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1.
Br J Radiol ; 93(1107): 20190673, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31600082

RESUMO

OBJECTIVE: The Pediatric Proton/Photon Consortium Registry (PPCR) is a comprehensive data registry composed of pediatric patients treated with radiation. It was established to expedite outcomes-based research. The attributes which allow the PPCR to be a successful collaboration are reviewed. METHODS AND MATERIALS: Current eligibility criteria are radiotherapy patients < 22 years treated at one of the 15 US participating institutions. Detailed health and treatment data are collected about the disease presentation and treatment exposures, and annually thereafter, in REDCap (Research Electronic Data Capture). DICOM (Digital Imaging and Communications in Medicine) imaging and radiation plans are collected through MIM/MIMcloud. An optional patient-reported quality-of-life (PedsQL) study is administered at 10 sites. RESULTS: Accrual started October 2012 with 2,775 participants enrolled as of 25 July 2019. Most patients, 62.0%, were treated for central nervous system (CNS) tumors, the most common of which are medulloblastoma (n = 349), ependymoma (n = 309), and glial/astrocytoma tumors (n = 279). The most common non-CNS diagnoses are rhabdomyosarcoma (n = 284), Ewing's sarcoma (n = 153), and neuroblastoma (n = 130). While the majority of participants are US residents, 18.7% come from 36 other countries. Over 685 patients participate in the PedsQL study. CONCLUSIONS: The PPCR is a valuable research platform capable of answering countless research questions that will ultimately improve patient care. Centers outside of the USA are invited to participate directly or may engage with the PPCR to align data collection strategies to facilitate large-scale international research. ADVANCES IN KNOWLEDGE: For investigators looking to carry out research in a large pediatric oncology cohort or interested in registry work, this paper provides an updated overview of the PPCR.


Assuntos
Coleta de Dados/normas , Neoplasias/radioterapia , Fótons/uso terapêutico , Terapia com Prótons/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Adolescente , Astrocitoma/radioterapia , Neoplasias do Sistema Nervoso Central/radioterapia , Neoplasias Cerebelares/radioterapia , Criança , Pré-Escolar , Computação em Nuvem , Ependimoma/radioterapia , Feminino , Glioma/radioterapia , Humanos , Lactente , Cooperação Internacional , Masculino , Meduloblastoma/radioterapia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Autorrelato , Adulto Jovem
2.
Pediatr Blood Cancer ; 67(1): e28012, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31544362

RESUMO

BACKGROUND: Most childhood medulloblastoma (MB) cases are curable using multimodal treatment, including craniospinal irradiation (CSI). However, late effects are a serious problem for survivors. This prospective registry study evaluated Japanese patients to determine whether a reduced radiation dose was feasible. PATIENTS AND METHODS: Patients with MB were classified as an infant group (<3 years old) and a high-risk (HR) group (≥3 years old with metastasis). The HR group received intrathecal methotrexate (IT-MTX) and high-dose chemotherapy (HDC) using thiotepa and melphalan, as well as concomitant radiotherapy with a recommended CSI dose of 18 Gy and a total local dose of 50 Gy. Radiotherapy was only considered for infants if residual tumors were present after the HDC. RESULTS: Between 1997 and 2006, we identified 28 HR patients (M1: 9, M2/3: 19) and 17 infant patients (M0: 11, M1: 3, M2/3: 3). During the median follow-up of 9.4 years for the entire HR group, the 5-year progression-free survival (PFS) rate was 82.1 ± 7.2% and the 5-year overall survival (OS) rate was 85.7 ± 6.6%. Subanalyses of the patients who received the recommended treatment revealed that the 5-year PFS and OS rates were both 90.5 ± 6.4%. In the infant group, the 5-year PFS rate was 52.9 ± 12.1% and the 5-year OS rate was 51.8 ± 12.4%. There were no serious adverse events associated with the IT-MTX and HDC treatments. CONCLUSION: Intensified chemotherapy using HDC and IT-MTX might allow for a reduced prophylactic radiation dose in patients with MB with metastases. Further studies are needed to validate these findings.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Cerebelares/tratamento farmacológico , Meduloblastoma/tratamento farmacológico , Sistema de Registros/estatística & dados numéricos , Adolescente , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/radioterapia , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Terapia Combinada , Irradiação Craniana , Ciclofosfamida/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Injeções Espinhais , Masculino , Meduloblastoma/patologia , Meduloblastoma/radioterapia , Melfalan/administração & dosagem , Metotrexato/administração & dosagem , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
3.
Pediatr Blood Cancer ; 67(1): e28027, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571408

