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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 terapêutico , Neoplasias do Tronco Encefálico/terapia , Quimiorradioterapia/mortalidade , Glioma Pontino Intrínseco Difuso/terapia , Adolescente , Adulto , Bevacizumab/administração & dosagem , Neoplasias do Tronco Encefálico/patologia , Criança , Pré-Escolar , Glioma Pontino Intrínseco Difuso/patologia , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Taxa de Sobrevida , Ácido Valproico/administração & dosagem , Adulto JovemRESUMO
OBJECTIVE: To determine if maternal distress predicts child adjustment outcomes or if child adjustment outcomes predict maternal distress among children newly diagnosed with cancer, and if a parent-focused intervention has downstream effects on child adjustment. METHODS: Mothers (n = 52) were randomly assigned to a clinic-based, interdisciplinary intervention for parents of children newly diagnosed with cancer. Measures of maternal distress and child adjustment were collected at baseline, posttreatment, and follow-up. RESULTS: A lagged relationship was identified between maternal distress and child internalizing symptoms, but not externalizing symptoms. The parent intervention reduced child internalizing and externalizing symptoms at follow-up. Only the child internalizing symptoms effect was mediated by reduced maternal distress. The child externalizing symptoms effect was mediated by unobserved parent factors. CONCLUSIONS: This study provides support for illness adjustment and coping models that emphasize the role of parent factors in driving child adjustment outcomes and is encouraging for future parent-focused intervention research.
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Adaptação Psicológica/fisiologia , Transtornos do Comportamento Infantil/psicologia , Mães/psicologia , Neoplasias/psicologia , Estresse Psicológico/psicologia , Estresse Psicológico/terapia , Adolescente , Adulto , Atitude Frente a Saúde , Criança , Transtornos do Comportamento Infantil/complicações , Pré-Escolar , Feminino , Seguimentos , Humanos , Controle Interno-Externo , Masculino , Pessoa de Meia-Idade , Mães/estatística & dados numéricos , Neoplasias/complicações , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Estresse Psicológico/diagnóstico , Adulto JovemRESUMO
PURPOSE: Chemotherapy for relapsed medulloblastoma has been inadequate, and most patients succumb to disease. METHODS: We retrospectively reviewed nine cases of relapsed medulloblastoma treated with bevacizumab, irinotecan, ± temozolomide. Patients received one to three prior therapeutic regimens. Five patients received 10 mg/kg bevacizumab and 125-150 mg/m(2) irinotecan IV every 2 weeks, with temozolomide, starting at a median dose of 150 mg/m(2) orally for 5 days monthly. Two patients received bevacizumab and irinotecan, but not temozolomide, due to provider preference. Two of nine patients received 15 mg/kg bevacizumab IV, 90 mg/m(2) irinotecan orally for five consecutive days, 100 mg/m(2)/day temozolomide IV for 5 days, and 1.5 mg/m(2) vincristine IV, each administered every 21 days. RESULTS: Median time to progression was 11 months. Median overall survival was 13 months. Objective tumor response at 3 months was 67 %, including six patients with partial response (PR) and three patients with stable disease (SD). At 6 months, objective response was 55 %, with two patients with PR and three with complete response. Additionally, one patient had SD and three had PD. Two patients remain alive and progression free at 15 and 55 months; another is alive with disease at 20 months. Toxicities included two patients with grade III neutropenia, two with grade III thrombocytopenia, one with grade III elevation of liver function tests, and one patient with grade III diarrhea. CONCLUSIONS: The combination of bevacizumab and irinotecan, with or without temozolomide, produces objective responses with minimal toxicity in children with recurrent medulloblastoma. Prospective clinical trials are needed to evaluate the efficacy of this strategy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Meduloblastoma/tratamento farmacológico , Adolescente , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Criança , Pré-Escolar , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Lactente , Irinotecano , Masculino , Recidiva , Estudos Retrospectivos , Temozolomida , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the feasibility and acceptability of an interdisciplinary intervention for mothers of children newly diagnosed with cancer and to estimate effect sizes for the intervention in reducing distress. Management of illness uncertainty was a key framework for the intervention. METHODS: Mothers (N = 52) were randomly assigned to the intervention or a treatment as usual group, completing measures at baseline and follow-up time points. RESULTS: Mothers' satisfaction ratings were consistently high, and intervention implementation appeared feasible. Significant mean effects or trends in favor of the intervention group were found for pre-to-post change on measures of distress. Evidence of a preventative effect was also observed; mothers in the intervention group tended to improve or remain stable in their adjustment, whereas many parents in the treatment as usual group showed worsening outcomes. CONCLUSIONS: An interdisciplinary intervention targeting maternal illness uncertainty has clinical value within this sample.
