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Find video protocols related to scientific articles indexed in Pubmed.
Subsequent neoplasms in survivors of childhood central nervous system tumors: risk after modern multimodal therapy.
Neuro-oncology
PUBLISHED: 11-15-2014
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Multimodal therapy has improved survival for some childhood CNS tumors. However, whether risk for subsequent neoplasms (SNs) also increases is unknown. We report the cumulative incidence of, and risk factors for, SNs after a childhood primary CNS tumor and determine whether treatment that combines radiation therapy (RT) with chemotherapy increases risk for SNs.
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Critical combinations of radiation dose and volume predict intelligence quotient and academic achievement scores after craniospinal irradiation in children with medulloblastoma.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 08-23-2014
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To prospectively follow children treated with craniospinal irradiation to determine critical combinations of radiation dose and volume that would predict for cognitive effects.
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Effect of cerebellum radiation dosimetry on cognitive outcomes in children with infratentorial ependymoma.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 08-19-2014
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Cognitive decline is a recognized effect of radiation therapy (RT) in children treated for brain tumors. The importance of the cerebellum and its contribution to cognition have been recognized; however, the effect of RT on cerebellum-linked neurocognitive deficits has yet to be explored.
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Prospective evaluation of local control and late effects of conformal radiation therapy in children, adolescents, and young adults with high-grade glioma.
Neuro-oncology
PUBLISHED: 06-07-2014
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A phase II trial of conformal radiotherapy (CRT) for pediatric high-grade glioma (HGG) was performed to evaluate disease control and late effects.
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MRI-based treatment planning with pseudo CT generated through atlas registration.
Med Phys
PUBLISHED: 05-03-2014
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To evaluate the feasibility and accuracy of magnetic resonance imaging (MRI)-based treatment planning using pseudo CTs generated through atlas registration.
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Pubertal development and primary ovarian insufficiency in female survivors of embryonal brain tumors following risk-adapted craniospinal irradiation and adjuvant chemotherapy.
Pediatr Blood Cancer
PUBLISHED: 03-17-2014
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Female survivors of central nervous system (CNS) tumors are at an increased risk for gonadal damage and variations in the timing of puberty following radiotherapy and alkylating agent-based chemotherapy.
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Reirradiation of recurrent medulloblastoma: Does clinical benefit outweigh risk for toxicity?
Cancer
PUBLISHED: 03-03-2014
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Patients with recurrent medulloblastoma (MB) have a dismal prognosis. There has been a reluctance to use radiation in the salvage therapy regimens for these patients because of concerns about toxicity and unknown efficacy. Comparing survival outcomes and toxicities in relapsed patients treated with and without radiation may help to define its role.
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Adaptive functioning of childhood brain tumor survivors following conformal radiation therapy.
J. Neurooncol.
PUBLISHED: 03-02-2014
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Adaptive functioning is not often examined in childhood brain tumor (BT) survivors, with the few existing investigations relying on examiner interviews. Parent questionnaires may provide similar information with decreased burden. The purpose of this study was: (1) to examine adaptive behaviors in BT survivors relative to healthy peer and cancer survivor groups, and (2) to explore the validity of a parent questionnaire in relation to an examiner administered interview. Participants (age 13.11 ± 2.98 years) were BT survivors treated with conformal radiation therapy (n = 50), healthy siblings of BT survivors (n = 39) and solid tumor (ST) survivors who did not receive CNS-directed therapy (n = 40). Parents completed the Adaptive Behavior Assessment System–2nd Edition (ABAS-II). For a subset of the BT cohort (n = 32), examiners interviewed the parents using the Vineland Adaptive Behavior Scales (VABS) within 12 months. Groups differed significantly on each of the ABAS-II indices and the general adaptive composite, with the BT group scoring lower than the sibling and ST groups across indices. Executive functioning, but not IQ, was associated with adaptive skills; no clear pattern of clinical and demographic predictors was established. VABS scores were correlated with ABAS-II scores on nearly all indices. BT survivors showed significantly lower adaptive functioning when compared to healthy and cancer controls. The ABAS-II proved sensitive to these behavioral limitations and was consistent with scores on the VABS. The use of a parent questionnaire to assess adaptive functioning enhances survivorship investigations by increasing flexibility of assessment and decreasing examiner burden.
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Pathologic risk-based adjuvant chemotherapy for unilateral retinoblastoma following enucleation.
J. Pediatr. Hematol. Oncol.
PUBLISHED: 03-01-2014
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There are no standardized diagnostic or treatment guidelines for patients with advanced unilateral retinoblastoma.
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The relationship between working memory and cerebral white matter volume in survivors of childhood brain tumors treated with conformal radiation therapy.
J. Neurooncol.
PUBLISHED: 02-20-2014
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Survivors of childhood brain tumors (BTs) treated with CNS-directed therapy show changes in cerebral white matter that are related to neurocognitive late effects. We examined the association between white matter volume and working memory ability in survivors treated with conformal radiation therapy (CRT). Fifty survivors (25 males, age at assessment = 13.14 ± 2.88, age at CRT = 7.41 ± 3.41 years) completed Digit Span from the Wechsler Intelligence Scales for Children, 4th Edition and experimental Self-Ordered Search (SOS) tasks as measures of working memory. Caregiver ratings were obtained using the Behavior Rating Inventory of Executive Function. MRI exams were acquired on a 1.5 T scanner. Volumes of normal appearing white matter (NAWM) were quantified using a well-validated automated segmentation and classification program. Correlational analyses demonstrated that NAWM volumes were significantly larger in males and participants with tumors located in the infratentorial space. Correlations between NAWM volume and Digit Span Backward were distributed across anterior and posterior regions, with evidence for greater right hemisphere involvement (r = .32-.34, p ? .05). Correlations between NAWM volume with Digit Span Backward (r = .44-.52; p ? .05) and NAWM volume with SOS-Object Total (r = .45-.52, p ? .05) were of greater magnitude in females. No relationship was found between NAWM volume and caregiver report. Working memory performance in survivors of pediatric BTs treated with CRT are related to regionally specific NAWM volume. Developmental differences in cerebral myelination may explain findings of greater risk for neurocognitive late effects in female survivors. Future studies are needed to better isolate vulnerable white matter pathways, thus facilitating the development of neuroprotective interventions.
