Executive and social functioning in pediatric posterior fossa tumor survivors and healthy controls.

Background: Executive and social functioning difficulty is well established in pediatric brain tumor survivors. Few studies have compared posterior fossa (PF) tumor survivors in comparison to their peers. The relationship between attention, processing speed, working memory, fatigue, and executive and social functioning was investigated to better understand the factors that impact executive and social functioning in PF tumor populations. Methods: Sixteen medulloblastomas, 9 low-grade astrocytomas (LGAs), and 17 healthy controls recruited from 4 sites completed measures of working memory and processing speed, and self-reported fatigue. One parent completed questionnaires on executive and social functioning. Results: There were no significant differences among all 3 groups on parent-reported executive and social functioning; of note, parents of LGA survivors expressed greater concerns regarding behavioral and cognitive regulation than did parents of medulloblastoma survivors and healthy controls. Parent-reported attention was related to parent-reported emotion, behavior, and cognitive regulation. Worse self-reported fatigue was associated with greater emotional dysregulation for the 2 PF tumor groups. Conclusions: Parents of PF tumor survivors described their children as performing similarly to their peers in most facets of executive and social functioning. While LGA survivors are traditionally thought to have more favorable outcomes, our finding of parent-reported executive functioning concerns to be worse for this group highlights the importance of long-term follow-up for all PF tumor survivors. Additionally, significant effects of attention on aspects of executive functioning in PF tumor survivors may inform current clinical practice and the future development of more effective interventions.

Impact of Anesthetic Exposures on the Neurocognitive Profiles of Pediatric Brain Tumor Survivors: A New Direction for Research and Multidisciplinary Collaboration.

Primary brain tumors are the most commonly diagnosed solid tumors in children, and pediatric brain tumor survivors experience lasting, pervasive deficits of neurocognitive functioning. Repeated exposure to anesthetic drugs is a necessary component not only of surgical resection but also of multimodal cancer care for the youngest patients with brain tumors. The potential for anesthetic neurotoxicity to worsen neurocognitive outcomes in this vulnerable group, therefore, warrants our attention and further study through multi-disciplinary collaboration. This review discusses neurocognitive functioning in pediatric brain tumor survivors, highlighting the findings of a recent study of children with tumors of the posterior fossa which identified treatment-related risk factors for neurocognitive difficulties, with those undergoing multimodal therapies (eg, chemotherapy and irradiation) experiencing the greatest deficits compared with healthy controls. The role of anesthetic neurotoxicity in long-term outcomes among pediatric brain tumor survivors is also reviewed.

Feasibility of serial neurocognitive assessment using Cogstate during and after therapy for childhood leukemia.

PURPOSE: Neurocognitive impairment is frequently observed among survivors of childhood acute lymphoblastic leukemia (ALL) within the domains of attention, working memory, processing speed, executive functioning, and learning and memory. However, few studies have characterized the trajectory of treatment-induced changes in neurocognitive function beginning in the first months of treatment, to test whether early changes predict impairment among survivors. If correct, we hypothesize that those children who are most susceptible to early impairment would be ideal subjects for clinical trials testing interventions designed to protect against treatment-related neurocognitive decline. METHODS: In this pilot study, we prospectively assessed neurocognitive functioning (attention, working memory, executive function, visual learning, and processing speed), using the Cogstate computerized battery at six time points during the 2 years of chemotherapy treatment and 1-year post-treatment (Dana-Farber Cancer Institute ALL Consortium protocol 11-001; NCT01574274). RESULTS: Forty-three patients with ALL consented to serial neurocognitive testing. Of the 31 participants who remained on study through the final time point, 1 year after completion of chemotherapy, 28 (90%) completed at least five of six planned Cogstate testing time points. Performance and completion checks indicated a high tolerability (≥ 88%) for all subtests. One year after completion of treatment, 10 of 29 patients (34%) exhibited neurocognitive function more than 2 standard deviations below age-matched norms on one or more Cogstate subtests. CONCLUSIONS: Serial collection of neurocognitive data (within a month of diagnosis with ALL, during therapy, and 1-year post-treatment) is feasible and can be informative for evaluating treatment-related neurocognitive impairment.

