RESUMO
Curative therapies for Ewing sarcoma have been developed within cooperative groups. Consecutive clinical trials have systematically assessed the impact and timing of local therapy and the activity of cytotoxic drugs and their combinations. They have led to an increase of long-term disease-free survival to around 70% in patients with localized disease. Translational research in ES remains an area in which interdisciplinary and international cooperation is essential for future progress. This article reviews current state-of-the art therapy, with a focus on trials performed in Europe, and summarizes novel strategies to further advance both the cure rates and quality of survival.
Assuntos
Neoplasias Ósseas/terapia , Comportamento Cooperativo , Comunicação Interdisciplinar , Sarcoma de Ewing/terapia , Neoplasias de Tecidos Moles/terapia , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Ósseas/mortalidade , Criança , Ensaios Clínicos como Assunto , Terapia Combinada , Progressão da Doença , Humanos , Terapia Neoadjuvante , Osteotomia , Radioterapia Adjuvante , Sarcoma de Ewing/mortalidade , Neoplasias de Tecidos Moles/mortalidade , Taxa de SobrevidaRESUMO
Teenagers and young adults (TYA) cancer contributes substantially to morbidity and mortality in a population with much to offer society. TYA place distinct challenges upon cancer care services, many reporting feeling marginalized and their needs not being met in adult or paediatric cancer services. Bone tumours such as osteosarcoma and Ewing sarcoma, because of their age at presentation and the complexity of their care, are where challenges in managing (TYA) with cancer have often been most readily apparent. Bone sarcomas may be managed by paediatric or medical oncologists, and require fastidious attention to protocol. A lack of recent improvement in survival in TYA with bone tumours may be linked to a lack of specialist care, poor concordance with therapy in some situations and TYA-specific pharmacology. Participation in clinical trials, particularly of young adults, is low, hindering progress. All these requirements may be best met by a concerted effort to create collaborative care between adult and paediatric experts in bone sarcoma, working together to meet TYA patients' needs.
Assuntos
Neoplasias Ósseas , Osteossarcoma , Adolescente , Adulto , Idade de Início , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/terapia , Consenso , Humanos , Osteossarcoma/epidemiologia , Osteossarcoma/terapia , Sarcoma de Ewing/epidemiologia , Sarcoma de Ewing/terapia , Adulto JovemRESUMO
BACKGROUND: Neoadjuvant chemotherapy improves outcome in osteosarcoma. Determination of optimum regimens for survival, toxicity and prognostic factors requires randomised controlled trials to be conducted. PATIENTS AND METHODS: Between 1983 and 2002, the European Osteosarcoma Intergroup recruited 1067 patients with localised extremity osteosarcoma to three randomised controlled trials. Standard treatment in each was doxorubicin 75 mg/m(2) and cisplatin 100 mg/m(2). Comparators were addition of methotrexate (BO02/80831), a multidrug regimen (BO03/80861) and a dose-intense schedule (BO06/80931). Standard survival analysis methods were used to identify prognostic factors, temporal and other influences on outcome. RESULTS: Five- and 10-year survival were 56% (95% confidence interval 53% to 59%) and 52%, respectively (49% to 55%), with no difference between trials or treatment arms. Median follow-up was 9.4 years. Age range was 3-40 years (median 15). Limb salvage was achieved in 69%. Five hundred and thirty-three patients received the standard arm, 79% completing treatment. Good histological response to preoperative chemotherapy, distal tumour location (all sites other than proximal humerus/femur) and female gender were associated with improved survival. CONCLUSIONS: Localised osteosarcoma will be cured in 50% of patients with cisplatin and doxorubicin. Large randomised trials can be conducted in this rare cancer. Failure to improve survival over 20 years argues for concerted collaborative international efforts to identify and rapidly test new treatments.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ossos do Braço/patologia , Neoplasias Ósseas/tratamento farmacológico , Ossos da Perna/patologia , Osteossarcoma/tratamento farmacológico , Sobrevida , Adolescente , Adulto , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Criança , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Gradação de Tumores , Recidiva Local de Neoplasia , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
A scoping exercise to define the preferred competencies of professionals involved in teenage and young adult (TYA) cancer care. Data were generated during two workshops with health professionals. In groups, they ranked skills, knowledge and attitudes, previously identified through a literature search, onto a diamond template. Data were also used from an education day with TYA professionals, who generated lists of key skills, knowledge and attitudes. Individually, professionals then selected the top five areas of competence to care for young people with cancer. The workshops generated three diamonds, which exhibited agreement of 13 principle skills, knowledge and attitudes. The top two being: 'expertise in treating paediatric and adult cancers' and 'understanding cancer'. The data from the education day suggested communication, technical knowledge and teamwork as being core role features for professionals who care for young people with cancer. Integration of both datasets; one derived inductively, the other deductively provides a comprehensive outline of core skills health professionals require to be proficient in young people's cancer care. These results will form the basis of future discussion around workforce strategies and inform a Delphi survey.
