Corrie Gidding

Psychosocial profile of pediatric brain tumor survivors with neurocognitive complaints

AbstractPurposenWith more children surviving a brain tumor, neurocognitive consequences of the tumor and its treatment become apparent, which could affect psychosocial functioning. The present study therefore aimed to assess psychosocial functioning of pediatric brain tumor survivors (PBTS) in detail.MethodsPsychosocial functioning of PBTS (8–18xa0years) with parent-reported neurocognitive complaints was compared to normative data on health-related quality of life (HRQOL), self-esteem, psychosocial adjustment, and executive functioning (one-sample t tests) and to a sibling control group on fatigue (independent-samples t test). Self-, parent-, and teacher-report questionnaires were included, where appropriate, providing complementary information.ResultsEighty-two PBTS (mean age 13.4xa0years, SD 3.2, 49xa0% males) and 43 healthy siblings (mean age 14.3, SD 2.4, 40xa0% males) were included. As compared to the normative population, PBTS themselves reported decreased physical, psychological, and generic HRQOL (dxa0=xa00.39–0.62, pxa0<xa00.008). Compared to siblings, increased fatigue-related concentration problems (dxa0=xa00.57, pxa0<xa00.01) were reported, although self-reported self-esteem and psychosocial adjustment seemed not to be affected. Parents of PBTS reported more psychosocial (dxa0=xa00.81, pxa0<xa00.000) and executive problems (dxa0=xa00.35–0.43, pxa0<xa00.016) in their child than parents of children in the normative population. Teachers indicated more psychosocial adjustment problems for female PBTS aged 8–11xa0years than for the female normative population (dxa0=xa00.69, pxa0<xa00.025), but they reported no more executive problems.ConclusionsPBTS with parent-reported neurocognitive complaints showed increased psychosocial problems, as reported by PBTS, parents, and teachers.Implications for cancer survivorsSystematic screening of psychosocial functioning is necessary so that tailored support from professionals can be offered to PBTS with neurocognitive complaints.

Acute toxicity profile of craniospinal irradiation with intensity-modulated radiation therapy in children with medulloblastoma: A prospective analysis

BackgroundTo report on the acute toxicity in children with medulloblastoma undergoing intensity-modulated radiation therapy (IMRT) with daily intrafractionally modulated junctions.MethodsNewly diagnosed patients, aged 3–21, with standard-risk (SR) or high-risk (HR) medulloblastoma were eligible. A dose of 23.4 or 36.0Gy in daily fractions of 1.8Gy was prescribed to the craniospinal axis, followed by a boost to the primary tumor bed (54 or 55.8Gy) and metastases (39.6–55.8Gy), when indicated. Weekly, an intravenous bolus of vincristine was combined for patients with SR medulloblastoma and patients participating in the COG-ACNS-0332 study. Common toxicity criteria (CTC, version 2.0) focusing on skin, alopecia, voice changes, conjunctivitis, anorexia, dysphagia, gastro-intestinal symptoms, headache, fatigue and hematological changes were scored weekly during radiotherapy.ResultsFrom 2010 to 2014, data from 15 consecutive patients (SR, nu2009=u20097; HR, nu2009=u20098) were collected. Within 72xa0h from onset of treatment, vomiting (66xa0%) and headache (46xa0%) occurred. During week 3 of treatment, a peak incidence in constipation (33xa0%) and abdominal pain/cramping (40xa0%) was observed, but only in the subgroup of patients (nu2009=u20099) receiving vincristine (constipation: 56 vs 0xa0%, Pu2009=u2009.04; pain/cramping: 67 vs 0xa0%, Pu2009=u2009.03). At week 6, 73xa0% of the patients developed faint erythema of the cranial skin with dry desquamation (40xa0%) or moist desquamation confined to the skin folds of the auricle (33xa0%). No reaction of the skin overlying the spinal target volume was observed.ConclusionsHeadache at onset and gastro-intestinal toxicity, especially in patients receiving weekly vincristine, were the major complaints of patients with medulloblastoma undergoing craniospinal irradiation with IMRT.

Timed performance weaknesses on computerized tasks in pediatric brain tumor survivors: A comparison with sibling controls.

