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BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. While there have been successes in the treatment of leukemia, less information is available on reasons for disparities in event-free survival (EFS) among underserved populations. METHODS: We partnered with a children's hospital at an academic institution to abstract data from the institution's cancer registry, the state cancer registry, and electronic medical records on cancer diagnosis, treatment, and outcomes for children with ALL (n = 275) diagnosed from 2005 to 2019 prior to age 20. We evaluated the relation between 1) race/ethnicity, 2) distance to the children's hospital, and 3) area deprivation with EFS, defined as time from diagnosis to relapse, death, or the end of the study period. We evaluated differences in EFS using Kaplan-Meier analysis with the log-rank test. We used the Cox Proportional Hazards Model for multivariable survival analyses. RESULTS: Most children were diagnosed with ALL under five years of age (45%) and with Pre-B ALL (87%). Twelve percent of children experienced a relapse and 5% died during induction or remission. EFS at 5 years was 82%. Non-Hispanic (NH) Black children had worse, though imprecise, EFS compared to NH White children (Adjusted Hazard Ratio: 2.07, 95% CI: 0.80, 5.38). Children residing in areas with higher deprivation had a higher adjusted hazard of poor outcomes compared to the least deprived areas, though estimates were imprecise (2nd quartile HR: 1.51, 3rd quartile: 1.85, 4th quartile: 1.62). We observed no association between distance to the children's hospital and EFS. CONCLUSION: We observed poorer EFS for NH Black children and children residing in areas with high deprivation, though the estimates were not statistically significant. Our next steps include further evaluating socioeconomic factors in both rural and urban children to identify disparities in outcomes for children with ALL and other childhood cancers.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Humanos , Adulto Joven , Adulto , Supervivencia sin Progresión , Oklahoma , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Análisis de Supervivencia , Recurrencia , Supervivencia sin EnfermedadRESUMEN
OBJECTIVE: Neurocutaneous syndromes have variable multisystem involvement. The multiorgan involvement, potential pathologies, and various treatment options necessitate collaboration and open discussion to ensure optimal treatment in any given patient. These disorders provide quintessential examples of chronic medical conditions that require a lifelong, multidisciplinary approach. The objectives of this study were to 1) perform a systematic review, thoroughly assessing different multidisciplinary clinic layouts utilized in centers worldwide; and 2) characterize an institutional experience with the management of these conditions, focusing on the patient demographics, clinical presentation, complications, and therapeutic strategies seen in a patient population. METHODS: A systematic review of studies involving multidisciplinary clinics and their reported structure was performed according to PRISMA guidelines using the PubMed database. Then a retrospective chart review of patients enrolled in the Oklahoma Children's Hospital Neurocutaneous Syndromes Clinic was conducted. RESULTS: A search of the PubMed database yielded 251 unique results. Of these, 15 papers were included in the analysis, which identified 16 clinics that treated more than 2000 patients worldwide. The majority of these clinics treated patients with neurofibromatosis (13/16). The remaining clinics treated patients with von Hippel-Lindau syndrome (n = 1), tuberous sclerosis complex (n = 1), and multiple neurocutaneous syndromes (n = 1). The most commonly represented subspecialties in these clinics were genetics (15/16) and neurology (13/16). Five clinics (31%) solely saw pediatric patients, 10 clinics saw a combination of children and adults, and the final clinic had separate pediatric and adult clinics. The retrospective chart review of the Neurocutaneous Syndromes Clinic demonstrated that 164 patients were enrolled and seen in the clinic from April 2013 to December 2021. Diagnoses were made based on clinical findings or results of genetic testing; 115 (70%) had neurofibromatosis type 1, 9 (5.5%) had neurofibromatosis type 2, 35 (21%) had tuberous sclerosis complex, 2 (1%) had von Hippel-Lindau syndrome, 2 (1%) had Gorlin syndrome, and the remaining patient (0.6%) had Aarskog-Scott syndrome. Patient demographics, clinical presentation, complications, and therapeutic strategies are also discussed. CONCLUSIONS: To the best of the authors' knowledge, this is the first detailed description of a comprehensive pediatric neurocutaneous clinic in the US that serves patients with multiple syndromes. There is currently heterogeneity between described multidisciplinary clinic structures and practices. More detailed accounts of clinic compositions and practices along with patient data and outcomes are needed in order to establish the most comprehensive and efficient multidisciplinary approach for neurocutaneous syndromes.