Assuntos
Competência Clínica/normas , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/psicologia , Neoplasias/terapia , Adolescente , Inglaterra , Feminino , Pessoal de Saúde/normas , Humanos , Masculino , Personalidade , Relações Médico-Paciente , Papel Profissional , Adulto JovemRESUMO
BACKGROUND: Few studies have examined epidemiological differences between ethnic groups for children and young adults with cancer. METHODS: Subjects aged 0-29 years, diagnosed between 1990 and 2005 in the former Yorkshire Regional Health Authority, were included in the analysis. Ethnicity (south Asian or not) was assigned using name analysis program and Hospital Episode Statistics data. Differences in incidence (per 1,000,000 person-years) rates and trends were analysed using joinpoint and Poisson regression analysis. RESULTS: Overall cancer incidence was similar for south Asians (12.1, 95% CI: 10.7-13.5; n=275) and non-south Asians (12.6, 95% CI: 12.2-13.1; n=3259). Annual incidence rates increased significantly by 1.9% per year on average (95% CI: 1.2-2.6%), especially for south Asians (7.0%; 95% CI: 4.2-9.9%). CONCLUSION: If present trends continue, the higher rate of increase seen among south Asians aged 0-29 years in Yorkshire will result in three times higher cancer incidence than non-south Asians by 2020.
Assuntos
Neoplasias/etnologia , Neoplasias/epidemiologia , Adolescente , Adulto , Ásia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Reino UnidoRESUMO
Ewing's sarcoma is thought to arise after developmental arrest of primitive neural cells during embryogenesis. Because basic fibroblast growth factor (bFGF) has a critical role in the regulation of cell survival, proliferation, and differentiation during embryogenesis, we have tested the hypothesis that bFGF and FGF receptors may contribute to the development of Ewing's sarcoma and may provide a mechanism for the modulation of their behavior. All four of the Ewing's sarcoma cell lines examined expressed bFGF and FGF receptors, which were detected by immunofluorescence and Western blotting. bFGF-induced a significant dose-dependent decrease in Ewing's sarcoma cell proliferation on plastic and reduced anchorage-independent growth in soft agar. Unexpectedly, this decrease in cell number reflected bFGF-induced apoptosis and necrosis, as demonstrated by electron microscopy, binding of annexin V, and staining with acridine orange. Induction of cell death was dependent on dosage of, and period of exposure to, bFGF. bFGF did not induce differentiation of Ewing's sarcoma cells in either the presence or the absence of serum or nerve growth factor. Treatment of NuNu mice with bFGF decreased growth of the highly tumorigenic Ewing's sarcoma cell lines. Histologically tumors grown in the NuNu mice treated with bFGF were less cellular than those in control mice, and showed an increased level of apoptotic nuclei. This is in contrast to the mitogenic effect bFGF has in most other cancer cells. In summary, bFGF decreases Ewing's sarcoma growth in vitro and in vivo by the induction of cell death. This novel observation may provide a new therapeutic strategy for Ewing's sarcomas.