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Adaptação Psicológica/fisiologia , Mães/psicologia , Neoplasias/psicologia , Psicoterapia/métodos , Estresse Psicológico/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Hospitais Pediátricos , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Estresse Psicológico/etiologia , Resultado do Tratamento , Adulto JovemRESUMO
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 , Criança , Humanos , Adulto Jovem , Adulto , Intervalo Livre de Progressão , Oklahoma , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Análise de Sobrevida , Recidiva , Intervalo Livre de DoençaRESUMO
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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BACKGROUND: The combination of irinotecan, temozolomide, and vincristine is appealing because of potentially synergistic mechanisms of action and non-overlapping toxicities. This phase I study was designed to determine the toxicity and maximum tolerated dose (MTD) of escalating daily protracted doses of irinotecan given in this combination. With extended accrual, we more fully explored the toxicity of multiple courses at the MTD. PROCEDURE: Patients under 22 years with recurrent or refractory solid tumors were eligible. A course of chemotherapy was given every 28 days. Cefpodoxime was given for diarrhea prophylaxis. Vincristine (1.5 mg/m2, max 2 mg) was given intravenously (IV) on days 1 and 8. Temozolomide (100 mg/m2/day) was given orally on days 1-5. Irinotecan was given IV over 1 hr on days 1-5 and 8-12. Dose escalation was done in the standard 3 + 3 cohort design, starting at 15 mg/m2/day. RESULTS: Twenty-five of 26 eligible patients were evaluable for toxicity and response. They received 111 courses (1-13, median 4). Dose limiting toxicity (DLT-pancreatitis, transaminitis) was seen in two of three patients at dose level 2 (20 mg/m2). No patients at level 1 had DLT during the first two cycles. Thus, the MTD of irinotecan in this combination is 15 mg/m2/day x 10 doses. Hematologic toxicity was mild and not prolonged. Grade 3 diarrhea was seen in five courses. Responses included two complete and two partial with 12 stable disease (SD) (median 6 months). CONCLUSIONS: This combination is safe and shows activity in pediatric patients with recurrent malignancy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Adolescente , Antibióticos Antineoplásicos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Criança , Pré-Escolar , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/análogos & derivados , Feminino , Humanos , Lactente , Irinotecano , Masculino , Dose Máxima Tolerável , Temozolomida , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto JovemRESUMO
PURPOSE: The current study sought to examine the relation of parental overprotection and perceived child vulnerability to parent-reported health-related quality of life in parents of children with cancer. METHODS: Parents (N = 89) of children who had been diagnosed with cancer completed measures of parental overprotection, perceived child vulnerability, and parent-proxy report of health-related quality of life. RESULTS: After controlling for theoretically relevant covariates, parental overprotection and perceived child vulnerability were both found to be significantly related to child health-related quality of life. Additional analyses revealed that perceived child vulnerability mediated the relationship between overprotective parenting behaviors and the child's health-related quality of life. CONCLUSION: The findings highlight the need to assess for these discrete parenting variables in parents of children with cancer and to develop interventions to target parental perceptions of vulnerability.
