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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer

Cleary, James M., Mamon, Harvey J., Szymonifka, Jackie, Bueno, Raphael, Choi, Noah, Donahue, Dean M., Fidias, Panos M., Gaissert, Henning A., Jaklitsch, Michael T., Kulke, Matthew H., Lynch, Thomas P., Mentzer, Steven J., Meyerhardt, Jeffrey A., Swanson, Richard S., Wain, John, Fuchs, Charles S., Enzinger, Peter C. 13 July 2016 (has links)
Background: Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation. Methods: This single arm phase 2 trial combined irinotecan, cisplatin, and celecoxib with concurrent radiation therapy. Patients with stage IIA-IVA esophageal cancer received weekly cisplatin 30 mg/m(2) plus irinotecan 65 mg/m(2) on weeks 1, 2, 4, and 5 concurrently with 5040 cGy of radiation therapy. Celecoxib 400 mg was taken orally twice daily during chemoradiation, up to 1 week before surgery, and for 6 months following surgery. Results: Forty patients were enrolled with stage IIa (30 %), stage IIb (20 %), stage III (22.5 %), and stage IVA (27.5 %) esophageal or gastroesophageal junction cancer (AJCC, 5th Edition). During chemoradiation, grade 3-4 treatment-related toxicity included dysphagia (20 %), anorexia (17.5 %), dehydration (17.5 %), nausea (15 %), neutropenia (12.5 %), diarrhea (10 %), fatigue (7.5 %), and febrile neutropenia (7.5 %). The pathological complete response rate was 32.5 %. The median progression free survival was 15.7 months and the median overall survival was 34.7 months. 15 % (n = 6) of patients treated on this study developed brain metastases. Conclusions: The addition of celecoxib to neoadjuvant cisplatin-irinotecan chemoradiation was tolerable; however, overall survival appeared comparable to prior studies using neoadjuvant cisplatin-irinotecan chemoradiation alone. Further studies adding celecoxib to neoadjuvant chemoradiation in esophageal cancer are not warranted.
2

POWERPIINC (PreOperative Window of Endocrine TheRapy Provides Information to Increase Compliance) trial: Changes in tumor proliferation index and quality of life with 7 days of preoperative tamoxifen

Cohen, Adam L., Factor, Rachel E., Mooney, Kathi, Salama, Mohamed E., Wade, Mark, Serpico, Victoria, Ostrander, Emily, Nelson, Edward, Porretta, Jane, Matsen, Cindy, Bernard, Philip, Boucher, Ken, Neumayer, Leigh 02 1900 (has links)
Objectives: A decrease in Ki67 during neoadjuvant therapy predicts response to tamoxifen. Previous trials have shown a decreased Ki67 in breast tumors with as little as two or more weeks of preoperative tamoxifen. Shortening the preoperative treatment time in window of opportunity clinical trials makes these trials more attractive to women. POWERPIINC examined the effect of 7 days of preoperative tamoxifen on breast tumor proliferation and patient symptoms. Methods: Women with untreated stage I/II, ER-positive, invasive breast cancer with no contraindications to tamoxifen were enrolled. Women received 20 mg of tamoxifen for 7 days up to the day of surgery. Proliferation was assessed by Ki67 immunohistochemistry before and after 7 days of tamoxifen. Symptoms and QOL were assessed by the FACT-ES and MENQOL. Adherence was measured by pill counts. Results: 52 women were enrolled, and 44 were evaluable for Ki67. The median age was 58.5 years, and the median tumor diameter was 1.2 cm. Most women (73%) were post-menopausal. Most tumors were PR positive (88%) and HER2-negative (92%). The Ki67 decreased by a geometric mean of 40% (95% CI 29%-63%), and 73% (95% CI 57%-85%) of women had tumors with decreased proliferation (p = 0.0001 by paired t-test). Adherence to taking tamoxifen during the preoperative period was 100%. Women reported minimal bother from psychosocial or physical symptoms at baseline or on the day of surgery. Conclusion: Seven days of tamoxifen showed a similar relative decrease in Ki67 as that reported for longer courses, was acceptable to women, and could be considered for window of opportunity studies.
3

Avaliação da expressão da proteína EZH2 na resposta do carcinoma de mama localmente avançado à quimioterapia neoadjuvante / EZH2 protein expression on the response to neoadjuvant chemotherapy in locally advanced breast cancer