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C11orf95-RELA fusions drive oncogenic NF-?B signalling in ependymoma.
Nature
PUBLISHED: 01-28-2014
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Members of the nuclear factor-?B (NF-?B) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-?B signalling is present in most human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-?B activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-?B signalling, and an uncharacterized gene, C11orf95. In each case, C11orf95-RELA fusions resulted from chromothripsis involving chromosome 11q13.1. C11orf95-RELA fusion proteins translocated spontaneously to the nucleus to activate NF-?B target genes, and rapidly transformed neural stem cells--the cell of origin of ependymoma--to form these tumours in mice. Our data identify a highly recurrent genetic alteration of RELA in human cancer, and the C11orf95-RELA fusion protein as a potential therapeutic target in supratentorial ependymoma.
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Emotional and behavioral functioning after conformal radiation therapy for pediatric ependymoma.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-22-2014
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The standard of care for pediatric patients with ependymoma involves postoperative radiation therapy. Prior research suggests that conformal radiation therapy (CRT) is associated with relative sparing of cognitive and academic functioning, but little is known about the effect of CRT on emotional and behavioral functioning.
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Evaluation of amifostine for protection against cisplatin-induced serious hearing loss in children treated for average-risk or high-risk medulloblastoma.
Neuro-oncology
PUBLISHED: 01-10-2014
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The purpose of this study was to evaluate amifostine for protection from cisplatin-induced serious hearing loss in patients with average-risk medulloblastoma by extending a previous analysis to a much larger sample size. In addition, this study aimed to assess amifostine with serious hearing loss in patients with high-risk medulloblastoma treated with cisplatin.
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Phase II Trial of Erlotinib during and after Radiotherapy in Children with Newly Diagnosed High-Grade Gliomas.
Front Oncol
PUBLISHED: 01-01-2014
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Epidermal growth factor receptor is overexpressed in most pediatric high-grade gliomas (HGG). Since erlotinib had shown activity in adults with HGG, we conducted a phase II trial of erlotinib and local radiotherapy (RT) in children with newly diagnosed HGG.
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Investigating the relationship between COMT polymorphisms and working memory performance among childhood brain tumor survivors.
Pediatr Blood Cancer
PUBLISHED: 05-22-2013
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Survivors of childhood brain tumors are at increased risk for neurocognitive impairments, including deficits in abilities supported by frontal brain regions. Catechol-O-methyltransferase (COMT) metabolizes dopamine in the prefrontal cortex, with the Met allele resulting in greater dopamine availability and better performance on frontally mediated tasks compared to the Val allele. Given the importance of identifying resiliency factors against the emergence of cognitive late effects, the current study examined the relationship between COMT genotype and working memory performance among childhood brain tumor survivors.
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Phase I trial, pharmacokinetics, and pharmacodynamics of vandetanib and dasatinib in children with newly diagnosed diffuse intrinsic pontine glioma.
Clin. Cancer Res.
PUBLISHED: 03-27-2013
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Testing of promising drug combinations is crucial in the treatment of diffuse intrinsic pontine glioma (DIPG). As the VEGF and platelet-derived growth factor (PDGF) pathways are critical in gliomas, we evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of vandetanib, a VEGFR-2 inhibitor, combined with dasatinib, a potent PDGFR inhibitor, during and after radiotherapy in children with newly diagnosed DIPG.
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Clinical controversies: proton therapy for pediatric tumors.
Semin Radiat Oncol
PUBLISHED: 03-12-2013
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Despite the claim in the published literature, the introduction of proton therapy for children is not analogous to the evolution of conformal photon irradiation relying on the understanding of the impact of altered dose distributions. The differences in radiobiological effect when comparing photons with protons mean that we are comparing a known entity with an unknown entity: the dose-volume histogram for proton therapy might mean something substantially different from the dose-volume histogram for photon therapy. The multifaceted difference between the 2 modalities supports the argument for careful evaluation, follow-up, and clinical trials with adverse event monitoring when using proton therapy in children. We review the current data on the outcome of proton therapy in a range of pediatric tumors and compare them with the often excellent results of photon therapy in the setting of multidisciplinary management of childhood cancer. It is hoped that the apparent dosimetric advantage of proton therapy over photons will lead to improved indications for therapy, disease control, and functional outcomes. Although physical dose distribution is of clear importance, the multimodality management of children by an expert pediatric oncology team and the availability of ancillary measures that improve the quality of treatment delivery may be more important than the actual beam. In addition, current estimates of the benefit of proton therapy over photon therapy based on toxicity reduction will only be realized when survivorship has been achieved. Once substantive proton therapy data become available, it will be necessary to demonstrate benefit in clinically relevant outcome measures in comparison with best existing photon outcome data. Such an effort will require improved funding and appreciation for late effects research. Only real clinical outcome data combined with better understanding of the radiobiological differences between protons and photons will help us to further reduce side effects in children and exploit the full curative potential of this relatively new modality.
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Computerized assessment of cognitive late effects among adolescent brain tumor survivors.
