RESUMO
This phase 1 study evaluated frontline brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (BV+CHP; 6 cycles, then up to 10 cycles of brentuximab vedotin monotherapy) in 26 patients with CD30+ peripheral T-cell lymphoma, including 19 with systemic anaplastic large cell lymphoma. All patients (100%) achieved an objective response, with a complete remission (CR) rate of 92%; none received a consolidative stem cell transplant. After a median observation period of 59.6 months (range, 4.6-66.0) from first dose, neither the median progression-free survival (PFS) nor the median overall survival (OS) was reached. No progression or death was observed beyond 35 months. The estimated 5-year PFS and OS rates were 52% and 80%, respectively. Eighteen of 19 patients (95%) with treatment-emergent peripheral neuropathy (PN) reported resolution or improvement of symptoms. Thirteen patients (50%) remained in remission at the end of the study, with PFS ranging from 37.8+ to 66.0+ months. Eight of these 13 patients received the maximum 16 cycles of study treatment. These final results demonstrate durable remissions in 50% of patients treated with frontline BV+CHP, suggesting a potentially curative treatment option for some patients. This trial was registered at www.clinicaltrials.gov as #NCT01309789.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Expressão Gênica , Antígeno Ki-1/genética , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brentuximab Vedotin , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Imunoconjugados/administração & dosagem , Estimativa de Kaplan-Meier , Antígeno Ki-1/metabolismo , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico , Adulto JovemRESUMO
OBJECTIVES: The objective of this study was to examine the association between tobacco and alcohol dose and type and the age of onset of pancreatic adenocarcinoma (PancCa). METHODS: Prospective data from the Pancreatic Cancer Collaborative Registry were used to examine the association between age of onset and variables of interest including: gender, race, birth country, educational status, family history of PancCa, diabetes status, and tobacco and alcohol use. Statistical analysis included logistic and linear regression, Cox proportional hazard regression, and time-to-event analysis. RESULTS: The median age to diagnosis for PancCa was 66.3 years (95% confidence intervals (CIs), 64.5-68.0). Males were more likely than females to be smokers (77% vs. 69%, P=0.0002) and heavy alcohol and beer consumers (19% vs. 6%, 34% vs. 19%, P<0.0001). In univariate analysis for effects on PancCa presentation age, the following were significant: gender, alcohol and tobacco use (amount, status and type), family history of PancCa, and body mass index. Both alcohol and tobacco had dose-dependent effects. In multivariate analysis, alcohol status and dose were independently associated with increased risk for earlier PancCa onset with greatest risk occurring in heavy drinkers (HR 1.62, 95% CI 1.04-2.54). Smoking status had the highest risk for earlier onset pancreatic cancer with a HR of 2.69 (95% CI, 1.97-3.68) for active smokers and independent effects for dose (P=0.019). The deleterious effects for alcohol and tobacco appear to resolve after 10 years of abstinence. CONCLUSIONS: Alcohol and tobacco use are associated with a dose-related increased risk for earlier age of onset of PancCa. Although beer drinkers develop pancreatic cancer at an earlier age than nondrinkers, alcohol type did not have a significant effect after controlling for alcohol dose.
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Adenocarcinoma/epidemiologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias Pancreáticas/epidemiologia , Fumar/efeitos adversos , Idade de Início , Idoso , Índice de Massa Corporal , Distribuição de Qui-Quadrado , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sistema de Registros , Fatores de RiscoRESUMO
Sjögren's syndrome (SS) is a chronic autoimmune rheumatic disease characterized by a progressive lymphocytic infiltration of salivary glands, resulting in xerostomia and other oral diseases. The pathogenesis and mechanisms of SS on periodontal tissues are not well understood. Furthermore, results of two systemic reviews and meta-analyses in which compared periodontal parameters of patients with SS to healthy subjects were different. To determine whether periodontal conditions in SS were different from healthy controls, we re-examined the issue with a random-effect model, avoiding recruiting active controls and inadequate data conversion. Outcome measures included probing pocket depth (PPD), clinical attachment loss (CAL), plaque index (PI), and gingival index (GI). Recruited individuals comprised 198 patients with SS and 180 subjects for healthy controls. Quantitative analysis revealed higher PI (WMDâ¯=â¯0.76, 95% CI: 0.30, 1.23) and GI (WMD of totalâ¯=â¯0.50, 95% CI: 0.01, 0.98) in SS patients who were not categorized into primary or secondary types of SS. PPD and CAL in SS patients was comparable with control subjects. However, heterogeneity was observed among included studies. Thus, results from this and previous analyses should be interpretated carefully, and a well-designed observational study regarding this issue should be conducted.
