Neurocognitive outcomes in pediatric brain tumors after treatment with proton versus photon radiation: a systematic review and meta-analysis

Background: Advances in cancer treatments, particularly the development of radiation therapy, have led to improvements in survival outcomes in children with brain tumors. However, radiation therapy is associated with significant long-term neurocognitive morbidity. The present systematic review and meta-analysis aimed to compare the neurocognitive outcomes of children and adolescents with brain tumors treated with photon radiation (XRT) or proton therapy (PBRT). Methods: A systematic search was conducted (PubMed, Embase, Cochrane, and Web of Science from inception until 02/01/2022) for studies comparing the neurocognitive outcomes of children and adolescents with brain tumors treated with XRT vs. PBRT. The pooled mean differences (expressed as Z scores) were calculated using a random effects method for those endpoints analyzed by a minimum of three studies. Results: Totally 10 studies (n = 630 patients, average age range: 1–20 years) met the inclusion criteria. Patients who had received PBRT achieved significantly higher scores (difference in Z scores ranging from 0.29–0.75, all P 0.05 in main analyses or sensitivity analyses) were found for nonverbal memory, verbal working memory and working memory index, processing speed index, or focused attention. Conclusions: Pediatric brain tumor patients who receive PBRT achieve significantly higher scores on most neurocognitive outcomes than those who receive XRT. Larger studies with long-term follow-ups are needed to confirm these results.14 página

Medulloblastoma has a global impact on health related quality of life: Findings from an international cohort.

BackgroundUnderstanding the global impact of medulloblastoma on health related quality of life (HRQL) is critical to characterizing the broad impact of this disease and realizing the benefits of modern treatments. We evaluated HRQL in an international cohort of pediatric medulloblastoma patients.MethodsSeventy-six patients were selected from 10 sites across North America, Europe, and Asia, who participated in the Medulloblastoma Advanced Genomics International Consortium (MAGIC). The Health Utilities Index (HUI) was administered to patients and/or parents at each site. Responses were used to determine overall HRQL and attributes (ie specific subdomains). The impact of various demographic and medical variables on HRQL was considered-including molecular subgroup.ResultsThe majority of patients reported having moderate or severe overall burden of morbidity for both the HUI2 and HUI3 (HUI2 = 60%; HUI3 = 72.1%) when proxy-assessed. Self-care in the HUI2 was rated as higher (ie better outcome) for patients from Western versus Eastern sites, P = .02. Patients with nonmetastatic status had higher values (ie better outcomes) for the HUI3 hearing, HUI3 pain, and HUI2 pain, all P < .05. Patients treated with a gross total resection also had better outcomes for the HUI3 hearing (P = .04). However, those who underwent a gross total resection reported having worse outcomes on the HUI3 vision (P = .02). No differences in HRQL were evident as a function of subgroup.ConclusionsBy examining an international sample of survivors, we characterized the worldwide impact of medulloblastoma. This is a critical first step in developing global standards for evaluating long-term outcomes

White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice

PurposePediatric patients treated with cranial radiation are at high risk of developing lasting cognitive impairments. We sought to identify anatomical changes in both gray matter (GM) and white matter (WM) in radiation-treated patients and in mice, in which the effect of radiation can be isolated from other factors, the time course of anatomical change can be established, and the effect of treatment age can be more fully characterized. Anatomical results were compared between species.Methods and MaterialsPatients were imaged with T1-weighted magnetic resonance imaging (MRI) after radiation treatment. Nineteen radiation-treated patients were divided into groups of 7 years of age and younger (7−) and 8 years and older (8+) and were compared to 41 controls. C57BL6 mice were treated with radiation (n=52) or sham treated (n=52) between postnatal days 16 and 36 and then assessed with in vivo and/or ex vivo MRI. In both cases, measurements of WM and GM volume, cortical thickness, area and volume, and hippocampal volume were compared between groups.ResultsWM volume was significantly decreased following treatment in 7− and 8+ treatment groups. GM volume was unchanged overall, but cortical thickness was slightly increased in the 7− group. Results in mice mostly mirrored these changes and provided a time course of change, showing early volume loss and normal growth. Hippocampal volume showed a decreasing trend with age in patients, an effect not observed in the mouse hippocampus but present in the olfactory bulb.ConclusionsChanges in mice treated with cranial radiation are similar to those in humans, including significant WM and GM alterations. Because mice did not receive any other treatment, the similarity across species supports the expectation that radiation is causative and suggests mice provide a representative model for studying impaired brain development after cranial radiation and testing novel treatments

Medulloblastoma has a global impact on health related quality of life: Findings from an international cohort

Background: Understanding the global impact of medulloblastoma on health related quality of life (HRQL) is critical to characterizing the broad impact of this disease and realizing the benefits of modern treatments. We evaluated HRQL in an international cohort of pediatric medulloblastoma patients. Methods: Seventy-six patients were selected from 10 sites across North America, Europe, and Asia, who participated in the Medulloblastoma Advanced Genomics International Consortium (MAGIC). The Health Utilities Index (HUI) was administered to patients and/or parents at each site. Responses were used to determine overall HRQL and attributes (ie specific subdomains). The impact of various demographic and medical variables on HRQL was considered—including molecular subgroup. Results: The majority of patients reported having moderate or severe overall burden of morbidity for both the HUI2 and HUI3 (HUI2 = 60%; HUI3 = 72.1%) when proxy-assessed. Self-care in the HUI2 was rated as higher (ie better outcome) for patients from Western versus Eastern sites, P =.02. Patients with nonmetastatic status had higher values (ie better outcomes) for the HUI3 hearing, HUI3 pain, and HUI2 pain, all P <.05. Patients treated with a gross total resection also had better outcomes for the HUI3 hearin