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Síndromes Neurocutáneos , Neurofibromatosis 1 , Esclerosis Tuberosa , Enfermedad de von Hippel-Lindau , Adulto , Niño , Humanos , Síndromes Neurocutáneos/diagnóstico , Síndromes Neurocutáneos/genética , Síndromes Neurocutáneos/terapia , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/genética , Estudios Retrospectivos , Esclerosis Tuberosa/complicaciones , Enfermedad de von Hippel-Lindau/complicaciones , Enfermedad de von Hippel-Lindau/genéticaRESUMEN
OBJECTIVE: The prognostic significance and genetic characteristics of H3 K27M-mutant diffuse midline gliomas (DMGs) in different anatomical locations requires further clarification. In this study, the authors integrated published data to investigate the differences between brainstem, thalamic, and spinal cord tumors. METHODS: PubMed and Web of Science databases were used to search for eligible articles. Studies were included if they provided individual patient data of H3 K27M-mutant DMGs with available tumor locations. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed to investigate the survival of each subgroup. RESULTS: Eight hundred four tumors were identified, including 467, 228, and 109 in the brainstem, thalamus, and spine, respectively. Brainstem tumors were primarily observed in young children, while patients with thalamic and spinal cord tumors afflicted older patients. The Ki-67 labeling index was highest in brainstem tumors. Compared to patients with brainstem tumors, those with thalamic (HR 0.573, 95% CI 0.463-0.709; p < 0.001) and spinal cord lesions (HR 0.460, 95% CI 0.341-0.621; p < 0.001) had a significantly better survival. When patients were stratified by age groups, superior overall survival (OS) of thalamic tumors was observed in comparison to brainstem tumors in young children and adolescents, whereas adult tumors had uniform OS regardless of anatomical sites. Genetically, mutations in HIST1H3B/C (H3.1) and ACVR1 genes were mostly detected in brainstem tumors, whereas spinal cord tumors were characterized by a higher incidence of mutations in the TERT promoter. CONCLUSIONS: This study demonstrated that H3 K27M-mutant DMGs have distinct clinical characteristics, prognoses, and molecular profiles in different anatomical locations.
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Introduction: Pediatric and adult H3K27M-mutant midline gliomas have variable clinical presentations, prognoses, and molecular backgrounds. In this study, we integrated data from published studies to investigate the differences between these two groups. Methods: PubMed and Web of Science were searched for potential data. Studies were included if they had available individual participant data on patients age of H3K27M-mutant midline gliomas. For time-to-event analyses, Kaplan-Meier analysis and Cox regression models were carried out; corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of age and clinical covariates on progression-free survival (PFS) and overall survival (OS). Results: We included 43 studies comprising 272 adults and 657 pediatric midline gliomas with H3K27M mutation for analyses. In adults, there was a male predilection whereas females were slightly more common than males in the pediatric group. Spinal cord tumors were more frequent in adults. The prevalence of H3.1 K27M mutation was significantly higher in the pediatric cohort. Compared to adult patients, pediatric H3K27M-mutant midline gliomas exhibited more aggressive features including higher rates of pathologic features of high-grade tumors and Ki67 proliferation index, and had a shorter PFS and OS. Genetically, ACVR1 mutations were more common whereas MGMT methylation, FGFR1, and NF1 mutations were less prevalent in the pediatric cohort. Conclusion: Pediatric H3K27M-mutant midline gliomas were demographically, clinically, and molecularly distinct from adult patients, highlighting an opportunity to refine the risk stratification for these neoplasms.