RESUMO
BACKGROUND: The goal of the present study was to quantify the population-based background serum concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by using data from the reference population of the 2005 University of Michigan Dioxin Exposure Study (UMDES) and the 2003-2004 National Health and Nutrition Examination Survey (NHANES). METHODS: Multiple imputation was used to impute the serum TCDD concentrations below the limit of detection by combining the 2 data sources. The background mean, quartiles, and 95th percentile serum TCDD concentrations were estimated by age and sex by using linear and quantile regressions for complex survey data. RESULTS: Any age- and sex-specific mean, quartiles, and 95th percentiles of background serum TCDD concentrations of study participants between ages 18 and 85 years can be estimated from the regressions for the UMDES reference population and the NHANES non-Hispanic white population. For example, for a 50-year-old man in the reference population of UMDES, the mean, quartiles, and 95th percentile serum TCDD concentrations are estimated to be 1.1, 0.6, 1.1, 1.8, and 3.3 parts per trillion, respectively. The study also shows that the UMDES reference population is a valid reference population for serum TCDD concentrations for other predominantly white populations in Michigan. CONCLUSION: The serum TCDD concentrations increased with age and increased more over age in women than in men, and hence estimation of background concentrations must be adjusted for age and sex. The methods and results discussed in this article have wide application in studies of the concentrations of chemicals in human serum and in environmental samples.
Assuntos
Poluentes Ambientais/sangue , Inquéritos Nutricionais , Dibenzodioxinas Policloradas/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Exposição Ambiental/análise , Feminino , Humanos , Masculino , Michigan , Pessoa de Meia-Idade , Valores de Referência , Análise de Regressão , Adulto JovemRESUMO
The product and direct role of the rssC gene of Serratia marcescens is unknown. For unraveling the role of the rssC gene, atomic force microscopy has been used to identify the surfaces of intact S. marcescens wild-type CH-1 cells and rssC mutant CH-1ΔC cells. The detailed surface topographies were directly visualized, and quantitative measurements of the physical properties of the membrane structures were provided. CH-1 and CH-1ΔC cells were observed before and after treatment with lysozyme, and their topography-related parameters, e.g., a valley-to-peak distance, mean height, surface roughness, and surface root-mean-square values, were defined and compared. The data obtained suggest that the cellular surface topography of mutant CH-1ΔC becomes rougher and more precipitous than that of wild-type CH-1 cells. Moreover, it was found that, compared with native wild-type CH-1, the cellular surface topography of lysozyme-treated CH-1 was not changed profoundly. The product of the rssC gene is thus predicted to be mainly responsible for fatty-acid biosynthesis of the S. marcescens outer membrane. This study represents the first direct observation of the structural changes in membranes of bacterial mutant cells and offers a new prospect for predicting gene expression in bacterial cells.
Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/fisiologia , Serratia marcescens/ultraestrutura , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Deleção de Genes , Microscopia de Força Atômica , Serratia marcescens/genética , Serratia marcescens/metabolismoRESUMO
BACKGROUND & AIMS: Cigarette smoking is an established risk factor for pancreatic cancer, but there is conflicting evidence regarding the effects of alcohol consumption. The effects of cigarettes and alcohol on age of sporadic pancreatic cancer diagnosis have not been examined; we evaluated the independent and synergistic effects of lifetime cigarette smoking and alcohol consumption on age at pancreatic cancer diagnosis in the United States. METHODS: We analyzed data on cigarette smoking and alcohol consumption from the IMPAC Services, Inc Cancer Information Resource File (CIRF), collected from June 1, 1993, to December 31, 2003, for 29,239 reported, histologically confirmed cases of pancreatic adenocarcinoma. We also analyzed data on cigarette smoking and alcohol consumption for 820 histologically confirmed cases of pancreatic adenocarcinoma from the University of Michigan Pancreatic Cancer Registry (UMPCR), collected from January 2004 to October 2007. RESULTS: Current cigarette smokers were diagnosed at significantly younger ages than never smokers, according to data from the CIRF and UMPCR (8.3 and 6.3 y, respectively); the UMPCR data indicated dose effects. Past and current alcohol consumption were associated with younger age at diagnosis in both databases. Current smokers who were current drinkers were diagnosed significantly earlier (CIRF, 10.2 y; UMPCR, 8.6 y) than abstainers. Past cigarette smoking was associated modestly with younger diagnosis age. CONCLUSIONS: Cigarette smoking and alcohol consumption were associated with younger age at pancreatic cancer presentation and have a combined effect on diagnosis age. Past cigarette smoking is less influential. Smoking cessation programs could help prevent pancreatic cancer.