RESUMO

BACKGROUND: Radiotherapy boost to the entire posterior fossa (PF) is standard of care for high-risk (H-R) medulloblastoma patients; the utility of tumor bed (TB)-only boost is unclear. The purpose of this study was to examine the impact of PF versus TB boost volume on tumor control and survival in the H-R medulloblastoma population. METHODS: Single-institution records for patients with H-R medulloblastoma were reviewed. The median craniospinal irradiation dose was 36 Gy (range, 23.4-45 Gy), and boost doses to either PF or TB were 54 to 55.8 Gy. PF (local) failures were scored as in-field, marginal (between 80% and 95% isodose lines), or distant. Kaplan-Meier methods and Cox proportional hazards were used to assess the impact of radiation boost technique on local control (LC) and survival endpoints. RESULTS: Thirty-two patients with H-R medulloblastoma were treated between 1990 and 2015, with a median follow-up length of 5.12 years. Twenty-two patients received PF boost, and 10 received TB boost. Patient and disease characteristic were comparable between groups. A total of 11 PF failures occurred, including 3 isolated LFs (2 in the PF and 1 in the TB group). Most PF failures were in-field: three of four in the TB group and six of seven in the PF group; the remainder were marginal failures. TB boost was not associated with inferior LC (hazard ratio [HR] 0.86, log-rank P = 0.81) or overall survival (HR 1.40, P = 0.56) compared with PF boost. CONCLUSION: Reduced-volume radiotherapy boost to the TB does not appear to compromise LC or survival in patients with H-R medulloblastoma; it may reduce the risk of ototoxicity.


Assuntos
Neoplasias Cerebelares/mortalidade , Radiação Cranioespinal/mortalidade , Meduloblastoma/mortalidade , Carga Tumoral , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/radioterapia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Meduloblastoma/patologia , Meduloblastoma/radioterapia , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
5.
J Neurooncol ; 145(1): 107-114, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31468270

RESUMO

PURPOSE: Children with recurrent medulloblastoma have a poor prognosis. Re-irradiation is an option for some patients, but has not been well-studied in the era of molecular characterization for pediatric medulloblastoma. METHODS: This was a retrospective cohort study of 14 children age 18 years and younger at initial diagnosis with recurrent medulloblastoma, who received two or more courses of radiation therapy (RT). Molecular subgrouping was performed using nanoString and was available for nine patients. The primary study endpoint was overall survival. RESULTS: Re-irradiation (RT2) was directed at the supratentorial brain in six patients, infratentorial brain in one patient, and spine in seven patients. In addition, six patients received stem cell transplant as part of salvage therapy. Median OS for all patients was 12.4 months. One patient with recurrent Wnt-activated medulloblastoma remains alive with 154 months' survival; median survival was not reached for four patients with Group 4 disease, while three with Shh-activated disease had median survival of 2.2 months. A single patient with Group 3 disease died 4.3 months after RT2. Patients treated with RT2 to the spine for diffuse disease had poorer OS (p = 0.02), as compared to focal RT2 for intracranial recurrence. Distant failure, outside RT2 volumes, was the predominant pattern of recurrence after RT2. CONCLUSIONS: Re-irradiation for recurrent pediatric medulloblastoma can offer some patients disease control, particularly those with focally recurrent disease in the brain. Prospective studies are needed to confirm subgroups of patients who may benefit most from RT2.


Assuntos
Neoplasias Cerebelares/radioterapia , Meduloblastoma/radioterapia , Reirradiação/métodos , Terapia de Salvação , Adolescente , Adulto , Neoplasias Cerebelares/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Meduloblastoma/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
6.
BMJ Case Rep ; 12(7)2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31320371

RESUMO

We report the first clinical case on the successful use of proton beam therapy in the management of malignant transformation of intracranial epidermoid cyst. A 43-year-old man was initially diagnosed as this disease with left facial paresis, hypesthesia and hypoalgesia in the territories of the trigeminal nerve. After failure of surgical interventions, he was referred to our radiation centre. We performed a postoperative proton beam therapy for treatment. We delivered a total dose of 57 GyE in 31 fractions. He tolerated the treatment well with mild acute toxicities and remained healthy and functional by 2-year follow-up postradiotherapy. No evidence of delayed radiation-induced neurotoxicity was observed.


Assuntos
Cistos do Sistema Nervoso Central/radioterapia , Neoplasias Cerebelares/radioterapia , Cisto Epidérmico/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Adulto , Transformação Celular Neoplásica , Cistos do Sistema Nervoso Central/diagnóstico por imagem , Cistos do Sistema Nervoso Central/patologia , Cistos do Sistema Nervoso Central/cirurgia , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/cirurgia , Ângulo Cerebelopontino , Cisto Epidérmico/diagnóstico por imagem , Cisto Epidérmico/patologia , Cisto Epidérmico/cirurgia , Humanos , Imagem por Ressonância Magnética , Masculino , Procedimentos Neurocirúrgicos , Terapia com Prótons , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia
7.
Cancer Radiother ; 23(5): 370-377, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31331843

