Impact of home-based cognitive or academic intervention on working memory and mathematics outcomes in pediatric brain tumor survivors: the Keys to Succeed pilot randomized controlled clinical trial.

Pediatric brain tumour survivors experience deficits in mathematics and working memory. An open question is whether it is most optimal to target direct cognitive skills (i.e. working memory) or focus on specific academic outcomes (i.e. mathematics) for in remediation. We conducted a pilot randomized controlled trial to determine the feasibility of comparing a working memory versus mathematics intervention. Pediatric brain tumor survivors (7-17 years) were randomly assigned to Cogmed or JumpMath interventions, or an Active Control/Reading group. All participants received Educational Liaison support and completed ~12-weeks of home-based intervention with weekly, telephone-based consultation in one of the three conditions. Standardized assessments of auditory and visual working memory, mathematics calculation and reasoning were completed pre- and post- intervention. Twenty-nine participants completed the interventions; 94% of parents reported a high degree of satisfaction with the interventions and ease of implementation. Participants in JumpMath demonstrated improved mathematics calculation from pre- to post- intervention (p=0.02). Further, participants in both Cogmed and JumpMath showed evidence of pre- to post- intervention improvements in auditory working memory relative to controls (p=0.01). The Cogmed group also showed improvements in visual working memory (p=0.03). Findings suggest that targeted intervention is feasible in survivors of pediatric brain tumors, though with a relatively low recruitment rate. With preliminary findings of improved calculation and working memory following JumpMath and working memory following Cogmed, this pilot trial lays the groundwork for future programs that investigate different inteCognitiveRehabilitationrventions that may be applied to target the unique needs of each survivor.

[Formula: see text]Examining parent and clinician views of a hospital-based pediatric neuropsychological service: a Canadian perspective.

Understanding how pediatric neuropsychological evaluations support families and the child's medical team is an important component of ensuring evidence-based care. For the first time within a Canadian context, we investigated the impact of neuropsychological assessments on parent knowledge, advocacy, and stress and the role of socioeconomic factors in parents' perceptions of the assessment. Responses from referring clinicians were also examined. As part of a hospital quality improvement project, 91 parents of children between the ages of 3 and 17 years (M = 8y7m; SD = 4y1m) and 45 clinician consumers (clinical staff who use neuropsychological services) completed one of two online questionnaires in English: Parent Overall Assessment of Supports and Testing, or Clinician Overall Assessment of Supports and Testing. Most parents indicated the neuropsychological evaluation promoted understanding of their child's cognitive profile and improved their ability to support their child at home and at school or in the community. Families characterized as being at higher social risk indicated that the evaluation led to more changes in how they approached their child at home than families with lower social risk status. Referring clinicians indicated neuropsychological reports were effective in communicating findings to them and patients/families. The most valuable sections of the report according to referring clinicians included the diagnosis/impression and recommendations sections. Parents and referral providers reported many benefits from the neuropsychological evaluation but also identified areas for service delivery improvement. Parent perceptions varied based on family and socio environmental factors, offering important targets for future research and clinical consideration.

Outcomes of haemoglobin Bart's hydrops fetalis following intrauterine transfusion in Ontario, Canada.

OBJECTIVES: With improved access to intrauterine transfusion (IUT), more fetuses with haemoglobin Bart's hydrops fetalis (HBHF; homozygous α0-thalassaemia) will survive. DESIGN: To evaluate the long-term outcome of affected fetuses with and without IUT in Ontario, Canada, we retrospectively collected data on IUTs and pregnancy outcomes in all cases of HBHF, from 1989 to 2014. Clinical outcome and neurocognitive profiles of long-term survivors were also collected and compared with data from 24 patients with transfusion-dependent ß-thalassaemia (TDT-ß). RESULTS: Of the 99 affected pregnancies (93 prenatally diagnosed), 68 resulted in miscarriage or elective termination of pregnancy. Twelve mothers (12%) continued their pregnancies without IUT, and none of those newborns survived the first week of life. All 13 fetuses that received IUT(s) were live-born, but 3 died due to severe hydrops at birth and 1 died due to infection. The remaining nine survivors, in comparison with TDT-ß patients, had earlier iron overload requiring iron chelation therapy. Endocrinopathies and short stature were more frequent in these patients. Neurocognitive outcome was not significantly affected in five patients who were assessed, and none were diagnosed with intellectual impairment. In three patients, MRI studies demonstrated brain white matter changes in keeping with 'silent' ischaemic infarcts. CONCLUSIONS: In patients with HBHF, IUT is associated with improved survival. While acceptable neurocognitive outcome can be expected, these patients have more clinical complications compared with their TDT-ß counterparts. The clinical and neurocognitive outcomes of HBHF should be discussed in detail when counselling and offering IUT for patients.