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Adenocarcinoma/epidemiologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias Pancreáticas/epidemiologia , Fumar/efeitos adversos , Adenocarcinoma/diagnóstico , Adenocarcinoma/etiologia , Fatores Etários , Idade de Início , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/etiologia , Fatores de Risco , Fatores Sexuais , Abandono do Hábito de Fumar , Estados Unidos/epidemiologiaRESUMO
As part of the University of Michigan Dioxin Exposure Study, the 29 congeners of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and dioxin-like polychlorinated biphenyls that have World Health Organization consensus toxic equivalency factors were measured in house dust from 764 homes using a population-based sampling design over selected regions in five Michigan counties. Twenty homes had a total toxic equivalency in house dust that was more than 2.5 standard deviations above the mean (i.e., defined to be outliers). This follow-up investigation describes the outlier house dust measurements and corresponding soil measurements and explores possible sources of these toxins in house dust. The congener distributions in the house dust outliers varied and were dominated (i.e., >50% of the total toxic equivalency) by either polychlorinated dibenzo-p-dioxins (n = 9), polychlorinated dibenzofurans (n = 1), or dioxin-like polychlorinated biphenyls (n = 9). Likely sources of contamination of house dust were identified in only three cases. In two cases, dust contamination appeared to be related to contaminated soil adjacent to the home; in one case, contamination was related to a source within the home (a carpet pad). In most cases, the source(s) of contamination of house dust could not be identified but appeared likely to be related to uncharacterized sources within the homes.
Assuntos
Poluição do Ar em Ambientes Fechados/análise , Benzofuranos/análise , Dioxinas/análise , Poeira/análise , Habitação , Bifenilos Policlorados/análise , Dibenzodioxinas Policloradas/análogos & derivados , Benzofuranos/sangue , Dibenzofuranos Policlorados , Dioxinas/sangue , Monitoramento Ambiental , Poluição Ambiental , Humanos , Bifenilos Policlorados/sangue , Dibenzodioxinas Policloradas/análise , Dibenzodioxinas Policloradas/sangueRESUMO
CONTEXT: For the general population, the dominant source of exposure to dioxin-like compounds is food. As part of the University of Michigan Dioxin Exposure Study (UMDES), we measured selected polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (PCBs) in serum of 946 subjects who were a representative sample of the general population in five Michigan counties. CASE PRESENTATION: The total toxic equivalency (TEQ; based on 2005 World Health Organization toxic equivalency factors) of serum from the index case was 211 ppt on a lipid-adjusted basis, which was the highest value observed in the UMDES study population. This subject had no apparent opportunity for exposure to dioxins, except that she had lived on property with soil contaminated with dioxins for almost 30 years, and had been a ceramics hobbyist for > 30 years. Soil from her property and clay that she used for ceramics were both contaminated with dioxins, but the congener patterns differed. DISCUSSION: The congener patterns in this subject's serum, soil, and ceramic clay suggest strongly that the dioxin contamination in clay and not soil was the dominant source of dioxin contamination in her serum. RELEVANCE TO PUBLIC HEALTH PRACTICE: It appears that ceramic clay, in particular the process of firing clay with unvented kilns, can be a significant nonfood and nonindustrial source of human exposure to dioxins among ceramics hobbyists. The extent of human exposure from ceramic clay is unclear, but it may be widespread. Further work is needed to more precisely characterize the routes of exposure.
