diffusivity ([MD]; higher values indicate white matter injury), fractional anisotropy ([FA]; lower values indicate white matter injury). Reliable-change indices measured changes in attention (Weschler Adult Intelligence Scale [WAIS-IV] digits-forward; Delis-Kaplan Executive Function System Trail Making [D-KEFS-TM] visual-scanning), and processing speed (WAIS-IV coding; D-KEFS-TM number-sequencing, letter-sequencing), accounting for practice effects. Linear mixed-effects models evaluated associations between mean radiation dose and biomarkers (volume, MD, FA) and imaging biomarkers and neurocognitive performance. Statistics were corrected for multiple comparisons. RESULTS: Processing speed declined at 6 months following radiation therapy (number sequencing, letter sequencing; P

Purpose The Open Payments transparency program publishes data on industry-physician payments, in part to discourage relationships considered inappropriate including gifts, meals, and speaker’s bureau fees. We evaluated trends in physician-level payments to test whether implementation of Open Payments resulted in fewer industry–radiation oncologist (RO) interactions or shifted interactions toward those considered more appropriate compared with medical oncologists (MOs) and other hospital-based physicians (HBPs). Methods and Materials We performed a retrospective, population-based cohort study of practicing US ROs versus MOs and HBPs in 2014 matched to general (nonresearch) payments between 2014 and 2018. Trends in payments were analyzed and reported by nature of payment. Values of payments to ROs from the top 10 companies were identified. Results From 2014 to 2018, 3379 (90.3%) ROs accepted 106,930 payments totaling $40.8 million. The per-physician number and value of payments was lower in radiation oncology than in medical oncology and higher than HBPs. The proportion of ROs accepting payments increased from 61.8% in 2014 to 64.2% in 2018; the proportion of MOs accepting payments decreased from 78.7% to 77.7%; and the proportion of HBPs decreased from 40.8% to 37.5%, respectively. The annual per-physician value and number of payments accepted by ROs and MOs increased. Payments in entertainment, meals, travel and lodging, and gifts increased among ROs and remained stable or decreased among MOs and HBPs. Consulting payments increased across all groups. Top RO payors produced novel cancer therapeutics, hydrogel spacers, radiation treatment machines, and opioids. Conclusions Industry payments to ROs have become more common since OP’s inception, while becoming less common for MOs and HBPs. Payments to ROs and MOs have become more frequent and of modestly increasing value compared with other HBPs, for whom the value is decreasing. No large changes in the nature of relationships were seen in ROs. Increased engagement with financial conflicts of interest is needed in radiation oncology.

Stereotactic radiosurgery (SRS) is used to treat cerebral arteriovenous malformations (AVMs). However, early evaluation of efficacy is difficult as structural magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) often does not demonstrate appreciable changes within the first 6 months. The aim of this study was to evaluate the use of four-dimensional (4D) flow MRI to quantify hemodynamic changes after SRS as early as 2 months. This was a retrospective observational study, which included 14 patients with both pre-SRS and post-SRS imaging obtained at multiple time points from 1 to 27 months after SRS. A 3T MRI Scanner was used to obtain T2 single-shot fast spin echo, time-of-flight MRA, and postcontrast 4D flow with three-dimensional velocity encoding between 150 and 200 cm/s. Post-hoc two-dimensional cross-sectional flow was measured for the dominant feeding artery, the draining vein, and the corresponding contralateral artery as a control. Measurements were performed by two independent observers, and reproducibility was assessed. Wilcoxon signed-rank tests were used to compare differences in flow, circumference, and pulsatility between the feeding artery and the contralateral artery both before and after SRS; and differences in nidus size and flow and circumference of the feeding artery and draining vein before and after SRS. Arterial flow (L/min) decreased in the primary feeding artery (mean: 0.1 ± 0.07 vs. 0.3 ± 0.2; p < 0.05) and normalized in comparison to the contralateral artery (mean: 0.1 ± 0.07 vs. 0.1 ± 0.07; p = 0.068). Flow decreased in the draining vein (mean: 0.1 ± 0.2 vs. 0.2 ± 0.2; p < 0.05), and the circumference of the draining vein also decreased (mean: 16.1 ± 8.3 vs. 15.7 ± 6.7; p < 0.05). AVM volume decreased after SRS (mean: 45.3 ± 84.8 vs. 38.1 ± 78.7; p < 0.05). However, circumference (mm) of the primary feeding artery remained similar after SRS (mean: 15.7 ± 2.7 vs. 16.1 ± 3.1; p = 0.600). 4D flow may be able to demonstrate early hemodynamic changes in AVMs treated with radiosurgery, and these changes appear to be more pronounced and occur earlier than the structural changes on standard MRI/MRA. Level of Evidence: 4 Technical Efficacy Stage: 1.

