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IMPORTANCE: Locoregionally advanced head and neck squamous cell cancer (HNSCC) is treated curatively; however, risk of recurrence remains high among some patients. The ERBB family blocker afatinib has shown efficacy in recurrent or metastatic HNSCC. OBJECTIVE: To assess whether afatinib therapy after definitive chemoradiotherapy (CRT) improves disease-free survival (DFS) in patients with HNSCC. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, phase 3, double-blind randomized clinical trial (LUX-Head & Neck 2) studied 617 patients from November 2, 2011, to July 4, 2016. Patients who had complete response after CRT, comprising radiotherapy with cisplatin or carboplatin, with or without resection of residual disease, for locoregionally advanced high- or intermediate-risk HNSCC of the oral cavity, hypopharynx, larynx, or oropharynx were included in the study. Data analysis was of the intention-to-treat population. INTERVENTIONS: Patients were randomized (2:1) to treatment with afatinib (40 mg/d) or placebo, stratified by nodal status (N0-2a or N2b-3) and Eastern Cooperative Oncology Group performance status (0 or 1). Treatment continued for 18 months or until disease recurrence, unacceptable adverse events, or patient withdrawal. MAIN OUTCOMES AND MEASURES: The primary end point was DFS, defined as time from the date of randomization to the date of tumor recurrence or secondary primary tumor or death from any cause. Secondary end points were DFS at 2 years, overall survival (defined as time from the date of randomization to death), and health-related quality of life. RESULTS: A total of 617 patients were studied (mean [SD] age, 58 [8.4] years; 528 male [85.6%]). Recruitment was stopped after a preplanned interim futility analysis on July 4, 2016, on recommendation from an independent data monitoring committee. Treatment was discontinued. Median DFS was 43.4 months (95% CI, 37.4 months to not estimable) in the afatinib group and not estimable (95% CI, 40.1 months to not estimable) in the placebo group (hazard ratio, 1.13; 95% CI, 0.81-1.57; stratified log-rank test P = .48). The most common grade 3 and 4 drug-related adverse effects were acneiform rash (61 [14.8%] of 411 patients in the afatinib group vs 1 [0.5%] of 206 patients in the placebo group), stomatitis (55 [13.4%] in the afatinib group vs 1 [0.5%] in the placebo group), and diarrhea (32 [7.8%] in the afatinib group vs 1 [0.5%] in the placebo group). CONCLUSIONS AND RELEVANCE: This study's findings indicate that treatment with afatinib after CRT did not improve DFS and was associated with more adverse events than placebo in patients with primary, unresected, clinically high- to intermediate-risk HNSCC. The use of adjuvant afatinib after CRT is not recommended. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01345669.
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OBJECTIVE: To describe stage I-III breast cancer (BC) molecular subtypes and outcomes among a cohort of patients from Brazil. METHODS: AMAZONA study is a retrospective cohort conducted from June 2008 to January 2009 including women of at least 18 years old, with histologically proven breast cancer, diagnosed in 2001 (nâ¯=â¯2198) and 2006 (nâ¯=â¯2714). In this analysis, we included patients who underwent surgery, had stage I-III disease and available pathological information (nâ¯=â¯2296). We estimated molecular subtypes by local immunohistochemical stains. Data was obtained from medical charts and public databases. RESULTS: Mean age at diagnosis was 54 years and 41.1% were younger than 50 years. 23.3% were diagnosed in stage I, 53.5% in stage II and 23.2% in stage III. 80.8% were treated in the public health system. 71.3% had hormonal receptor positive disease, 15.7% were HER-2 positive and 21.1% had triple-negative breast cancer. 55.6% were treated with mastectomy and 96.2% received adjuvant treatment (82.2% chemotherapy). 13.4% of HER-2 positive patients received adjuvant trastuzumab. Overall survival rate at 5 years was 96.84% for stage I, 94.16% for stage II and 70.48% for stage III. Molecular subtypes were independent prognostic factor in stages II and III patients. CONCLUSIONS: Brazilian women have a higher risk of being diagnosed with late stage breast cancer and younger age than in high-income countries. Luminal-like disease is the most common molecular subtype in the country. Triple negative and HER-2 positive had the worst prognosis.