Assuntos
Neoplasias Ósseas/patologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Sarcoma de Ewing/patologia , Neoplasias de Tecidos Moles/patologia , Animais , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Contagem de Células , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Fator 2 de Crescimento de Fibroblastos/biossíntese , Humanos , Camundongos , Camundongos Nus , Necrose , Fator de Crescimento Neural/farmacologia , Tumores Neuroectodérmicos Primitivos Periféricos/tratamento farmacológico , Tumores Neuroectodérmicos Primitivos Periféricos/metabolismo , Tumores Neuroectodérmicos Primitivos Periféricos/patologia , Receptores de Fatores de Crescimento de Fibroblastos/biossíntese , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/metabolismo , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: To examine the relationship between received dose, received dose-intensity (RDI), and survival in patients with osteosarcoma. PATIENTS AND METHODS: Between 1983 and 1993, the European Osteosarcoma Intergroup (EOI) conducted two randomized trials involving patients with high-grade, nonmetastatic, biopsy-proven osteosarcoma of the extremity. These trials shared a common treatment arm of doxorubicin (DOX) 75 mg/m(2) and cisplatin (CDDP) 100 mg/m(2) planned for six cycles at 3-week intervals. Definitive surgery was scheduled at week 9, after three cycles. Survival time was calculated from 122 days, the scheduled end of chemotherapy. RESULTS: A total of 287 patients randomized to DOX/CDDP received at least one cycle of chemotherapy, and 232 (81%) received all six cycles. On average, 79% of the intended dose of DOX and 80% of the intended dose of CDDP was given. Mean time to completion of chemotherapy was 1.27 times that specified by the protocol. Mean RDI was 0.64 for DOX (SD = 0.19) and 0.65 for CDDP (SD = 0.18). Progression-free survival was lower for those who received one to five cycles compared with those who completed all six cycles (hazards ratio, 1.69; 95% confidence interval, 1.03 to 2.78). Survival and progression-free survival were lowest for patients with RDI less than 0.6, although these differences were not statistically significant at the 5% level. There was no clear evidence of preoperative dose or dose-intensity influencing histologic response. CONCLUSION: This analysis did not establish a clear survival benefit for increasing received dose or dose-intensity in the context of this two-drug regimen. The hypothesis that increasing dose-intensity may improve survival in osteosarcoma requires prospective evaluation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Adolescente , Neoplasias Ósseas/cirurgia , Criança , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Esquema de Medicação , Extremidades , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Terapia Neoadjuvante , Osteossarcoma/cirurgia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: The aim of this study was to define the pharmacokinetics of carboplatin in children and use the data to develop a pediatric dose formula. It was anticipated that renal function would be a major determinant of carboplatin disposition and the relationship between carboplatin clearance and glomerular filtration rate (GFR) was examined in detail. PATIENTS AND METHODS: Plasma carboplatin pharmacokinetics were measured as ultrafiltrable platinum in 22 patients (5 to 63 kg) following 200 to 1,000 mg/m2 of carboplatin. GFR was measured by the plasma clearance of chromium 51-edathamil (51Cr-EDTA). RESULTS: Carboplatin pharmacokinetics in children were best described in most patients (16 of 22) by a two-compartment model. The dose-normalized area under the plasma carboplatin concentration versus time curve (AUC) ranged from 3.1 to 9.6 mg/mL.min/400 mg/m2 and there was only a weak linear relationship between carboplatin dose and AUC (R2 = .31). There was a significant relationship between absolute carboplatin and 51Cr-EDTA clearances (R2 = .56), but the relationship was weaker (R2 = .28) when both clearances were normalized for body surface area. Carboplatin plasma clearance was predicted by the equation: clearance = GFR (mL/min) + 0.36 x body weight (BW; kg), and a modified form of the adult carboplatin dose formula is proposed: dose (mg) = target AUC x (GFR [mL/min] + [0.36 x BW(kg)]). Two further equations were developed that use the 51Cr-EDTA half-life (t1/2) to calculate the GFR and these may reduce errors resulting from inaccurate measurement of the volume of distribution for 51Cr-EDTA. In patients treated with single-agent carboplatin or carboplatin plus vincristine, there was a significant sigmoidal relationship between AUC and thrombocytopenia (R2 = .56). CONCLUSION: GFR-based carboplatin dosing in children should be feasible and will be evaluated prospectively.