Comparison of neuropsychological functioning in pediatric posterior fossa tumor survivors: Medulloblastoma, low-grade astrocytoma, and healthy controls.

BACKGROUND: Neuropsychological comparison of medulloblastoma (MB) and cerebellar low-grade astrocytoma (LGA) survivors to controls can clarify treatment-related neurocognitive late effects. While both brain tumor groups undergo surgery to the posterior fossa, children with MB additionally receive craniospinal irradiation with boost and chemotherapy. This study provides an updated comparison of neuropsychological functioning in these two groups and examines effects of demographic risk factors upon outcomes. PROCEDURE: Forty-two children (16 MB, nine LGA, and 17 controls) completed measures of intellectual functioning, verbal learning/memory, visual-motor integration, and fine-motor functioning. The effects of age at diagnosis, time since diagnosis, gender, fatigue, and social status on neuropsychological functioning were examined. RESULTS: MB survivors demonstrated the worst neurocognitive late effects, but they were less severe and extensive than in prior studies. LGA survivors' mean scores were below normative expectations in working memory, processing speed, and fine-motor functioning. In this overall sample, processing speed difficulties were independent of fine-motor functioning and fatigue. Higher parental education was associated with better intellectual functioning, working memory, delayed recall, and visual-motor integration. Neuropsychological function was not associated with gender, age at diagnosis, or time since diagnosis. CONCLUSION: The results support that contemporary treatment approaches with craniospinal irradiation plus boost and chemotherapy confer the greatest risk for late effects, while surgical resection is associated with subtle but important neurocognitive difficulties. Ultimately, this study furthers our understanding of factors impacting neuropsychological function in pediatric MB and LGA survivors and contributes to empirical support for close monitoring and targeted interventions into survivorship.

Long-term neuropsychological outcomes of survivors of young childhood brain tumors treated on the Head Start II protocol.

BACKGROUND: The Head Start treatment protocols have focused on curing young children with brain tumors while avoiding or delaying radiotherapy through using a combination of high-dose, marrow-ablative chemotherapy and autologous hematopoietic cell transplantation (AuHCT). Late effects data from treatment on the Head Start II (HS II) protocol have previously been published for short-term follow-up (STF) at a mean of 39.7 months post-diagnosis. The current study examines long-term follow-up (LTF) outcomes from the same cohort. METHODS: Eighteen HS II patients diagnosed with malignant brain tumors <10 years of age at diagnosis completed a neurocognitive battery and parents completed psychological questionnaires at a mean of 104.7 months' post-diagnosis. RESULTS: There was no significant change in Full Scale IQ at LTF compared to baseline or STF. Similarly, most domains had no significant change from STF, including verbal IQ, performance IQ, academics, receptive language, learning/memory, visual-motor integration, and externalizing behaviors. Internalizing behaviors increased slightly at LTF. Clinically, most domains were within the average range, except for low average mathematics and receptive language. Additionally, performance did not significantly differ by age at diagnosis or time since diagnosis. Of note, children treated with high-dose methotrexate for disseminated disease or atypical teratoid/rhabdoid tumor displayed worse neurocognitive outcomes. CONCLUSIONS: These results extend prior findings of relative stability in intellectual functioning for a LTF period. Ultimately, this study supports that treatment strategies for avoiding or delaying radiotherapy using high-dose, marrow-ablative chemotherapy and AuHCT may decrease the risk of neurocognitive and social-emotional declines in young pediatric brain tumor survivors.

The Care of Children With Cancer During the COVID-19 Pandemic.