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Silicatos de Alumínio , Dioxinas/toxicidade , Exposição Ambiental , Idoso , Argila , Dioxinas/sangue , Feminino , HumanosRESUMO
The number needed to treat (NNT) with brentuximab vedotin consolidation therapy post-autologous stem cell transplant (ASCT) versus placebo in the phase 3 AETHERA trial to avoid one additional event of disease progression/death was evaluated. AETHERA included 329 Hodgkin lymphoma patients at increased risk of progression post-ASCT who received brentuximab vedotin 1.8 mg/kg (n = 165) or placebo (n = 164) on day 1 of each 21-d cycle (up to 16 cycles). Over 60 months, the NNT with brentuximab vedotin ranged from 4.08 to 7.79 for the intent-to-treat population, 3.18-6.07 for patients with ≥2 risk factors, and 2.98-5.65 for patients with ≥3 risk factors. At various time points, and dependent on the risk group, 3-8 patients would need to be treated with brentuximab vedotin consolidation therapy to prevent a disease progression/death, compared with placebo. Patients with increased risk of relapse may benefit most from brentuximab vedotin.
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Antineoplásicos Imunológicos/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Imunoconjugados/uso terapêutico , Neoplasia Residual/patologia , Adolescente , Adulto , Idoso , Brentuximab Vedotin , Terapia Combinada , Quimioterapia de Consolidação , Progressão da Doença , Feminino , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/mortalidade , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Transplante Autólogo , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: The Radiation Therapy Oncology Group (RTOG) developed a prognostic classification based on a recursive partitioning analysis (RPA) of patient pretreatment characteristics from three completed brain metastases randomized trials. Clinical trials for patients with brain metastases generally exclude small-cell lung cancer (SCLC) cases. We hypothesize that the RPA classes are valid in the setting of SCLC brain metastases. METHODS AND MATERIALS: A retrospective review of 154 SCLC patients with brain metastases treated between April 1983 and May 2005 was performed. RPA criteria used for class assignment were Karnofsky performance status (KPS), primary tumor status (PT), presence of extracranial metastases (ED), and age. RESULTS: Median survival was 4.9 months, with 4 patients (2.6%) alive at analysis. Median follow-up was 4.7 months (range, 0.3-40.3 months). Median age was 65 (range, 42-85 years). Median KPS was 70 (range, 40-100). Number of patients with controlled PT and no ED was 20 (13%) and with ED, 27 (18%); without controlled PT and ED, 34 (22%) and with ED, 73 (47%). RPA class distribution was: Class I: 8 (5%); Class II: 96 (62%); Class III: 51 (33%). Median survivals (in months) by RPA class were: Class I: 8.6; Class II: 4.2; Class III: 2.3 (p = 0.0023). CONCLUSIONS: Survivals for SCLC-only brain metastases replicate the results from the RTOG RPA classification. These classes are therefore valid for brain metastases from SCLC, support the inclusion of SCLC patients in future brain metastases trials, and may also serve as a basis for historical comparisons.
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Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma de Células Pequenas/mortalidade , Carcinoma de Células Pequenas/secundário , Neoplasias Pulmonares , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/classificação , Carcinoma de Células Pequenas/classificação , Irradiação Craniana , Seguimentos , Humanos , Avaliação de Estado de Karnofsky , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
PURPOSE: Intensity-modulated radiotherapy (IMRT) is being increasingly used for the treatment of pituitary adenomas. However, there have been few published data on the short- and long-term outcomes of this treatment. This is the initial report of the Cleveland Clinic's experience. METHODS AND MATERIALS: Between February 1998 and December 2003, 34 patients with pituitary adenomas were treated with IMRT. A retrospective chart review was conducted for data analysis. RESULTS: With a median follow-up of 42.5 months, the treatment has proven to be well tolerated, with performance status remaining stable in 90% of patients. Radiographic local control was 89%, and among patients with secretory tumors, 100% had a biochemical response. Only 1 patient required salvage surgery for progressive disease, giving a clinical progression free survival of 97%. The only patient who received more than 46 Gy experienced optic neuropathy 8 months after radiation. Smaller tumor volume significantly correlated with subjective improvements in nonvisual neurologic complaints (p = 0.03), and larger tumor volume significantly correlated with subjective worsening of visual symptoms (p = 0.05). New hormonal supplementation was required for 40% of patients. Younger patients were significantly more likely to require hormonal supplementation (p = 0.03). CONCLUSIONS: Intensity-modulated radiation therapy is a safe and effective treatment for pituitary adenomas over the short term. Longer follow-up is necessary to determine if IMRT confers any advantage with respect to either tumor control or toxicity over conventional radiation modalities.