RESUMO

PUPOSE: Medulloblastoma is the most common primary malignant central nervous system tumor in childhood, accounting for 16-25% of cases (1). New treatment approaches have led to improved survival rates; however toxicities are still a major concern. PATIENTS AND METHODS: Participants were selected from the records of patients who were treated with craniospinal irradiation for medulloblastoma. Between January 2008 and December 2012, 62 patients were diagnosed with medulloblastoma at the national institute of oncology Rabat, 27 patients were still alive at the time of the study, of which n=16 patients were included in the study. The mean age of patients at the time of the study was 9.6 years. All children were treated with radiation therapy and chemotherapy, according to standard protocols. Median follow-up between treatment and evaluation was 4 years. All the children were assessed with the Wechsler Intelligence Scale for Children - fourth Edition (WISC-IV) three to five years after completion of radiotherapy. The test was administered by two well-trained psychologists in a distraction-free environment. The scoring was then reviewed by a psychologist from Brooklyn College. RESULTS: The mean standard score Full-Scale Intelligence Quotient (FSIQ) (M=63, SD=12.6) was found to be in the extremely low range and in the 1st percentile rank (PR), compared to the general population. All the measured primary index scales were below typical performance: verbal comprehension (M=67.7, SD=13.1), perceptual reasoning (M=63.5, SD=13.8) and processing speed (M=62.7, SD=15.5) were all found to be in the extremely low range, while xorking memory (M=75.5, SD=10.8) was found to be in the borderline range compared to the general population. To identify factors influencing the results, we performed both univariate and multivariate analyses. Age at the time of radiotherapy, initial clinical stage, total cranial radiotherapy dose, socioeconomic status, and the time of evaluation were identified as significantly impacting cognitive scores in the univariate analysis. In the multivariate analysis, only age at the time of radiotherapy and initial clinical stage remained factors significantly impacting cognitive outcomes with P=0.001 and P<0.001 respectively. CONCLUSION: Our study is evidence that tremendous efforts are still to be made in low-income countries to correctly measure neurocognitive dysfunction in medulloblastoma survivors and to prepare those patients to a typical life after the completion of treatment.


Assuntos
Neoplasias Cerebelares/radioterapia , Irradiação Craniana/efeitos adversos , Meduloblastoma/radioterapia , Transtornos Neurocognitivos/etiologia , Fatores Etários , Antineoplásicos/uso terapêutico , Neoplasias Cerebelares/tratamento farmacológico , Criança , Pré-Escolar , Terapia Combinada , Seguimentos , Substância Cinzenta/lesões , Substância Cinzenta/patologia , Hipocampo/lesões , Hipocampo/patologia , Humanos , Meduloblastoma/tratamento farmacológico , Transtornos da Memória/etiologia , Transtornos da Memória/patologia , Transtornos Neurocognitivos/patologia , Tamanho do Órgão , Modelos de Riscos Proporcionais , Escalas de Wechsler , Substância Branca/lesões , Substância Branca/patologia
8.
J Neurooncol ; 144(2): 283-291, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31236820

RESUMO

PURPOSE: To report outcomes of salvage re-irradiation (re-RT) in recurrent/progressive medulloblastoma (MB). METHODS: Medical records of patients treated with curative-intent re-RT as multi-modality management for recurrent/progressive MB between 2008 and 2018 were analyzed retrospectively. RESULTS: A total of 28 patients (median age 18 years at index diagnosis) were included. Molecular subgrouping was done using real-time reverse transcriptase polymerase chain reaction (RT-PCR) based on the differential expression of select set of 12 protein coding genes and 9 microRNAs. Fifteen of 17 (88%) patients with sonic hedgehog (SHH)-MB developed isolated local recurrence within the index tumor-bed, while 5 of 7 (72%) patients with Group 4 MB developed localized relapse outside the posterior fossa. Diffuse neuraxial dissemination was seen in 2 patients with SHH-MB, and one each of Group 4 and wingless (WNT)-MB. Molecular subgrouping was not known in 3 patients. The dose and volume of re-RT was based on site and patterns of relapse, comprising unifocal in 18 (64%), multi-focal in 3 (11%), and repeat craniospinal irradiation (re-CSI) in 7 (25%) patients. Median interval from primary irradiation to re-RT was 49.5 months (range 24-98 months) with median cumulative biologically effective dose of 117 Gy (range 78-132 Gy). All patients received platinum-based salvage chemotherapy either before or after re-RT. One patient developed symptomatic radiation necrosis following re-CSI. At a median follow-up of 24 months (range 6-84 months), 2-year post-re-RT progression-free survival (PFS) and overall survival (OS) was 46% and 51% respectively. Younger age (< 18 years) at index diagnosis, primary risk stratification (standard-risk) and molecular subgrouping (Group 4) were associated with significantly better post-re-RT outcomes. CONCLUSION: Salvage re-RT provides good local control and encouraging survival outcomes with acceptable toxicity in selected patients with recurrent/progressive MB.