The COVID-19 pandemic has considerably changed health services for children with cancer worldwide by creating barriers throughout the care continuum. Reports available at this time suggest that asymptomatic and mild upper and lower respiratory tract syndromes are the most common presentation of COVID-19 in children with cancer. Nonetheless, severe cases of COVID-19 and deaths secondary to the infection have been reported. In addition to the direct effects of the severe acute respiratory syndrome coronavirus 2, children with cancer have suffered from the collateral consequences of the pandemic, including decreased access to diagnosis and cancer-directed therapy. The COVID-19 pandemic has presented unprecedented challenges to safe and effective care of children with cancer, including their enrollment in therapeutic clinical trials. Data from the Children's Oncology Group and Cancer Research U.K. Clinical Trials Unit show variability in the enrollment of children with cancer in clinical trials during the COVID-19 pandemic. However, the overall effects on outcomes for children with cancer undergoing care during the pandemic remain largely unknown. In this article, we review the current knowledge about the direct and collateral effects of the COVID-19 pandemic, including on clinical trial enrollment and operations.

Neuropsychological outcomes on Head Start III: a prospective, multi-institutional clinical trial for young children diagnosed with malignant brain tumors.

BACKGROUND: Current pediatric brain tumor treatment focuses on titrating toxicity based on risk factors while simultaneously improving survivorship. The Head Start (HS) protocols I to IV (1991-present) use high-dose chemotherapy (HDCTx) with an aim of reducing or eliminating cranial irradiation in very young children, the most vulnerable to its effects. METHODS: We examined estimated Full Scale IQ, overall Adaptive Functioning, Working Memory, Processing Speed, and Verbal and Nonverbal Memory outcome data for 43 HS III patients diagnosed between ages 2 months and 7 years from 15 institutions in the United States and Canada. RESULTS: At a mean of 5.12 years postdiagnosis, the HS III patients performed within the average to low-average ranges across these variables; however, individual variability was noted with scores ranging from superior to impaired, and the sample as a whole performed lower than age expectations. Performance did not significantly differ by sex or ethnicity, diagnosis, or for those treated with an intravenous methotrexate dose of 400 mg/kg vs 270 mg/kg. Additionally, performance did not significantly differ by age at diagnosis or length of follow-up. CONCLUSIONS: The results, indicating overall average to low-average neurocognitive functioning, are encouraging, though significant individual variability was noted. Those who were younger at diagnosis, received more intensive methotrexate, and were further out from treatment were not at significantly increased risk of cognitive decline within our sample, suggesting a strategy of using HDCTx and autologous hematopoietic progenitor cell rescue to reduce or eliminate irradiation may allow for continued CNS development in young children treated for a brain tumor.

Excellent outcome of young children with nodular desmoplastic medulloblastoma treated on "Head Start" III: a multi-institutional, prospective clinical trial.

BACKGROUND: "Head Start" III, was a prospective clinical trial using intensive induction followed by myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR) to either avoid or reduce the dose/volume of irradiation in young children with medulloblastoma. METHODS: Following surgery, patients received 5 cycles of induction followed by myeloablative chemotherapy using carboplatin, thiotepa, and etoposide with AuHCR. Irradiation was reserved for children >6 years old at diagnosis or with residual tumor post-induction. RESULTS: Between 2003 and 2009, 92 children <10 years old with medulloblastoma were enrolled. Five-year event-free survival (EFS) and overall survival (OS) rates (±SE) were 46 ±â€…5% and 62 ±â€…5% for all patients, 61 ±â€…8% and 77 ±â€…7% for localized medulloblastoma, and 35 ±â€…7% and 52 ±â€…7% for disseminated patients. Nodular/desmoplastic (ND) medulloblastoma patients had 5-year EFS and OS (±SE) rates of 89 ±â€…6% and 89 ±â€…6% compared with 26 ±â€…6% and 53 ±â€…7% for classic and 38 ±â€…13% and 46 ±â€…14% for large-cell/anaplastic (LCA) medulloblastoma, respectively. In multivariate Cox regression analysis, histology was the only significant independent predictor of EFS after adjusting for stage, extent of resection, regimen, age, and sex (P <0.0001). Five-year irradiation-free EFS was 78 ±â€…8% for ND and 21 ±â€…5% for classic/LCA medulloblastoma patients. Myelosuppression was the most common toxicity, with 2 toxic deaths. Twenty-four survivors completed neurocognitive evaluation at a mean of 4.9 years post-diagnosis. IQ and memory scores were within average range overall, whereas processing speed and adaptive functioning were low-average. CONCLUSION: We report excellent survival and preservation of mean IQ and memory for young children with ND medulloblastoma using high-dose chemotherapy, with most patients surviving without irradiation.