Assuntos
Carboplatina/administração & dosagem , Carboplatina/farmacocinética , Neoplasias/metabolismo , Adolescente , Carboplatina/efeitos adversos , Criança , Pré-Escolar , Radioisótopos de Cromo , Ácido Edético , Feminino , Taxa de Filtração Glomerular , Humanos , Lactente , Testes de Função Renal , Masculino , Neoplasias/tratamento farmacológicoRESUMO
PURPOSE: The goal of this study was to evaluate the toxicity of iodine 131 metaiodobenzylguanidine (mIBG) in metastatic neuroblastoma. PATIENTS AND METHODS: A multicenter phase I study of 131I mIBG has been undertaken by the United Kingdom Children's Cancer Study Group (UKCCSG) in children with advanced chemoresistant neuroblastoma. Activity prescription was based on a prescribed whole-body radiation dose, which was established for individual patients by performing an initial tracer investigation with 75 MBq of 131I mIBG. An activity was derived from this pharmacokinetic study that would deliver an initial whole-body-absorbed radiation dose of 1 Gy. Subsequent dose escalations were based on observed toxicity. RESULTS: Twenty-five patients, aged 1 to 10 years, were treated with prescribed whole-body dose levels of 1.0 Gy (n = 2), 2.0 Gy (n = 13), and 2.5 Gy (n = 10). This necessitated administration of 2.4 to 12.1 GBq of activity. Hematologic, hepatic, kidney, and adrenal toxicity were observed, with bone marrow suppression being the principal dose-limiting toxicity. Bone marrow toxicity increased with prescribed whole-body-absorbed radiation dose, with 80% of patients developing grade 3 or 4 thrombocytopenia at a prescribed whole-body radiation dose of 2.5 Gy. Objective evidence of tumor response was seen in soft tissue (primary or nodal disease), bone, and bone marrow, with an overall response rate of 33% (partial response, n = 8; static disease, n = 9; progressive disease, n = 7). CONCLUSIONS: This study has established an effective method of activity prescription that predicts subsequent toxicity, with the maximally tolerated dose being sufficient activity to deliver a whole-body-absorbed radiation dose of 2.5 Gy. The objective response rate is comparable to other single agents in chemoresistant neuroblastoma and suggests that 131I mIBG may be a useful method for targeting radiotherapy in metastatic neuroblastoma.
Assuntos
Radioisótopos do Iodo/uso terapêutico , Neuroblastoma/radioterapia , 3-Iodobenzilguanidina , Criança , Pré-Escolar , Resistência a Medicamentos , Humanos , Lactente , Radioisótopos do Iodo/administração & dosagem , Iodobenzenos/efeitos adversos , Dosagem Radioterapêutica , Resultado do TratamentoRESUMO
PURPOSE: In this prospective, multicenter study, the independent prognostic power of neuroblastoma cells detected by reverse transcriptase polymerase chain reaction (RT-PCR) for tyrosine hydroxylase (TH) mRNA was evaluated. PATIENTS AND METHODS: The clinical significance of disease detected by RT-PCR in peripheral blood from children at diagnosis was compared with established prognostic markers [ie, age, lactate dehydrogenase (LDH), neuron-specific enolase, ferritin, and MYCN gene amplification] by multivariate analysis. The value of disease detection by RT-PCR during treatment and follow-up was also examined. RESULTS: TH mRNA was detected in peripheral blood from 33 of 49 (67%) children with stage 4 neuroblastoma > 1 year old at diagnosis and was a significant predictive factor for overall survival [hazard ratio (HR) = 2.40, 95% confidence interval (CI) 1.19 to 4.84, P =.014) and event-free survival (HR = 2.09, 95% CI 1.06 to 4.17, P =.034) in a multivariate analysis. Detection of disease in blood from clinically disease-free children was related to increased risk of death (HR 2.54, 95% CI 1.42 to 4.55, P =.0014). CONCLUSION: TH mRNA in peripheral blood of children with neuroblastoma is a poor prognostic indicator, reflecting the propensity for dissemination via the bloodstream. When combined with a serum LDH > 1500 IU/L, this is the most powerful poor prognostic model at diagnosis for children > 1 year old with stage 4 disease. The detection of TH mRNA in peripheral blood from clinically disease-free children is related to increased risk of relapse and death.