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Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Adulto , Brasil , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Mastectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/classificação , Neoplasias de Mama Triplo Negativas/patologia , Adulto JovemRESUMO
PURPOSE: Chemoradiotherapy is the standard treatment for patients with inoperable locally advanced oesophageal cancer. We sought to assess the safety and efficacy of chemoradiation combined with nimotuzumab, a humanised antibody directed against epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: Untreated patients with inoperable locally advanced oesophageal cancer and no distant metastases were randomised to chemoradiotherapy (cisplatin and fluorouracil combined with external beam radiation) alone or in combination with nimotuzumab. The primary end-point was the endoscopic complete response (eCR) rate, and secondary end-points comprised quality of life (QoL) and safety. The combined eCR and pathologic complete response (cEPCR) and overall survival (OS) were also evaluated. RESULTS: We enrolled 107 patients with a mean age of 59 years, and 93% had squamous cell carcinoma. Toxicity was manageable in both arms with no important differences in adverse events (AEs). We performed post-treatment endoscopies in 67 patients, including 60 who had a biopsy. In the intent-to-treat population, the eCR rates with and without nimotuzumab were 47.2% and 33.3% (P = 0.17), respectively, and the cEPCR rates were 62.3% and 37.0% (P = 0.02), respectively. With a median follow-up of 14.7 months, the hazard ratio (HR) for OS was 0.68 (95% confidence interval (CI): 0.44-1.07; P = 0.09) with a median OS of 15.9 months for the nimotuzumab arm and 11.5 months for the control arm. Regarding QoL, a significant difference was observed for the physical subscale score (P = 0.03) with lower values for the control arm. CONCLUSION: Combined chemoradiotherapy plus nimotuzumab is safe for patients with locally advanced oesophageal cancer, it appears to increase the cEPCR rate, and without compromising QoL. CLINICAL TRIALS: Identification number: EF024-201; Trial registry: NCT01249352.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/etiologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Neoplasias Esofágicas/patologia , Fadiga/etiologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Análise de SobrevidaRESUMO
INTRODUCTION: Angiogenesis (AG) is essential for epithelial ovarian cancer (EOC) development. Vascular endothelial growth factor (VEGF), encoded by the VEGF gene, and endostatin, the product of the COL18A1 gene, act as a potent promoter and an inhibitor of AG, respectively. In the present study, we tested whether VEGF C936T and COL18A1 D104N polymorphisms alter the risk of EOC. METHODS: Genomic DNA from 131 EOC patients and 137 controls were analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. The differences between groups were analyzed by χ (2) or Fisher's exact test and logistic regression analysis. RESULTS: The frequency of the VEGF 936CC genotype was higher in patients than in controls (84.8% vs. 75.3%, P = 0.03). Individuals with respective genotypes had a 1.98 (95% CI 1.04-3.78)-fold increased risk of EOC than those with the remaining genotypes. An excess of VEGF 936CC plus COL18A1 DN genotype was seen in patients when compared to controls (48.6% vs. 30.5%); however, only a tendency toward a statistically significant difference in genotype frequencies was found in the study (P = 0.06), reflecting a trend toward an increased risk of 2.44 for EOC in carriers of the combined genotype. CONCLUSION: Our data present, for the first time, preliminary evidence that VEGF C936T alone or combined with the COL18A1 D104N polymorphism of AG constitutes an important inherited EOC determinant.