Utilization of integrative medicine differs by age among pediatric oncology patients.

PURPOSE: Coping with symptoms related to cancer treatment is challenging for pediatric patients with cancer and their caregivers. Additionally, caring for pediatric patients requires specialized expertise to incorporate age-appropriate interventions to improve outcomes. Despite the increase in pediatric inpatient integrative medicine (IM) therapies, there is a paucity of knowledge about whether the utilization of IM therapies differs by patient age. METHODS: We conducted a retrospective analysis on IM utilization among pediatric inpatients between 2008 and 2016 in a tertiary urban cancer center using electronic medical records. Multivariable logistic regression models examined the relationship between age and specific type of IM utilization, adjusting for specific demographic factors. RESULTS: Between 2008 and 2016, the pediatric inpatient IM service had 20 686 visits and treated 1877 unique patients. A significant age difference (P < 0.001) by modality was noted: dance therapy (mean age ± standard deviation: 5.9 ± 5.3 years), music therapy (8.0±7.0 years), mind-body therapies (13.0 ± 7.7 years), massage (14.5 ± 7.8 years), and acupuncture (20.0 ± 7.9 years). In multivariable analysis, the association between age and use of specific IM therapies remained significant (P < 0.001 for all). CONCLUSION: Specific types of inpatient IM therapy usage significantly differed by the age of pediatric patients with cancer; therefore, designing and providing age-appropriate IM interventions with consideration for developmental stage are needed to ensure that the most appropriate and effective therapies are provided to children with cancer.

Central and Peripheral Effects of Transcutaneous Acupuncture Treatment for Nausea in Patients with Diabetic Gastroparesis.

BACKGROUND/AIMS: Nausea, an unpleasant symptom of diabetic gastroparesis (DMGP), has been reported to be alleviated by needleless transcutaneous electrical acupuncture (TEA). Our study was designed to utilize electroencephalography (EEG) and electrogastrography (EGG) recordings to investigate the central and peripheral responses of TEA in the treatment of nausea in DMGP patients. METHODS: Eleven DMGP subjects underwent simultaneous EEG and EGG testing while grading the severity of nausea following 30-minute intervals of: (1) baseline, (2) visual stimulation (VS) to provoke more nausea, (3) active VS together with TEA, and (4) TEA alone, and a final 15-minute recording without any intervention. RESULTS: The nausea score was increased to 5.9 ± 1.5 with VS (P < 0.05, vs 3.5 ± 1.0 at baseline), then reduced to 3.5 ± 1.2 with VS plus TEA, and to 2.5 ± 1.3 with TEA alone, while it continued at a score of 2.9 ± 1.0 post TEA (all significant, P < 0.05, vs VS without TEA). The mean percentage of normal gastric slow waves was decreased to 60.0 ± 5.7% with VS (P < 0.05, vs 66.6 ± 4.5% at baseline), then improved to 69.2 ± 4.8% with VS plus TEA, and maintained at 70 ± 3.6% with TEA alone. During initial VS, EEG signals showed right inferior frontal activity as the prominent finding, but during VS with TEA, left inferior frontal activity predominated. CONCLUSIONS: In DMGP, TEA improves gastric dysrhythmia and ameliorates nausea. TEA treatment of nausea provoked by VS resulted in a change of dominance from right to left inferior frontal lobe activity. These data provide new understandings of peripheral and central mechanisms for nausea, and potential future directions for DMGP treatment approaches.

Enhanced Long-Term Brain Magnetic Resonance Imaging Evaluation of Children with Sickle Cell Disease after Hematopoietic Cell Transplantation.