Assuntos
Células Neoplásicas Circulantes , Neuroblastoma/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tirosina 3-Mono-Oxigenase/genética , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neuroblastoma/genética , Prognóstico , Estudos Prospectivos , RNA Mensageiro/análise , Análise de Sobrevida , Tirosina 3-Mono-Oxigenase/análise , Tirosina 3-Mono-Oxigenase/biossínteseRESUMO
PURPOSE AND METHODS: Future progress in the care of children with cancer requires appropriate evaluations of promising new agents for pediatric indications, beginning with well-conducted phase I trials. This report summarizes current guidelines for the conduct of pediatric phase I trials and represents a consensus between American and European investigators. The primary objective of pediatric phase I trials is to define safe and appropriate doses and schedules of new agents that can subsequently be used in phase II trials to test for activity against specific childhood malignancies. Prioritization of agents for evaluation in children is critical, since many more investigational agents are evaluated in adult patients than can be systematically evaluated in children. Considerations used in prioritizing agents include activity in xenograft models, novel mechanism of action, favorable drug-resistance profile, and activity observed in adult trials of the agent. RESULTS AND CONCLUSION: Distinctive characteristics of pediatric phase I trials, in comparison to adult phase I trials, include the necessity for multiinstitutional participation and their higher starting dose (typically 80% of the adult maximum-tolerated dose [MTD]), both of which reflect the relative unavailability of appropriate patients. The application of uniform eligibility criteria and standard definitions for MTD and dose-limiting toxicity (DLT) help to assure that pediatric phase I trials are safely conducted and reliably identify appropriate doses and schedules of agents for phase II evaluation. Where possible, pediatric phase I trials also define the pharmacokinetic behavior of new agents in children.
Assuntos
Antineoplásicos/uso terapêutico , Ensaios Clínicos Fase I como Assunto/normas , Neoplasias/terapia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Criança , Pré-Escolar , Guias como Assunto , Humanos , LactenteRESUMO
p21ras is a membrane-associated guanine nucleotide-binding protein with intrinsic GTPase activity. This protein is important in the regulation of cell growth and differentiation in a number of different cell types. Therefore, the aim of the present study was to examine the role of p21ras and regulators of its activity in the differentiation of neuroblastoma cells induced by retinoic acid (RA). Phosphorylation of p21ras is regulated by the GTPase activity of type I GAP120 and neurofibromin. RA-induced differentiation of the two neuroblastoma cell lines SK-N-SH and IMR-32 was closely related to growth inhibition. Differentiation induced by RA resulted in an increase in both type I GAP120 and neurofibromin mRNAs. This increase was accompanied by a decrease in the activation of p21ras. These results suggest that, in neuroblastoma, activation of p21ras is not associated with RA-induced differentiation. However, the GTPase activating proteins type I GAP120 and neurofibromin may have effector functions in RA-induced differentiation of neuroblastoma.
Assuntos
Ceratolíticos/farmacologia , Neuroblastoma/patologia , Proteínas/efeitos dos fármacos , Proteínas Proto-Oncogênicas p21(ras)/efeitos dos fármacos , Tretinoína/farmacologia , Sequência de Bases , Western Blotting , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Proteínas Ativadoras de GTPase , Humanos , Dados de Sequência Molecular , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neurofibromina 1 , Reação em Cadeia da Polimerase , Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacos , Proteínas Ativadoras de ras GTPaseRESUMO
Disseminating disease in neuroblastoma is of considerable clinical importance. Detection of circulating neuroblastoma cells using tyrosine hydroxylase (TH) as a tissue-specific target for reverse transcriptase-polymerase chain reaction has proved to be a sensitive and specific method for the detection of contaminating tumour cells in peripheral blood. The aim of this study was to report the early clinical observations made using this technology in neuroblastoma patient blood samples. A strong association was found between the detection of neuroblastoma cells in circulation with the detection of neuroblastoma in bone marrow. This method may be of use to monitor disease status and identify early signs of relapse in clinically disease-free patients. These results show that RT-PCR detection of TH mRNA is a relatively noninvasive, sensitive method for the detection of circulating tumour cells in neuroblastoma patients.
Assuntos
Neuroblastoma/patologia , Reação em Cadeia da Polimerase/métodos , Tirosina 3-Mono-Oxigenase/sangue , Criança , Eletroforese em Gel de Ágar , Seguimentos , Humanos , Invasividade Neoplásica , Neoplasia Residual , Neuroblastoma/sangue , Neuroblastoma/enzimologia , RNA Mensageiro/sangue , RNA Neoplásico/sangue , Recidiva , Tirosina 3-Mono-Oxigenase/genéticaRESUMO
The t(11.22)(q24.q12) results in expression of a chimeric RNA product, EWS-FLI1. This RNA product is expressed in over 85% of tumours belonging to the Ewing's family, and is increasingly used as a definitive characteristic of these tumours. In this study, we evaluated reverse transcriptase-polymerase chain (RT-PCR) for EWS-FLI1 fusion transcripts in 18 neurally derived small round cell tumours. These included six Ewing's family tumours and 12 neuroblastomas. EWS-FLI1 fusion transcripts were identified in all six Ewing's tumours, but also in two of the 12 neuroblastomas. One neuroblastoma contained the classic type 1 fusion transcript, and the second a type 1 transcript containing a 66 bp (base pair) insert that was not derived from the EWS or FLI1 gene. The presence of EWS-FLI1 fusion products in RNA extracted from primary neuroblastoma suggests the identification of EWS-FLI1 fusion transcripts is not pathognomonic for tumours of the Ewing's family. The clinical significance of these fusion transcripts in neuroblastoma is not known.
Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Neoplasias/genética , Neuroblastoma/genética , Proteínas Proto-Oncogênicas , Proteínas Recombinantes de Fusão/genética , Ribonucleoproteínas/genética , Transativadores/genética , Translocação Genética , Adolescente , Sequência de Bases , Neoplasias Ósseas/genética , Criança , Pré-Escolar , Ribonucleoproteínas Nucleares Heterogêneas , Humanos , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Proteína Proto-Oncogênica c-fli-1 , RNA Mensageiro/genética , RNA Neoplásico/genética , Proteína EWS de Ligação a RNA , Sarcoma de Ewing/genéticaRESUMO
The aim of this study was to investigate survival rates for adolescents with cancer and identify factors associated with differential long-term prognosis in Yorkshire, UK. A survival analysis of a population-based cohort of young adults aged 15-24 years, diagnosed with a malignancy in the former Yorkshire Regional Health Authority between 1985 and 1994 was carried out. The main outcome was death from all causes. Overall survival for the 1097 adolescents with a malignancy increased by 30% between 1985-1989 and 1990-1994 (P=0.004). This improvement was reflected in most subgroups of cancer. Large scale geographical differences in survival rates were observed across Yorkshire, with an increased risk of death in North Yorkshire and Humberside of 34% and 45%, respectively, compared with West Yorkshire. Small scale analyses showed reduced survival in areas of high population density, but no consistent trends were associated with socio-economic status. Improved survival from all cancers in young adults over the last decade is clearly seen. Reasons for differential survival by geographical area are unclear and warrant further investigation.
Assuntos
Neoplasias/mortalidade , Adolescente , Adulto , Estudos de Coortes , Inglaterra/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Modelos de Riscos Proporcionais , Fatores de Risco , Taxa de SobrevidaRESUMO
The highly urbanised northern English city of Bradford contains a diverse population from different ethnic backgrounds, including a high proportion of south Asians. We aimed to identify the effect of ethnic group on the incidence and temporal trends of childhood cancer in Bradford. Children (0-14 years) from the district of Bradford, who were diagnosed with a malignancy between 1974 and 1997, were selected from a population-based register. Each child was classified as south Asian (Indian, Pakistani and Bangladeshi), or not, based on their full name using 2 computer algorithms and individual inspection. Mid-year population estimates were used to calculate incidence rates and differences were assessed using Poisson regression. The study included 318 children, of whom 81 (25%) were south Asian. The incidence of all cancers in south Asian children (14.9 per 100,000 person years, 95% CI 11.6-18.2) was higher than non-south Asian children (12.0, 10.5-13.5) although not significantly so (P=0.14). Comparisons by diagnostic subgroup showed no major differences apart from significantly higher rates of acute myeloid leukaemia (AML) in south Asian children (1.9 versus 0.7, P=0.02). The age-specific incidence peaks of all childhood cancers and leukaemias were present in south Asian children aged 5-9 years compared with 0-4 years olds in the non-south Asian population. Non-significant increases of 1.4 and 1.5% in the average annual incidence of all cancers were seen for south Asians and non-south Asians respectively, with a significant rise for non-south Asians with leukaemia of 3.0% (P=0.04). Our timely study shows patterns of occurrence of childhood cancer that differ with respect to ethnic group. Differences are particularly apparent in the excess of AML and incidence peak in 5-9 year olds in south Asian children.