J. Neurooncol.
PUBLISHED: 02-19-2013
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Advantages of computerized assessment of neuropsychological functions include improved standardization and increased reliability of response time variables. Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is a computerized battery developed for monitoring recovery following mild brain injuries that assesses attention, memory and processing speed. Despite evidence that core areas of deficit among cancer survivors are those assessed by ImPACT, it has not previously been used with this population. Twenty four childhood brain tumor (BT) survivors treated with conformal radiation therapy (mean age = 15.7 ± 1.6; mean age at irradiation = 9.8 ± 2.5), twenty solid tumor (ST) survivors treated without CNS-directed therapy (mean age = 16.2 ± 1.8) and twenty healthy siblings (mean age = 15.1 ± 1.6 years) were administered an age modified version of ImPACT. Additional computerized measures of working memory and recognition memory were administered. Univariate ANOVAs revealed group differences (p < 0.05) on measures of recognition memory, spatial working memory, processing speed and reaction time, with BT survivors performing significantly worse than ST survivors and siblings. Pearson correlation coefficients revealed significant associations between ImPACT memory tasks and computerized forced choice recognition tasks (rs = 0.30-0.33, p < 0.05). Multiple surgical resections, hydrocephalus and CSF shunt placement most consistently predicted worse ImPACT performance using linear mixed models (p < 0.05). The ImPACT test battery demonstrated sensitivity to cognitive late effects experienced by some BT survivors with clinical predictors of performance consistent with the pediatric oncology literature. Correlations with measures of similar constructs provide evidence for convergent validity. Findings offer initial support for the utility of ImPACT for monitoring of cognitive late effects.
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Evaluation of children with craniopharyngioma using carbon-11 methionine PET prior to proton therapy.
Neuro-oncology
PUBLISHED: 02-13-2013
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Fluorine-18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET) is limited in its evaluation of brain tumors due to the high basal activity of the cerebral cortex and white matter. Carbon-11 methionine ((11)C MET) has little uptake under normal conditions. We prospectively investigated the uptake of (18)F FDG and (11)C MET PET in patients with craniopharyngioma prior to proton therapy.
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The utility of parent report in the assessment of working memory among childhood brain tumor survivors.
J Int Neuropsychol Soc
PUBLISHED: 01-28-2013
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Childhood brain tumor survivors are at increased risk for neurocognitive impairments, including working memory (WM) problems. WM is typically assessed using performance measures. Little is known about the value of parent ratings for identifying WM difficulties, the relationship between rater and performance measures, or predictors of parent-reported WM problems in this population. Accordingly, the current study examined the utility of parent report in detecting WM difficulties among childhood brain tumor survivors treated with conformal radiation therapy (n = 50) relative to siblings (n = 40) and solid tumor survivors not receiving central nervous system-directed therapy (n = 40). Parents completed the Behavior Rating Inventory of Executive Function (BRIEF). Participants were administered WM measures (digit span, self-ordered search tasks). Findings revealed parents rated brain tumor survivors as having significantly more WM problems (p < .01) compared to controls. However, the BRIEF-WM scale demonstrated poor sensitivity and specificity for detecting performance-based problems. Significant, albeit modest, correlations were found between the BRIEF-WM scale and performance measures (r = -.24-.22; p < .05) for the combined group. Age at testing, socioeconomic status, and IQ were significant predictors of parent reported WM problems. Rater and performance measures offer complimentary yet different information in assessing WM, which reiterates the importance of using both within the context of clinical assessment.
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Differences in brainstem fiber tract response to radiation: a longitudinal diffusion tensor imaging study.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-17-2013
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To determine whether radiation-induced changes in white matter tracts are uniform across the brainstem.
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Growth hormone secretion after conformal radiation therapy in pediatric patients with localized brain tumors.
J. Clin. Oncol.
PUBLISHED: 10-31-2011
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Growth hormone deficiency (GHD) after radiation therapy negatively affects growth and development and quality of life in children with brain tumors.
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Effects of irradiation on brain vasculature using an in situ tumor model.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 06-06-2011
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Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model.
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Dosimetric consequences of rotational errors in radiation therapy of pediatric brain tumor patients.
Radiother Oncol
PUBLISHED: 06-03-2011
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To quantify the rotational offsets and estimate the dose effect of rotation on the target volume and normal tissues in children with brain tumor.
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Role of adaptive radiation therapy for pediatric patients with diffuse pontine glioma.
J Appl Clin Med Phys
PUBLISHED: 05-19-2011
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We investigate the role of adaptive radiation therapy in pediatric patients with diffuse pontine glioma and the impact of steroid-related weight gain on treatment parameters utilizing cone-beam CT. Fifteen patients with diffuse pontine glioma were treated with three-dimensional conformal radiation therapy and enrolled on a daily localization protocol. The median age was 6 years (range: 2-13 years). Patient charts were examined to obtain the prescribed daily dose of dexamethasone and weight. The original treatment plan was recalculated based on the data obtained from the daily cone-beam CT. The changes in target and critical structure doses were calculated using gEUD. Correlations between prescribed dexamethasone, weight gain, source-to-skin distance (SSD) changes and dosimetric changes were investigated. Eleven of the 15 patients gained weight during radiation therapy, with an average gain of 2.2 kg (8.0%). The mean gEUD decreased was 0.57 Gy (range: 0.24-1.4 Gy) for the PTV, and the mean gEUD increase for critical structures was 1.14%. No strong correlations between prescribed dexamethasone doses, weight gain and dosimetric changes were found. Change in SSD vs. dose to PTV was correlated (R² = 0.51). Weight gain and changes to the external surface are apparent in these patients; however, the dosimetric changes to the target and critical structures were small and in most cases did not warrant an adaptive plan. The potential exists for a decrease in target dose in these patients; therefore, they should be monitored to assess for replanning when necessary.
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Intensity-modulated arc therapy for pediatric posterior fossa tumors.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 05-11-2011
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To compare intensity-modulated arc therapy (IMAT) to noncoplanar intensity-modulated radiation therapy (IMRT) in the treatment of pediatric posterior fossa tumors.
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Post-operative radiation improves survival in children younger than 3 years with intracranial ependymoma.