Progressive neurovasculopathy in children with sickle cell disease (SCD) results in decreased cognitive function and quality of life (QoL). Hematopoietic cell transplantation (HCT) is believed to halt progression of neurovasculopathy. Quantitative analysis of T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) for white matter hyperintensity (WMH) burden provides a meaningful estimate of small vessel cerebrovascular disease. We asked if quantitative analysis of WMH could complement standardized clinical assessment of MRI/magnetic resonance angiography (MRA) for assessing SCD central nervous system vasculopathy before and after HCT. Retrospective longitudinal clinical examination of scheduled annual MRI/MRA and quantitative analysis of WMH were performed before and 1 to 7 years after HCT at scheduled annual intervals, along with QoL measurements, in children who had engrafted after HCT. Of 18 patients alive and persistently engrafted (median age, 9.1 years), pretransplantation MRI demonstrated that 9 and 5 had sickle-related stroke and/or small infarcts, respectively. Patients were divided into WMH severity tertiles based on pretransplantation WMH volumes. MRI and WMH were assessed 1 to 7 years after HCT. MRI/MRA and WMH volume were stable or slightly better in 17 of 18 patients. By parent- and self-report, post-HCT QoL improved for children in the lowest WMH tertile significantly more than in the other groups. Based on this single-institution retrospective sample, we report that WMH appears to quantitatively support MRI-based findings that HCT stabilizes long-term small and large vessel cerebrovascular changes and is associated with the degree of improved QoL. While confirmation in larger prospective studies and evaluation by neurocognitive testing are needed, these findings suggest that WMH is a useful biomarker of neurovasculopathy after transplantation for SCD.

Glutamine for the treatment of vincristine-induced neuropathy in children and adolescents with cancer.

BACKGROUND: Vincristine is an integral treatment component of many childhood tumors with potentially dose-limiting sensory and/or motor neuropathy. Results from a pilot study on the incidence of vincristine-induced peripheral neuropathy (VIPN) as well as the efficacy and safety of glutamine in reducing signs and symptoms of VIPN in children with cancer are presented. METHODS: Fifty-six patients between the ages of 5-21 with newly diagnosed leukemia, lymphoma, extracranial solid tumor or medulloblastoma and expected to receive a minimum cumulative dose of 6 mg/m2 of vincristine over a 30-week period were eligible. Patients' neurological functioning was monitored every 3 weeks using clinical history, exam, and assessment of motor functioning. Upon identification of neuropathy, patients were randomized to either glutamine (6 g/m2 per dose twice daily, maximum 10 g/dose) or placebo for a 3-week period followed by 3-week wash out period (Time 3). RESULTS: Forty-nine patients were fully evaluable and 100 % developed neuropathy per study definitions. No significant differences in demographics or side effects were noted between the randomized groups. The distribution of sensory neuropathy scores between the two groups was statistically significant after the intervention (p = 0.022). Children receiving glutamine also rated their quality of life (QoL) as 8.42 points higher on the PedsQL total score than those receiving placebo (p = 0.031). CONCLUSIONS: Glutamine supplementation is well tolerated and associated with improvements in sensory function and self-reported overall quality of life. Future studies are warranted to confirm the efficacy of glutamine for the treatment of vincristine-related sensory neuropathy in pediatric cancer patients.

Feasibility of baseline neurocognitive assessment using Cogstate during the first month of therapy for childhood leukemia.

PURPOSE: Neurocognitive impairment is frequently observed among acute lymphoblastic leukemia (ALL) survivors within the domains of intelligence, attention, processing speed, working memory, learning, and memory. However, few have investigated treatment-induced changes in neurocognitive function during the first months of treatment. Additionally, dysfunction during treatment may be preceded by changes in biomarkers measured within cerebrospinal fluid (CSF). Identification of acute declines in neurocognitive function, as well as predictive genotypes or biomarkers, could guide therapeutic trials of protective interventions. METHODS: This study collects CSF while prospectively assessing neurocognitive functioning (working memory, executive function, learning, processing speed, and attention) of ALL patients using the Cogstate computerized battery at six time points during and after the 2 years of leukemia treatment on a Dana-Farber Cancer Institute ALL Consortium trial. RESULTS: Baseline data collected during the first 3 weeks of induction chemotherapy indicate reliable data as all subjects (N = 34) completed Cogstate baseline testing, while completion and performance checks indicate that 100 % of subjects completed testing and complied with test requirements. The majority (85 %) exhibited normal function compared with age peers. Preliminary analysis of CSF biomarkers (folate, homocysteine, 8-isoprostane, and myelin basic protein) similarly reveals values at baseline within expected normal ranges. CONCLUSIONS: The first month of induction therapy for ALL is a reliable baseline for detecting treatment-induced changes in neurocognitive functioning. Consequently, serial data collection might identify subgroups of ALL patients at increased risk for neurocognitive decline, warranting proactive interventions to improve their level of functioning both during treatment and into survivorship.