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Adenoma/radioterapia , Neoplasias Hipofisárias/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We used dual-polarization interferometry (DPI) to study the interaction kinetics between a 'homopolyvalent' antigen (Ag) and a monoclonal antibody (Ab). A model system, which uses a monoclonal Ab against a homopentameric Ag, C-reactive protein (CRP), is presented with principle and experiments for the study of the interactions between an Ab and an Ag that has multiple identical epitopes. This allows evaluation of the dissociation constant (K(D)) and of the binding stoichiometry by DPI based on measurements of phase changes of Ab-Ag complexes in the transverse magnetic (TM) and transverse electric (TE) polarization modes. The average experimental value of K(D) found by the DPI technique for anti-CRP Ab was shown to be in close agreement with the value obtained by an indirect competition-enzyme-linked immunosorbent assay (ELISA). Moreover, the total number of Ab combining sites on the DPI sensor chip was calculated, and the binding stoichiometry of the surface Ag-Ab complex was obtained. This study illustrates the advantages of the DPI method in biosensing in its capacity for simultaneous evaluation of the thickness and refractive index (density, mass) of adsorbed layers. This allowed a comprehensive analysis of affinity reactions between an Ab having two binding sites and a multi-sited Ag.
Assuntos
Anticorpos Monoclonais/imunologia , Complexo Antígeno-Anticorpo/análise , Complexo Antígeno-Anticorpo/imunologia , Técnicas Biossensoriais/métodos , Proteína C-Reativa/imunologia , Imunoensaio/métodos , Modelos Imunológicos , Reações Antígeno-Anticorpo/imunologia , Técnicas Biossensoriais/instrumentação , Simulação por Computador , Imunoensaio/instrumentação , Cinética , Microscopia de Interferência/instrumentação , Microscopia de Interferência/métodos , Microscopia de Polarização/instrumentação , Microscopia de Polarização/métodosRESUMO
In order to develop the C-reactive protein (CRP) sensor chips for clinical detection of atherosclerosis and coronary heart disease, we used an atomic force microscope (AFM) and a dual polarization interferometric (DPI) biosensor to probe the surface ultrastructure and to measure the dimensions of CRP. A single pentagonal structure was directly visualized by AFM, and quantitative measurements of the dimensions of the protein were provided. The average height calculated for each pentagonal CRP particle was approximately 3.03+/-0.37 nm, which basically corresponds to that (36 A in protomer diameter) previously obtained from the structure of CRP determined by X-ray crystallography. Moreover, a experiment using dual polarization interferometric (DPI) as a biosensor was then performed, and the average monolayer thickness value (3.18+/-0.43 nm) that was calculated basically corresponds to that obtained from the experimental value (3.03+/-0.37 nm) of the height measured by an AFM method for CRP. Further investigations will be performed to study the surface ultrastructure of a single pentagonal CRP molecule, and for this purpose a CRP sample (at low concentration) was scanned in vacuum by AFM. The higher-resolution images clearly revealed the presence of doughnut-shaped CRP molecules. In addition, phase images of CRP molecules were captured simultaneously with their height images, and the lateral dimensions of the doughnut-shaped CRP molecules were then measured. It was found that the average values calculated for the outer diameter (11.13+/-1.47 nm) and pore diameter (3.52+/-0.42 nm) are respectively close to those (102 A in outer diameter and 30 A in pore diameter) previously obtained from the structure of CRP determined by X-ray crystallography. This study represents the first direct characterization of the surface ultrastructure and dimensional measurement of the CRP molecule on the sensor chip.
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Técnicas Biossensoriais/instrumentação , Proteína C-Reativa/química , Microscopia de Força Atômica , Proteína C-Reativa/ultraestrutura , InterferometriaRESUMO
OBJECT: The maximal tolerated dose (MTD) for stereotactic radiosurgery (SRS) for brain tumors was established by the Radiation Therapy Oncology Group (RTOG) in protocol 90-05, which defined three dose groups based on the maximal tumor diameter. The goal in this retrospective study was to determine whether differences in doses to the margins of brain metastases affect the ability of SRS to achieve local control. METHODS: Between 1997 and 2003, 202 patients harboring 375 tumors that met study entry criteria underwent SRS for treatment of one or multiple brain metastases. The median overall follow-up duration was 10.7 months (range 3-83 months). A dose of 24 Gy to the tumor margin had a significantly lower risk of local failure than 15 or 18 Gy (p = 0.0005; hazard ratio 0.277, confidence interval [CI] 0.134-0.573), whereas the 15- and 18-Gy groups were not significantly different from each other (p = 0.82) in this regard. The 1-year local control rate was 85% (95% CI 78-92%) in tumors treated with 24 Gy, compared with 49% (CI 30-68%) in tumors treated with 18 Gy and 45% (CI 23-67%) in tumors treated with 15 Gy. Overall patient survival was independent of dose to the tumor margin. CONCLUSIONS: Use of the RTOG 90-05 dosing scheme for brain metastases is associated with a variable local control rate. Tumors larger than 2 cm are less effectively controlled than smaller lesions, which can be safely treated with 24 Gy. Prospective evaluations of the relationship between dose to the tumor margin and local control should be performed to confirm these observations.