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Neoplasias , Relações Pais-Filho , Qualidade de Vida , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Nível de Saúde , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Inquéritos e Questionários , Populações Vulneráveis , Adulto JovemRESUMO
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 Diretamente Observada , Adesão à Medicação/estatística & dados numéricos , Mercaptopurina/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Envio de Mensagens de Texto , Adolescente , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Mercaptopurina/administração & dosagem , Educação de Pacientes como AssuntoRESUMO
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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BACKGROUND: Treatment of childhood brain tumors has often been associated with long-term cognitive morbidity in children. Our previous research identified age at diagnosis, polytherapy and brain radiation dose as treatment factors affecting neuropsychological outcome most strongly in children with cancer 1. Our current goal was to measure the change across different cognitive functions. PROCEDURE: This study examined the cognitive outcome over repeat testing in a heterogeneous sample of 18 children with brain tumors. Tumor types included medulloblastoma and glioma. ANOVA's for repeated measures were used to evaluate the changes in cognitive domains across follow-up evaluations. RESULTS: Consistent with previous findings, the most deleterious effects were seen on IQ indices of non verbal cognitive ability, visual perceptual skills and information processing speed. Analyses reveal that the attentional factor, Freedom from Distractibility, is the only IQ index that declines over subsequent testing. The statistical decline was attributable to a significant decline on the arithmetic subtest, as well as a non-significant trend for the auditory attention span subtest. CONCLUSIONS: This study reveals that while most indices remained stable over repeat testing, auditory attention and concentration skills decline. Long-term outcome is discussed in light of the high prevalence of attention and mathematic difficulties reported in these children and the need for preventive and remedial approaches.
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Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Neoplasias Encefálicas/psicologia , Transtornos Cognitivos/etiologia , Adolescente , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/terapia , Criança , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Testes PsicológicosRESUMO
Irinotecan is increasingly being used in pediatric oncology. Amelioration of diarrhea associated with protracted irinotecan administration may reduce morbidity and improve dose intensity. In this review, we discuss what is known about the pathogenesis of this toxicity as well as potential predisposing genetic factors. We comprehensively summarize the literature regarding available prevention and treatment strategies, and report data on the use of cephalosporin prophylaxis in 51 patients treated on various pediatric trials. This approach is feasible in children and allows for tolerance of higher doses of protracted irinotecan.
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Antineoplásicos Fitogênicos/efeitos adversos , Camptotecina/análogos & derivados , Diarreia/induzido quimicamente , Diarreia/prevenção & controle , Antineoplásicos Fitogênicos/uso terapêutico , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Cefalosporinas/uso terapêutico , Criança , Diarreia/genética , Predisposição Genética para Doença , Humanos , IrinotecanoRESUMO
BACKGROUND: To examine the relationship of self-reported parental overprotection, perceived child vulnerability, and parenting stress to parent-reported behavioral, emotional, and social adjustment of children currently on treatment for cancer. PROCEDURE: Parents of 62 children (34 boys, 28 girls) currently on treatment for cancer were recruited from an outpatient pediatric cancer clinic. Children ranged in age from 2 to 12 years; age at diagnosis ranged from 1.33 to 11.83 years. RESULTS: Higher levels of parenting stress, but not parental overprotection or perceived child vulnerability, were associated with poorer behavioral and social adjustment. Higher levels of perceived child vulnerability and parenting stress, but not parental overprotection, were independently associated with poorer emotional adjustment. CONCLUSIONS: Specific parenting variables appear to be related to specific adjustment outcomes in children with cancer. Longitudinal follow-up of these children is necessary to determine the developmental trajectory of parent variables and long-term child outcomes.
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Comportamento Infantil , Emoções , Neoplasias/psicologia , Relações Pais-Filho , Ajustamento Social , Estresse Psicológico/psicologia , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
Antiphospholipid antibodies (aPL) can cause thromboembolic events, but the reason for the thrombogenesis has not been fully elucidated. Studies show that the true pathogenic targets of aPL are plasma proteins involved in hemostasis (eg, beta(2)-glycoprotein I and prothrombin). These plasma proteins in turn bind to phospholipids, leading to the misclassification as "antiphospholipid" antibodies. The hemostatic system has abundant checks and balances to avoid excess hemorrhage and thrombosis. Thus, thrombosis requires more than interrupting one protein in the complex system. This review examines host genetic factors important in predisposition to thrombosis associated with aPL and concentrates on how antibodies in antiphospholipid syndrome interact with our natural anticoagulants and lead to thrombosis.