J. Neurooncol.
PUBLISHED: 03-04-2011
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Concerns regarding long-term toxicities have led to the avoidance of post-operative radiation (PORT) in young children with intracranial ependymoma. We investigated the association between post-operative radiation therapy and overall survival (OS) in children younger than 3 years and compared their survival to other age groups. The study sample from the SEER database included 804 patients with intracranial ependymoma, grades 2-3, and diagnosed between 1988 and 2005. OS was estimated using the Kaplan-Meier method, and hazard ratios (HR) and 95% confidence limits (CL) were calculated based on multivariable Cox proportional hazards models. A total of 804 patients were selected and PORT was administered to 35% of patients younger than 3 years. With a median follow-up of 3 years (range 0.1-18 years), the 3 year OS was 61% for children younger than 3 years, 83% for those ages 3-20 years, and 69% for patients older than 20 years (P < 0.001). In multivariable analysis, OS was significantly improved for patients receiving PORT (HR 0.8, 95% CL 0.6-0.9), and gross total resection (HR 0.6, 95% CL 0.5-0.8). Among children younger than 3 years, the 3 year OS was significantly greater among those who received PORT compared to those who did not (81% vs. 56%, respectively, P = 0.005). The majority of children younger than 3 years with intracranial ependymoma did not receive PORT. Children younger than 3 years who did not receive PORT had a relatively poor outcome, while those who received radiation therapy had a survival similar to older patients.
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Novel assessment of renal motion in children as measured via four-dimensional computed tomography.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 03-04-2011
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Abdominal intensity-modulated radiation therapy and proton therapy require quantification of target and organ motion to optimize localization and treatment. Although addressed in adults, there is no available literature on this issue in pediatric patients. We assessed physiologic renal motion in pediatric patients.
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Dependence of intrafraction motion on fraction duration for pediatric patients with brain tumors.
J Appl Clin Med Phys
PUBLISHED: 02-23-2011
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The purpose of this study was to quantify the intrafraction motion of pediatric patients with brain tumors during radiation therapy and investigate any correlation between motion, use of general anesthesia, and daily treatment duration. 100 pediatric patients with a mean age of 8.5 years (range: 1.0 to 17.8) were included in this prospective study. Forty-one patients required general anesthesia during treatment, mean age 4.8 years; 59 patients did not, mean age 11.2 years. Each patient had an intracranial tumor and was treated in the supine position with a thermoplastic facemask and headrest for immobilization. A pretreatment localization CBCT was acquired for each treatment fraction and a post-treatment CBCT was acquired every other fraction. If the magnitude of the patients position pre-CBCT offset was ? 2 mm, the position was corrected. The difference between the patients position based on the post-CBCT and the assumed position at the start of treatment (either the pre-CBCT offset if the magnitude was < 2 mm, or 0 offset due to correction) was determined and labeled intrafraction motion. Correlations between daily treatment duration and intrafraction motion were examined. There was an average of 14.2 post-CBCTs acquired per patient. The magnitude of the mean intrafraction motion was 1.2 ± 0.8 mm for patients requiring general anesthesia, and 1.5 ± 1.2 mm for those without (p < 0.001). The mean offset in each direction was less than 0.5 mm for both cohorts. There was no correlation between daily treatment duration and the magnitude of intrafraction motion. The intrafraction motion of pediatric patients undergoing external beam therapy for intracranial tumors is small, < 2 mm, and is independent of the daily treatment duration.
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Sequencing of local therapy affects the pattern of treatment failure and survival in children with atypical teratoid rhabdoid tumors of the central nervous system.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-22-2011
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To assess the pattern of treatment failure associated with current therapeutic paradigms for childhood atypical teratoid rhabdoid tumors (AT/RT).
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Excessive daytime sleepiness and sleep-disordered breathing disturbances in survivors of childhood central nervous system tumors.
Pediatr Blood Cancer
PUBLISHED: 02-14-2011
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Improvements in treatment and management for pediatric central nervous system (CNS) tumors have increased survival rates, allowing clinicians to focus on long-term sequelae, including sleep disorders. The objective of this study was to describe a series of CNS tumor survivors who had sleep evaluations that included polysomnography (PSG) with attention to sleep disorder in relation to the tumor site.
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Brain tumor therapy-induced changes in normal-appearing brainstem measured with longitudinal diffusion tensor imaging.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-08-2011
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To characterize therapy-induced changes in normal-appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI).
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On the benefits and risks of proton therapy in pediatric craniopharyngioma.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-05-2011
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Craniopharyngioma is a pediatric brain tumor whose volume is prone to change during radiation therapy. We compared photon- and proton-based irradiation methods to determine the effect of tumor volume change on target coverage and normal tissue irradiation in these patients.
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Survival and long-term health and cognitive outcomes after low-grade glioma.
Neuro-oncology
PUBLISHED: 12-22-2010
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Long-term morbidity for children with low-grade glioma (LGG) requires exposure-specific characterization. Overall survival (OS) and progression-free survival (PFS) were estimated for 361 children diagnosed with LGG between 1985 and 2007 at a single institution. Five-year survivors (n = 240) received risk-based clinical assessment. Cumulative incidence of late effects 15 years from diagnosis were estimated. Risk factors for adverse health were identified using Fine and Grays approach to Coxs proportional hazards model, accounting for death as a competing risk. OS at 15 years was 86% (95% confidence interval [CI] 82%-90%), and PFS was 55% (95% CI 51%-58%). Among the 240 5-year survivors, the 5-, 10-, and 15-year cumulative incidence of adverse outcomes included blindness: 10%, 13%, and 18%, respectively; hearing loss: 8%, 14%, and 22%; obesity/overweight: 18%, 35%, and 53%; hyperinsulinism: 1%, 5%, and 24%; growth hormone deficiency: 13%, 27%, and 29%;thyroid hormone deficiency: 16%, 28%, and 33%; and adrenocorticotropic hormone (ACTH) deficiency: 12%, 22%, and 26%. Multivariable models demonstrated radiation therapy to be a significant independent predictor of hearing loss, growth hormone deficiency, abnormal thyroid function, and ACTH deficiency. Diencephalic location was a statistically significant independent risk factor for blindness, growth hormone deficiency, abnormal thyroid function, and ACTH deficiency. Among the 182 5-year survivors assessed for intellectual function, 34% had an intelligence quotient (IQ) below average (<85), associated with younger age at diagnosis, epilepsy, and shunt placement. Survivors of childhood LGG experience substantial long-term adverse effects that continue to increase well beyond the 5-year survival time point.
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Phase I study of vandetanib during and after radiotherapy in children with diffuse intrinsic pontine glioma.