ABSTRACT With more children surviving a brain tumor, insight into the late effects of the disease and treatment is of high importance. This study focused on profiling the neurocognitive functions that might be affected after treatment for a pediatric brain tumor, using a broad battery of computerized tests. Predictors that may influence neurocognitive functioning were also investigated. A total of 82 pediatric brain tumor survivors (PBTSs) aged 8–18 years (M = 13.85, SD = 3.15, 49% males) with parent-reported neurocognitive complaints were compared to a control group of 43 siblings (age M = 14.27, SD = 2.44, 40% males) using linear mixed models. Neurocognitive performance was assessed using measures of attention, processing speed, memory, executive functioning, visuomotor integration (VMI), and intelligence. Tumor type, treatment, tumor location, hydrocephalus, gender, age at diagnosis, and time since diagnosis were entered into regression analyzes as predictors for neurocognitive functioning. The PBTSs showed slower processing speeds and lower intelligence (range effect sizes .71–.82, p < .001), as well as deficits in executive attention, short-term memory, executive functioning, and VMI (range effect sizes .40–.57, p < .05). Older age at assessment was associated with better neurocognitive functioning (B = .450, p < .001) and younger age at diagnosis was associated with lower intelligence (B = .328, p < .05). Medical risk factors, e.g., hydrocephalus, did not show an association with neurocognitive functioning. Late effects in PBTSs include a broad range of neurocognitive deficits. The results suggest that even PBTSs that were traditionally viewed as low risk for neurocognitive problems (e.g., surgery only, no hydrocephalus) may suffer from decreased neurocognitive functioning.

Neurofeedback ineffective in paediatric brain tumour survivors: Results of a double-blind randomised placebo-controlled trial

BACKGROUNDnMany paediatric brain tumour survivors (PBTS) suffer from neurocognitive impairments. Promising effects of neurofeedback (NF) on neurocognitive functioning have been reported, however research into NF for PBTS has not been conducted. We investigated the effects of NF on neurocognitive functioning in PBTS using a double-blind randomised placebo-controlled trial with a parallel-group design (Pediatric Research on Improving Speed, Memory, and Attention; the PRISMA study).nnnMETHODSnEligible for inclusion were PBTS with neurocognitive complaints, aged 8-18 years, >2 years post-treatment. They were recruited from five medical centres in the Netherlands. A randomisation table assigned participants to 30 sessions (two per week) of either NF or placebo feedback (PF) (ratio 1:1). Participants, parents, trainers, and researchers handling the data were blinded to group assignment. Participants were assessed pre-, post- and 6 months post-training to determine whether NF training would lead to improved functioning as compared with PF training. Primary outcome measures were attention, processing speed, memory, executive functioning, visuomotor integration, and intelligence. Linear mixed models analyses were used to test differences between NF and PF training over time.nnnRESULTSnA total of 82 children were enrolled (mean age 13.9 years, standard deviation = 3.2, 49% males); 80 participants were randomised (NF: nxa0=xa040, PF nxa0=xa040); 71 participants completed the training (NF: nxa0=xa034, PF: nxa0=xa037); 68 participants completed training and 6 months post-training assessment (NF: nxa0=xa033, PF: nxa0=xa035). Similar improvements were found over time for the two treatment groups on the primary outcomes (all ps > 0.15).nnnCONCLUSIONnResults indicated no specific treatment-effects of NF on neurocognitive functioning of PBTS.

Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma

The brain cancer medulloblastoma consists of different transcriptional subgroups. To characterize medulloblastoma at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a large cohort of SHH (Sonic Hedgehog), group 3, and group 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence and resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. The second profile showed enrichment for DNA damage, as well as apoptotic and neuronal signaling. Integrative analysis demonstrated that heterogeneous transcriptional input converges on these protein-signaling profiles: all SHH and a subset of group 3 patients exhibited the MYC-like protein-signaling profile; the majority of the other group 3 subset and group 4 patients displayed the DNA damage/apoptotic/neuronal signaling profile. Functional analysis of enriched pathways highlighted cell-cycle progression and protein synthesis as therapeutic targets for MYC-like medulloblastoma.