Brain biomarkers and neuropsychological outcomes of pediatric posterior fossa brain tumor survivors treated with surgical resection with or without adjuvant chemotherapy.

PURPOSE: Children with brain tumors experience cognitive late effects, often related to cranial radiation. We sought to determine differential effects of surgery and chemotherapy on brain structure and neuropsychological outcomes in children who did not receive cranial radiation therapy (CRT). METHODS: Twenty-eight children with a history of posterior fossa tumor (17 treated with surgery, 11 treated with surgery and chemotherapy) underwent neuroimaging and neuropsychological assessment a mean of 4.5 years (surgery group) to 9 years (surgery + chemotherapy group) posttreatment, along with 18 healthy sibling controls. Psychometric measures assessed IQ, language, executive functions, processing speed, memory, and social-emotional functioning. Group differences and correlations between diffusion tensor imaging findings and psychometric scores were examined. RESULTS: The z-score mapping demonstrated fractional anisotropy (FA) values were ≥2 standard deviations lower in white matter tracts, prefrontal cortex gray matter, hippocampus, thalamus, basal ganglia, and pons between patient groups, indicating microstructural damage associated with chemotherapy. Patients scored lower than controls on visuoconstructional reasoning and memory (P ≤ .02). Lower FA in the uncinate fasciculus (R = -0.82 to -0.91) and higher FA in the thalamus (R = 0.73-0.91) associated with higher IQ scores, and higher FA in the thalamus associated with higher scores on spatial working memory (R = 0.82). CONCLUSIONS: Posterior fossa brain tumor treatment with surgery and chemotherapy affects brain microstructure and neuropsychological functioning years into survivorship, with spatial processes the most vulnerable. Biomarkers indicating cellular changes in the thalamus, hippocampus, pons, prefrontal cortex, and white matter tracts associate with lower psychometric scores.

Maturation of Brain Microstructure and Metabolism Associates with Increased Capacity for Self-Regulation during the Transition from Childhood to Adolescence.

Children ages 9-12 years face increasing social and academic expectations that require mastery of their thoughts, emotions, and behavior. Little is known about the development of neural pathways integral to these improving capacities during the transition from childhood to adolescence. Among 234 healthy, inner-city male and female youth (species Homo sapiens) 9-12 years of age followed by the Columbia Center for Children's Environmental Health, we acquired diffusion tensor imaging, multiplanar chemical shift imaging, and cognitive measures requiring self-regulation. We found that increasing age was associated with increased fractional anisotropy and decreased apparent diffusion coefficient, most prominently in the frontal and cingulate cortices, striatum, thalamus, deep white matter, and cerebellum. Additionally, we found increasing age was associated with increased N-acetyl-l-aspartate (NAA) in the anterior cingulate and insular cortices, and decreased NAA in posterior cingulate and parietal cortices. Age-associated changes in microstructure and neurometabolite concentrations partially mediated age-related improvements in performance on executive function tests. Together, these findings suggest that maturation of key regions within cortico-striatal-thalamo-cortical circuits subserve the emergence of improved self-regulatory capacities during the transition from childhood to adolescence.SIGNIFICANCE STATEMENT Few imaging studies of normal brain development have focused on a population of inner-city, racial/ethnic minority youth during the transition from childhood to adolescence, a period when self-regulatory capacities rapidly improve. We used DTI and MPCSI to provide unique windows into brain maturation during this developmental epoch, assessing its mediating influences on age-related improvement in performance on self-regulatory tasks. Our findings suggest that rapid maturation of cortico-striato-thalamo-cortical circuits, represented as progressive white-matter maturation (increasing FA and increasing NAA, Ch, Cr concentrations accompanying advancing age) in frontal regions and related subcortical projections and synaptic pruning (decreasing NAA, Ch, Cr, Glx) in posterior regions, support age-related improvements in executive functioning and self-regulatory capacities in youth 9-12 years of age.

Dose-dependent cranial irradiation associations with brain structures and neuropsychological outcomes in children with posterior fossa brain tumors.