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INTRODUCTION: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients. METHODS: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan-Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS). RESULT: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR 1.446; 95% CI 1.143-1.829) whereas ACVR1 (HR 0.712; 95% CI 0.518-0.976) and FGFR1 mutations (HR 0.408; 95% CI 0.208-0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR 0.620; 95% CI 0.386-0.996). Adjusted for age, gender, and tumor location, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors. CONCLUSIONS: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. This may aid neuro-oncologists in appropriate risk stratification.
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Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/genética , Glioma/genética , Histonas/genética , Humanos , Mutación , PronósticoRESUMEN
BACKGROUND: Outcomes in children and adolescents with recurrent or progressive high-grade glioma are poor, with a historical median overall survival of 5.6 months. Pediatric high-grade gliomas are largely immunologically silent or "cold," with few tumor-infiltrating lymphocytes. Preclinically, pediatric brain tumors are highly sensitive to oncolytic virotherapy with genetically engineered herpes simplex virus type 1 (HSV-1) G207, which lacks genes essential for replication in normal brain tissue. METHODS: We conducted a phase 1 trial of G207, which used a 3+3 design with four dose cohorts of children and adolescents with biopsy-confirmed recurrent or progressive supratentorial brain tumors. Patients underwent stereotactic placement of up to four intratumoral catheters. The following day, they received G207 (107 or 108 plaque-forming units) by controlled-rate infusion over a period of 6 hours. Cohorts 3 and 4 received radiation (5 Gy) to the gross tumor volume within 24 hours after G207 administration. Viral shedding from saliva, conjunctiva, and blood was assessed by culture and polymerase-chain-reaction assay. Matched pre- and post-treatment tissue samples were examined for tumor-infiltrating lymphocytes by immunohistologic analysis. RESULTS: Twelve patients 7 to 18 years of age with high-grade glioma received G207. No dose-limiting toxic effects or serious adverse events were attributed to G207 by the investigators. Twenty grade 1 adverse events were possibly related to G207. No virus shedding was detected. Radiographic, neuropathological, or clinical responses were seen in 11 patients. The median overall survival was 12.2 months (95% confidence interval, 8.0 to 16.4); as of June 5, 2020, a total of 4 of 11 patients were still alive 18 months after G207 treatment. G207 markedly increased the number of tumor-infiltrating lymphocytes. CONCLUSIONS: Intratumoral G207 alone and with radiation had an acceptable adverse-event profile with evidence of responses in patients with recurrent or progressive pediatric high-grade glioma. G207 converted immunologically "cold" tumors to "hot." (Supported by the Food and Drug Administration and others; ClinicalTrials.gov number, NCT02457845.).
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Neoplasias Encefálicas/terapia , Glioma/terapia , Viroterapia Oncolítica , Adolescente , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapia , Niño , Preescolar , Terapia Combinada , Femenino , Glioma/diagnóstico por imagen , Glioma/patología , Glioma/radioterapia , Humanos , Estimación de Kaplan-Meier , Células Asesinas Naturales , Recuento de Leucocitos , Masculino , Viroterapia Oncolítica/efectos adversos , Linfocitos TRESUMEN
BACKGROUND: The aim of our study is to determine the incidence, timing, and risk factors for cerebral vasculopathy after cranial proton and photon radiation for pediatric brain tumors. METHODS: We performed a single-institution retrospective review of a cohort of children treated with proton radiation for brain tumors. MRA and/or MRI were reviewed for evidence of cerebral vascular stenosis and infarcts. Twenty-one similar studies (17 photon, 4 proton) were identified by systematic literature review. RESULTS: For 81 patients with median follow-up of 3 years, the rates of overall and severe vasculopathy were 9.9% and 6.2% respectively, occurring a median of 2 years post radiation. Dose to optic chiasm greater than 45 Gy and suprasellar location were significant risk factors. Results were consistent with 4 prior proton studies (752 patients) that reported incidence of 5% to 6.7%, 1.5 to 3 years post radiation. With significantly longer follow-up (3.7-19 years), 9 studies (1108 patients) with traditional photon radiation reported a higher rate (6.3%-20%) and longer time to vasculopathy (2-28 years). Significant risk factors were neurofibromatosis type 1 (NF-1; rate 7.6%-60%) and suprasellar tumors (9%-20%). In 10 studies with photon radiation (1708 patients), the stroke rate was 2% to 18.8% (2.3-24 years post radiation). CONCLUSIONS: Childhood brain tumor survivors need screening for vasculopathy after cranial radiation, especially with higher dose to optic chiasm, NF-1, and suprasellar tumors. Prospective studies are needed to identify risk groups, and ideal modality and timing, for screening of this toxicity.