Assuntos
Neoplasias/etnologia , Adolescente , Distribuição por Idade , Ásia/etnologia , Criança , Pré-Escolar , Inglaterra/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Leucemia/etnologia , Masculino , Neoplasias/epidemiologia , Análise de Regressão , Distribuição por SexoRESUMO
The effect of ethnicity and socio-economic status on the survival of a population-based cohort of 1979 children diagnosed with cancer between 1974 and 1995 was investigated. Ethnicity was assigned by computer algorithms and visual inspection as south Asian (or not) for each child, based on their full name. Socio-economic status was measured using the Carstairs index, based on census areas of case residence at diagnosis. 15 children (0.8%) were lost to follow-up. Log-rank tests showed survival from all cancers did not differ between south Asians and other children and no increased risk was observed for south Asians in any diagnostic category, although numbers were small. Increasing levels of deprivation were associated with significant trends of poorer survival from all cancers, leukaemias and brain tumours. Risk of death was typically higher for children from the most deprived areas although differences were not statistically significant after accounting for other factors including ethnicity. Taking all children with malignant disease together, neither ethnicity nor socio-economic status appear to influence survival after taking other factors into consideration.
Assuntos
Neoplasias/mortalidade , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Inglaterra/epidemiologia , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Neoplasias/economia , Neoplasias/etnologia , Sistema de Registros , Fatores de Risco , Fatores Socioeconômicos , Taxa de Sobrevida , SobreviventesRESUMO
The aims of this study were to perform the first systematic review of molecular and biological tumour markers in tumours of the Ewing's sarcoma family (ESFT), and evaluate the current evidence for their clinical use. A well-defined, reproducible search strategy was used to identify the relevant literature from 1966 to February 2000. Papers were independently assessed for tumour markers used in the screening, diagnosis, prognosis or monitoring of patients with ESFT. Eighty-four papers studying the use of 70 different tumour markers in ESFT's were identified. Low-quality, inconsistent reporting limited meta-analysis to that of prognostic data for 28 markers. Patients with tumours lacking S-100 protein expression have a better overall survival (OS) (hazard ratio (HR)=0.41, 95% confidence interval (CI) 0.19, 0.89) than those with expression; patients with high levels of serum LDH had a worse OS and disease-free survival (DFS) (OS: HR=2.92, CI 2.16, 3.94, DFS: HR=3.38, 95% CI 2.28, 4.99); patients with localised disease and tumours expressing type 1 EWS-FLI1 fusion transcripts had an improved DFS compared with those with other fusion transcript types (HR=0.17, 95% CI 0.079, 0.37). The knowledge base formed should facilitate more informative future research. Improved statistical reporting and large, multicentre prospective studies are advocated.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias Ósseas/diagnóstico , Proteínas de Fusão Oncogênica/genética , Sarcoma de Ewing/diagnóstico , Fatores de Transcrição/genética , Neoplasias Ósseas/genética , Humanos , Programas de Rastreamento/métodos , Prognóstico , Proteína Proto-Oncogênica c-fli-1 , Proteína EWS de Ligação a RNA , Sarcoma de Ewing/genética , Design de SoftwareRESUMO
A UK multi-centre study has been carried out to collect medical and dosimetry data from treatments with 131I-metaiodobenzylguanidine (mIBG) for patients suffering from resistant neuroblastoma. All data have been acquired in a standardised way, following strict physics and clinical protocols. The accuracy of three different methods of dose prescription was studied. The results show that the most accurate method involved the use of an initial tracer study to determine the therapeutic activity required to deliver a predetermined absorbed whole-body (WB) dose.
Assuntos
Antineoplásicos/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Iodobenzenos/uso terapêutico , Neuroblastoma/radioterapia , 3-Iodobenzilguanidina , Criança , Humanos , Radiometria , Dosagem RadioterapêuticaRESUMO
Desmoplastic small round cell tumor (DSRCT) has recently been described as a discrete tumor entity. It is distinguished from other small round cell tumors by its prominent desmoplastic quality, its preponderance in adolescent males, its almost exclusive intraabdominal location, a multi-immunophenotypic profile, and its aggressive nature. Diagnosis on histology alone is not always unequivocal. A recurrent t(11;22)(p13;q12) translocation has recently been described in this tumor, and a chimeric RNA fusion product formed from the WT1 and EWS genes is detectable by reverse transcriptase-polymerase chain reaction (RT-PCR). We describe the use of a multi-faceted approach using conventional G-banding, fluorescence in situ hybridization (FISH) and RT-PCR to assist the diagnosis of a case of DSRCT with a complex variant t(11;22;21)(p13;q12;q22.1) translocation and demonstrate the value of a combined approach to genetic investigation of solid tumors.