BACKGROUND: Posterior fossa irradiation with or without whole brain irradiation results in high doses of radiation to the thalamus, hippocampus, and putamen, structures critical to cognitive functioning. As a result, children with brain tumors treated with cranial irradiation (CRT) may experience significant cognitive late effects. We sought to determine the effect of radiation to those structures on neuropsychological outcome. METHODS: Forty-seven children with a history of posterior fossa tumor (17 treated with surgery; 11 with surgery and chemotherapy; and 19 with surgery, chemotherapy, and CRT) underwent neuroimaging and neuropsychological assessment at a mean of 4.8 years after treatment, along with 17 healthy sibling controls. The putamen, thalamus, and hippocampus were segmented on each participant's magnetic resonance imaging for diffusion indices and volumes, and in the radiation treatment group, radiation dose to each structure was calculated. RESULTS: Performance on visuoconstruction and spatial learning and memory was lower in patient groups than controls. Volume of the thalamus, when controlling for age, was smaller in the patient group treated with CRT than other groups. Higher radiation doses to the putamen correlated with higher fractional anisotropy in that structure. Higher radiation dose to the hippocampus correlated with lower spatial learning, and higher dose to thalami and putamina to lower verbal and nonverbal reasoning. CONCLUSIONS: All children with posterior fossa tumors, regardless of treatment modality, had cognitive deficits compared to their sibling controls. Posterior fossa irradiation may affect thalamic volume and aspects of verbal and nonverbal cognitive functioning.

White matter tract changes in pediatric posterior fossa brain tumor survivors after surgery and chemotherapy.

Background: Survivors of pediatric posterior fossa brain tumors are susceptible to the adverse effects of treatment as they grow into adulthood. While the exact neurobiological mechanisms of these outcomes are not yet understood, the effects of treatment on white matter (WM) tracts in the brain can be visualized using diffusion tensor (DT) imaging. We investigated these WM microstructural differences using the statistical method tract-specific analysis (TSA). We applied TSA to the DT images of 25 children with a history of posterior fossa tumor (15 treated with surgery, 10 treated with surgery and chemotherapy) along with 21 healthy controls. Between these 3 groups, we examined differences in the most used DTI metric, fractional anisotropy (FA), in 11 major brain WM tracts. Results: Lower FA was found in the splenium of the corpus callosum (CC), the bilateral corticospinal tract (CST), the right inferior frontal occipital fasciculus (IFOF) and the left uncinate fasciculus (UF) in children with brain tumors as compared to healthy controls. Lower FA, an indicator of microstructural damage to WM, was observed in 4 of the 11 WM tracts examined in both groups of children with a history of posterior fossa tumor, with an additional tract unique to children who received surgery and chemotherapy (left UF). Conclusions: Our findings indicate that a history of tumor in the posterior fossa and surgical resection may have effects on the WM in other parts of the brain.

Factors Associated with Interest in Complementary and Alternative Medicine Among Young Adult Survivors of Childhood Cancer.

Background: Use of complementary and alternative medicine (CAM) by those undergoing cancer treatment is common. While some childhood cancer survivors (CCS) may use CAM to treat late effects, others may lack information about available alternative therapies. We sought to determine characteristics associated with seeking more information about CAM among an ethnically diverse sample of young adult CCS. Methods: Young adult CCS were selected from the population-based Los Angeles SEER cancer registry and surveyed at ages 18 to 39 as part of the Project Forward Cohort. Associations between demographic, clinical, and other factors with seeking information on CAM were examined with t-tests, Chi Square analyses, and logistic regression. Results: Among 1106 participants surveyed, 182 (18%) reported interest in obtaining more information on CAM. Interest in CAM was highest among males, older (vs. younger) participants, those born outside the U.S., those with a history of relapsed/recurrent or second cancers, those with greater depressive symptoms, and those with poorer self-rated health. Among Hispanic/Latino/Latinx respondents, depressive symptoms, birth outside the U.S., and higher Latino culture orientation was positively associated with CAM interest. Discussion: Depressive symptoms and unresolved health problems are associated with a need for information about alternative forms of therapy, particularly in those with born outside the U.S. Healthcare providers caring for CCS can incorporate appropriate CAM information to help address unmet physical and mental health needs.

Adding a Parent to the Brain Tumor Team: Evaluating a Peer Support Intervention for Parents of Children With Brain Tumors.

Childhood brain tumors often present profound challenges to patients and families. To address these challenges, the California Chapter of the Pediatric Brain Tumor Foundation provides hospital-based support services to parents of children with brain tumors from a Veteran Parent (VP). This mixed-methods, cross-sectional study was designed to evaluate the effectiveness of the intervention using validated tools to compare parental resilience and impact of illness on the family between parents who met with the VP and those who did not. Two-tailed t tests assessed significant differences in scores on the PedsQL Family Impact module and Connor-Davidson Resilience Scale (CD-RISC-25). Additional qualitative data gleaned from focus groups with stakeholders (health care providers and parents) were analyzed using key constructs of social support theory with Atlas.ti. Although there were no significant differences in overall scores on the PedsQL Family Impact module or CD-RISC-25 between groups, parents in the intervention group scored better on items related to handling difficult decisions and painful feelings. Overarching themes emerged from focus groups around participants' experiences with the program and included informational and emotional support, peer parent relatedness, changed outlook, and empowerment. Results reveal the impact of peer parent support and need for emotional and instrumental support.