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BACKGROUND: The goal of this study was to evaluate extent of surgical resection, and timing and volume of re-irradiation, on survival for children with locally recurrent ependymoma. METHODS: Children with locally recurrent ependymoma treated with a second course of fractionated radiotherapy (RT2) from 6 North American cancer centers were reviewed. The index time was from the start of RT2 unless otherwise stated. RESULTS: Thirty-five patients were included in the study. The median doses for first radiation (RT1) and RT2 were 55.8 and 54 Gy, respectively. Median follow-up time was 5.6 years. Median overall survival (OS) for all patients from RT2 was 65 months. Gross total resection (GTR) was performed in 46% and 66% of patients prior to RT1 and RT2, respectively. GTR prior to RT2 was independently associated with improved progression-free survival (PFS) for all patients (HR 0.41, P = 0.04), with an OS benefit (HR 0.26, P = 0.03) for infratentorial tumors. Median PFS was superior with craniospinal irradiation (CSI) RT2 (not reached) compared to focal RT2 (56.9 months; log-rank P = 0.03). All distant failures (except one) occurred after focal RT2. Local failures after focal RT2 were predominantly in patients with less than GTR pre-RT2. CONCLUSIONS: Patients with locally recurrent pediatric ependymoma should be considered for re-treatment with repeat maximal safe resection (ideally GTR) and CSI re-irradiation, with careful discussion of the potential side effects of these treatments.
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Importance: Suboptimal adherence to oral mercaptopurine treatment in children with acute lymphoblastic leukemia (ALL) increases the risk of relapse. A frequently expressed barrier to adherence is forgetfulness, which is often overcome by parental vigilance. Objective: To determine whether a multicomponent intervention, compared with education alone, will result in a higher proportion of patients with ALL who have mercaptopurine adherence rates 95% or higher, for all study participants and among patients younger than 12 years and vs those aged 12 years and older. Design, Setting, and Participants: The adherence intervention trial was an investigator-initiated, multi-institutional, parallel-group, unblinded, randomized clinical trial conducted between July 16, 2012, and August 8, 2018, at 59 Children's Oncology Group institutions in the US, enrolling patients with ALL diagnosed through age 21 years and receiving mercaptopurine for maintenance. The date of final follow-up was January 2, 2019. Data analysis was performed from February to October 2019. Interventions: Patients were randomized 1:1 to education alone or the intervention package, which consisted of education and personalized text message reminders daily to prompt directly supervised therapy. Four weeks of baseline adherence monitoring were followed with a 16-week intervention. Main Outcomes and Measures: The primary end point was the proportion of patients with adherence rates 95% or higher over the duration of the intervention for all study participants, and for those younger than 12 years vs those aged 12 years and older. Results: There were 444 evaluable patients (median age, 8.1 years; interquartile range, 5.3-14.3 years), including 230 in the intervention group and 214 in the education group. Three hundred two patients (68.0%) were boys, 180 (40.5%) were non-Hispanic White, 170 (38.3%) were Hispanic, 43 (9.7%) were African American, and 51 (11.5%) were Asian or of mixed race/ethnicity. The proportion of patients with adherence rates 95% or higher did not differ between the intervention vs education groups (65% vs 59%; odds ratio, 1.33; 95% CI, 1.0-2.0; P = .08). Exploratory analyses showed that among patients aged 12 years and older, those in the intervention group had higher mean (SE) adherence rates than those in the education group (93.1% [1.1%] vs 90.0% [1.3%]; difference, 3.1%; 95% CI, 0.1%-6.0%; P = .04). In particular, among patients aged 12 years and older with baseline adherence less than 90%, those in the intervention group had higher mean (SE) adherence rates than those in the education group (83.4% [2.5%] vs 74.6% [3.4%]; difference, 8.8%; 95% CI, 2.2%-15.4%; P = .008). No safety concerns were identified. Conclusions and Relevance: Although this multicomponent intervention did not result in an increase in the proportion of patients with ALL who had mercaptopurine adherence rates 95% or higher, it did identify a high-risk subpopulation to target for future adherence intervention strategies: adolescents with low baseline adherence. Trial Registration: ClinicalTrials.gov Identifier: NCT01503632.