Cognitive Correlates of Math Performance in School-Aged Children with Sickle Cell Disease and Silent Cerebral Infarcts.

OBJECTIVE: Attention, processing speed, executive functioning, and math difficulties are common in youth with sickle cell disease (SCD) with silent cerebral infarcts (SCI). This study investigated the cognitive underpinnings of math difficulties in children with SCD and SCI. METHOD: Youth (n = 68) with SCD and SCI completed measures of attention [Digit Span forward (DSF); Conners Continuous Performance Test-Third Edition/Kiddie Conners Continuous Performance Test-Second Edition (CPT-3/KCPT-2)]; working memory [Wechsler Intelligence Scales (WPPSI-IV, WISC-IV, WISC-V, WAIS-IV), Working Memory Index (WMI), Digit Span backwards (DSB)]; processing speed [WPPSI-IV, WISC-IV, WISC-V, WAIS-IV Processing Speed Index (PSI)]; math reasoning [Wechsler Individual Achievement Test-Third Edition (WIAT-III) Mathematics composite (MC)]; and math fluency [WIAT-III Math Fluency composite (MF)] as part of a clinical neuropsychological evaluation. Parent ratings of attention and executive functioning were obtained [Behavior Assessment System for Children-Third Edition (BASC-3), Behavior Rating Inventory of Executive Function (BRIEF)]. RESULTS: MC was positively correlated with WMI (r = 0.59, p = 0.00), PSI (r = 0.40, p < 0.001), DSF (r = 0.29, p = 0.03), DSB (r = 0.47, p < 0.001), and MF (r = 0.71, p < 0.001). Correlations between MC, sustained attention, and parent ratings were nonsignificant. The linear regression model using correlated variables was significant [F(4,51) = 8.29, R2 = 0.39, p < 0.001]. WMI was the only significant variable within the model (p = 0.02). CONCLUSIONS: Working memory deficits account for significant variance in untimed mathematical performance in this population-consistent with other populations with white matter dysfunction. Interventions targeting both mathematics and working memory may be beneficial.

Intellectual changes after radiation for children with brain tumors: which brain structures are most important?

BACKGROUND: The objective of this study was to evaluate the contribution of radiation dose to different intracranial structures on changes in intellectual function for children with brain tumors. METHODS: We evaluated children with brain tumors treated in 2005-2017 who had longitudinal neuropsychological assessments and available photon dosimetric data (if radiation therapy [RT] given). Full Scale Intelligence Quotient (FSIQ) and index scores were evaluated (perceptual reasoning index [PRI], processing speed index [PSI], verbal comprehension index [VCI], and working memory index [WMI]). Multivariable linear mixed effects models were used to model endpoints, with age at RT and dose to different brain regions as fixed effects and patient-specific random intercepts. P-values (P*) were adjusted for multiple comparisons. RESULTS: Sixty-nine patients were included, 56 of whom received RT. Median neuropsychological follow-up was 3.2 years. Right temporal lobe mean dose was strongly associated with decline in FSIQ (P* = 0.005); with each gray increase in mean dose, there was a decrease of 0.052 FSIQ points per year. Dose to 50% (D50) of the supratentorial brain was associated with decline in PSI (P* = 0.006) and WMI (P* = 0.001). Right and left hippocampus D50 were individually strongly associated with declines in VCI (P* = 0.009 for each). Presence of a ventriculoperitoneal shunt decreased FSIQ by 10 points. CONCLUSIONS: We reported associations between dosimetry to specific brain regions and intellectual outcomes, with suggested avoidance structures during RT planning. These models can help clinicians anticipate changes in neurocognition post-RT and guide selection of an optimal RT plan.