Assuntos
Neoplasias Cerebelares/mortalidade , Meduloblastoma/mortalidade , Recidiva Local de Neoplasia/mortalidade , Reirradiação/mortalidade , Medição de Risco/métodos , Terapia de Salvação , Adolescente , Adulto , Fatores Etários , Neoplasias Cerebelares/classificação , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/radioterapia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Meduloblastoma/classificação , Meduloblastoma/patologia , Meduloblastoma/radioterapia , Recidiva Local de Neoplasia/classificação , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
9.
Folia Neuropathol ; 57(1): 80-86, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038191

RESUMO

We hereby report a case of a 10-year-old girl in whom neurosurgery was performed for cerebellar vermis medulloblastoma in April 2000. After resection the patient underwent chemotherapy followed by radiotherapy, receiving 53.07 Gy to posterior fossa and 35.07 Gy to the rest of the craniospinal axis. In 2012, she was diagnosed with anaplastic astrocytoma, which was located within the high-dose region. Surgical resection of the tumour was performed. Postoperatively, the patient received radiation therapy (50.4 Gy) with concurrent temozolomide, followed by 6 cycles of adjuvant temozolomide. Five years after the diagnosis of anaplastic astrocytoma, the patient remains asymptomatic.


Assuntos
Astrocitoma/etiologia , Neoplasias Encefálicas/etiologia , Neoplasias Cerebelares/radioterapia , Meduloblastoma/radioterapia , Neoplasias Induzidas por Radiação , Criança , Irradiação Craniana/efeitos adversos , Feminino , Humanos
10.
World Neurosurg ; 128: 230-233, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31082554

RESUMO

BACKGROUND: Pilocytic astrocytoma is a benign glial tumor typically presenting in children. It is rare for adults to present with pilocytic astrocytoma and even less likely to manifest with multiple foci of lesions especially in nonoptic or hypothalamic locations. CASE DESCRIPTION: Our patient was a 37-year old man presenting with varied cranial neuropathies, cerebellar dysfunction, and long tract signs, with imaging demonstrating 3 discrete ill-defined contrast-enhancing lesions affecting the cerebellar peduncles, brainstem, and cervicomedullary junction. Neuronavigation-guided biopsy confirmed World Health Organization grade 1 pilocytic astrocytoma; the patient was treated with radiotherapy. CONCLUSIONS: To our knowledge, we believe this is the first reported case with multifocal infratentorial pilocytic astrocytoma on presentation in an adult patient in the absence of a prior history of associated risk factors such as neurofibromatosis 1 or chemoradiotherapeutic intervention.


Assuntos
Astrocitoma/diagnóstico por imagem , Neoplasias Infratentoriais/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Adulto , Astrocitoma/patologia , Astrocitoma/radioterapia , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/radioterapia , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/radioterapia , Humanos , Biópsia Guiada por Imagem , Neoplasias Infratentoriais/patologia , Neoplasias Infratentoriais/radioterapia , Imagem por Ressonância Magnética , Masculino , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/radioterapia , Neuronavegação , Radioterapia
11.
World Neurosurg ; 128: e835-e840, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31082560

RESUMO

OBJECTIVE: Meningeal melanocytomas of the central nervous system are extremely rare, with an incidence of 1 per 10 million individuals. Cases of primary cerebellopontine angle melanocytoma (PCPAM) have only been described in single case reports. The goal of the present study was to analyze the surgical management of PCPAM, with a particular focus on early and late treatment outcomes and recurrence rates. METHODS: The patients who had undergone surgery for PCPAM from January 2004 to May 2018 were identified by a local database query. The patients were evaluated for initial symptoms, pre- and postoperative facial and cochlear nerve function, complications, and recurrence rate by reviewing the patients' medical records. RESULTS: We identified 4 patients with PCPAM of >1500 cerebellopontine angle lesions (∼0.2%) that had been surgically treated at our department in the past 14 years. Of the 4 patients, 2 were men and 2 were women, with a mean age of 47 years. Anatomical facial and cochlear nerve preservation was achieved in all 4 patients. One patient experienced a new moderate facial palsy immediately after surgery (House-Brackmann grade III). Of the 4 patients, 3 had undergone radiotherapy and 1 had undergone ion beam therapy for tumor recurrence (6 years after surgery). Of the 4 patients, 3 had presented with tumor recurrence at 2, 3, and 6 years of follow-up respectively. The long-term follow-up examination had not yet been conducted for 1 patient. CONCLUSIONS: At long-term follow-up, 3 patients had developed recurrence. Because of the high recurrence rate of PCPAM, we believe that radiotherapy in addition to surgery should be considered in the future to avoid early recurrence.