J. Clin. Oncol.
PUBLISHED: 10-04-2010
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To evaluate the safety, maximum-tolerated dose, pharmacokinetics, and pharmacodynamics of vandetanib, an oral vascular endothelial growth factor receptor 2 (VEGFR2) and epidermal growth factor receptor inhibitor, administered once daily during and after radiotherapy in children with newly diagnosed diffuse intrinsic pontine glioma.
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Region-specific radiotherapy and neuropsychological outcomes in adult survivors of childhood CNS malignancies.
Neuro-oncology
PUBLISHED: 08-17-2010
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Childhood cancer survivors exposed to CNS irradiation are at increased risk for neurocognitive deficits; however, limited data exist linking outcomes with region-specific exposure to CNS irradiation. We report associations between region-specific radiation dose and self-reported neurocognitive and health-related quality of life (HRQOL) outcomes in 818 adult survivors of childhood central nervous system (CNS) malignancies from the Childhood Cancer Survivor Study. Survivors were compared with a sibling group and national normative samples to calculate standardized scores. Cumulative radiation dose was calculated for 4 specific brain regions. Logistic regression was used to estimate the association between radiation dose to specific brain regions and outcome measures of functional impairment adjusted for clinical and demographic factors, including sex and age at diagnosis. High radiation dose levels to temporal regions were associated with a higher risk for memory impairment (radiation doses ?30 to <50 Gy: OR, 1.95; 95% CI, 1.01-3.78; dose ?50 Gy: OR, 2.34; 95% CI, 1.25-4.39) compared with those with no radiation exposure. No such association was seen with radiation exposure to other regions. Exposure to temporal regions was associated with more social and general health problems, whereas exposure to frontal regions was associated with general health problems and physical performance limitations. Adult survivors of childhood CNS malignancies report higher rates of neuropsychological and HRQOL outcomes, which vary as a function of dose to specific neuroanatomical regions. Survivors with a history of radiation exposure to temporal brain regions are at increased risk for impairment in memory and social functioning.
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Health status in long-term survivors of pediatric craniopharyngiomas.
J Neurosci Nurs
PUBLISHED: 07-02-2010
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Craniopharyngiomas are the third most common pediatric brain tumor and most common pediatric suprasellar tumor. Contemporary treatment of craniopharyngiomas uses limited surgery and radiation in an effort to minimize morbidity, but the long-term health status of patients treated in this fashion has not been well described. The purpose of this study was to analyze the health status of long-term survivors of pediatric craniopharyngioma treated primarily with radiation and conservative surgical resection. Medical records of all long-term survivors of craniopharyngioma treated at St. Jude Childrens Research Hospital and then transferred to the long-term follow-up clinic were reviewed. The initial cohort comprised 55 patients. Of these, 51 (93%) were alive at the time of this analysis. The median age at diagnosis was 7.1 years (range, 1.2-17.6 years), and 29 (57%) were male. At the time of analysis, the median survival was 7.6 years (range, 5.0-21.3 years). Diagnosis and treatment included surgical biopsy, resection (n = 50), and radiation therapy (n=48). Only 1 patient received chemotherapy. Polyendocrinopathy was the most common morbidity, with hypothyroidism (96%), adrenocorticotropic hormone deficiency (84%), and diabetes insipidus (53%) occurring most frequently. Half of the patients were hypogonadal, and 33 (65%) were overweight or obese. The most common neurologic problems included shunt dependence (37%), seizures (28%), and headaches (39%). Psychological and educational deficits were also identified in a significant number of these individuals. Despite efforts to reduce morbidity in these patients, many survivors remain burdened with significant medical complications. In a small percentage of patients, complications may result in death even during extended remission of craniopharyngioma. Because of the broad spectrum or morbidities experienced, survivors of craniopharyngioma continue to benefit from multidisciplinary care.
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Dosimetric effect of target expansion and setup uncertainty during radiation therapy in pediatric craniopharyngioma.
Radiother Oncol
PUBLISHED: 06-15-2010
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Investigate the effect of tumor change and setup uncertainties on target coverage for pediatric craniopharyngioma during RT.
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Daily image-guided localization for neuroblastoma.
J Appl Clin Med Phys
PUBLISHED: 06-09-2010
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The purpose was to quantify the setup margin for pediatric patients with neuro-blastoma using cone beam CT imaging (CBCT) and ultrasound localization. Ten patients, with a median age of 4.3 years (1.8 to 7.9) underwent daily pretreatment localization CBCT and every other day post-treatment CBCT to calculate interfractional and intrafraction movement. Localization was based on CBCT to treatment planning CT registration in the lumbar spine region. Each subject was treated in the supine position under IV general anesthesia using intensity-modulated radiation therapy. Patients were repositioned based on the daily pretreatment CBCT. Required setup margins based on inter- and intrafraction positioning errors were calculated based on weekly and daily imaging scenarios. Four patients had ultra-sound localization of the kidneys performed before the CBCT. Correlation between daily CBCT and ultrasound was investigated. A lateral, longitudinal and vertical setup margin of 5.4, 5.6, and 5.9 mm is required without daily CBCT. When daily CBCT was incorporated, the setup margin was reduced to 1.5, 2.1, and 1.7 mm. There was no correlation between the suggested ultrasound shifts and the shifts based on the CBCT. Daily localization based on CBCT of the lumbar spine can reduce the required setup margin for neuroblastoma patients, thereby reducing normal tissue exposure for this young patient population. The internal margin needs further investigation before PTV reduction can be made. Ultrasound localization was highly variable and not correlated to CBCT shifts.
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Inter- and intrafractional positional uncertainties in pediatric radiotherapy patients with brain and head and neck tumors.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 06-03-2010
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To estimate radiation therapy planning margins based on inter- and intrafractional uncertainty for pediatric brain and head and neck tumor patients at different imaging frequencies.
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Cross-species genomics matches driver mutations and cell compartments to model ependymoma.