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Biomarcadores Tumorais/genética , Colágenos Associados a Fibrilas/genética , Neoplasias Ovarianas/genética , Polimorfismo Genético/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Estudos de Casos e Controles , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prognóstico , Regiões Promotoras Genéticas , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Exposure of ovarian cells to estrogen, which is detoxified by glutathione S-transferases (GSTs), has been associated with epithelial ovarian cancer (EOC) development. OBJECTIVES: We tested in this study whether the GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms alter the risk of EOC. MATERIALS AND METHODS: Genomic DNA from 132 EOC patients and 132 controls was analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. The differences between groups were analyzed by χ
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Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Polimorfismo de Fragmento de Restrição , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Carcinoma Epitelial do Ovário , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Neoplasias Epiteliais e Glandulares/epidemiologia , Neoplasias Ovarianas/epidemiologia , Fatores de RiscoRESUMO
PURPOSE: Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo-controlled phase IIB trial assessed sorafenib with capecitabine for locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) -negative breast cancer. PATIENTS AND METHODS: Patients were randomly assigned to first- or second-line capecitabine 1,000 mg/m(2) orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The primary end point was progression-free survival (PFS). RESULTS: In total, 229 patients were enrolled. The addition of sorafenib to capecitabine resulted in a significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23; P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and hand-foot skin reaction/hand- foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4 toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%). Reasons for discontinuation in the sorafenib and placebo arms included disease progression (63% v 82%, respectively), adverse events (20% v 9%, respectively), and death (0% v 1%, respectively). CONCLUSION: Addition of sorafenib to capecitabine improved PFS in patients with HER2-negative advanced breast cancer. The dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients. A phase III confirmatory trial has been initiated with a reduced sorafenib dose.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/análise , Administração Oral , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzenossulfonatos/administração & dosagem , Brasil , Neoplasias da Mama/química , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Método Duplo-Cego , Esquema de Medicação , Europa (Continente) , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Invasividade Neoplásica , Niacinamida/análogos & derivados , Compostos de Fenilureia , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/administração & dosagem , Piridinas/administração & dosagem , Sorafenibe , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Worldwide incidence of melanoma has increased in recent years faster than any other cancer. Although it represents only 4% of skin cancers it is nevertheless responsible for 60% of skin cancer deaths. This makes melanoma a public health problem. OBJECTIVES: The aim of this study was the development of a continuous program for melanoma prevention and early detection. METHODS: A city of around 130,000 inhabitants in the state of São Paulo, Brazil, was chosen for the development of a pilot project covering primary prevention and early diagnosis of melanoma. A nursing team worked for approximately 30 days in each of the 13 health centers in the city of Jaú (SP), providing guidance on self-examination of the skin, photoprotection and recognition of early signs of melanoma. Patients with suspicious lesions were immediately sent to the reference hospital for medical and dermoscopic screening. Excisional biopsies were performed on suspected melanomas. RESULTS: 4 four cases of early stage melanoma and 3 dysplastic nevi were diagnosed. Of the people interviewed, 74% worked either part-time or full-time exposed to sun and over 60% claimed to never use sunscreen. CONCLUSION: This is a new and effective model for melanoma prevention and early diagnosis. In short, the melanoma prevention program is able to quickly identify suspicious lesions, leading to early diagnosis and better chances of survival.
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Promoção da Saúde/métodos , Programas de Rastreamento/métodos , Melanoma/prevenção & controle , Prevenção Primária/métodos , Neoplasias Cutâneas/prevenção & controle , Adulto , Diagnóstico Precoce , Feminino , Educação em Saúde , Humanos , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Prognóstico , Avaliação de Programas e Projetos de Saúde , Neoplasias Cutâneas/diagnóstico , Adulto JovemRESUMO
55 patients with advanced cutaneous squamous cell carcinoma (CSCC) of the trunk and extremities were studied. A Tissue Microarray was constructed using immunohistochemistry to quantify expression of the HER family, E-cadherins, and podoplanin. Clinical and histopathological factors related to lymph node metastasis and prognosis were also established. Primary tumor positivity was 25.5% for EGFR, 87.3% for HER-3, and 48.1% for HER-4. Metastases were positive for EGFR in 41.7%, for HER-3 in 83.3%, and HER-4 in 43.5%. HER-2 was negative in all samples. Membrane E-cadherin and cytoplasmic E-cadherin were positive in 47.3% and 30.2% of primary tumors and 45.5% and 27.3% of metastases, respectively. Podoplanin was positive in 41.8% of primary tumors and 41.7% of metastases. Intratumoral lymphocytic infiltrate was associated with lymph node metastasis. Patients with T3 tumors had better cancer-specific survival (CSS) than those with T4 tumors; patients with no lymph node involvement had better CSS than patients with N1 tumors. Undifferentiated tumors and hyperexpression of podoplanin were negative prognostic indicators on multivariate analysis.