Assuntos
Neoplasias Cerebelares/cirurgia , Ângulo Cerebelopontino/cirurgia , Neurocitoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adulto , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/radioterapia , Nervo Coclear , Terapia Combinada , Nervo Facial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neurocitoma/patologia , Neurocitoma/radioterapia , Resultado do Tratamento
12.
Strahlenther Onkol ; 195(9): 843-850, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31025053

RESUMO

PURPOSE: Pediatric radiotherapy (RT) is a highly specialized field, requiring great experience to delineate correctly tumor targets and organs at risk. To reduce treatment failures related to planning inaccuracies and to obtain robust clinical results despite the limited numbers of enrolled pediatric patients, the SIOP PNET5MB clinical trial on medulloblastoma requires a real-time, pre-radiation review of the RT treatment (craniospinal irradiation and boost plan) under the direct responsibility of the national coordinator center. Here we describe the centralized radiotherapy quality assurance (QA) program developed in Italy for this purpose. METHODS: Using the software package VODCA (MSS, Hagendorn, Switzerland, www.vodca.ch ), we developed a cloud platform able to handle computed tomography (CT) images and RT objects and to support the complete workflow required by the review process in the context of the SIOP PNET5 trial. RESULTS: All Italian centers participating in the PNET5 trial adopted the proposed QA system. 24 patients were successfully enrolled and reviewed. For 15 patients (62.5%), one or more plan revisions were requested for the craniospinal irradiation plan and for 11 patients (45.8%) plan revisions were requested for the boost. RT was delivered after the plan was centrally approved for all enrolled patients. So far, in Italy, no patients have been excluded from PNET5 due to dosimetric incompliance to the protocol or for exceeding the RT starting time limit. CONCLUSION: The cloud platform successfully supported the trial workflow, producing official review documents. This efficient QA was crucial to guarantee optimized treatments and protocol compliance for all pediatric patients enrolled in the SIOP protocol.


Assuntos
Neoplasias Cerebelares/radioterapia , Computação em Nuvem , Meduloblastoma/radioterapia , Tumores Neuroectodérmicos Primitivos/radioterapia , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Especialização , Criança , Humanos , Órgãos em Risco/efeitos da radiação , Radiometria , Planejamento da Radioterapia Assistida por Computador/métodos , Design de Software , Fluxo de Trabalho
13.
Acta Neurochir (Wien) ; 161(2): 343-349, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30652202

RESUMO

BACKGROUND: Hemangioblastomas (HB) are benign tumors of the central nervous system (CNS) that can appear sporadic or as part of von Hippel-Lindau (VHL) disease. It is often curable with surgical resection, but upon relapse, the disease exhibits a treatment-refractory course. CASE REPORT: A patient treated for sporadic cerebellar HB relapsed 12 years post-surgery. She developed disseminated disease throughout the CNS, including leptomeningeal manifestations. Repeat surgery and craniospinal radiation therapy were unsuccessful. CONCLUSION: This case is in line with previous publications on disseminated non-VHL HB. Available treatment options are inefficient, emphasizing the need for improved understanding of HB biology to identify therapeutic targets.


Assuntos
Neoplasias Cerebelares/cirurgia , Hemangioblastoma/cirurgia , Doença de von Hippel-Lindau/patologia , Adulto , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/radioterapia , Diagnóstico Diferencial , Feminino , Hemangioblastoma/patologia , Hemangioblastoma/radioterapia , Humanos , Metástase Neoplásica , Doença de von Hippel-Lindau/genética
14.
J Neurooncol ; 141(2): 403-411, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30467812

RESUMO

PURPOSE: Advantages to computerized cognitive assessment include increased precision of response time measurement and greater availability of alternate forms. Cogstate is a computerized cognitive battery developed to monitor attention, memory, and processing speed. Although the literature suggests the domains assessed by Cogstate are areas of deficit in children undergoing treatment for medulloblastoma, the validity of Cogstate in this population has not been previously investigated. METHODS: Children participating in an ongoing prospective trial of risk-adapted therapy for newly diagnosed medulloblastoma (n = 73; mean age at baseline = 12.1 years) were administered Cogstate at baseline (after surgery, prior to adjuvant therapy) and 3 months later (6 weeks after completion of radiation therapy). Gold-standard neuropsychological measures of similar functions were administered at baseline. RESULTS: Linear mixed models revealed performance within age expectations at baseline across Cogstate tasks. Following radiation therapy, there was a decline in performance on Cogstate measures of reaction time (Identification and One Back). Females exhibited slower reaction time on One Back and Detection tasks at baseline. Higher-dose radiation therapy and younger age were associated with greater declines in performance. Pearson correlations revealed small-to-moderate correlations between Cogstate reaction time and working memory tasks with well-validated neuropsychological measures. CONCLUSIONS: Cogstate is sensitive to acute cognitive effects experienced by some children with medulloblastoma and demonstrates associations with clinical predictors established in the literature. Correlations with neuropsychological measures of similar constructs offer additional evidence of validity. The findings provide support for the utility of Cogstate in monitoring acute cognitive effects in pediatric cancer.