Neusquen, Lucienne Pereira Del Grossi 23 October 2012 (has links)
INTRODUÇÃO: O tratamento de escolha do carcinoma de mama localmente avançado é a quimioterapia neoadjuvante, porém, em virtude da heterogeneidade tumoral, sabe-se que nem todos os tumores responderão a esse tratamento. Neste contexto, avaliamos a proteína EZH2 (Enhancer of Zest Homolog 2), uma histona-metiltransferase catalisadora da trimetilação da lisina 27 da histona H3, com objetivos de avaliar sua expressão na predição da resposta do carcinoma de mama localmente avançado à quimioterapia neoadjuvante e de correlacionar sua expressão com a análise imunoistoquímica dos marcadores prognósticos usuais (proteínas HER2, Ki- 67, receptores hormonais de estrogênio e progesterona) e do p53. MÉTODOS: Foram obtidos fragmentos de tumor de 37 pacientes com carcinoma invasivo de mama nos estádios IIb e IIIa, submetidas à quimioterapia neoadjuvante com agentes antracíclicos. As pacientes pertenciam a 2 grupos. O Grupo 1 era composto de 19 pacientes que apresentaram resposta objetiva ao tratamento quimioterápico. No Grupo 2, as 18 pacientes não apresentaram essa resposta. Através da construção de arranjo em matriz de amostras teciduais, realizamos análise imunoistoquímica das expressões das proteínas HER2, Ki-67, p53, dos receptores de estrogênio e progesterona e da EZH2. RESULTADOS: O grupo de pacientes que não responde à quimioterapia tem, em média, idade significativamente superior (56,5 anos) ao das pacientes com resposta à quimioterapia (46,5 anos), porém os grupos não diferiram em relação ao número de ciclos de quimioterapia e em relação aos valores dos receptores hormonais e de HER2, Ki-67 e EZH2. A comparação entre a faixa etária, o número de ciclos de quimioterapia e os marcadores biológicos tumorais não demonstrou diferença significativa entre os grupos. A relação linear dos valores da proteína EZH2 com a idade, o número de ciclos de quimioterapia e os valores dos receptores hormonais foi negativa; e com as proteínas HER2 e Ki-67 a relação foi positiva. Para o grupo de pacientes que respondem ou não à quimioterapia neoadjuvante, não houve associação com as taxas de proteína EZH2. CONCLUSÕES: A proteína EZH2 correlaciona-se negativamente com os receptores hormonais de estrogênio e de progesterona e, positivamente com as proteínas HER2 e Ki-67. A expressão dessa proteína não se correlacionou com a resposta clínica do carcinoma de mama localmente avançado à quimioterapia neoadjuvante à base de antracíclicos. / INTRODUCTION: Neoadjuvant chemotherapy is the treatment of choice for patients with locally advanced breast cancer, however, because of tumor heterogeneity, not all tumors will respond to this treatment. In this context, we evaluated the EZH2 protein (Enhancer of Zest Homolog 2), a histone methyltransferase. EZH2 catalyses the trimethylation of lysine 27 of histone H3. The purposes of this study were to evaluate the expression of EZH2 for predicting tumor response to neoadjuvant chemotherapy in locally advanced breast cancer and its relation to usual prognostic markers (HER2, Ki-67, hormonal receptors of estrogen and progesterone - ER and PR) and p53. METHODS: Thirty-seven paraffin-embedded tumor blocks from different patients with stages IIb and IIIa invasive breast cancer. All of them have received neoadjuvant anthracycline-containing chemotherapy. The patients belonged to two different groups. Group 1 comprised 19 patients with objective response to chemotherapy, and Group 2, comprised 18 patients with no response to treatment. A TMA-based (tissue microarray) immunohistochemical analysis of HER2, Ki-67, p53, estrogen and progesterone receptors and EZH2 was performed. RESULTS: The group of patients who did not achieve a response had higher age (56.5 years) than the patients with response to chemotherapy (46.5 years), but the groups did not differ from the number of cycles of chemotherapy, and from the values of hormone receptors and HER2, Ki-67 and EZH2. The analysis of age, number of cycles of chemotherapy and biological tumor markers did not show a significant difference between the two groups. There was a negative linear relationship between EZH2 values and age, number of cycles of chemotherapy and hormone receptors. There was a positive linear relationship between EZH2 and HER2 and Ki-67. There was no association between EZH2 expression and response to chemotherapy. CONCLUSIONS: EZH2 protein is negatively correlated with hormonal receptors (ER and PR), and positively correlated with HER2 and Ki-67. There was no correlation between EZH2 expression and response to neoadjuvant anthracyclinecontaining chemotherapy.
4

Avaliação da expressão da proteína EZH2 na resposta do carcinoma de mama localmente avançado à quimioterapia neoadjuvante / EZH2 protein expression on the response to neoadjuvant chemotherapy in locally advanced breast cancer