PURPOSE: Primary brain tumor patients are vulnerable to depression and anxiety symptoms, which may affect their neurocognitive functioning. We performed a prospective longitudinal analysis to examine the association between depression and anxiety symptoms and domain-specific neurocognitive functioning in primary brain tumor patients receiving radiation therapy (RT). METHODS AND MATERIALS: On a prospective trial, 54 primary brain tumor patients receiving RT underwent comprehensive neurocognitive evaluation at baseline (pre-RT), and 3, 6, and 12 months post-RT. Neurocognitive assessments measured attention/processing speed, verbal and visuospatial memory, and executive functioning, including Delis-Kaplan Executive Function System Trail-Making Test (DKEFS-TMT), DKEFS Verbal Fluency, and Brief Visuospatial Memory Test-Revised. Depression and anxiety symptoms were also assessed at each time point with Beck Depression and Anxiety Inventories (BDI-II and BAI), respectively. Higher scores reflect more numerous or severe depression or anxiety symptoms. Univariable and multivariable linear mixed-effects models assessed associations between BDI-II and BAI scores and domain-specific neurocognitive scores over time, controlling for pre-existing depression or anxiety disorders and other patient, tumor, and treatment characteristics. RESULTS: Higher BAI scores were associated with worse attention and processing speed in univariable analyses: DKEFS-TMT visual scanning (P = .003), number sequencing (P = .011), and letter sequencing (P

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of adult CNS cancers ranging from noninvasive and surgically curable pilocytic astrocytomas to metastatic brain disease. The involvement of an interdisciplinary team, including neurosurgeons, radiation therapists, oncologists, neurologists, and neuroradiologists, is a key factor in the appropriate management of CNS cancers. Integrated histopathologic and molecular characterization of brain tumors such as gliomas should be standard practice. This article describes NCCN Guidelines recommendations for WHO grade I, II, III, and IV gliomas. Treatment of brain metastases, the most common intracranial tumors in adults, is also described.

Purpose We used quantitative magnetic resonance imaging to prospectively analyze the association between microstructural damage to memory-associated structures within the medial temporal lobe and longitudinal memory performance after brain radiation therapy (RT). Methods and Materials Patients with a primary brain tumor receiving fractionated brain RT were enrolled on a prospective trial (n = 27). Patients underwent high-resolution volumetric brain magnetic resonance imaging, diffusion-weighted imaging, and neurocognitive testing before and 3, 6, and 12 months post-RT. Medial temporal lobe regions (hippocampus; entorhinal, parahippocampal, and temporal pole white matter [WM]) were autosegmented, quantifying volume and diffusion biomarkers of WM integrity (mean diffusivity [MD]; fractional anisotropy [FA]). Reliable change indices measured changes in verbal (Hopkins Verbal Learning Test-Revised) and visuospatial (Brief Visuospatial Memory Test-Revised [BVMT-R]) memory. Linear mixed-effects models assessed longitudinal associations between imaging parameters and memory. Results Visuospatial memory significantly declined at 6 months post-RT (mean reliable change indices, –1.3; P = .012). Concurrent chemotherapy and seizures trended toward a significant association with greater decline in visuospatial memory (P = .053 and P = .054, respectively). Higher mean dose to the left temporal pole WM was significantly associated with decreased FA (r = –0.667; P = .002). Over all time points, smaller right hippocampal volume (P = .021), lower right entorhinal FA (P = .023), greater right entorhinal MD (P = .047), and greater temporal pole MD (BVMT-R total recall, P = .003; BVMT-R delayed recall, P = .042) were associated with worse visuospatial memory. The interaction between right entorhinal MD (BVMT-R total recall, P = .021; BVMT-R delayed recall, P = .004) and temporal pole FA (BVMT-R delayed recall, P = .024) significantly predicted visuospatial memory performance. Conclusions Brain tumor patients exhibited visuospatial memory decline post-RT. Microstructural damage to critical memory regions, including the hippocampus and medial temporal lobe WM, were associated with post-RT memory decline. The integrity of medial temporal lobe structures is critical to memory performance post-RT, representing possible avoidance targets for memory preservation.

BackgroundRadiation recall pneumonitis (RRP) is a poorly understood clinical syndrome in which patients develop radiation pneumonitis triggered by a systemic agent, often years after the completion of radiation therapy. Immune checkpoint blockade agents have only recently been posited as a trigger for RRP. Here, we present three cases of immunotherapy-induced RRP.Case PresentationOur first patient was diagnosed with primary lung adenocarcinoma, and 4.5 years after completing radiation therapy developed symptomatic RRP immediately following a second dose of nivolumab-containing immunotherapy regimen. Our second patient was diagnosed with primary bladder cancer metastatic to the mediastinum, which was treated twice with radiation therapy. He developed RRP in the days following his second course of ipilimumab-pembrolizumab which was months after his second course of radiation that he received. Our final patient was diagnosed with metastatic small cell lung cancer and received local consolidative radiation therapy in addition to whole-brain radiation. He developed RRP on the 11th day after concluding his 4th cycle of nivolumab-ipilimumab, approximately 7 months after having had completed chest radiation therapy.ConclusionsImmunotherapy-induced RRP is a rare diagnosis which can present more focally than traditional immunotherapy pneumonitis and which must be clinically differentiated from other local processes such as pneumonia. Further research should explore the mechanisms underlying these radiation recall reactions as many patients receive radiation and immunotherapy during the course of their cancer treatment.