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Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECT: Oligodendrogliomas are rare primary brain tumors. They comprise approximately 5 to 33% of all glial tumors but differ from astrocytomas by being associated with a more favorable prognosis, making their correct identification important. Allelic loss of chromosome arms 1p and 19q is found in a substantial subpopulation of tumors with an oligodendroglioma phenotype. Anaplastic oligodendrogliomas with allelic loss of 1p have been associated with chemosensitivity and a longer patient survival period. METHODS: Oligodendroglial neoplasms were studied using fluorescence in situ hybridization of formalin-fixed, paraffin-embedded tissue specimens; reference and target probe sets were used to map the telomeric regions of 1p and 19q. The results were correlated with the clinical characteristics of patients treated at our institution between 1993 and 2003. Data obtained in 96 patients were analyzed. This included 63 patients (65.6%) with World Health Organization (WHO) Grade II oligodendroglioma, 22 (23%) with Grade III oligodendroglioma, and 11 (11.4%) with mixed oligoastrocytoma. Analysis of 1p in patients with pure oligodendroglioma revealed a loss of 1p in 42 patients (49.4%). In 46 of these patients 19q was lost and in 70 (82.3%) there was concordance for combined loss or retention of both 1p and 19q (p < 0.0001). Patients with oligodendroglioma in whom a loss of 1p was present fared significantly better, and this outcome was unrelated to the treatment modality or WHO grade, compared with patients in whom 1p was intact (p < 0.05). CONCLUSIONS: To the authors' knowledge, this study includes the largest published series of WHO Grade II oligodendroglioma and 1p analysis. The results suggest that the association between long-term survival and 1p loss in oligodendroglioma is unrelated to treatment. The authors of further prospective studies may better determine the true value of the allelic loss of 1p and its implication for clinical decision making.
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Cromossomos Humanos Par 1 , Genótipo , Perda de Heterozigosidade/genética , Oligodendroglioma/genética , Neoplasias Supratentoriais/genética , Adolescente , Adulto , Idoso , Encéfalo/patologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Cromossomos Humanos Par 19 , Técnicas de Apoio para a Decisão , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Oligodendroglioma/mortalidade , Oligodendroglioma/patologia , Oligodendroglioma/cirurgia , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Neoplasias Supratentoriais/mortalidade , Neoplasias Supratentoriais/patologia , Neoplasias Supratentoriais/cirurgia , Taxa de SobrevidaRESUMO
PURPOSE: To determine survival and changes in neurologic function and Karnofsky performance status (KPS) in a series of patients treated for low-grade astrocytoma of the spinal cord during the past two decades. METHODS: This study consisted of 14 patients with pathologically confirmed low-grade astrocytoma of the spinal cord who were treated between 1980 and 2003. All patients underwent decompressive laminectomy followed by biopsy (n = 7), subtotal resection (n = 6), or gross total resection (n = 1). Ten patients underwent postoperative radiotherapy (median total dose 50 Gy in 28 fractions). The overall survival, progression-free survival, and changes in neurologic function and KPS were measured. RESULTS: The overall survival rate at 5, 10, and 20 years was 100%, 75%, and 60%, respectively. The progression-free survival rate at 5, 10, and 20 years was 93%, 80%, and 60%, respectively. Neither overall survival nor progression-free survival was clearly correlated with any patient, tumor, or treatment factors. Neurologic function and KPS worsened after surgery in 8 (57%) of 14 and 9 (69%) of 13 patients, respectively. At a mean follow-up of 10.2 years, neurologic function had stabilized or improved in 8 (73%) of 11 remaining patients, but the KPS had worsened in 5 (50%) of 10. Most patients who were employed before surgery were working at last follow-up. CONCLUSION: Patients who undergo gross total resection of their tumor may be followed closely. Patients who undergo limited resection should continue to receive postoperative RT (50.4 Gy in 1.8-Gy fractions). The functional measures should be routinely evaluated to appreciate the treatment outcomes.