Assuntos
Neoplasias Cerebelares/psicologia , Neoplasias Cerebelares/radioterapia , Disfunção Cognitiva/diagnóstico , Irradiação Craniana/efeitos adversos , Diagnóstico por Computador , Meduloblastoma/psicologia , Meduloblastoma/radioterapia , Testes Neuropsicológicos , Adolescente , Adulto , Neoplasias Cerebelares/complicações , Criança , Pré-Escolar , Disfunção Cognitiva/etiologia , Feminino , Humanos , Masculino , Meduloblastoma/complicações , Tempo de Reação , Software , Adulto Jovem
15.
Int J Radiat Oncol Biol Phys ; 103(3): 728-737, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30366006

RESUMO

PURPOSE: Craniospinal irradiation (CSI) is a crucial component of treatment for medulloblastoma (MB), a brain tumor clinically stratified into prognostically distinct molecular subgroups. Preclinical models of clinically relevant CSI offer the potential to study radiation dose and volume effects in these subgroups and to identify subgroup-specific combination adjuvant therapies, particularly for very-high-risk MB in which treatments are often unsuccessful. METHODS AND MATERIALS: The commercially available Small Animal Radiation Research Platform equipped with a motorized variable collimator was used for image-guided CSI. Mice were implanted in brain cortices with patient-derived orthotopic xenografts (PDOXs) of very-high-risk Group 3 (G3) or Sonic Hedgehog (SHH) MB and were treated with fully fractionated CSI at 2 Gy/fraction for a cumulative 36 Gy. Radiation therapy dose response effects on tumor burden and overall survival were assessed. The pattern of treatment failure was determined using bioluminescence and then confirmed histologically. Acute toxicity was appraised by body weight measurements and blood work. RESULTS: We established an accurate and efficient preclinical protocol to administer CSI reproducibly to mice harboring MB. CSI improved the survival of mice bearing very-high-risk G3 or SHH MB PDOXs. However, radiation therapy dose responses across models suggested significant radio-responsiveness to conventionally fractionated CSI ≥20 Gy. CSI was well tolerated; mice had no significant changes in body weight, and acute leukopenia developed but resolved soon after therapy completion. CONCLUSIONS: Our protocol for preclinical CSI delivery was effective and well tolerated, and it can be readily integrated into preclinical pipelines for MB and other central nervous system-seeding tumors.


Assuntos
Neoplasias Cerebelares/radioterapia , Irradiação Craniana/métodos , Radiação Cranioespinal/métodos , Meduloblastoma/radioterapia , Radioterapia Guiada por Imagem/métodos , Animais , Peso Corporal , Encéfalo/patologia , Encéfalo/efeitos da radiação , Modelos Animais de Doenças , Luminescência , Camundongos , Camundongos Endogâmicos NOD , Camundongos Nus , Recidiva Local de Neoplasia , Transplante de Neoplasias , Doses de Radiação , Lesões por Radiação/etiologia , Radioterapia , Dosagem Radioterapêutica
16.
Pract Radiat Oncol ; 9(1): e22-e28, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30036592

RESUMO

PURPOSE: This study aimed to evaluate the impact on spine growth in children with medulloblastoma using either photon or electron craniospinal irradiation (CSI). METHODS AND MATERIALS: This was a single institution retrospective review of children who were treated with CSI for medulloblastoma. Spine growth was measured on magnetic resonance imaging scans at defined locations on the basis of a published predictive model of spine growth after CSI. Differences between spine growth in the anterior, middle, and posterior aspect of the designated vertebral segments were also assessed. Differences between the groups treated with photons or electrons were assessed with student's t test. RESULTS: A total of 19 patients (10 patients treated with electrons and 9 with photons) with a median follow-up time of 45.5 months (confidence interval, 34.9-55.1 months) were evaluated. Patients treated with electrons were younger than those who received photons (5.1 years [range, 3.8-9.0 years] vs 9.6 years [range, 3.5-12.9 years]); however, there were no differences in other clinical characteristics, treatment, or follow-up between the groups. Spine growth rate for patients treated with electrons fit the predictive model (104% ± 5.2%), but patients treated with photons had growth that was faster than predicted by the model (150% ± 47%) and different from that observed with electrons. The differences between treatment the modalities were statistically significant (P = .03). For patients treated with photons, there were no statistical differences between the growth rate of the anterior vertebral body compared with the posterior aspect, but for patients treated with electrons, a faster spine growth in the anterior L1-L5 lumbar spine was observed compared with the posterior lumbar spine (3.90 vs 2.52 mm/year; P = .006) without differences in the cervical or thoracic spine. CONCLUSIONS: The use of electrons to treat the craniospinal axis in children with medulloblastoma resulted in no significant difference in spine growth compared with the predicted spine growth on the basis of previously published models using photons, but with a clinically insignificant faster spine growth rate in the anterior lumbar spine.