PURPOSE/OBJECTIVE(S) The entorhinal cortex in the medial temporal lobe is a critical part of the hippocampal memory system, crucial for memory formation and consolidation. Studies show the entorhinal cortex is particularly vulnerable to dose-dependent atrophy. We examined the association between entorhinal cortical volume and longitudinal verbal and visuospatial memory function in a prospective cohort of primary brain tumor patients. MATERIALS/METHODS Primary brain tumor patients (n = 50) undergoing fractionated brain RT were enrolled in a prospective trial and underwent volumetric brain MRI and verbal and visuospatial memory assessments (Hopkins Verbal Learning Test Total/Delayed [HVLT-Total, HVLT-Delayed] and Brief Visuospatial Memory Test Total/Delayed [BVMT-Total, BVMT-Delayed]) at baseline and 3-, 6-, and 12-months post-RT. Reliable change indices (RCI-PE) measured change in scores, adjusting for practice effects, and one-sample t-tests evaluated for significance. Left- and right-sided entorhinal cortices were autosegmented; tumor, surgical bed, and edema were censored to avoid confounding. Entorhinal cortical volume was measured, and linear mixed-effects modeling assessed entorhinal cortical volume as a longitudinal predictor of memory scores after controlling for time and subject-specific effects. P-values were corrected for multiple comparisons. RESULTS Among the cohort, median patient age was 50 years, 50% had gliomas, and 52% had left sided tumors. Median number of years of formal education was 15 (range 10-20). HVLT-Total/Delayed and BVMT-Total scores declined from baseline to 12 months post-RT (HVLT-Total RCI = -0.74, P = 0.032; HVLT-Delayed RCI = -1.39, P < 0001; BVMT-Total RCI = -0.64, P = 0.034). Patients with higher education attainment had less change in delayed verbal memory (baseline to 12 months, P = 0.01). Mean doses to right and left entorhinal cortices were not significantly different (P = 0.99). Higher radiation dose to the right entorhinal cortex was significantly associated with volume atrophy (P < 0.0001). Left entorhinal cortical atrophy was associated with worse total and delayed verbal memory performance (HVLT-Total P = 0.002, HVLT-Delayed P = 0.023). CONCLUSION Higher educational attainment was associated with less memory decline among primary brain tumor patients after RT. The right entorhinal cortex displayed significant radiation dose-dependent atrophy. Left entorhinal cortical atrophy predicted worse total and delayed verbal memory performance after RT. Beyond the hippocampus, the entorhinal cortex is also a critically important memory structure. HYPOTHESIS Atrophy of the entorhinal cortex is associated with worse visuospatial and verbal memory in the first year after brain radiotherapy.

Background We explored fine motor skills (FMS) before and after brain radiotherapy (RT), analyzing associations between longitudinal FMS and imaging biomarkers of cortical and white matter (WM) integrity in motor regions of interest (ROIs). Methods On a prospective trial, 52 primary brain tumor patients receiving fractionated brain RT underwent volumetric brain MRI, diffusion tensor imaging, and FMS assessments (Delis-Kaplan Executive Function System Trail Making Test Motor Speed [DKEFS-MS], Grooved Pegboard Dominant Hands [PDH], and Grooved Pegboard Nondominant Hands [PNDH]) at baseline and 3-, 6-, and 12-month post-RT. Motor ROIs autosegmented included: sensorimotor cortices and superficial WM, corticospinal tracts, cerebellar cortices and WM, and basal ganglia. Volume (cc) was measured in all ROIs at each timepoint. Diffusion biomarkers (FA [fractional anisotropy] and MD [mean diffusivity]) were additionally measured in WM ROIs. Linear mixed-effects models assessed biomarkers as predictors of FMS scores. P values were corrected for multiple comparisons. Results Higher RT dose was associated with right paracentral cortical thinning (β = −2.42 Gy/(month × mm), P = .03) and higher right precentral WM MD (β = 0.69 Gy/(month × µm2/ms), P = .04). Higher left (β = 38.7 points/(month × µm2/ms), P = .004) and right (β = 42.4 points/(month × µm2/ms), P = .01) cerebellar WM MD, left precentral cortical atrophy (β = −8.67 points/(month × mm), P = .02), and reduced right cerebral peduncle FA (β = −0.50 points/month, P = .01) were associated with worse DKEFS-MS performance. Left precentral cortex thinning was associated with worse PDH scores (β = −17.3 points/(month × mm), P = .02). Left (β = −0.87 points/(month × cm3), P = .001) and right (β = −0.64 points/(month × cm3), P = .02) cerebellar cortex, left pons (β = −19.8 points/(month × cm3), P = .02), and right pallidum (β = −10.8 points/(month × cm3), P = .02) atrophy and reduced right internal capsule FA (β = −1.02 points/month, P = .03) were associated with worse PNDH performance. Conclusions Biomarkers of microstructural injury in motor-associated brain regions were associated with worse FMS. Dose avoidance in these areas may preserve FMS.