Assuntos
Astrocitoma/mortalidade , Neoplasias da Medula Espinal/mortalidade , Adulto , Idoso , Astrocitoma/fisiopatologia , Astrocitoma/radioterapia , Astrocitoma/cirurgia , Pré-Escolar , Feminino , Humanos , Avaliação de Estado de Karnofsky , Laminectomia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Radioterapia/efeitos adversos , Neoplasias da Medula Espinal/fisiopatologia , Neoplasias da Medula Espinal/radioterapia , Neoplasias da Medula Espinal/cirurgia , Taxa de Sobrevida , Falha de TratamentoRESUMO
PURPOSE: There have been conflicting reports in the literature regarding the prognostic significance of epidermal growth factor receptor (EGFR) amplification in patients with glioblastoma multiforme (GBM). The purpose of this study is to determine the prognostic significance of EGFR amplification in patients with GBM treated at the Cleveland Clinic Foundation. METHODS AND MATERIALS: A retrospective review of GBM patients treated with surgery at the Cleveland Clinic Foundation was performed. Amplification of EGFR was evaluated with fluorescence in situ hybridization in a total of 107 patients diagnosed between December 1995 and May 2003. In addition to EGFR status, various prognostic factors were evaluated to determine the factors that influenced survival and radiographic response rate. The median follow-up was 9 months. RESULTS: The overall median survival was 9.8 months, with a 1-year survival of 40%. Of the 107 patients in whom EGFR status was evaluated, 36 (33.6%) were found to have EGFR amplification. On multivariate analysis, median survival was found to be significantly improved for patients with age < 60 (12.6 months vs. 8 months, p = 0.0061), patients with Karnofsky Performance Status > or = 70 (12.1 months vs. 4.4 months, p < 0.0001), patients who had undergone subtotal resection or gross total resection (11.1 months vs. 4.1 months, p = 0.002), and patients who received a radiation dose > or = 60 Gy compared with no radiation (12.7 months vs. 3 months, p < 0.0001). There was no association of EGFR amplification with survival. When stratified by age (< 60 vs. > or = 60), EGFR status still did not reach statistical significance in predicting for survival. For the 81 patients who had radiographic follow-up, the 1-year overall local control was 14%. On univariate analysis, only treatment with radiation (< 60 Gy vs. > or = 60 Gy vs. no radiation, p = 0.03) was found to predict for improved local control. Treatment with radiation did not remain statistically significant on multivariate analysis. CONCLUSION: Epidermal growth factor receptor amplification was not found to be a significant prognostic indicator of overall survival or radiographic local control in patients with GBM treated with surgery at the Cleveland Clinic Foundation. Further studies are needed to fully delineate the significance of this molecular marker in patients with GBM.
Assuntos
Neoplasias Encefálicas/genética , Receptores ErbB/genética , Amplificação de Genes , Glioblastoma/genética , Proteínas de Neoplasias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Humanos , Pessoa de Meia-Idade , Prognóstico , Dosagem Radioterapêutica , Análise de SobrevidaRESUMO
The purpose of this study was to evaluate tumor control, complications, and outcome from intensity-modulated radiation therapy (IMRT) for intracranial meningiomas. Between July 1997 and November 2003, patients with intracranial meningiomas were treated at our institution with the NOMOS Peacock system utilizing the Multileaf Intensity Modulating Collimator (MIMiC). Thirty-five patients with 37 lesions (35 benign and two atypical histology) were identified with a minimum of six months of radiologic follow-up for this retrospective review. The median age of the patients was 65 years with a median KPS of 90 prior to treatment with IMRT. The median MRI/CT follow-up for the 37 treated lesions was 19.1 months (range 6.4-62.4 months). Twenty meningiomas (54%) were previously treated with surgery/radiosurgery prior to IMRT, and 17 meningiomas (46%) were treated with IMRT primarily after diagnosis was established by MRI/CT. The median time from previous surgery to treatment with IMRT was 18.1 months. The median tumor dose was 50.4 Gy prescribed to the 87% isodose line providing a median target coverage of 95%. Local control was at 97% three years after treatment with IMRT. Only three patients exhibited local failure after treatment. Although local control was slightly better in the upfront-IMRT lesions as compared to the lesions treated with prior surgery/radiosurgery (100% vs 95%), this difference was not statistically significant. On univariate analysis, the IMRT prescription dose and maximum dose were found to be predictors for local control (p=0.05). On multivariate analysis, these factors did not remain significant for influencing local control. No long-term complications from IMRT were documented among the 35 patients. In conclusion, intensity-modulated radiation therapy is a safe and effective treatment for some intracranial meningiomas. A greater number of patients with longer follow-up after treatment may be needed to determine treatment variables predicting for long-term tumor control.