Group-Based Trajectory Modeling of Distress and Well-Being Among Caregivers of Children Undergoing Hematopoetic Stem Cell Transplant.

Objective: To examine the trajectories of caregiver psychological responses in the year following their child's hematopoetic stem cell transplant (HSCT), and whether cognitive and social processing strategies differentiated between trajectories. Method: One hundred and eight caregivers randomized to the control condition of a cognitive-behavioral intervention study completed measures of distress, coping, and social support at baseline, 1 month, 6 months, and 1 year post HSCT of their child. Results: The majority reported moderate or low anxiety, depression, or distress that decreased over time, but a small group demonstrated high anxiety, depression, or distress that persisted or increased over time. Maladaptive coping was highest among caregivers in the high-persistent distress subgroup compared with the moderate-decreasing and low-stable groups. Adaptive coping was minimally associated with trajectory subgroups. Conclusions: Screening HSCT caregivers for distress and maladaptive coping may be useful in identifying caregivers likely to experience persistently high distress who may benefit from psychological intervention.

Physical Activity and Cognitive Development: A Meta-Analysis.

RESEARCH QUESTION: Is there an association between regular exercise, defined as a structured program of increased physical activity at least 1 month in duration, and improvements in measures of executive functions compared with children who engage in their normal daily activities? CONTEXT: The association between increased physical activity and changes in performance on tasks of executive functions have not been well elucidated in children. Executive functioning is important to intellectual development and academic success in children, and inexpensive, nonpharmacological methods for the treatment of executive dysfunction represent an attractive interventional target. OBJECTIVE: To estimate the effect of a structured regular exercise program on neuropsychological domains of executive function in children ages 7 to 12. DATA SOURCES: We performed a systematic review of English and non-English articles using Cochrane Library, EBSCO CINAHL, Ovid MEDLINE, PSYCInfo, Pubmed, and Web of Science, including all years allowed by each individual search engine. The search string used was "(exercise OR phys*) AND (cognit* OR executive) AND (child* OR preadolesc*)." The authors of the studies selected for review were contacted for any unpublished data. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials, which enrolled children between the ages of 7 and 12, with randomization to either normal activity or a structured physical activity intervention consisting of scheduled aerobic exercise, at least once per week, for a period of at least 1 month. Eligible studies must have included a neuropsychological battery of tests that measured at least 1 executive function both before and after the intervention was completed. STUDY APPRAISAL: Two independent reviewers examined the screened studies in detail for potential inclusion. The results of the individual examinations were compared; if any discrepancies were present, a third party analyzed the study to determine if it should be included in the meta-analysis. RESULTS: A total of 18 studies were identified by abstract as candidates for inclusion. From these 18 studies, 8 were independently selected by 2 authors for inclusion in the final analysis; there were no selection discrepancies between authors with regard to the studies to be included. In all, 770 subjects were included, 339 in the control group and 431 in the intervention group. All 8 studies contained a measure of inhibitory control; no other domain of executive function was measured frequently enough to perform meta-analysis, so only measures of inhibitory control were pooled and analyzed. A Cohen d effect size was calculated for each measure using the method of Morris for controlled pre-post control measurement studies. The studies were then combined in a random effects model using Comprehensive Meta Analysis software (Biostat, Englewood, NJ) for Windows (Microsoft, Redmond, WA). All studies showed a positive effect of regular exercise with improvements in measures of inhibitory control, but none were statistically significant for this measure. When pooled, the model revealed a combined Cohen d effect size of 0.2 (95% confidence interval, 0.03-0.37; P=0.021), indicating a small improvement of inhibitory control with long-term physical activity. Heterogeneity was very low (I=0). LIMITATIONS: Many studies used different neuropsychological tests to assess inhibitory control, which may have introduced unforeseen confounders. Other domains of executive functions were not measured frequently enough to perform meta-analysis. Despite attempts to gather unpublished data, positive results were observed in all of the included studies, raising the possibility of publication bias. CONCLUSIONS AND IMPLICATIONS: Increased regular physical activity is associated with a small and measurable, improvement in neuropsychological tests of executive functions, specifically inhibitory control. Executive functions play an important role in complex behavior, and may contribute to academic and career achievement as well as success in social interaction. This finding provides support for the important interaction between exercise and cognitive functioning.