Nature
PUBLISHED: 05-13-2010
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Understanding the biology that underlies histologically similar but molecularly distinct subgroups of cancer has proven difficult because their defining genetic alterations are often numerous, and the cellular origins of most cancers remain unknown. We sought to decipher this heterogeneity by integrating matched genetic alterations and candidate cells of origin to generate accurate disease models. First, we identified subgroups of human ependymoma, a form of neural tumour that arises throughout the central nervous system (CNS). Subgroup-specific alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. To select cellular compartments most likely to give rise to subgroups of ependymoma, we matched the transcriptomes of human tumours to those of mouse neural stem cells (NSCs), isolated from different regions of the CNS at different developmental stages, with an intact or deleted Ink4a/Arf locus (that encodes Cdkn2a and b). The transcriptome of human supratentorial ependymomas with amplified EPHB2 and deleted INK4A/ARF matched only that of embryonic cerebral Ink4a/Arf(-/-) NSCs. Notably, activation of Ephb2 signalling in these, but not other, NSCs generated the first mouse model of ependymoma, which is highly penetrant and accurately models the histology and transcriptome of one subgroup of human supratentorial tumour. Further, comparative analysis of matched mouse and human tumours revealed selective deregulation in the expression and copy number of genes that control synaptogenesis, pinpointing disruption of this pathway as a critical event in the production of this ependymoma subgroup. Our data demonstrate the power of cross-species genomics to meticulously match subgroup-specific driver mutations with cellular compartments to model and interrogate cancer subgroups.
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Radiation therapy for pediatric craniopharyngioma.
Neurosurg Focus
PUBLISHED: 04-07-2010
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The treatment of craniopharyngioma is highly controversial. Continued advances in limited surgery and radiation therapy have maintained excellent local disease control while minimizing treatment-related sequelae. Further analyses of outcomes are necessary to characterize the long-term effects of radiation therapy.
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Jaw dysfunction related to pterygoid and masseter muscle dosimetry after radiation therapy in children and young adults with head-and-neck sarcomas.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 03-29-2010
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To investigate the relationship between jaw function, patient and treatment variables, and radiation dosimetry of the mandibular muscles and joints in children and young adults receiving radiation for soft-tissue and bone sarcomas.
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Improved intratumoral oxygenation through vascular normalization increases glioma sensitivity to ionizing radiation.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 03-27-2010
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Ionizing radiation, an important component of glioma therapy, is critically dependent on tumor oxygenation. However, gliomas are notable for areas of necrosis and hypoxia, which foster radioresistance. We hypothesized that pharmacologic manipulation of the typically dysfunctional tumor vasculature would improve intratumoral oxygenation and, thus, the antiglioma efficacy of ionizing radiation.
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Irradiation of pediatric high-grade spinal cord tumors.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 03-24-2010
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To report the outcome using radiation therapy (RT) for pediatric patients with high-grade spinal cord tumors.
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Dysembryoplastic neuroepithelial tumors and cognitive outcome: cure at a price?
Cancer
PUBLISHED: 03-09-2010
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Dysembryoplastic neuroepithelial tumors (DNETs) are benign glioneuronal tumors that occur in children. These tumors are characterized by seizures, lack of neurologic deficits, and a seemingly benign course after resection.
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Auditory late effects of childhood cancer therapy: a report from the Childrens Oncology Group.
Pediatrics
PUBLISHED: 03-01-2010
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Children treated for malignancies may be at risk for early- or delayed-onset hearing loss that can affect learning, communication, school performance, social interaction, and overall quality of life. Survivors at particular risk include those treated with platinum compounds (cisplatin and/or carboplatin) for neuroblastoma, hepatoblastoma, osteosarcoma, or germ-cell tumors and/or those treated with radiation that affects the ear at doses of >30 Gy for pediatric head and neck tumors. The aims of the Auditory/Hearing Late Effects Task Force of the Childrens Oncology Group in this report were to (1) review ototoxicity resulting from childhood cancer therapy including platinum compounds (cisplatin and carboplatin) and radiation, (2) describe briefly cochlear pathophysiology and genetics of cisplatin-related hearing loss, (3) explain the impact of hearing loss resulting from chemotherapy and radiation, and (4) offer recommendations regarding evaluation and management of pediatric patients who are at risk for treatment-related hearing loss. A questionnaire is included as a tool to assist pediatricians in assessment.
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Radiation associated brainstem injury.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-23-2010
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Publications relating brainstem radiation toxicity to quantitative dose and dose-volume measures derived from three-dimensional treatment planning were reviewed. Despite the clinical importance of brainstem toxicity, most studies reporting brainstem effects after irradiation have fewer than 100 patients. There is limited evidence relating toxicity to small volumes receiving doses above 60-64 Gy using conventional fractionation and no definitive criteria regarding more subtle dose-volume effects or effects after hypofractionated treatment. On the basis of the available data, the entire brainstem may be treated to 54 Gy using conventional fractionation using photons with limited risk of severe or permanent neurological effects. Smaller volumes of the brainstem (1-10 mL) may be irradiated to maximum doses of 59 Gy for dose fractions 64 Gy.
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Radiation dose-volume effects in the brain.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-23-2010
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We have reviewed the published data regarding radiotherapy (RT)-induced brain injury. Radiation necrosis appears a median of 1-2 years after RT; however, cognitive decline develops over many years. The incidence and severity is dose and volume dependent and can also be increased by chemotherapy, age, diabetes, and spatial factors. For fractionated RT with a fraction size of <2.5 Gy, an incidence of radiation necrosis of 5% and 10% is predicted to occur at a biologically effective dose of 120 Gy (range, 100-140) and 150 Gy (range, 140-170), respectively. For twice-daily fractionation, a steep increase in toxicity appears to occur when the biologically effective dose is >80 Gy. For large fraction sizes (>or=2.5 Gy), the incidence and severity of toxicity is unpredictable. For single fraction radiosurgery, a clear correlation has been demonstrated between the target size and the risk of adverse events. Substantial variation among different centers reported outcomes have prevented us from making toxicity-risk predictions. Cognitive dysfunction in children is largely seen for whole brain doses of >or=18 Gy. No substantial evidence has shown that RT induces irreversible cognitive decline in adults within 4 years of RT.