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FUNDAMENTO: A incidência do melanoma aumentou nos últimos anos mais rapidamente do que qualquer outro câncer. Embora represente apenas 4 por cento dos cânceres de pele, é o responsável por 60 por cento das mortes por esta neoplasia. Isto torna o melanoma um problema de saúde pública. OBJETIVOS: O presente estudo propôs o desenvolvimento de um Programa Contínuo de Prevenção do Melanoma, por meio da realização da prevenção primária e do diagnóstico precoce desta neoplasia. MÉTODOS: Foi tomada como piloto uma cidade de aproximadamente 130.000 habitantes. Uma equipe de enfermagem esteve presente por cerca de 30 dias em cada um dos 13 postos de saúde da cidade de Jaú (SP), realizando orientações quanto ao autoexame da pele, fotoproteção e sinais precoces do melanoma. O paciente com lesão suspeita era encaminhado imediatamente ao hospital de referência para dermatoscopia e triagem médica, sendo excisada quando suspeita. RESULTADOS: Foram diagnosticados 4 casos de melanoma em fase inicial e 3 nevos displásicos. Dos entrevistados, 74 por cento trabalham expostos ao sol, variando de meio período ao completo, e mais de 60 por cento nunca fizeram uso de filtro solar. CONCLUSÃO: Este modelo de programa de prevenção é inédito, exclusivo e demonstrou ser eficaz na prevenção e diagnóstico precoce do melanoma em uma cidade de 130.000 habitantes do Estado de São Paulo. Com esclarecimento à população e orientação à equipe de saúde, realiza-se uma rápida triagem e identificam-se lesões suspeitas de melanoma para que, com o diagnóstico em suas fases iniciais, o paciente apresente melhor prognóstico.
BACKGROUND: Worldwide incidence of melanoma has increased in recent years faster than any other cancer. Although it represents only 4 percent of skin cancers it is nevertheless responsible for 60 percent of skin cancer deaths. This makes melanoma a public health problem. OBJECTIVES: The aim of this study was the development of a continuous program for melanoma prevention and early detection. METHODS: A city of around 130,000 inhabitants in the state of São Paulo, Brazil, was chosen for the development of a pilot project covering primary prevention and early diagnosis of melanoma. A nursing team worked for approximately 30 days in each of the 13 health centers in the city of Jaú (SP), providing guidance on self-examination of the skin, photoprotection and recognition of early signs of melanoma. Patients with suspicious lesions were immediately sent to the reference hospital for medical and dermoscopic screening. Excisional biopsies were performed on suspected melanomas. RESULTS: 4 four cases of early stage melanoma and 3 dysplastic nevi were diagnosed. Of the people interviewed, 74 percent worked either part-time or full-time exposed to sun and over 60 percent claimed to never use sunscreen. CONCLUSION: This is a new and effective model for melanoma prevention and early diagnosis. In short, the melanoma prevention program is able to quickly identify suspicious lesions, leading to early diagnosis and better chances of survival.
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Promoção da Saúde/métodos , Programas de Rastreamento/métodos , Melanoma/prevenção & controle , Prevenção Primária/métodos , Neoplasias Cutâneas/prevenção & controle , Diagnóstico Precoce , Educação em Saúde , Melanoma/diagnóstico , Prognóstico , Avaliação de Programas e Projetos de Saúde , Neoplasias Cutâneas/diagnósticoAssuntos
Especialização , Internato e Residência , Oncologia/educação , Oncologia , Oncologia/tendênciasRESUMO
Um caso raro de linfangiomatose envolvendo unilateralmente o retroperitôneo, canal femural e rim ipsilateral é relatado. As características clínicas e formas de tratamento säo revistas.
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Humanos , Masculino , Adulto , Linfangioma/diagnóstico , Linfangioma/cirurgia , Neoplasias Retroperitoneais/diagnóstico , Neoplasias Retroperitoneais/cirurgiaRESUMO
Os dados referentes às pessoas residentes no município e com diagnóstico confirmado entre janeiro de 2000 e dezembro de 2004 já foram coletados e brevemente serão divulgados através de uma publicação específica. Atualmente estão sendo coletados os dados do período janeiro/2005 a dezembro/2008.São registros que nos fornecem informações permanentes sobre o número de casos novos nessa área delimitada, permitindo detectar setores onde a população local é mais afetada pela doença, fatores ambientais que possam estar relacionados e influenciar na prevalência da doença, identificar grupos étnicos afetados promovendo assim investigações epidemiológicas e estudos específicos. As informações obtidas desses registros também auxiliam na determinação da necessidade de campanhas junto à população na detecção precoce e prevenção do câncer, como também na avaliação de novas técnicas diagnósticas.