Pleomorphic xanthoastrocytoma (PXA) is an uncommon primary brain tumor where radiation therapy is utilized for recurrence or adjuvant treatment after surgery. This chapter addresses considerations for contouring and treatment planning approaches.

Background and purpose Recently published HyTEC report summarized lung toxicity data and proposed guidelines of mean lung dose (MLD)

Background and purpose Executive function (EF) decline is common after brain 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 set-shifting 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 3-months post-RT. CAC changes were characterized by increased RD bilaterally. From baseline to 6-months 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.

cIMPACT‐NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to evaluate and make practical recommendations on recent advances in the field of CNS tumor classification, particularly in light of the rapid progress in molecular insights into these neoplasms. For Round 2 of its deliberations, cIMPACT‐NOW Working Committee 3 was reconstituted and convened in Utrecht, The Netherlands, for a meeting designed to review putative new CNS tumor types in advance of any future World Health Organization meeting on CNS tumor classification. In preparatory activities for the meeting and at the actual meeting, a list of possible entities was assembled and each type and subtype debated. Working Committee 3 recommended that a substantial number of newly recognized types and subtypes should be considered for inclusion in future CNS tumor classifications. In addition, the group endorsed a number of principles—relating to classification categories, approaches to classification, nomenclature, and grading—that the group hopes will also inform the future classification of CNS neoplasms.

BACKGROUND AND PURPOSE: Treatment with bevacizumab is standard of care for recurrent high-grade gliomas; however, monitoring response to treatment following bevacizumab remains a challenge. The purpose of this study was to determine whether quantifying the sharpness of the fluid-attenuated inversion recovery hyperintense border using a measure derived from texture analysis—edge contrast—improves the evaluation of response to bevacizumab in patients with high-grade gliomas. MATERIALS AND METHODS: MRIs were evaluated in 33 patients with high-grade gliomas before and after the initiation of bevacizumab. Volumes of interest within the FLAIR hyperintense region were segmented. Edge contrast magnitude for each VOI was extracted using gradients of the 3D FLAIR images. Cox proportional hazards models were generated to determine the relationship between edge contrast and progression-free survival/overall survival using age and the extent of surgical resection as covariates. RESULTS: After bevacizumab, lower edge contrast of the FLAIR hyperintense region was associated with poorer progression-free survival (P = .009) and overall survival (P = .022) among patients with high-grade gliomas. Kaplan-Meier curves revealed that edge contrast cutoff significantly stratified patients for both progression-free survival (log-rank χ2 = 8.3, P = .003) and overall survival (log-rank χ2 = 5.5, P = .019). CONCLUSIONS: Texture analysis using edge contrast of the FLAIR hyperintense region may be an important predictive indicator in patients with high-grade gliomas following treatment with bevacizumab. Specifically, low FLAIR edge contrast may partially reflect areas of early tumor infiltration. This study adds to a growing body of literature proposing that quantifying features may be important for determining outcomes in patients with high-grade gliomas.

Brain AVMs treated with stereotactic radiosurgery typically demonstrate a minimum latency period of 1–3 years between treatment and nidus obliteration. Assessment of treatment response is usually limited to evaluation of AVM nidus structural changes using conventional MR imaging and MRA techniques. This report describes the use of 4D Flow MRI to also measure radiation-induced hemodynamic changes in a Spetzler-Martin grade III AVM, which were detectable as early as 6 months after treatment.

Before treatment delivery of respiratory‐gated radiation therapy (RT) in patients with implanted fiducials, both the patient position and the gating window thresholds must be set. In linac‐based RT, this is currently done manually and setup accuracy will therefore be dependent on the skill of the user. In this study, we present an automatic method for finding the patient position and the gating window thresholds. Our method uses sequentially acquired anterior–posterior (AP) and lateral fluoroscopic imaging with simultaneous breathing amplitude monitoring and intends to reach 100% gating accuracy while keeping the duty cycle as high as possible. We retrospectively compared clinically used setups to the automatic setups by our method in five pancreatic cancer patients treated with hypofractionated RT. In 15 investigated fractions, the average (±standard deviation) differences between the clinical and automatic setups were −0.4 ± 0.8 mm, −1.0 ± 1.1 mm, and 1.8 ± 1.3 mm in the left–right (LR), the AP, and the superior–inferior (SI) direction, respectively. For the clinical setups, typical interfractional setup variations were 1–2 mm in the LR and AP directions, and 2–3 mm in the SI direction. Using the automatic method, the duty cycle could be improved in six fractions, in four fractions the duty cycle had to be lowered to improve gating accuracy, and in five fractions both duty cycle and gating accuracy could be improved. Our automatic method has the potential to increase accuracy and decrease user dependence of setup for patients with implanted fiducials treated with respiratory‐gated RT. After fluoroscopic image acquisition, the calculated patient shifts and gating window thresholds are calculated in 1–2 s. The method gives the user the possibility to evaluate the effect of different patient positions and gating window thresholds on gating accuracy and duty cycle. If deemed necessary, it can be used at any time during treatment delivery.