Assuntos
Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Recidiva Local de Neoplasia/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Irradiação Craniana , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico , Meningioma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/cirurgia , Radiocirurgia , Radioterapia Conformacional , Estudos Retrospectivos , Terapia de Salvação , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Orteronel (TAK-700) is an investigational, nonsteroidal, reversible, selective 17,20-lyase inhibitor. This study examined orteronel in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel therapy. PATIENTS AND METHODS: In our study, 1,099 men were randomly assigned in a 2:1 schedule to receive orteronel 400 mg plus prednisone 5 mg twice daily or placebo plus prednisone 5 mg twice daily, stratified by region (Europe, North America [NA], and non-Europe/NA) and Brief Pain Inventory-Short Form worst pain score. Primary end point was overall survival (OS). Key secondary end points (radiographic progression-free survival [rPFS], ≥ 50% decrease of prostate-specific antigen [PSA50], and pain response at 12 weeks) were to undergo statistical testing only if the primary end point analysis was significant. RESULTS: The study was unblinded after crossing a prespecified OS futility boundary. The median OS was 17.0 months versus 15.2 months with orteronel-prednisone versus placebo-prednisone (hazard ratio [HR], 0.886; 95% CI, 0.739 to 1.062; P = .190). Improved rPFS was observed with orteronel-prednisone (median, 8.3 v 5.7 months; HR, 0.760; 95% CI, 0.653 to 0.885; P < .001). Orteronel-prednisone showed advantages over placebo-prednisone in PSA50 rate (25% v 10%, P < .001) and time to PSA progression (median, 5.5 v 2.9 months, P < .001) but not pain response rate (12% v 9%; P = .128). Adverse events (all grades) were generally more frequent with orteronel-prednisone, including nausea (42% v 26%), vomiting (36% v 17%), fatigue (29% v 23%), and increased amylase (14% v 2%). CONCLUSION: Our study did not meet the primary end point of OS. Longer rPFS and a higher PSA50 rate with orteronel-prednisone indicate antitumor activity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Intervalo Livre de Doença , Docetaxel , Método Duplo-Cego , Esquema de Medicação , Europa (Continente) , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Naftalenos/administração & dosagem , Naftalenos/efeitos adversos , Gradação de Tumores , América do Norte , Razão de Chances , Medição da Dor , Prednisona/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/administração & dosagem , Resultado do TratamentoRESUMO
PURPOSE: To analyze the factors that affect survival in patients with brain metastases (BM) from breast cancer who were treated with whole brain radiotherapy (WBRT). METHODS AND MATERIALS: We identified 116 women with breast cancer who were treated with WBRT alone between February 1984 and September 2000. All patients had treatment and follow-up data available in their medical charts, which we extracted for this retrospective study. We evaluated a number of potential predictors of survival after WBRT: age, primary tumor stage, control of primary tumor, presence of other systemic metastases, site of systemic metastases, Karnofsky performance status, Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis class, total dose of WBRT, and number of BM. Eighteen patients received a total dose >3000 cGy and 7 received a partial brain boost. RESULTS: For the entire cohort, the median survival from the start of WBRT was 4.2 months. The 1-year survival rate was 17%, and the 2-year survival rate was 2%. Using univariate analysis, only Karnofsky performance status (p = 0. 0084), recursive partitioning analysis class (p = 0. 0147), and total WBRT dose (p = 0.0001) were predictive of longer survival. In multivariate analysis, Karnofsky performance status was the only significant predictor. CONCLUSION: Overall survival in breast cancer patients with BM treated with WBRT is poor. We recommend breast cancer patients with BM be enrolled in prospective trials to improve results.