Lucienne Pereira Del Grossi Neusquen 23 October 2012 (has links)
INTRODUÇÃO: O tratamento de escolha do carcinoma de mama localmente avançado é a quimioterapia neoadjuvante, porém, em virtude da heterogeneidade tumoral, sabe-se que nem todos os tumores responderão a esse tratamento. Neste contexto, avaliamos a proteína EZH2 (Enhancer of Zest Homolog 2), uma histona-metiltransferase catalisadora da trimetilação da lisina 27 da histona H3, com objetivos de avaliar sua expressão na predição da resposta do carcinoma de mama localmente avançado à quimioterapia neoadjuvante e de correlacionar sua expressão com a análise imunoistoquímica dos marcadores prognósticos usuais (proteínas HER2, Ki- 67, receptores hormonais de estrogênio e progesterona) e do p53. MÉTODOS: Foram obtidos fragmentos de tumor de 37 pacientes com carcinoma invasivo de mama nos estádios IIb e IIIa, submetidas à quimioterapia neoadjuvante com agentes antracíclicos. As pacientes pertenciam a 2 grupos. O Grupo 1 era composto de 19 pacientes que apresentaram resposta objetiva ao tratamento quimioterápico. No Grupo 2, as 18 pacientes não apresentaram essa resposta. Através da construção de arranjo em matriz de amostras teciduais, realizamos análise imunoistoquímica das expressões das proteínas HER2, Ki-67, p53, dos receptores de estrogênio e progesterona e da EZH2. RESULTADOS: O grupo de pacientes que não responde à quimioterapia tem, em média, idade significativamente superior (56,5 anos) ao das pacientes com resposta à quimioterapia (46,5 anos), porém os grupos não diferiram em relação ao número de ciclos de quimioterapia e em relação aos valores dos receptores hormonais e de HER2, Ki-67 e EZH2. A comparação entre a faixa etária, o número de ciclos de quimioterapia e os marcadores biológicos tumorais não demonstrou diferença significativa entre os grupos. A relação linear dos valores da proteína EZH2 com a idade, o número de ciclos de quimioterapia e os valores dos receptores hormonais foi negativa; e com as proteínas HER2 e Ki-67 a relação foi positiva. Para o grupo de pacientes que respondem ou não à quimioterapia neoadjuvante, não houve associação com as taxas de proteína EZH2. CONCLUSÕES: A proteína EZH2 correlaciona-se negativamente com os receptores hormonais de estrogênio e de progesterona e, positivamente com as proteínas HER2 e Ki-67. A expressão dessa proteína não se correlacionou com a resposta clínica do carcinoma de mama localmente avançado à quimioterapia neoadjuvante à base de antracíclicos. / INTRODUCTION: Neoadjuvant chemotherapy is the treatment of choice for patients with locally advanced breast cancer, however, because of tumor heterogeneity, not all tumors will respond to this treatment. In this context, we evaluated the EZH2 protein (Enhancer of Zest Homolog 2), a histone methyltransferase. EZH2 catalyses the trimethylation of lysine 27 of histone H3. The purposes of this study were to evaluate the expression of EZH2 for predicting tumor response to neoadjuvant chemotherapy in locally advanced breast cancer and its relation to usual prognostic markers (HER2, Ki-67, hormonal receptors of estrogen and progesterone - ER and PR) and p53. METHODS: Thirty-seven paraffin-embedded tumor blocks from different patients with stages IIb and IIIa invasive breast cancer. All of them have received neoadjuvant anthracycline-containing chemotherapy. The patients belonged to two different groups. Group 1 comprised 19 patients with objective response to chemotherapy, and Group 2, comprised 18 patients with no response to treatment. A TMA-based (tissue microarray) immunohistochemical analysis of HER2, Ki-67, p53, estrogen and progesterone receptors and EZH2 was performed. RESULTS: The group of patients who did not achieve a response had higher age (56.5 years) than the patients with response to chemotherapy (46.5 years), but the groups did not differ from the number of cycles of chemotherapy, and from the values of hormone receptors and HER2, Ki-67 and EZH2. The analysis of age, number of cycles of chemotherapy and biological tumor markers did not show a significant difference between the two groups. There was a negative linear relationship between EZH2 values and age, number of cycles of chemotherapy and hormone receptors. There was a positive linear relationship between EZH2 and HER2 and Ki-67. There was no association between EZH2 expression and response to chemotherapy. CONCLUSIONS: EZH2 protein is negatively correlated with hormonal receptors (ER and PR), and positively correlated with HER2 and Ki-67. There was no correlation between EZH2 expression and response to neoadjuvant anthracyclinecontaining chemotherapy.
5

Estudo retrospectivo do impacto da terapêutica neo-adjuvante do carcinoma de esôfago na sobrevida dos pacientes operados na Faculdade de Ciências Médicas da Unicamp / Retrospective study of results of neo-adjuvant therapy of esophgeal carcinoma in the survival of the operated patients in the College of Medicine of UNICAMP