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Dosimetric effect of setup motion and target volume margin reduction in pediatric ependymoma.
Radiother Oncol
PUBLISHED: 02-17-2010
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Quantify the dosimetric effect of inter- and intrafractional motion on intensity-modulated radiation therapy (IMRT) and three-dimensional (3D) planning via changes in the generalized equivalent uniform dose (gEUD), predicted tumor control probability (TCP) and normal tissue complication probability (NTCP) for pediatric ependymoma.
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Malignant transformation of irradiated craniopharyngioma in children: report of 2 cases.
J Neurosurg Pediatr
PUBLISHED: 02-04-2010
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Malignant transformation of craniopharyngioma is a rare event; only 3 cases have been reported in children, all in the Japanese literature. The authors describe 2 additional pediatric cases. Treatment in both of these cases consisted of multiple resections and external beam radiation therapy (EBRT). Malignant transformation occurred 7 and 8 years after EBRT. The authors also review another 6 cases in adults. A possible causative association with radiation therapy is discussed. As radiation is currently an important option in the management of craniopharyngiomas, this association requires further study.
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Proton beam therapy in pediatric oncology.
Cancer J
PUBLISHED: 08-13-2009
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Pediatric caregivers and parents are eager to know the role of proton beam therapy (PBT) in the treatment of children with brain and solid tumors and other diseases for which radiation therapy is indicated. Although the number of children treated with PBT for the most common pediatric tumors is relatively small and outcome data are clearly lacking, modeling radiation dose, volume, and outcomes based on photon benchmark data and clinical experience suggest an advantage for PBT and an opportunity to reduce or eliminate many of the early and late effects of radiation therapy. As the number of centers available to treat children increases, it is incumbent on those with access to this modality to optimize other critical aspects of radiotherapy and cancer care and follow-up that are requisite to achieving disease control and high-quality survivorship. Even though the focus of pediatric radiation oncology is weighted toward side effect reduction, there is an opportunity for dose escalation or biologically optimized radiotherapy in a number of diseases or settings in which high-dose irradiation is considered unapproachable. Justification for PBT in pediatric patients should be realized once the costs of treating acute symptoms, growth hormone deficiency, orthopedic deformities, and secondary malignancies are studied and reduced.
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Phase II trial of conformal radiation therapy for pediatric low-grade glioma.
J. Clin. Oncol.
PUBLISHED: 07-06-2009
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The use of radiotherapy in pediatric low-grade glioma (LGG) is controversial, especially for young patients. We conducted a phase II trial of conformal radiation therapy (CRT) to estimate disease control by using a 10-mm clinical target volume (CTV) margin.
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Late effects of conformal radiation therapy for pediatric patients with low-grade glioma: prospective evaluation of cognitive, endocrine, and hearing deficits.
J. Clin. Oncol.
PUBLISHED: 07-06-2009
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We conducted a prospective trial to evaluate late effects in pediatric patients with low-grade glioma (LGG) treated with conformal radiation therapy (CRT).
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Cytokine and growth factor responses after radiotherapy for localized ependymoma.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 04-22-2009
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To determine the time course and clinical significance of cytokines and peptide growth factors in pediatric patients with ependymoma treated with postoperative radiotherapy (RT).
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A pilot study of risk-adapted radiotherapy and chemotherapy in patients with supratentorial PNET.
Neuro-oncology
PUBLISHED: 03-20-2009
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We undertook this study to estimate the event-free survival (EFS) of patients with newly diagnosed supratentorial primitive neuroectodermal tumor (SPNET) treated with risk-adapted craniospinal irradiation (CSI) with additional radiation to the primary tumor site and subsequent high-dose chemotherapy supported by stem cell rescue. Between 1996 and 2003, 16 patients with SPNET were enrolled. High-risk (HR) disease was differentiated from average-risk (AR) disease by the presence of residual tumor (M(0) and tumor size > 1.5 cm(2)) or disseminated disease in the neuraxis (M(1)-M(3)). Patients received risk-adapted CSI: those with AR disease received 23.4 Gy; those with HR disease, 36-39.6 Gy. The tumor bed received a total of 55.8 Gy. Subsequently, all patients received four cycles of high-dose cyclophosphamide, cisplatin, and vincristine with stem cell support. The median age at diagnosis was 7.9 years; eight patients were female. Seven patients had pineal PNET. Twelve patients are alive at a median follow-up of 5.4 years. The 5-year EFS and overall survival (OS) estimates for all patients were 68% +/- 14% and 73% +/- 13%. The 5-year EFS and OS estimates were 75% +/- 17% and 88% +/- 13%, respectively, for the eight patients with AR disease and 60% +/- 19% and 58% +/- 19%, respectively, for the eight with HR disease. No deaths were due to toxicity. High-dose cyclophosphamide-based chemotherapy with stem cell support after risk-adapted CSI results in excellent EFS estimates for patients with newly diagnosed AR SPNET. Further, this chemotherapy allows for a reduction in the dose of CSI used to treat AR SPNET without compromising EFS.
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Evolution of neurological impairment in pediatric infratentorial ependymoma patients.
J. Neurooncol.
PUBLISHED: 03-16-2009
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Infratentorial ependymoma is a common central nervous system tumor of childhood and in patients >1 year of age is treated with maximally feasible surgical resection and radiotherapy. Because of this tumor typically arises within the 4th ventricle and can invade the brainstem, patients are at risk for significant neurological impairment.
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Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study.
Lancet Oncol.
PUBLISHED: 03-11-2009
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Therapy for ependymoma includes aggressive surgical intervention and radiotherapy administered by use of methods that keep the risk of side-effects to a minimum. We extended this treatment approach to include children under the age of 3 years with the aim of improving tumour control.
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Locoregional tumor progression after radiation therapy influences overall survival in pediatric patients with neuroblastoma.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-24-2009
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There is renewed attention to primary site irradiation and local control for patients with high-risk neuroblastoma (NB). We conducted a retrospective review to identify factors that might predict for locoregional tumor control and its impact on overall survival.