The Use of Aromatherapy to Reduce Chemotherapy-Induced Nausea in Children With Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial.

INTRODUCTION: Chemotherapy-induced nausea can be distressing and difficult to manage in children with cancer. The purpose of this study was to investigate the utility of ginger aromatherapy in relieving chemotherapy-induced nausea in children with cancer. METHOD: This randomized, double-blind, placebo-controlled study of 49 children with cancer explored whether inhalation of the aroma of essential oil of ginger during chemotherapy decreased nausea compared with a placebo (water) or control (Johnson's baby shampoo) measured by prechemotherapy and postchemotherapy assessment with the Pediatric Nausea Assessment Tool (PeNAT). RESULTS: While well received, well tolerated, nontoxic, and noninvasive, ginger aromatherapy did not significantly decrease nausea in patients enrolled in this study. Among 21 patients who indicated feeling nausea prechemotherapy, 67% reported improvement, 5% worsening, and 28% no change in their postinfusion PeNAT score. We failed to detect a statistical significant difference in the change in PeNAT scores among the three groups.

Diffusion Tensor Imaging and Neurobehavioral Outcome in Children With Brain Tumors Treated With Chemotherapy.

BACKGROUND: Childhood brain tumor survivors (CBTS) often experience treatment-related neurocognitive deficits affecting quality of life (QOL), but systemic chemotherapy contributions to outcomes are unclear. Our objective was to relate brain tissue changes to neurocognitive and QOL effects after systemic myeloablative chemotherapy with autologous hematopoietic progenitor cell rescue in CBTS. PROCEDURE: Regional brain volumes and diffusion tensor indices were correlated with neurocognitive, behavioral, and QOL measures, and compared between 8 CBTS (mean age 8.5 years, mean age at diagnosis 32 months), and 9 healthy controls (mean 9.3 years). RESULTS: Overall QOL, school, and psychosocial functioning were significantly lower in patients (P < .05). Most patients scored within normative ranges on neurocognitive and behavioral assessment. Elevated mean diffusivity and decreased fractional anisotropy, indicating gray and white matter injury, respectively, appeared in memory and executive functioning areas. Low scores on Inhibition on the Neuropsychological Assessment-II were correlated with elevated mean diffusivity in prefrontal cortex. CONCLUSIONS: Brain injury, decreased QOL, and to a lesser extent, executive functioning deficits appear in CBTS treated with myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue. Early cognitive and psychological assessment and intervention are warranted in this population.

Central nervous system injury and neurobiobehavioral function in children with brain tumors: a review of the literature.

BACKGROUND: Children with brain tumors present a complex set of factors when considering treatment decisions, including type and location of tumor and age of the child. Two-thirds of children will survive, but historically have had poorer neurocognitive and quality-of-life outcomes when compared with survivors of other childhood cancers. Delaying or forgoing cranial radiation completely is thought to lead to improved neurobiobehavioral outcomes, but there is still relatively little research in this area. OBJECTIVES: The objectives of this study were to review and consolidate what is known about the effects of cranial radiation and chemotherapy on normal brain tissue and to synthesize that information relative to neurobiobehavioral findings in children with brain tumors. METHODS: A literature search using PubMed and PsycINFO from 2000 to 2011 was done using a variety of terms related to childhood brain tumor treatment and outcome. A total of 70 articles were reviewed, and 40 were chosen for inclusion in the review based on most relevance to this population. RESULTS: Both cranial radiation and certain chemotherapy agents cause damage to or loss of healthy neurons, as well as a decrease in the number of progenitor cells of the hippocampus. However, in general, children treated with chemotherapy alone appear to have less of a neurobiobehavioral impact than those treated with cranial radiation. CONCLUSIONS: The trend toward delaying or postponing cranial radiation when possible may improve overall neurocognitive and quality-of-life outcomes. IMPLICATIONS FOR PRACTICE: Nurses require knowledge of these issues when discussing treatment with families and with caring for long-term survivors.