Tercioti Junior, Valdir, 1975- 16 August 2018 (has links)
Orientadores: Nelson Adami Andreollo, Luiz Roberto Lopes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-16T06:07:19Z (GMT). No. of bitstreams: 1 TerciotiJunior_Valdir_M.pdf: 3600998 bytes, checksum: 6867e524b51d1a71d777c2132d9f2244 (MD5) Previous issue date: 2010 / Resumo: A neoplasia de esôfago é a oitava neoplasia mais incidente no Brasil, mantendo alta letalidade a despeito da melhora do tratamento cirúrgico nas últimas décadas. Os tratamentos utilizados dividem-se em: I) paliativos (sondas para nutrição enteral, próteses endoscópicas, gastrostomia, jejunostomia, derivação esôfago-gástrica, quimioterapia, radioterapia) e; II) curativos (esofagectomias isoladas, terapias neo-adjuvantes e terapias adjuvantes). Sendo assim, estratégias de tratamento neo-adjuvante tornam-se objeto de estudo. O objetivo do trabalho é avaliar em estudo retrospectivo não-randomizado a morbidade, a mortalidade e a sobrevida dos pacientes operados na Faculdade de Ciências Médicas da UNICAMP no período de 1979 a 2006, divididos em três grupos: I) esofagectomia; II) radioterapia neo-adjuvante seguido de esofagectomia; e III) radioterapia-quimioterapia neo-adjuvante seguido de esofagectomia. Na análise dos resultados, os grupos não diferem significativamente quanto ao sexo, cor, idade, alguns sintomas pré-operatórios (pirose, tabagismo), complicações pós-operatórias, mortalidade, N patológico, grau de diferenciação histológica e estadiamento; os grupos diferem significativamente em relação a outros sintomas (disfagia, dor retroesternal, etilismo), localização tumoral, T patológico e resposta tumoral. As conclusões mostram diferenças de sobrevida entre os grupos após a exclusão dos óbitos peri-operatórios, com benefício estatisticamente significativo para a terapêutica neo-adjuvante / Abstract: Neoplasm of esophagus cancer is the eighth highest incidence in Brazil, maintaining a high mortality rate despite the improvement of surgical treatment in recent decades. Treatments are divided into: I) palliative (nasogastric tube for enteral nutrition, prosthetics, endoscopic gastrostomy, jejunostomy, esophageal-gastric bypass, chemotherapy, radiotherapy) and; II) radical (esophagectomy isolated, neo-adjuvant therapy and adjuvant therapy) . Thus, neoadjuvant treatment strategies become the object of study. The objective is to evaluate with a non-randomized retrospective study morbidity, mortality and survival of patients operated in the Faculty of Medical Sciences of Campinas in the period 1979-2006, divided into three groups: I) esophagectomy; II) neoadjuvant radiotherapy followed by esophagectomy, and III) neoadjuvant radiotherapy and chemotherapy followed by esophagectomy. Results show that groups did not differ significantly regarding gender, race, age, some preoperative symptoms (heartburn, smoking), postoperative complications, mortality, N pathological, histological grade and stage; groups differ significantly for other symptoms (dysphagia, retrosternal pain, alcoholism), tumor location, T and pathological tumor response. Findings show differences in survival between groups after the exclusion of perioperative deaths, with statistically significant benefit for neoadjuvant therapy / Mestrado / Cirurgia / Mestre em Cirurgia
6

Avaliação da implantação do Fluxo Gerenciado FGC20, modelo de gerenciamento do protocolo clínico institucional para o tratamento neoadjuvante de adenocarcinoma de reto / Integrated care pathway for rectal cancer: implementation evaluation

