Survivors Of Posterior Fossa Brain Tumors Research Articles

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

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. 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). 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.

Physical ACTivity in Survivorship (PACTS): study protocol for a randomized controlled trial evaluating a goal-directed therapeutic exercise program in pediatric posterior fossa brain tumor survivors

BackgroundPosterior fossa brain tumors (PFBT) are the most common solid tumor in children. Recent increases in survival rates are encouraging; however, survivors may experience a plethora of disease- and treatment-related complications that can persist into adulthood. Therapeutic exercise interventions have been shown to improve quality of survivorship in other pediatric cancer diagnoses. There is also evidence that goal-directed interventions are effective at improving motor activities, function, and self-care in children with complex health conditions. Yet, there is currently no evidence on the efficacy of goal-directed therapeutic exercise in pediatric PFBT survivors. The Physical ACTivity in Survivorship (PACTS) study aims to investigate the effects of a novel goal-directed therapeutic exercise program on cardiorespiratory fitness and physical activity-related goal attainment in pediatric survivors of PFBT.MethodPFBT survivors, aged five to 17 years, who underwent surgery at least 12 months earlier and completed radiation therapy and/or chemotherapy at least 6 months prior will be recruited from the Queensland Children’s Hospital (Brisbane, Australia) (target n = 48). Following baseline assessment, participants are randomized into either the intervention or usual care group. The intervention group will receive weekly individualized, goal-directed exercise therapy delivered face-to-face for 12 weeks, along with an accompanying home-based program (three sessions per week). Outcomes will be assessed at baseline, immediately post-intervention, and at 6- and 12-months post-intervention. The primary outcomes are cardiorespiratory fitness (Peak VO2) and physical activity-related goal attainment. Secondary outcomes are cardiorespiratory endurance, high-level mobility skills, functional muscle strength, habitual physical activity, gait, balance, quality of life, fatigue, participation, perceived movement skill competence and parameters of body composition.DiscussionPACTS is the first study to investigate the efficacy of goal-directed therapeutic exercise in children with PFBT and provide evidence needed to inform clinical practice recommendations for managing quality of survivorship in PFBT survivors.Trial registrationACTRN12619000841178.

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

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). 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 4.5years (surgery group) to 9years (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. 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). 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.

Long-term quality of life in children treated for posterior fossa brain tumors

In the face of increasing survival, quality of life (QOL) has become an important indicator of treatment success in children with posterior fossa brain tumors (PFBTs). The authors' objective was to assess the long-term QOL in survivors of PFBT. The authors conducted a cross-sectional study of children who, between birth and age 18 years at diagnosis, had previously been treated at their institution for a PFBT. At the time of assessment for this study, children were between 5 and 19 years old and had received standard treatment for PFBT ending at least 6 months before the assessment. The QOL was measured with the Pediatric Quality of Life Inventory (PedsQL) generic score scales and the Health Utilities Index Mark 3 (HUI3). Multivariate analyses were used to assess several variables (patient related, treatment related, and socioeconomic) for association with QOL. A total of 62 children participated in the study (median age at assessment 11.9 years, interquartile range [IQR] 7.8-14.8, and median age at tumor diagnosis of 4.9 years, IQR 2.5-6.9). Median time since active treatment for their PFBT was 5.2 years (IQR 2.4-10.1). Tumor types included cerebellar pilocytic astrocytoma (45.2%), medulloblastoma (30.6%), ependymoma (11.3%), and brainstem astrocytoma (11.3%). Adjuvant therapy included chemotherapy (40.3%) or radiotherapy (14.5% focal and 21.0% craniospinal radiotherapy). Permanent treatment for hydrocephalus was required in 38.7% of the patients. Tumors recurred in 11.3%, requiring repeat treatment in these patients. The median HUI3 utility score was 0.91 (IQR 0.71-1.00) and the median PedsQL total score was 78.3 (IQR 64.1-92.4). Only the following variables were significantly associated with decreased QOL in multivariable model testing (all p < 0.05): need for permanent hydrocephalus treatment, large ventricle size, decreased family functioning, and lower family income. As a group, long-term survivors of pediatric PFBT appear to have QOL indicators that are similar to those of the general population, although a reasonable minority of patients experience poor outcomes. Although several confounding variables likely remain in this retrospective study, important associations with QOL include the presence of hydrocephalus and socioeconomic factors. The study sample size, however, was limited and the presence of other important factors cannot be excluded.

Brain structural abnormalities in survivors of pediatric posterior fossa brain tumors: A voxel-based morphometry study using free-form deformation

Voxel-based morphometry was used to compare brain structure of survivors of posterior fossa brain tumor (PFBT) with that of normal sibling controls to investigate disease- or cancer treatment-induced changes. Two different spatial normalization approaches that are available in public domain software (free-form deformation (FFD) and discrete cosine transform (DCT)) were compared for accuracy of normalization in the PFBT patients. Anatomical landmark matching demonstrated that spatial normalization was more accurate with FFD than with DCT. Voxel-based morphometry of the FFD-normalized magnetic resonance images from PFBT survivors and sibling controls detected reduced gray matter density in the thalamus and entorhinal cortex and reduced white matter density in the internal capsule, hypothalamus, corpus callosum, and cuneus of the occipital lobe in the PFBT survivors. Identification of these morphologic lesions may help localize the neural substrates of disease- or therapy-induced cognitive deficits in survivors of childhood cancer.