Purpose/objective(s) Impairment in fine motor skills (FMS), including motor speed and coordination, can occur after brain radiotherapy. FMS are essential for activities of daily living including writing, typing, and eating. Using a normal tissue complication probability (NTCP) framework, we sought to determine dosimetric predictors of FMS decline in a prospective cohort of brain tumor patients treated with RT. Materials/methods On a prospective clinical trial, 52 primary brain tumor patients receiving fractionated brain RT underwent volumetric MRI, diffusion tensor imaging, and FMS assessments (Delis-Kaplan Executive Function System Trail Making Test Motor Speed [DKEFS-MS], Grooved Pegboard Dominant [PDH] and Non-dominant [PNDH] Hands) at baseline and 6 months post-RT. Reliable change indices adjusting for practice effects (RCI-PEs) were calculated, with RCI-PE > 0.5 considered FMS decline. Motor regions of interest (ROIs) were autosegmented using an open-source software for processing and analyzing brain MRI images and atlas-based tractography, including: sensorimotor cortices and superficial white matter (WM), corticospinal tracts, cerebellar cortices and WM, and basal ganglia. Censoring masks excluded tumor, surgical cavity, scarring, and edema from analyses. Planning CTs were co-registered to MRIs to extract DVH parameters for each ROI, including maximum/mean doses and Vx (structure volume receiving ≥ x Gy). Fisher's exact test on median splits and logistic regressions were used to test for dosimetric predictors of FMS decline. Results At baseline and 6 months, 41 and 39 patients completed DKEFS-MS and PDH/PNDH tests, respectively. Median prescription dose was 59.4 Gy. Most patients (84.3%) were right-handed. There were several significant associations between increasing doses in left-sided ROIs and decline on PDH performance at 6 months, which occurred in 14 of 41 patients (Table, P Conclusion Increasing doses to left-sided motor ROIs including cortical, WM, and basal ganglia structures were associated with decline in dominant hand FMS at 6 months post-RT in this largely right-handed cohort. These areas may represent avoidance targets for preserving FMS in brain tumor patients.

Purpose/Objective(s) SRS for brain metastases is associated with a high rate (52%-64%) of cognitive deterioration. We performed a phase II clinical trial of critical white matter and hippocampal sparing brain SRS in patients with limited brain metastases, to improve cognitive preservation. We present feasibility of this approach and interim results. Materials/Methods Adult patients with limited volume ( 6 months, pathologic confirmation of malignancy. Prior WBRT was exclusionary. High resolution volumetric MRI with diffusion tensor imaging was performed pre-SRS and at 1-, 3- and 6-months post SRS. Regions of interest (ROIs) were segmented using robust, automated atlas-based tractography and hippocampal (HC) parcellation methods. 20 white matter (WM) tracts critical for cognitive functioning and fine motor skills, and the HC were designated as ROIs to spare during SRS planning. Knowledge-based SRS planning was employed, and all attempts were made to achieve ROI dose constraints without sacrificing target coverage or other OAR doses. Single fraction max dose constraints were 12 Gy for WM/8.4 Gy for HC (iso-effective doses used for 3 and 5 fraction SRS). A well-validated battery of neurocognitive (NCA) tests, including verbal memory and language, was performed pre and 3 months post SRS. Raw scores were converted to t-scores adjusting for age, sex, and years of education. Decline was considered > 1 standard deviation drop. Results Median age of cohort (n = 31) was 66 years and 58% were female. Most common primary was NSCLC (39%) or melanoma (23%), and 90% of patients had 1-3 brain metastases. Prescription doses ranged from 21-30 Gy in 1-5 fractions; 10 patients were treated with both single and multi-fraction SRS to different targets. Max dose constraints for ROIs were met on 69% of SRS plans. Across plans, constraints were met for 98% of 595 WM tracts and 97% of 64 HC treated. At 6 months post SRS there were no local failures. To date (median follow up: 6 months), 5 patients have died from systemic disease progression and 1 patient from distant brain disease progression. For patients in whom pre and 3-month NCA scores were available (n = 13), 97% of WM ROIs and 100% of HC ROIs met study constraints. At 3 months, 74% of patients had no decline on HVLT total/delayed recall memory tests. Similarly, 93% and 89% showed no decline on BNT and DKEFS letter fluency language tests, respectively. There was no significant change in NCA test scores in the cohort from pre to 3 months post SRS (paired t-test, P-values > 0.05). Conclusion Critical WM and HC sparing brain SRS using automated segmentation/planning tools is achievable and feasible, though can depend on proximity to targets. Sparing these critical structures may improve cognitive preservation in domains such as verbal memory and language. Author Disclosure S. Unnikrishnan: None. R. Karunamuni: None. G. Kim: None. M. Connor: None. M.A. Salans: None. P. Sanghvi: Speaker's Bureau; Varian, VisionRT.A. Bruggeman: Research Grant; American Society of Clinical Oncology. D.R. Simpson: None. J. Yu: None. A. Reyes: None. A. Stasenko: None. K.L. Moore: Research Grant; Varian Medical Systems Inc. Honoraria; Varian Medical Systems Inc. Travel Expenses; Varian Medical Systems Inc. V. Moiseenko: None. C. McDonald: Research Grant; GE.J.A. Hattangadi-Gluth: Research Grant; NIH/NCI. Honoraria; Varian Medical Systems. Consultant; Varian Medical Systems. Site PI for cooperative group trials at UCSD for CNS; Site-PI; NCCN.