Reirradiation for recurrent craniopharyngioma.

PURPOSE: Reirradiation is rarely administered to patients with recurrent craniopharyngioma owing to concerns regarding visual and endocrine side effects. The purpose of this case series was to evaluate our institutional experience of patients with craniopharyngioma treated with 2 courses of fractionated radiation therapy. METHODS AND MATERIALS: A retrospective study was performed of all patients with craniopharyngioma treated with 2 courses of fractionated radiation therapy at a single institution. Electronic medical records and radiation therapy records were reviewed. RESULTS: We identified 4 eligible patients with recurrent craniopharyngioma. With a median follow-up of 33 months after reirradiation, 3 patients attained disease control; 1 patient developed progressive disease, 27 months after reirradiation. In 3 evaluable patients, vision remained stable or improved after reirradiation; one patient had no light perception before reirradiation. None of the patients experienced additional endocrine toxicities after reirradiation, apart from one patient who had low serum thyroid stimulating hormone before reirradiation and later developed hypothyroidism after treatment. CONCLUSIONS: Reirradiation may represent a safe and effective therapeutic option for selected patients with recurrent, refractory craniopharyngioma and without other salvage treatment options. Larger studies with longer-term follow up are warranted to better understand outcomes in these patients.

Neuropsychological impact of trametinib in pediatric low-grade glioma: A case series.

Clinical trials of MEK inhibitors are underway in pediatric low-grade glioma (PLGG) with BRAF oncogene mutations and recurrent/refractory disease. Cognitive and behavioral impacts of MEK inhibitors, such as trametinib, are unknown as these outcomes have not yet been studied. This case series compared cognition and behavior in eight PLGG cases prior to and while on treatment with trametinib compared to four PLGG controls. Intelligence in the trametinib cases was mainly unchanged while on treatment, with mild decline in one of seven cases with complete data. Parent-reported depression symptoms increased in five of eight trametinib cases relative to one of four controls.

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 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. CONCLUSIONS: By 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.

Superior Intellectual Outcomes After Proton Radiotherapy Compared With Photon Radiotherapy for Pediatric Medulloblastoma.

PURPOSE: Proton radiotherapy (PRT) may lessen the neuropsychological risk traditionally associated with cranial radiotherapy for the treatment of pediatric brain tumors by reducing the dose to normal tissue compared with that of photon radiotherapy (XRT). We examined the change in intellectual scores over time in patients with pediatric medulloblastoma treated with craniospinal PRT versus XRT. METHODS: Intelligence test scores were obtained for a sample of pediatric patients treated between 2007 and 2018 on the same medulloblastoma protocols that differed only in radiotherapy modality (PRT v XRT). Growth curve analyses compared change in scores over time since diagnosis between groups. RESULTS: Longitudinal intelligence data from 79 patients (37 PRT, 42 XRT) were examined. Groups were similar on most demographic/clinical variables, including sex (67.1% male), age at diagnosis (mean, 8.6 years), craniospinal irradiation dose (median, 23.4 Gy), length of follow-up (mean, 4.3 years), and parental education (mean, 14.3 years). Boost dose (P < .001) and boost margin (P = .001) differed between groups. Adjusting for covariates, the PRT group exhibited superior long-term outcomes in global intelligence quotient (IQ), perceptual reasoning, and working memory compared with the XRT group (all P < .05). The XRT group exhibited a significant decline in global IQ, working memory, and processing speed (all P < .05). The PRT group exhibited stable scores over time in all domains with the exception of processing speed (P = .003). CONCLUSION: To our knowledge, this is the first study to compare intellectual trajectories between pediatric patients treated for medulloblastoma with PRT versus those treated with XRT on comparable, contemporary protocols. PRT was associated with more favorable intellectual outcomes in most domains compared with XRT, although processing speed emerged as a vulnerable domain for both groups. This study provides the strongest evidence to date of an intellectual sparing advantage with PRT in the treatment of pediatric medulloblastoma.