Kobayashi, Silvia Takanohashi 21 October 2016 (has links)
Introdução. O Fluxo Gerenciado FGC20 é um protocolo institucional que define as etapas do tratamento neoadjuvante para adenocarcinoma de reto, com quimioterapia e radioterapia concomitantes e posterior cirurgia. Sua implantação no Instituto do Câncer do Estado de São Paulo (ICESP), a partir de março de 2011, envolveu as áreas assistenciais médicas, multiprofissionais e administrativas, com o estabelecimento da sequência das etapas e intervalos desejáveis. Objetivos. Avaliar a implantação do modelo de gerenciamento do protocolo clínico institucional para o tratamento neoadjuvante do adenocarcinoma de reto, nomeado Fluxo Gerenciado FGC20, adotado no ICESP. Pacientes e métodos. Foi construído um modelo lógico operacional para descrever o processo de implantação do fluxo gerenciado FGC20. Indicadores de monitoramento foram definidos a partir do modelo lógico e comparados com o período prévio à implantação. Dois grupos foram comparados: grupo controle, de pacientes cuja entrada ocorreu entre 06/05/2008 a 11/05/2011(prévio à implantação, nomeado grupo PreFluxo); e grupo experimental, de pacientes com início de atendimento entre 12/05/2011 a 31/12/2013 (posterior à implantação, nomeado grupo FGC20). Foram incluídos pacientes consecutivos, com diagnóstico de câncer de reto, tratados com quimioterapia e radioterapia concomitantes e posterior realização de cirurgia, e excluídos pacientes metastáticos ao diagnóstico inicial, pacientes com tratamento prévio ao início do tratamento no serviço e pacientes que não realizaram o tratamento neoadjuvante. Foram observados os intervalos de tempo entre as etapas do tratamento e recursos utilizados, dentre consultas, exames, internações, quimioterapia, radioterapia e cirurgia. O estudo de descrição de custos foi apresentado em Reais de 2015 na perspectiva do serviço. Resultados. De um total de 624 pacientes, foram analisados 330 pacientes: 112 do grupo PréFluxo e 218 do grupo FGC20. Em relação aos indicadores de monitoramento da implantação, 66% dos pacientes do grupo FGC20 realizaram a 1ª consulta no intervalo < 15 dias, 75% dos pacientes ficaram dentro da meta esperada de 14 semanas para o intervalo entre o final da neoadjuvância e a cirurgia (mediana de 13,2 semanas grupo FGC20 e 20 semanas grupo PréFluxo) e 73% dos pacientes completaram todas as etapas do fluxo gerenciado no intervalo <189 dias (mediana de 176,4 dias grupo FGC20 e 261,5 dias grupo PréFluxo). No grupo PréFluxo, houve maior número de consultas com oncologistas clínicos, tomografias computadorizadas, ressonâncias magnéticas e sessões de radioterapia (p < 0,001), bem como maior média de eventos de passagens no Setor de Emergência e na Unidade de Terapia Intensiva, em relação ao grupo FGC20 (p<0,001) e a média de custo por paciente tratado no grupo PréFluxo foi de R$ 40.935,68 e mediana de R$ 37.948,05. No grupo Fluxo Gerenciado, a média de custo por paciente tratado foi de R$ 40.368,18 e a mediana de R$ 35.341,32 respectivamente. A média de sobrevida global foi de 5,99 (5,59-6,40) e de 7,01 (6,47-7,54) anos, para os grupos PreFluxo e FGC20, respectivamente (p=0,83). Conclusões. A implantação do fluxo gerenciado promoveu reduções em todos os intervalos de tempo entre as etapas do tratamento. Não houve diferenças estatisticamente significantes na sobrevida global e no custo por paciente tratado entre os grupos. Custos de diárias e consultas foram os segmentos mais representativos no custo total do tratamento do paciente com câncer de reto / Background. The FGC20 is an integrated care pathway started in May 2011 at Instituto do Cancer do Estado de Sao Paulo (ICESP) for neoadjuvant treatment of adenocarcinoma of rectum. The implementation involved a multidisciplinary team to standardize patient care and to define steps, interventions and goals. Objectives. To evaluate the implementation of a clinical care pathway of rectal cancer in a Brazilian tertiary academic oncology hospital. Patients and Methods: An operational logical model of the integrated care pathway was developed to describe the pathway implementation. Two cohorts of diagnosed rectal cancer patients were compared: a control cohort from May 06th, 2008 through May 11th, 2011 (before the implementation, named group Pre FGC20), and a cohort from May 12th, 2011 through December 31th, 2013 (after implementation, named group FGC20). We included consecutive patients treated with concomitant chemoradiotherapy (nCRT) followed by surgery. Patients with prior treatment or who have not performed the nCRT treatment or with metastatic disease at diagnosis were excluded. Time intervals between treatment steps and resources used, including consultations, exams, hospitalizations, chemotherapy, radiotherapy and surgery were assessed. Cost description study from the hospital perspective is presented in 2015 Reais. Results. From a total of 624 patients, 330 were included: 112 PreFGC20 and 218 FGC20. Implementation indicators of the group FGC20 were identified based on the logic model: 66% had the first consultation < 15 days, 75% < 14 weeks interval between the neoadjuvant treatment and surgery (Group PreFGC20: 20 weeks, median; group FGC20: 13.2 weeks, median) and 73% < 189 days to complete all treatment steps (Group PreFGC20: 261.5 days, median; group FGC20: 176.4 days, median). We found higher utilization of consultations with clinical oncologists, CT, MRIs and radiotherapy sessions in the Group PreFGC20 compared with the FGC20 Group (p < 0.001), and also more utilization of emergency room and intensive care unit in Group PreFGC20 (p < 0.001). Median cost per treated patient in Group PreFGC20 was R$ 37.948,05 and mean cost was R$ 40.935,68. Median cost per treated patient in Group FGC20 was R$ 35.341,32 and mean cost was R$ 40.368,18. The mean overall survival in the Pre-MFC20 group and MFC20 group were 5.99 (5.59-6.40) and 7.01 (6.47-7.54) years, respectively (p=0.83) Conclusions. The implementation of the ICP promoted reductions in all time intervals between treatment steps. There were no statistically significant difference in overall survival and cost per patient treated between the groups. Daily costs and consultations were the most representative segments in total cost of the rectal cancer patient treatment
7

Pesquisa do Linfonodo Sentinela em Pacientes portadoras de CÃncer de Mama localmente avanÃado e submetidas à quimioterapia neoadjuvante / Linfonodo sentry in cancer in breast local advanced pÃs-quimioterapia neoadjuvante