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Terapia por Observación Directa , Cumplimiento de la Medicación/estadística & datos numéricos , Mercaptopurina/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Envío de Mensajes de Texto , Adolescente , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Masculino , Mercaptopurina/administración & dosificación , Educación del Paciente como AsuntoRESUMEN
PURPOSE: To study the efficacy and tolerability of valproic acid (VPA) and radiation, followed by VPA and bevacizumab in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG). METHODS: Children 3 to 21 years of age received radiation therapy and VPA at 15 mg/kg/day and dose adjusted to maintain a trough range of 85 to 115 µg/mL. VPA was continued post-radiation, and bevacizumab was started at 10 mg/kg intravenously biweekly, four weeks after completing radiation therapy. RESULTS: From September 2009 through August 2015, 20 DIPG and 18 HGG patients were enrolled (NCT00879437). During radiation and VPA, grade 3 or higher toxicities requiring discontinuation or modification of VPA dosing included grade 3 thrombocytopenia (1), grade 3 weight gain (1), and grade 3 pancreatitis (1). During VPA and bevacizumab, the most common grade 3 or higher toxicities were grade 3 neutropenia (3), grade 3 thrombocytopenia (3), grade 3 fatigue (3), and grade 3 hypertension (4). Two patients discontinued protocol therapy prior to disease progression (one grade 4 thrombosis and one grade 1 intratumoral hemorrhage). Median event-free survival (EFS) and overall survival (OS) for DIPG were 7.8 (95% CI 5.6-8.2) and 10.3 (7.4-13.4) months, and estimated one-year EFS was 12% (2%-31%). Median EFS and OS for HGG were 9.1 (6.4-11) and 12.1 (10-22.1) months, and estimated one-year EFS was 24% (7%-45%). Four patients with glioblastoma and mismatch-repair deficiency syndrome had EFS of 28.5, 16.7, 10.4, and 9 months. CONCLUSION: Addition of VPA and bevacizumab to radiation was well tolerated but did not appear to improve EFS or OS in children with DIPG or HGG.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Tronco Encefálico/terapia , Quimioradioterapia/mortalidad , Glioma Pontino Intrínseco Difuso/terapia , Adolescente , Adulto , Bevacizumab/administración & dosificación , Neoplasias del Tronco Encefálico/patología , Niño , Preescolar , Glioma Pontino Intrínseco Difuso/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Tasa de Supervivencia , Ácido Valproico/administración & dosificación , Adulto JovenRESUMEN
Patients with hemophilia suffer from repeated episodes of hemarthrosis leading to chronic inflammation and synovitis. Radiosynovectomy is an effective nonsurgical modality that can reduce inflammation, pain, and hemarthrosis in such cases. We describe an adolescent male with severe Hemophilia A, who developed arterial vasculitis and perivasculitis targeting the brachiocephalic, right common carotid, and right subclabvian arteries occurring within few days after difficult Phosphorus-32 radiosynovectomy, possibly as a complication of the procedure. Despite prophylaxis with recombinant FVIII therapy, he developed chronic synovitis and underwent radionuclide synovectomy with P-32 injection to the left ankle and right knee. Five days later, he developed pain in the lower right neck and right upper chest. Computed tomography and magnetic resonance imaging and angiography demonstrated inflammation involving the arteries of the right thoracic inlet. Geiger-Mueller meter indicated increased radioactivity not only in the left ankle and right knee but also in the right upper chest. Detection of radioisotope at the right thoracic inlet corresponding to the area of vasculitis was indicative of likely deposition of the P-32 isotope in an area exposed to maximum cardiac output and increased blood flow, leading to subclavian, carotid, and innominate arteritis with surrounding edema.