Outcome of young children with high-grade glioma treated with irradiation-avoiding intensive chemotherapy regimens: Final report of the Head Start II and III trials.

PURPOSE: To report the final analysis of survival outcomes for children with newly diagnosed high-grade glioma (HGG) treated on the "Head Start" (HS) II and III protocols with chemotherapy and intent to avoid irradiation in children <6 years old. PATIENTS AND METHODS: Between 1997 and 2009, 32 eligible children were enrolled in HS II and III with anaplastic astrocytoma (AA, n = 19), glioblastoma multiforme (GBM, n = 11), or other HGG (n = 2). Central pathology review was completed on 78% of patients. Patients with predominantly brainstem tumors were excluded. Patients were to be treated with single induction chemotherapy regimen C, comprising four cycles of vincristine, carboplatin, and temozolomide. Following induction, patients underwent marrow-ablative chemotherapy and autologous hematopoietic cell rescue. Irradiation was used for patients with residual tumor after consolidation or >6 years old or at the time of tumor progression. RESULTS: The 5-year event-free survival (EFS) and overall survival (OS) for all HGG patients were 25 ± 8% and 36 ± 9%, respectively. The EFS at 5 years for patients with AA and GBM were 24 ± 11% and 30 ± 16%, respectively (P = 0.65). The OS at 5 years for patients with AA and GBM was 34 ± 12% and 35 ± 16%, respectively (P = 0.83). Children <36 months old experienced improved 5-year EFS and OS of 44 ± 17% and 63 ± 17%, compared with children 36-71 months old (31 ± 13% and 38 ± 14%) and children >72 months old (0% and 13 ± 12%). CONCLUSIONS: Irradiation-avoiding treatment strategies should be evaluated further in young children with HGG given similar survival rates to older children receiving standard irradiation-containing therapies.

A randomized clinical trial of a parent-focused social-cognitive processing intervention for caregivers of children undergoing hematopoetic stem cell transplantation.

OBJECTIVE: Providing care to one's child during and after a hematopoietic stem cell transplant (HSCT) is a universally stressful experience, but few psychological interventions have been developed to reduce caregiver distress. The goal of this study was to test the efficacy of a brief cognitive-behavioral intervention delivered to primary caregivers. METHOD: Two hundred eighteen caregivers were assigned either best-practice psychosocial care (BPC) or a parent social-cognitive intervention program (P-SCIP). The 5 session P-SCIP was delivered during the HSCT hospitalization. Caregivers completed measures of distress, optimism, coping, and fear appraisals preintervention, 1, 6 months, and 1 year. RESULTS: P-SCIP reduced caregiver's distress significantly more than BPC between the pretransplant assessment (Time 1) and 1-month follow-up assessment (Time 2). P-SCIP had a stronger effect than BPC among caregivers who began the hospitalization reporting higher depression and anxiety, and among caregivers whose children developed graft-versus-host disease (GvHD). Long-term treatment effects of P-SCIP were seen in traumatic distress among caregivers who reported higher anxiety pretransplant as well as among caregivers whose children had GvHD at HSCT discharge. CONCLUSIONS: Screening caregivers for elevations in pretransplant anxiety and targeting interventions specifically to these caregivers, as well as targeting caregivers to children who develop GvHD, may prove beneficial.