Paulo Henrique Walter de Aguiar 27 December 2007 (has links)
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / estudar o linfonodo sentinela em pacientes portadoras de cÃncer na mama localmente avanÃado e que foram submetidos a quimioterapia neoadjuvante, compararando-o com os linfonodos axilares nÃo-sentinelas. Verificar a taxa de identificaÃÃo do linfonodo sentinela nestas pacientes, assim como estimar a sensibilidade, especificidade, falso-negativo, valor preditivo negativo e acurÃcia do mÃtodo. Metodologia: estudo transversal de validaÃÃo de teste diagnÃstico, envolvendo 34 pacientes oriundas do AmbulatÃrio da Maternidade-Escola Assis Chateaubriand. As pacientes portadoras de cÃncer na mama localmente avanÃado foram submetidas a quimioterapia neoadjuvante e aquelas que apresentaram axila clinicamente negativa para metÃstase de cÃncer de mama foram submetidas a biopsia do linfonodo sentinela e linfadenectomia axilar, utilizando administraÃÃo subareolar de azul patente, e este, apÃs sua identificaÃÃo, foi estudado mediante o exame de citologia de contato e parafina e comparado com conteÃdo linfÃtico axilar nÃo-sentinela. Realizada anÃlise descritiva e anÃlise dos testes utilizando teste t de Student, as proporÃÃes dos testes foram consideradas significativamente diferentes quando a probabilidade de estas serem semelhantes foi menor ou igual a 0,05. Resultados: Quando foi testada a citologia de contato intra-operatÃrio e parafina linfonodo sentinela e padrÃo-ouro os linfonodos sentinelas e nÃo-sentinelas, a taxa de identificaÃÃo do linfonodo sentinela foi de 85,3%. A sensibilidade foi de 84,62% e a especificidade de 100%. O valor preditivo negativo de 87,99% e taxa de falso-negativo de 12,01%. A acurÃcia foi de 92,77%. Dado observado na amostra foi a diferenÃa significativa do nÃmero mÃdio do total de linfonodos observados entre o grupo de pacientes com tempo de intervenÃÃo cirÃrgica Ãtimo p=0,037. Quando foi testada apenas a citologia de contato intraoperatÃria do linfonodo sentinela e padrÃo-ouro, a parafina dos linfonodos sentinelas e nÃo-sentinelas a sensibilidade foi de 62,50%, a especificidade de 100%, valor preditivo negativo de 75,04%, falso-negativo de 24,96% e acurÃcia de 82,38%. ConclusÃo: a citologia de contato intraoperatÃrio do linfonodo sentinela para pacientes com cÃncer de mama localmente avanÃados com axila clinicamente negativa apÃs quimoterapia neoadjuvante apresenta baixa sensibilidade e taxa de falso-negativo elevada. / Aims: investigating sentinel lymph node in patients with locally advanced breast cancer whom were administered neoadjuvant chemotherapy, by contrast to non-sentinel axillary lymph nodes. Verifying the identification of sentinel lymph node rate in these patients, as well as estimating methodâs sensibility, specificity, false-negative and accuracy. Methodology: transversal study for validation of a diagnostic test, with 34 patients from Maternidade-Escola Assis Chateaubriandâs ambulatory. The locally advanced breast cancer patients were treated with neoadjuvant chemotherapy, and the ones with cancer metastasis clinically negative axilla were submitted to sentinel lymph node biopsy and axillary lymphadenectomy, using subareolar patent blue, and, after its identification, it was studied with contact cytology and paraffin and it was compared with non-sentinel axillary lymph content. The descriptive analysis of tests used Studentâs t-test, and tests proportions were considered significantly different when their similarity possibility was less or equal to 0.05. Results: When intraoperatory contact cytology study, paraffin sentinel lymph node and gold standar, sentinel and non-sentinel lymph nodes, the sentinel lymph node identification rate was 85.3%. Sensibility was 84.62%, and specificity was 100%. The predictive negative value was 87.99%, and the false-negative rate was 12.01%. Accuracy rate was 92.77%. The study points the significant difference of total lymph nodes mean number observed among the group with optimal time of surgical intervention p=0.037. When only the intraoperatory contact cytology of sentinel lymph node and gold pattern, the paraffin of sentinel and non-sentinel lymph nodes, sensibility was 62.50%, specificity 100%, predictive negative value 75.04%, false-negative 24.96%, and accuracy 82.38%. Conclusion: intraoperatory contact cytology of sentinel lymph node to locally advanced breast cancer patients with clinically negative axilla after neoadjuvant chemotherapy presents low sensibility and high false-negative rates.
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Avaliação da implantação do Fluxo Gerenciado FGC20, modelo de gerenciamento do protocolo clínico institucional para o tratamento neoadjuvante de adenocarcinoma de reto / Integrated care pathway for rectal cancer: implementation evaluation