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The NAA10-NAA15 complex (NatA) is an N-terminal acetyltransferase that catalyzes N-terminal acetylation of ~40% of all human proteins. N-terminal acetylation has several different roles in the cell, including altering protein stability and degradation, protein localization and protein-protein interactions. In recent years several X-linked NAA10 variants have been associated with genetic disorders. We have identified a previously undescribed NAA10 c.215T>C p.(Ile72Thr) variant in three boys from two unrelated families with a milder phenotypic spectrum in comparison to most of the previously described patients with NAA10 variants. These boys have development delay, intellectual disability, and cardiac abnormalities as overlapping phenotypes. Functional studies reveal that NAA10 Ile72Thr is destabilized, while binding to NAA15 most likely is intact. Surprisingly, the NatA activity of NAA10 Ile72Thr appears normal while its monomeric activity is decreased. This study further broadens the phenotypic spectrum associated with NAA10 deficiency, and adds to the evidence that genotype-phenotype correlations for NAA10 variants are much more complex than initially anticipated.
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Cardiomiopatía Hipertrófica/genética , Discapacidades del Desarrollo/genética , Discapacidad Intelectual/genética , Acetiltransferasa A N-Terminal/genética , Acetiltransferasa E N-Terminal/genética , Fenotipo , Cardiomiopatía Hipertrófica/patología , Preescolar , Discapacidades del Desarrollo/patología , Estabilidad de Enzimas , Células HeLa , Humanos , Lactante , Discapacidad Intelectual/patología , Masculino , Mutación , Acetiltransferasa A N-Terminal/química , Acetiltransferasa A N-Terminal/metabolismo , Acetiltransferasa E N-Terminal/química , Acetiltransferasa E N-Terminal/metabolismo , Unión Proteica , SíndromeRESUMEN
A 5-year-old boy presented with worsening headaches for 3 months. On examination, he was found to have a hairless fatty tissue nevus of the scalp (nevus psiloliparus), subcutaneous soft tissue masses on the right side of his face, neck, mandible and right buttock and epibulbar dermoid of the right eye (choristoma) (). Magnetic resonance imaging revealed a large suprasellar mass, which was debulked and found to be a pilocytic astrocytoma. Testing was not performed for the BRAF/KIAA1549 fusion or BRAFV600E mutation. Seven years later, he was started on adjuvant chemotherapy for gradual tumor progression. Over the ensuing 3 years, he had further disease progression despite treatment with 3 frontline chemotherapy regimens: vinblastine, carboplatin/vincristine, and irinotecan/bevacizumab. Targeted sequencing of tissue from the right gluteal mass, revealed a mosaic activating FGFR1 c.1966A>G (p.Lys656Glu) mutation, absent in normal left gluteal tissue, confirming the diagnosis of encephalocraniocutaneous lipomatosis (ECCL), belonging to the family of RASopathies (including neurofibromatosis type I, Noonan syndrome, Costello syndrome), with constitutive activation of the mitogen-activated protein kinase (MAPK) pathway, and an increased risk of developing neoplasms. He was started on trametinib, a MEK inhibitor, off-label, targeting the MAPK pathway downstream from FGFR1, with stable tumor size at last follow-up, after 6 months on therapy.
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Oftalmopatías/diagnóstico , Lipomatosis/diagnóstico , Síndromes Neurocutáneos/diagnóstico , Astrocitoma/diagnóstico , Preescolar , Progresión de la Enfermedad , Oftalmopatías/diagnóstico por imagen , Oftalmopatías/genética , Humanos , Lipomatosis/diagnóstico por imagen , Lipomatosis/genética , Imagen por Resonancia Magnética , Masculino , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Síndromes Neurocutáneos/diagnóstico por imagen , Síndromes Neurocutáneos/genética , Piridonas/uso terapéutico , Pirimidinonas/uso terapéutico , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Resultado del TratamientoRESUMEN
[This corrects the article DOI: 10.1155/2017/3757423.].