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Síndrome Antifosfolipídica/fisiopatologia , Trombose/fisiopatologia , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/genética , Hemostasia/imunologia , Humanos , Trombofilia/genética , Trombofilia/fisiopatologia , Trombose/tratamento farmacológico , Trombose/etiologiaRESUMO
[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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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.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/secundário , Neoplasias Cerebelares/tratamento farmacológico , Meduloblastoma/tratamento farmacológico , Bevacizumab/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Cerebelares/patologia , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Feminino , Humanos , Irinotecano , Meduloblastoma/secundário , Temozolomida , Adulto JovemRESUMO
BACKGROUND: Chronic subdural hematoma in the pediatric population often results from trauma. Asymptomatic and benign-appearing subdural collections are generally managed conservatively without operative intervention. Primary intracranial sarcomas are uncommon entities. Diagnosis of sarcoma can be difficult because these lesions often manifest as apparent hematoma. CASE DESCRIPTION: Presented is the case of a primary intracranial mucoid spindle cell sarcoma that arose in a child with a history of benign-appearing bilateral subdural fluid collections in the setting of nonaccidental trauma. The patient was initially managed conservatively because her neurological examination result was normal and her subdural collections decreased in size on repeated imaging. The collections did not resolve completely. Years later, she exhibited weakness, seizure, and an increase in the size of her subdural fluid collection. Subdural drainage was attempted without significant effect. Cytologic assessment of fluid was negative for malignant cells. Magnetic resonance imaging revealed multiple enhancing masses along the subdural collection. The patient eventually underwent craniotomy in which a diagnosis of sarcoma was obtained. Pathological and radiographic findings as well as oncological management are reviewed. The authors also review the natural history and treatment of primary intracranial sarcoma in the pediatric population. CONCLUSIONS: Early contrasted magnetic resonance imaging should be obtained in patients with subdural fluid collections that appear asymmetric or do not resolve in the expected time course, despite having a normal neurologic examination result. Negative cytologic assessment does not exclude sarcoma diagnosis.
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Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico , Hematoma Subdural Crônico/etiologia , Sarcoma/complicações , Sarcoma/diagnóstico , Neoplasias Encefálicas/cirurgia , Pré-Escolar , Feminino , Hematoma Subdural Crônico/diagnóstico , Hematoma Subdural Crônico/cirurgia , Humanos , Sarcoma/cirurgiaRESUMO
Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals [(Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05)], as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients.
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Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Iminas/uso terapêutico , Animais , Antineoplásicos/toxicidade , Benzenossulfonatos/toxicidade , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Proliferação de Células/efeitos dos fármacos , Criança , Decorina/metabolismo , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Iminas/toxicidade , Imuno-Histoquímica , Camundongos , Camundongos Nus , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sulfatases/metabolismo , Taxa de Sobrevida , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
PURPOSE: To report on a novel translocation related to a suprasellar primitive neuroectodermal tumor (sPNET) and retinoblastoma. DESIGN: Case report. METHODS: A 6-year-old girl underwent genetic testing after developing unilateral retinoblastoma subsequent to treatment (surgery, chemotherapy, and stem-cell rescue) for a sPNET found at 1 year of age. RESULTS: Genetic testing found the girl's karyotype to be 46,XX,t(11;13)(q21;q14.2); a novel translocation not previously reported in patients with either retinoblastoma or sPNET. CONCLUSIONS: Our patient had a novel translocation affecting the retinoblastoma 1 (RB1) gene, 46,XX,t(11;13)(q21;q14.2) resulting in the late development of unilateral retinoblastoma. Although she only developed unilateral retinoblastoma, her central nervous system was affected at a very early age. How her complex mutation resulted in retinoblastoma and antecedent sPNET remains unknown.