Silvia Takanohashi Kobayashi 21 October 2016 (has links)
Introdução. O Fluxo Gerenciado FGC20 é um protocolo institucional que define as etapas do tratamento neoadjuvante para adenocarcinoma de reto, com quimioterapia e radioterapia concomitantes e posterior cirurgia. Sua implantação no Instituto do Câncer do Estado de São Paulo (ICESP), a partir de março de 2011, envolveu as áreas assistenciais médicas, multiprofissionais e administrativas, com o estabelecimento da sequência das etapas e intervalos desejáveis. Objetivos. Avaliar a implantação do modelo de gerenciamento do protocolo clínico institucional para o tratamento neoadjuvante do adenocarcinoma de reto, nomeado Fluxo Gerenciado FGC20, adotado no ICESP. Pacientes e métodos. Foi construído um modelo lógico operacional para descrever o processo de implantação do fluxo gerenciado FGC20. Indicadores de monitoramento foram definidos a partir do modelo lógico e comparados com o período prévio à implantação. Dois grupos foram comparados: grupo controle, de pacientes cuja entrada ocorreu entre 06/05/2008 a 11/05/2011(prévio à implantação, nomeado grupo PreFluxo); e grupo experimental, de pacientes com início de atendimento entre 12/05/2011 a 31/12/2013 (posterior à implantação, nomeado grupo FGC20). Foram incluídos pacientes consecutivos, com diagnóstico de câncer de reto, tratados com quimioterapia e radioterapia concomitantes e posterior realização de cirurgia, e excluídos pacientes metastáticos ao diagnóstico inicial, pacientes com tratamento prévio ao início do tratamento no serviço e pacientes que não realizaram o tratamento neoadjuvante. Foram observados os intervalos de tempo entre as etapas do tratamento e recursos utilizados, dentre consultas, exames, internações, quimioterapia, radioterapia e cirurgia. O estudo de descrição de custos foi apresentado em Reais de 2015 na perspectiva do serviço. Resultados. De um total de 624 pacientes, foram analisados 330 pacientes: 112 do grupo PréFluxo e 218 do grupo FGC20. Em relação aos indicadores de monitoramento da implantação, 66% dos pacientes do grupo FGC20 realizaram a 1ª consulta no intervalo < 15 dias, 75% dos pacientes ficaram dentro da meta esperada de 14 semanas para o intervalo entre o final da neoadjuvância e a cirurgia (mediana de 13,2 semanas grupo FGC20 e 20 semanas grupo PréFluxo) e 73% dos pacientes completaram todas as etapas do fluxo gerenciado no intervalo <189 dias (mediana de 176,4 dias grupo FGC20 e 261,5 dias grupo PréFluxo). No grupo PréFluxo, houve maior número de consultas com oncologistas clínicos, tomografias computadorizadas, ressonâncias magnéticas e sessões de radioterapia (p < 0,001), bem como maior média de eventos de passagens no Setor de Emergência e na Unidade de Terapia Intensiva, em relação ao grupo FGC20 (p<0,001) e a média de custo por paciente tratado no grupo PréFluxo foi de R$ 40.935,68 e mediana de R$ 37.948,05. No grupo Fluxo Gerenciado, a média de custo por paciente tratado foi de R$ 40.368,18 e a mediana de R$ 35.341,32 respectivamente. A média de sobrevida global foi de 5,99 (5,59-6,40) e de 7,01 (6,47-7,54) anos, para os grupos PreFluxo e FGC20, respectivamente (p=0,83). Conclusões. A implantação do fluxo gerenciado promoveu reduções em todos os intervalos de tempo entre as etapas do tratamento. Não houve diferenças estatisticamente significantes na sobrevida global e no custo por paciente tratado entre os grupos. Custos de diárias e consultas foram os segmentos mais representativos no custo total do tratamento do paciente com câncer de reto / Background. The FGC20 is an integrated care pathway started in May 2011 at Instituto do Cancer do Estado de Sao Paulo (ICESP) for neoadjuvant treatment of adenocarcinoma of rectum. The implementation involved a multidisciplinary team to standardize patient care and to define steps, interventions and goals. Objectives. To evaluate the implementation of a clinical care pathway of rectal cancer in a Brazilian tertiary academic oncology hospital. Patients and Methods: An operational logical model of the integrated care pathway was developed to describe the pathway implementation. Two cohorts of diagnosed rectal cancer patients were compared: a control cohort from May 06th, 2008 through May 11th, 2011 (before the implementation, named group Pre FGC20), and a cohort from May 12th, 2011 through December 31th, 2013 (after implementation, named group FGC20). We included consecutive patients treated with concomitant chemoradiotherapy (nCRT) followed by surgery. Patients with prior treatment or who have not performed the nCRT treatment or with metastatic disease at diagnosis were excluded. Time intervals between treatment steps and resources used, including consultations, exams, hospitalizations, chemotherapy, radiotherapy and surgery were assessed. Cost description study from the hospital perspective is presented in 2015 Reais. Results. From a total of 624 patients, 330 were included: 112 PreFGC20 and 218 FGC20. Implementation indicators of the group FGC20 were identified based on the logic model: 66% had the first consultation < 15 days, 75% < 14 weeks interval between the neoadjuvant treatment and surgery (Group PreFGC20: 20 weeks, median; group FGC20: 13.2 weeks, median) and 73% < 189 days to complete all treatment steps (Group PreFGC20: 261.5 days, median; group FGC20: 176.4 days, median). We found higher utilization of consultations with clinical oncologists, CT, MRIs and radiotherapy sessions in the Group PreFGC20 compared with the FGC20 Group (p < 0.001), and also more utilization of emergency room and intensive care unit in Group PreFGC20 (p < 0.001). Median cost per treated patient in Group PreFGC20 was R$ 37.948,05 and mean cost was R$ 40.935,68. Median cost per treated patient in Group FGC20 was R$ 35.341,32 and mean cost was R$ 40.368,18. The mean overall survival in the Pre-MFC20 group and MFC20 group were 5.99 (5.59-6.40) and 7.01 (6.47-7.54) years, respectively (p=0.83) Conclusions. The implementation of the ICP promoted reductions in all time intervals between treatment steps. There were no statistically significant difference in overall survival and cost per patient treated between the groups. Daily costs and consultations were the most representative segments in total cost of the rectal cancer patient treatment
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Cancer-associated fibroblasts and FHL2 protein as prognostic markers and possible therapeutic targets in colorectal cancer