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Investigating verbal and visual auditory learning after conformal radiation therapy for childhood ependymoma.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-23-2009
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The primary objective of this study was to determine whether children with localized ependymoma experience a decline in verbal or visual-auditory learning after conformal radiation therapy (CRT). The secondary objective was to investigate the impact of age and select clinical factors on learning before and after treatment.
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Preliminary results from a prospective study using limited margin radiotherapy in pediatric and young adult patients with high-grade nonrhabdomyosarcoma soft-tissue sarcoma.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-13-2009
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To demonstrate the safety and efficacy of limited margin radiotherapy in the local control of pediatric and young adult patients with high-grade nonrhabdomyosarcoma soft tissue sarcoma (NRSTS).
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Predicting behavioral problems in craniopharyngioma survivors after conformal radiation therapy.
Pediatr Blood Cancer
PUBLISHED: 02-05-2009
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Although radiation therapy is a primary treatment for craniopharyngioma, it can exacerbate existing problems related to the tumor and pre-irradiation management. Survival is often marked by neurologic deficits, panhypopituitarism, diabetes insipidus, cognitive deficiencies, and behavioral and social problems.
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Factors associated with neurological recovery of brainstem function following postoperative conformal radiation therapy for infratentorial ependymoma.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-29-2009
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To identify risk factors associated with incomplete neurological recovery in pediatric patients with infratentorial ependymoma treated with postoperative conformal radiation therapy (CRT).
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Radiation-induced astrogliosis and blood-brain barrier damage can be abrogated using anti-TNF treatment.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-22-2009
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In this article, we investigate the role of tumor necrosis factor-alpha (TNF) in the initiation of acute damage to the blood-brain barrier (BBB) and brain tissue following radiotherapy (RT) for CNS tumors.
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Phase I and pharmacokinetic studies of erlotinib administered concurrently with radiotherapy for children, adolescents, and young adults with high-grade glioma.
Clin. Cancer Res.
PUBLISHED: 01-17-2009
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To estimate the maximum-tolerated dose (MTD) of erlotinib administered during and after radiotherapy, and to describe the pharmacokinetics of erlotinib and its metabolite OSI-420 in patients between 3 and 25 years with newly diagnosed high-grade glioma who did not require enzyme-inducing anticonvulsants.
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Dosimetric impact of intrafractional patient motion in pediatric brain tumor patients.
Med Dosim
PUBLISHED: 01-09-2009
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The purpose of this study was to determine the dosimetric consequences of intrafractional patient motion on the clinical target volume (CTV), spinal cord, and optic nerves for non-sedated pediatric brain tumor patients. The patients were immobilized for treatment using a customized thermoplastic full-face mask and bite-block attached to an array of reflectors. The array was optically tracked by infra-red cameras at a frequency of 10 Hz. Patients were localized based on skin/mask marks and weekly films were taken to ensure proper setup. Before each noncoplanar field was delivered, the deviation from baseline of the array was recorded. The systematic error (SE) and random error (RE) were calculated. Direct simulation of the intrafractional motion was used to quantify the dosimetric changes to the targets and critical structures. Nine patients utilizing the optical tracking system were evaluated. The patient cohort had a mean of 31 +/- 1.5 treatment fractions; motion data were acquired for a mean of 26 +/- 6.2 fractions. The mean age was 15.6 +/- 4.1 years. The SE and RE were 0.4 and 1.1 mm in the posterior-anterior, 0.5 and 1.0 mm in left-right, and 0.6 and 1.3 mm in superior-inferior directions, respectively. The dosimetric effects of the motion on the CTV were negligible; however, the dose to the critical structures was increased. Patient motion during treatment does affect the dose to critical structures, therefore, planning risk volumes are needed to properly assess the dose to normal tissues. Because the motion did not affect the dose to the CTV, the 3-mm PTV margin used is sufficient to account for intrafractional motion, given the patient is properly localized at the start of treatment.
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Childrens Oncology Groups 2013 blueprint for research: radiation oncology.
Pediatr Blood Cancer
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Radiation therapy (RT) is used to treat children with CNS tumors, solid tumors or Hodgkin lymphoma. Pediatric radiation oncologists have provided critical input into the development and implementation of concepts for clinical trials to further define the modalitys role and test newer methods to reduce side effects or intensify therapy. The quality of pediatric oncology clinical trials that include radiation therapy is linked to the quality of guidelines. Radiation oncology is an adult medical specialty; thus, pediatric radiation oncologists are uniquely positioned to work with adult cancer investigators in the reorganized US National Cancer Institute Clinic Trials Network.
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Childrens Oncology Groups 2013 blueprint for research: central nervous system tumors.
Pediatr Blood Cancer
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In the US, approximately 2,500 children are diagnosed annually with brain tumors. Their survival ranges from >90% to <10%. For children with medulloblastoma, the most common malignant brain tumor, 5-year survival ranges from >80% (standard-risk) to 60% (high-risk). For those with high-grade gliomas (HGGs) including diffuse intrinsic pontine gliomas, 5-year survival remains <10%. Sixty-five percent patients with ependymoma are cured after surgery and radiation therapy depending on the degree of resection and histopathology of the tumor. Phase II trials for brain tumors will investigate agents that act on cMET, PDGFRA, or EZH2 in HGG, DIPG, or medulloblastoma, respectively. Phase III trials will explore risk-based therapy stratification guided by molecular and clinical traits of children with medulloblastoma or ependymoma.
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Longitudinal investigation of adaptive functioning following conformal irradiation for pediatric craniopharyngioma and low-grade glioma.
Int. J. Radiat. Oncol. Biol. Phys.
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Children treated for brain tumors with conformal radiation therapy experience preserved cognitive outcomes. Early evidence suggests that adaptive functions or independent-living skills may be spared. This longitudinal investigation prospectively examined intellectual and adaptive functioning during the first 5 years following irradiation for childhood craniopharyngioma and low-grade glioma (LGG). The effect of visual impairment on adaptive outcomes was investigated.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.