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Chronic hyponatremia is very rare in children and is often seen in the setting of congestive heart failure or liver failure in adults. Here, we report an 8-year-old child with hypothalamic glioma who presented with severe hyponatremia. Initial management consisted of fluid restriction. This was very difficult for the child to follow and the child developed bizarre drinking habits requiring intervention from child psychiatry. So therapy was initiated with low dose V2 receptor antagonist under close inpatient monitoring. While initial response was reassuring, her sodium levels tended to drift down with longer duration of treatment requiring us to increase the dose frequently. Her response to therapy and her stable clinical situation off therapy suggest that she may have reset osmostat.
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While cancer is relatively rare in children under 20, it is the leading cause of disease-related death among children aged 5 to 14 years. We aimed to describe the incidence and survival of childhood cancer in Oklahoma from 1997-2012. We calculated age-adjusted incidence rates and five-year observed survival by cancer type using Oklahoma Central Cancer Registry and Surveillance, Epidemiology, and End Results program data among children diagnosed with cancer under the age of 20 from 1997-2012. The average annual age-adjusted incidence rate of childhood cancer was 168.9 per million for the US and 171.7 per million for Oklahoma. Overall, Oklahoma had lower survival from childhood cancer compared to the US (77.0% v. 80.6%). In recent years, research has been conducted on the epidemiology of childhood cancer. Little research has been done, however, on the incidence or survival of childhood cancer at state levels and none focused exclusively on Oklahoma.
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Supervivientes de Cáncer/estadística & datos numéricos , Neoplasias/epidemiología , Grupos Raciales/estadística & datos numéricos , Adolescente , Niño , Preescolar , Humanos , Incidencia , Lactante , Recién Nacido , Oklahoma/epidemiología , Sistema de Registros , Programa de VERF , Análisis de Supervivencia , Adulto JovenRESUMEN
Psychosocial distress is a salient construct experienced by families of children with newly diagnosed cancer, but little is known about parental appraisal of the child's illness and the subsequent impact this may have on child and parent functioning. The goal of the present study was to examine the interrelationships among multiple parent illness appraisals, parent adjustment outcomes, and parent-reported child quality of life in parents of children diagnosed with cancer. Parents completed measures of illness appraisal (illness uncertainty and attitude toward illness), parent adjustment (general distress, posttraumatic stress, parenting stress), and child quality of life (general and cancer-related). Path analysis revealed direct effects for parent illness uncertainty and illness attitudes on all 3 measures of parent adjustment. Illness uncertainty, but not illness attitudes, demonstrated a direct effect on parent-reported child general quality of life; parenting stress had direct effects on general and cancer-related quality of life. Exploratory analyses indicated that parent illness uncertainty and illness attitudes conferred indirect effects on parent-reported general and cancer-related quality of life through parenting stress. Negative parent illness appraisals appear to have adverse impacts on parents' psychosocial functioning and have implications for the well-being of their child with cancer.
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Neoplasias/psicología , Relaciones Padres-Hijo , Padres/psicología , Calidad de Vida , Estrés Psicológico , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , MasculinoRESUMEN
There is little evidence to guide the choice of chemotherapeutic agents for osseous metastases in medulloblastoma. Recently, triple therapy with temozolomide, irinotecan, and bevacizumab has been reported to have efficacy in recurrent medulloblastoma, and this regimen alone and in combination with other agents has been tested in several early-phase clinical trials. Here we report a 20-year-old woman with multiply-relapsed medulloblastoma with numerous osseous metastases 8 years after original diagnosis who responded dramatically to temozolomide, irinotecan, and bevacizumab therapy. This case highlights the potential for this regimen in treating osseous metastases in medulloblastoma.