Purpose/Objective(s) Attention and processing speed, an important neurocognitive function, is subserved in the brain by critical white matter (WM): the corpus callosum (CC) and intra-hemispheric white matter tracts (IHWM). We sought to characterize the dose-response relationship of these structures with decline in attention/processing speed at 6 months post-RT in patients with primary brain tumors, with particular attention to low doses. Materials/Methods On a prospective trial, 52 primary brain tumor patients receiving fractionated brain RT underwent volumetric MRI, diffusion tensor imaging, and neurocognitive assessments (for processing speed: Delis-Kaplan Executive Function System Trail Making (D-KEFS-TM) Number Sequencing (TM-NS), D-KEFS-TM Letter Sequencing (TM-LS), and Weschler Adult Intelligence Scale (WAIS-IV) Coding; for attention: D-KEFS-TM Visual Scanning (TM-VS) test and WAIS-IV Digit Span Digits Forward (DF) test. Reliable change indices were calculated and adjusted for practice effects (RCI-PE), with decrease in RCI-PE scored as decline. Regions of interest (ROIs) were autosegmented using open source software and atlas-based tractography, including: CC, all WM w/wo CC, total IHWM without CC, and right/left IHWM without CC. Censoring masks excluded tumor, surgical cavity, scarring, and edema. Planning CTs were co-registered to MRIs to extract DVH parameters for each ROI, including V10 Gy and V20 Gy. Univariate logistic regressions were used to test for dosimetric predictors of decline. Results Median age was 47y. Most patients (61.5%) had gliomas. Median prescription RT dose was 59.4 Gy. At baseline and 6 months, 37-43 patients completed the neurocognitive assessments, with 61-78% showing decline. Several significant associations between increasing relative volumes exposed to low dose and decline were seen in all assessments except TM-NS (Table). Investigation of mean and maximum dose parameters yielded similar results. Conclusion While maximum dose is typically considered the most relevant dosimetric parameter for toxicity endpoints in the brain, we also detected several significant logistic relationships between V10 and V20 to more diffuse white matter networks (CC and IHWM) and decline in attention and processing speed post-RT. Minimization of low dose bath, whether by planning optimization or use of more conformal modalities like protons, may be clinically relevant for preservation of these critical neurocognitive functions.

Purpose/Objective(s) Mid-career faculty often report lower career satisfaction compared to those in their early or late career. Attrition, particularly of female faculty, is a major concern for academic medicine. Curricula for early-career faculty provide structure for professional development, but similar programming is less robust for mid- and late-career faculty. This qualitative prospective study aimed to explore and identify career needs and perceived obstacles to improve the experience and success of mid-career radiation oncology faculty. Materials/Methods Associate Professors at a single academic medical center and affiliated regional centers were invited to participate in semi-structured small group interviews between February and April 2019. Performed by an expert in medical anthropology, interviews covered the following themes: 1) Present to future career goals, 2) Visions guiding career work and aims, 3) Obstacles in achieving career goals, 4) Resources to assist achieving career goals, 5) Balancing work/life priorities, and 6) Immediate needs for current work. All interviews were audio-recorded, de-identified, and transcribed, then a conventional content analysis approach was employed by a qualitative research expert. Results Eight small group interviews were conducted, with 5 female and 12 male Associate Professors in total. The cohort included 10 physicians and 7 medical physicists, spanning clinical and research focused careers, and satellite and main site locations. The key themes elicited several sub-themes as responses, presented below. Conclusion This study suggests an unmet need for formal mentorship, sponsorship for leadership positions, and institutional resources targeting mid-level faculty in academic radiation oncology. Future efforts will address design and implementation of a strategic mid-career development program.

For many years, the diagnosis and classification of gliomas have been based on histology. Although studies including large populations of patients demonstrated the prognostic value of histologic phenotype, variability in outcomes within histologic groups limited the utility of this system. Nonetheless, histology was the only proven and widely accessible tool available at the time, thus it was used for clinical trial entry criteria, and therefore determined the recommended treatment options. Research to identify molecular changes that underlie glioma progression has led to the discovery of molecular features that have greater diagnostic and prognostic value than histology. Analyses of these molecular markers across populations from randomized clinical trials have shown that some of these markers are also predictive of response to specific types of treatment, which has prompted significant changes to the recommended treatment options for grade III (anaplastic) gliomas.