Assuntos
Neoplasias Cerebelares/radioterapia , Radiação Cranioespinal , Elétrons , Meduloblastoma/radioterapia , Órgãos em Risco/efeitos da radiação , Fótons , Coluna Vertebral/patologia , Adolescente , Neoplasias Cerebelares/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Meduloblastoma/patologia , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Coluna Vertebral/efeitos da radiação
17.
Lancet Oncol ; 19(12): 1602-1616, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30392813

RESUMO

BACKGROUND: Most children with medulloblastoma fall within the standard-risk clinical disease group defined by absence of high-risk features (metastatic disease, large-cell/anaplastic histology, and MYC amplification), which includes 50-60% of patients and has a 5-year event-free survival of 75-85%. Within standard-risk medulloblastoma, patients in the WNT subgroup are established as having a favourable prognosis; however, outcome prediction for the remaining majority of patients is imprecise. We sought to identify novel prognostic biomarkers to enable improved risk-adapted therapies. METHODS: The HIT-SIOP PNET 4 trial recruited 338 patients aged 4-21 years with medulloblastoma between Jan 1, 2001, and Dec 31, 2006, in 120 treatment institutions in seven European countries to investigate hyperfractionated radiotherapy versus standard radiotherapy. In this retrospective analysis, we assessed the remaining tumour samples from patients in the HIT-SIOP PNET 4 trial (n=136). We assessed the clinical behaviour of the molecularly defined WNT and SHH subgroups, and identified novel independent prognostic markers and models for standard-risk patients with non-WNT/non-SHH disease. Because of the scarcity and low quality of available genomic material, we used a mass spectrometry-minimal methylation classifier assay (MS-MIMIC) to assess methylation subgroup and a molecular inversion probe array to detect genome-wide copy number aberrations. Prognostic biomarkers and models identified were validated in an independent, demographically matched cohort (n=70) of medulloblastoma patients with non-WNT/non-SHH standard-risk disease treated with conventional therapies (maximal surgical resection followed by adjuvant craniospinal irradiation [all patients] and chemotherapy [65 of 70 patients], at UK Children's Cancer and Leukaemia Group and European Society for Paediatric Oncology (SIOPE) associated treatment centres between 1990 and 2014. These samples were analysed by Illumina 450k DNA methylation microarray. HIT-SIOP PNET 4 is registered with ClinicalTrials.gov, number NCT01351870. FINDINGS: We analysed methylation subgroup, genome-wide copy number aberrations, and mutational features in 136 assessable tumour samples from the HIT-SIOP PNET 4 cohort, representing 40% of the 338 patients in the trial cohort. This cohort of 136 samples consisted of 28 (21%) classified as WNT, 17 (13%) as SHH, and 91 (67%) as non-WNT/non-SHH (we considered Group3 and Group4 medulloblastoma together in our analysis because of their similar molecular and clinical features). Favourable outcomes for WNT tumours were confirmed in patients younger than 16 years, and all relapse events in SHH (four [24%] of 17) occurred in patients with TP53 mutation (TP53mut) or chromosome 17p loss. A novel whole chromosomal aberration signature associated with increased ploidy and multiple non-random whole chromosomal aberrations was identified in 38 (42%) of the 91 samples from patients with non-WNT/non-SHH medulloblastoma in the HIT-SIOP PNET 4 cohort. Biomarkers associated with this whole chromosomal aberration signature (at least two of chromosome 7 gain, chromosome 8 loss, and chromosome 11 loss) predicted favourable prognosis. Patients with non-WNT/non-SHH medulloblastoma could be reclassified by these markers as having favourable-risk or high-risk disease. In patients in the HIT-SIOP PNET4 cohort with non-WNT/non-SHH medulloblastoma, with a median follow-up of 6·7 years (IQR 5·8-8·2), 5-year event-free survival was 100% in the favourable-risk group and 68% (95% CI 57·5-82·7; p=0·00014) in the high-risk group. In the validation cohort, with a median follow-up of 5·6 years (IQR 3·1-8·1), 5-year event-free survival was 94·7% (95% CI 85·2-100) in the favourable-risk group and 58·6% (95% CI 45·1-76·1) in the high-risk group (hazard ratio 9·41, 95% CI 1·25-70·57; p=0·029). Our comprehensive molecular investigation identified subgroup-specific risk models which allowed 69 (51%) of 134 accessible patients from the standard-risk medulloblastoma HIT-SIOP PNET 4 cohort to be assigned to a favourable-risk group. INTERPRETATION: We define a whole chromosomal signature that allows the assignment of non-WNT/non-SHH medulloblastoma patients normally classified as standard-risk into favourable-risk and high-risk categories. In addition to patients younger than 16 years with WNT tumours, patients with non-WNT/non-SHH tumours with our defined whole chromosomal aberration signature and patients with SHH-TP53wild-type tumours should be considered for therapy de-escalation in future biomarker-driven, risk-adapted clinical trials. The remaining subgroups of patients with high-risk medulloblastoma might benefit from more intensive therapies. FUNDING: Cancer Research UK, Swedish Childhood Cancer Foundation, French Ministry of Health/French National Cancer Institute, and the German Children's Cancer Foundation.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Cerebelares/genética , Aberrações Cromossômicas , Cromossomos Humanos/genética , Meduloblastoma/genética , Técnicas de Diagnóstico Molecular , Adolescente , Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/mortalidade , Neoplasias Cerebelares/radioterapia , Criança , Pré-Escolar , Variações do Número de Cópias de DNA , Metilação de DNA , Fracionamento da Dose de Radiação , Europa (Continente) , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Meduloblastoma/diagnóstico , Meduloblastoma/mortalidade , Meduloblastoma/terapia , Estudos Multicêntricos como Assunto , Mutação , Fenótipo , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
19.
BMJ Case Rep ; 20182018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30068577