Children’s family income is associated with cognitive function and volume of anterior not posterior hippocampus

The hippocampus is thought to underlie income gaps in children’s cognition. Here, the authors find that the stress-sensitive anterior (but not posterior) hippocampus mediates income-gaps in memory and vocabulary, especially in children whose families earn ≤$75k annually

Diffusion tensor imaging of white matter after cranial radiation in children for medulloblastoma: Correlation with IQ1

Treatment of children with cranial-spinal radiation (CSR) for brain tumors is associated with adverse intellectual outcome and white matter damage. However, the correlation between IQ and measures of white matter integrity has received little attention. We examined apparent diffusion coefficient (ADC), fractional anisotropy (FA), and intelligence in pediatric patients treated with CSR for medulloblastoma relative to control subjects. ADC and FA measures were obtained for eight patients and eight control children and evaluated in multiple regions of interest in the cerebral hemispheres. Mean ADC and mean FA for each region were calculated, group differences were evaluated, and the relationship between these measures and intelligence were examined. In our study group, decreased IQ was associated with increased ADC and decreased FA (P < 0.01). Mean IQ for the CSR group was lower than that for the control group, but the difference was not significant when controlling for overall mean FA or ADC (P > 0.10). Overall mean FA was lower and ADC was higher in the CSR group relative to controls (P < 0.01). Specifically, FA was lower in the genu of the corpus callosum, the anterior and posterior limbs of the internal capsule, inferior frontal white matter, and high frontal white matter, and ADC was higher in all regions in patients relative to controls (P < 0.01). Compromised white matter integrity was observed for multiple regions within the cerebral hemispheres following CSR. A novel finding was that microscopic damage in normal-appearing white matter, as indexed by higher ADC and lower FA, was related to poor intellectual outcome relative to age-matched controls

Sleep differentially and profoundly impairs recall memory in a patient with fornix damage

In March 2020, CT, a kind, bright, and friendly young woman underwent surgery for a midline tumor involving her septum pellucidum and extending down into her fornices bilaterally. Following tumor diagnosis and surgery, CT experienced significant memory deficits: CT’s family reported that she could remember things throughout the day, but when she woke up in the morning or following a nap she would expect to be in the hospital, forgetting all the information that she had learned before sleep. The current study aimed to empirically validate CT’s pattern of sleep-dependent memory loss and explore its neurological underpinnings. On two successive days, CT and age-matched controls watched an episode of a TV show and took a nap or stayed awake before completing a memory test. Although CT performed numerically worse than controls in both conditions, sleep profoundly exacerbated her memory impairment, such that she could not recall any details following a nap. This effect was replicated in a second testing session. In high-resolution MRI scans, we observed evidence of the trans-callosal surgical approach’s impact on the mid-anterior corpus callosum, showed that CT had perturbed white matter particularly in the right fornix column, and demonstrated that CT’s hippocampal volumes did not differ from controls. These findings suggest that the fornix is important for sleep-dependent consolidation of episodic memories. As the primary output pathway of the hippocampus, the fornix may ensure that specific memories are replayed during sleep, maintain the balance of sleep stages, or allow for the retrieval of memories following sleep

Early changes in white matter predict intellectual outcome in children treated for posterior fossa tumors

Purpose: Prospective and longitudinal neuroimaging studies of posterior fossa tumors are scarce. Here we evaluate the early changes in white matter and intellectual outcome up to 3 years after diagnosis. Patients and methods: Twenty-two children with posterior fossa tumors and 24 similarly-aged healthy children participated. Patients included: (a) 12 individuals who received surgery, cranial-spinal radiation (CSR), and focal radiation to the tumor bed (CSR group) and (b) 10 individuals who received local therapy, either surgery only or surgery and focal radiation to the tumor bed (Local group). Diffusion tensor imaging (DTI) and intelligence measures were obtained an average of 3 months after diagnosis and then at 12, 24, and 36 months later. DTI tractography and voxel-wise approaches were employed. The Neurological Predictor Scale was used to summarize the type and amount of treatment for PF tumor patients. Linear mixed modelling was used to evaluate group differences at baseline and changes over time in DTI metrics for both the specific white matter tracts and voxel-wise, as well as for intelligence measures. Results: Based on tractography, patients treated with CSR had significantly higher Axial and Mean diffusivity in the cortical-spinal tracts (CST) 3 month after diagnosis – particularly on the right side, p  .10. Voxel-wise analyses revealed multiple areas of white matter compromise in both patients groups. Notably, both patient groups had lower scores on intelligence measures compared to the Control group: The CSR group displayed lower performance 3 months following diagnosis, ps  0.10, whereas the Local group displayed no differences at 3 months, ps> 0.10, but their performance declined over time, ps < 0.01. At baseline, higher MD in right CST predicted lower Perceptual Reasoning scores across all participants, p = .001. Furthermore, lower FA in left IFOF at baseline predicted decline in Processing Speed over time, p = .001. In patients, more aggressive treatment protocols and presence of mutism were related to lower performance on intelligence measures at baseline, ps < 0.04. Conclusions: Children treated with CSR displayed diffuse white matter compromise and poor intellectual outcome shortly after radiation treatment. There was evidence of subsequent growth of white matter structure, but stable intellectual insult. Conversely, in children treated with either surgery only or surgery and focal radiation to the tumor bed we observed less compromise of white matter early following treatment and no intellectual insult compared to healthy children. However, declines in intellectual function were evident for these children, though their performance remained within the average normative range. Overall, results suggest that early intervention is necessary to circumvent these deficits. Keywords: Brain tumor, Children, Cognition, White matter, Diffusion tensor imaging, Longitudina