Our purpose was to investigate the association between imaging biomarkers of radiation-induced white matter (WM) injury within perisylvian regions and longitudinal language decline in patients with brain tumors.Patients with primary brain tumors (n = 44) on a prospective trial underwent brain magnetic resonance imaging, diffusion-weighted imaging, and language assessments of naming (Boston Naming Test [BNT]) and fluency (Delis-Kaplan Executive Function System Category Fluency [DKEFS-CF]) at baseline and 3, 6, and 12 months after fractionated radiation therapy (RT). Reliable change indices of language function (0-6 months), accounting for practice effects (RCI-PE), evaluated decline. Bilateral perisylvian WM regions (superficial WM subadjacent to Broca's area and the superior temporal gyrus [STG], inferior longitudinal fasciculus [ILF], inferior fronto-occipital fasciculus [IFOF], and arcuate fasciculus) were autosegmented. We quantified volume and diffusion measures of WM microstructure: fractional anisotropy (FA; lower values indicate disruption) and mean diffusivity (MD; higher values indicate injury). Linear mixed-effects models assessed mean dose as predictor of imaging biomarker change and imaging biomarkers as longitudinal predictors of language scores.DKEFS-CF scores declined at 6 months post-RT (RCI-PE, -0.483; P = .01), whereas BNT scores improved (RCI-PE, 0.262; P = .04). Higher mean dose to left and right regions was predictive of decreased volume (left-STG, P = .02; right-ILF and IFOF, P = .03), decreased FA (left-WM tracts, all P.01; right-STG and IFOF, P.02), and increased MD of left-WM tracts (all P.03). Volume loss within left-Broca's area (P = .01), left-ILF (P = .01), left-IFOF (P = .01), and left-arcuate fasciculus (P = .04) was associated with lower BNT scores. Lower FA correlated with poorer DKEFS-CF and BNT scores within left-ILF (P = .02, not significant), left-IFOF (P = .02, .04), and left-arcuate fasciculus (P = .01, .01), respectively. Poorer DKEFS-CF scores correlated with increased MD values within the left-arcuate fasciculus (P = .03). Right-sided biomarkers did not correlate with language scores.Patients with primary brain tumors experience language fluency decline post-RT. Poorer fluency and naming function may be explained by microstructural injury to left-sided perisylvian WM, representing potential dose-avoidance targets for language preservation.

Background Radionuclide radium-223 improves survival in men with metastatic castrate-resistant prostate cancer. The United States (US) Food and Drug Administration Adverse Events Reporting System (FAERS) is a post-market pharmacovigilance database valuable for adverse event (AE) assessments. We analyzed FAERS to identify disproportionate AE signals related to radium-223, and to explore radium-223’s international utilization. Materials and Methods We identified 2182 radium-223 cases associated with AE(s) from 2013 to 2018. The duration of radium-223 therapy was calculated. Reporting odds ratio (ROR) and proportional reporting ratio (PRR), with 95% confidence intervals (CIs), were calculated for AEs of interest. ROR shows disproportionate signals if the lower limit of the 95% CI > 1. PRR shows disproportionate signals if PRR ≥ 2, χ2 statistic ≥ 4, and ≥ 3 AEs were reported. We identified any US Food and Drug Administration enforcement actions for radium-223. Results A majority (60.8%) of events occurred outside the US. Among patients with radium-223-associated AEs, the median therapy duration was only 56 days (corresponding to 2-3 treatment cycles). Disproportionate signals were detected for general health deterioration (ROR, 5.03; 95% CI, 4.23-5.98 and PRR, 4.94; 95% CI, 4.16-5.87), bone pain (ROR, 4.53; 95% CI, 3.67-5.59 and PRR, 4.48; 95% CI, 3.63-5.53), and hematologic AEs including anemia (ROR, 2.89; 95% CI, 2.55-3.27 and PRR, 2.80; 95% CI, 2.48-3.17), thrombocytopenia (ROR, 3.22; 95% CI, 2.77-3.74 and PRR, 3.16; 95% CI, 2.72-3.67), and pancytopenia/bone marrow failure (ROR, 4.83; 95% CI, 4.11-5.67 and PRR, 4.73; 95% CI, 4.03-5.55). There were no enforcement actions for radium-223. Conclusions Patients with metastatic castrate-resistant prostate cancer experiencing AEs are only receiving one-half the prescription dose of radium-223 required for survival benefit. Radium-223 is associated with health deterioration, bone pain, and hematologic AEs. Real-world analyses are important for ongoing radium-223 risk-benefit assessments.