RESUMO

We report a case of a 63-year-old woman who was presented to the emergency department with an occipital haemorrhage secondary to a pancreatic cerebral metastasis. Pancreatic cancer is the ninth most common cancer in women in Australia, and distant disease is present in 70% of patients with pancreatic cancer at the time of diagnosis. However, metastases to the brain are rare, accounting for only 0.33%-0.57% cases antemortem. Herein, we discuss the management of this unusual case to highlight the importance of recognising unusual central nervous system involvement of cancers, a problem which may be increasing in prevalence.


Assuntos
Neoplasias Cerebelares/secundário , Hemorragia Cerebral/patologia , Irradiação Craniana , Lobo Occipital/patologia , Neoplasias Pancreáticas/patologia , Anorexia/etiologia , Neoplasias Cerebelares/complicações , Neoplasias Cerebelares/radioterapia , Hemorragia Cerebral/etiologia , Evolução Fatal , Feminino , Cefaleia/etiologia , Humanos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/terapia , Radioterapia Adjuvante , Tomografia Computadorizada por Raios X
20.
J Neurosci ; 38(38): 8251-8261, 2018 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-30126966

RESUMO

Medulloblastomas, the most common malignant brain tumor in children, are typically treated with radiotherapy. Refinement of this treatment has greatly improved survival rates in this patient population. However, radiotherapy also profoundly affects the developing brain and is associated with reduced hippocampal volume and blunted hippocampal neurogenesis. Such hippocampal (as well as extrahippocampal) abnormalities likely contribute to cognitive impairments in this population. While several aspects of memory have been examined in this population, the impact of radiotherapy on autobiographical memory has not previously been evaluated. Here we evaluated autobiographical memory in male and female patients who received radiotherapy for posterior fossa tumors (PFTs), including medulloblastoma, during childhood. Using the Children's Autobiographical Interview, we retrospectively assessed episodic and nonepisodic details for events that either preceded (i.e., remote) or followed (i.e., recent) treatment. For post-treatment events, PFT patients reported fewer episodic details compared with control subjects. For pretreatment events, PFT patients reported equivalent episodic details compared with control subjects. In a range of conditions associated with reduced hippocampal volume (including medial temporal lobe amnesia, mild cognitive impairment, Alzheimer's disease, temporal lobe epilepsy, transient epileptic amnesia, frontal temporal dementia, traumatic brain injury, encephalitis, and aging), loss of episodic details (even in remote memories) accompanies hippocampal volume loss. It is therefore surprising that pretreatment episodic memories in PFT patients with reduced hippocampal volume are retained. We discuss these findings in light of the anterograde and retrograde impact on memory of experimentally suppressing hippocampal neurogenesis in rodents.SIGNIFICANCE STATEMENT Pediatric medulloblastoma survivors develop cognitive dysfunction following cranial radiotherapy treatment. We report that radiotherapy treatment impairs the ability to form new autobiographical memories, but spares preoperatively acquired autobiographical memories. Reductions in hippocampal volume and cortical volume in regions of the recollection network appear to contribute to this pattern of preserved preoperative, but impaired postoperative, memory. These findings have significant implications for understanding disrupted mnemonic processing in the medial temporal lobe memory system and in the broader recollection network, which are inadvertently affected by standard treatment methods for medulloblastoma tumors in children.


Assuntos
Neoplasias Cerebelares/psicologia , Irradiação Craniana/efeitos adversos , Hipocampo/efeitos da radiação , Meduloblastoma/psicologia , Memória Episódica , Rememoração Mental/efeitos da radiação , Adolescente , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/radioterapia , Criança , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Meduloblastoma/diagnóstico por imagem , Meduloblastoma/radioterapia , Testes Neuropsicológicos , Tamanho do Órgão , Estudos Retrospectivos
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