IntroductionWe investigated multi-domain baseline neurocognition of primary brain tumor patients prior to radiotherapy (RT), including clinical predictors of function and association between pre-RT and post-RT impairment on a prospective trial.MethodsA multi-domain neuropsychological battery (memory, executive functioning, language, attention, processing) was performed on 37 patients, pre-RT and 3-(n = 21), 6-(n = 22) and 12-(n = 14) months post-RT. Impairment rate was the proportion of patients with standardized T-scores ≤ 1.5 standard deviations below normative means. Per-patient impairment across all domains was calculated using a global deficit score (GDS; higher value indicates more impairment). Associations between baseline GDS and clinical variables were tested. Global GDS impairment rate at each time point was the fraction of patients with GDS scores > 0.5.ResultsStatistically significant baseline neurocognitive impairments were identified on 4 memory (all p ≤ 0.03) and 2 out of 3 (p = 0.01, p = 0.027) executive functioning tests. Per-patient baseline GDS was significantly associated with tumor volume (p = 0.048), tumor type (p = 0.043), seizure history (p = 0.007), and use of anti-epileptics (p = 0.009). The percentage of patients with the same impairment status at 3-, 6-, and 12-months as at baseline were 88%, 85%, and 85% respectively.ConclusionsMemory and executive functioning impairment were the most common cognitive deficits prior to RT. Patients with larger tumors, more aggressive histology, and use of anti-epileptics had higher baseline GDS values. GDS is a promising tool to encompass multi-domain neurocognitive function, and baseline GDS can identify those at risk of cognitive impairment.

BACKGROUND AND PURPOSE The amygdalae are deep brain nuclei critical to emotional processing and the creation and storage of memory. It is not known whether the amygdalae are affected by brain radiotherapy (RT). We sought to quantify dose-dependent amygdala change one year after brain RT. MATERIALS AND METHODS 52 patients with primary brain tumors were retrospectively identified. Study patients underwent high-resolution, volumetric magnetic resonance imaging before RT and 1 year afterward. Images were processed using FDA-cleared software for automated segmentation of amygdala volume. Tumor, surgical changes, and segmentation errors were manually censored. Mean amygdala RT dose was tested for correlation with amygdala volume change 1 year after RT via the Pearson correlation coefficient. A linear mixed-effects model was constructed to evaluate potential predictors of amygdala volume change, including age, tumor hemisphere, sex, seizure history, and bevacizumab treatment during the study period. As 51 of 52 patients received chemotherapy, possible chemotherapy effects could not be studied. A two-tailed p-value

BACKGROUND For patients with cancer, marijuana may be an alternative to prescription opioid analgesics. This study analyzed self-reported marijuana and prescription opioid use among people with cancer over a 10-year time period. METHODS Population-based data sets from the US National Health and Nutrition Examination Survey between 2005 and 2014 were compiled for respondents aged 20 to 60 years. Respondents with cancer and respondents without cancer were propensity score-matched (1:2) by demographics to compare substance use. Outcomes included current marijuana and prescription opioid use (ie, within the past 30 days). Pearson chi-square tests and logistic regressions were performed; a 2-tailed P value

Author(s): Karunamuni, Roshan A; White, Nathan S; McDonald, Carrie R; Connor, Michael; Pettersson, Niclas; Seibert, Tyler M; Kuperman, Joshua; Farid, Nikdokht; Moiseenko, Vitali; Dale, Anders M; Hattangadi-Gluth, Jona A | Abstract: PurposeWe used multi-b-value diffusion models to characterize microstructural white matter changes after brain radiation into fast and slow components, in order to better understand the pathophysiology of radiation-induced tissue damage.MethodsFourteen patients were included in this retrospective analysis with imaging prior to, and at 1, 4-5, and 9-10 months after radiotherapy (RT). Diffusion signal decay within brain white matter was fit to a biexponential model to separate changes within the slow and fast components. Linear mixed-effects models were used to obtain estimates of the effect of radiation dose and time on the model parameters.ResultsWe found an increase of 0.11 × 10-4 and 0.14 × 10-4 mm2 /s in the fast diffusion coefficient per unit dose-time (Gy-month) in the longitudinal and transverse directions, respectively. By contrast, the longitudinal slow diffusion coefficient decreased independently of dose, by 0.18 × 10-4 , 0.16 × 10-4 , and 0.098 × 10-4 mm2 /s at 1, 4, and 9 months post-RT, respectively.ConclusionsRadiation-induced white matter changes in the first year following RT are driven by dose-dependent increases in the fast component and dose-independent decreases in the slow component.

BackgroundRadiation-induced cognitive impairment may be mediated by hippocampal damage, but the structural integrity of this region in tumor patients at baseline is unclear. Hippocampal volumes of 31 glioma patients prior to receiving radiotherapy were compared to a group of 34 healthy controls.Materials and methodsLeft and right hippocampi on T1-weighted pre-contrast magnetic resonance images were automatically segmented using Freesurfer, and visually inspected for segmentation errors. Normalized hippocampal volume for each subject was calculated as the sum of left and right hippocampal volumes divided by the estimated total intracranial volume. The normalized amygdala volume was similarly analyzed as a reference structure.ResultsA Wilcoxon rank-sum test showed a significant difference in normalized hippocampal volumes between patients and controls (mean value 0.499 vs. 0.524, p = .01). No statistically significant difference was found for the amygdala. A post-hoc analysis revealed a significant difference in normalized hippocampal volumes between patients who had experienced seizures (mean value: 0.480, p