Verset, Laurine 21 September 2016 (has links)
Les tumeurs sont constituées de deux groupes cellulaires :les cellules tumorales et les cellules dites « hôtes ». Au sein de ce dernier groupe, on retrouve les cellules endothéliales, les cellules inflammatoires mais également les fibroblastes associés au cancer (FAC). De plus en plus de données dans la littérature suggèrent l’importance des FAC dans l’invasion tumorale et le développement métastatique. De nombreuses études immunohistochimiques ont démontré le rôle pronostique des FAC dans différents cancers. Les traitements néoadjuvants modifient l’environnement tumoral mais l’impact de ces traitements sur les FAC est assez méconnu.Notre travail porte, tout d’abord, sur une revue de littérature à propos de l’impact pronostique négatif des FAC dans différents cancers. Ensuite, nous avons étudié le ratio des FAC SMA+/surface épithéliale tumorale dans une cohorte de patients ayant été opérés d’un adénocarcinome rectal ayant bénéficié ou pas d’une thérapie néoadjuvante. La comparaison du ratio entre les groupes traités et non traités a montré un ratio plus élevé chez les patients ayant bénéficié d’une thérapie néoadjuvante. Par ailleurs, les tumeurs présentant un ratio élevé présentent également un indice de prolifération faible suggérant que la thérapie néoadjuvante modifie l’environnement tumoral par une majoration des FAC aux dépens des cellules tumorales et par l’acquisition d’un phénotype quiescent des cellules tumorales. Finalement, chez les patients traités par une thérapie néoadjuvante, un ratio supérieur à un est associé à une survie sans récidive mauvaise.Nous nous sommes ensuite intéressés à la protéine FHL2 qui est exprimée par les FAC mais également par les cellules tumorales. L’étude de l’expression immunohistochimique de la protéine FHL2 sur un tissue microarray de cancers coliques a démontré que celle-ci est exprimée fréquemment dans les FAC de cancers coliques alors que l’expression dans les cellules tumorales est plus variable. Nous avons démontré que les tumeurs coliques exprimant fortement FHL2 sont associées à un plus mauvais pronostic (survie et survie sans récidive). Ce résultat est probablement lié à l’implication de cette protéine dans la transition épithélio-mésenchymateuse.Finalement, nous avons étudié la possibilité d’une interaction entre FHL2 et ADAM-17. Nous avons démontré que cette interaction est plus fréquente dans le cancer colique comparé au tissu colique normal. Ce dernier résultat ouvre la voie vers un partenaire potentiel de FHL2 qui pourrait notamment interférer avec la voie de signalisation de l’EGF. / Tumours are composed of two cellular groups: the tumoural cells and the host cells. In this latter, we find endothelial cells, inflammatory cells but also the cancer-associated fibroblasts (CAFs). More and more litterature data suggest a key role of CAFs in the tumoural invasion and in the metastatic development. Several immunohistochemical studies have highlighted the prognostic role of CAFs in different cancers. Neoadjuvant treatments modulate the tumoural environment but the impact of such treatment on the CAFs is relatively unknown.In the first part of this thesis we revise the current knowledge on the adverse prognostic impact of CAFs in different cancers. We studied by immunohistochemistry the ratio CAFs SMA+/tumoural epithelial area within a patient cohort operated for rectal adenocarcinoma receiving or not a neoadjuvant treatment. The comparison of the ratio between the treated group and the non-treated group showed that this ratio is higher in patients treated with neoadjuvant therapy. Moreover, rectal cancer with a high ratio displayed a lower proliferation rate suggesting that the neoadjuvant treatment modifies the tumoural environment by an increase of CAFs and by acquisition of a quiescent phenotype of the tumoural cells. In the group of patients treated with neoadjuvant treatment, a ratio >1 was associated with an adverse impact on recurrence free survival.Secondly, we studied Four-and-a-half LIM Domain protein 2 (FHL2) which is a protein expressed by CAFs but also by the tumoural cells. Immunohistochemical study of FHL2 expression on a colon cancer tissue microarray demonstrated that FHL2 is frequently expressed in colon cancer CAFs while its expression is variable in the tumoural cells. We demonstrated that high FHL2 expression in colon cancer is related to poor prognosis (overall survival and metastasis free survival). Aggressive behaviour in such tumours might be related to the implication of FHL2 in epithelial-to-mesenchymal transition.Finally, we studied a possible interaction between FHL2 and ADAM-17. We demonstrated that this interaction is more frequent in colon cancer compared to normal colonic tissue, suggesting a role for it in colon cancer development. This interaction possibly interferes with the EGF pathway / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished
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Efikasnost lečenja bolesnika u IIIA stadijumu nemikrocelularnog karcinoma bronha operisanih nakon neoadjuvantne terapije / The effectiveness of treatment for patients in the stage IIIA nonsmall cell lung cancer who were operated after neoadjuvant therapy

Đukić Nevena 14 December 2016 (has links)
<p>Karcinom bronha najče&scaron;ći uzrok smrti među malignim bolesti u svetu. U XX veku je registrovan značajan porast kako incidence, tako i mortaliteta karcinoma bronha u većini zemalja. Medijana preživljavanja u svim stadijumima bolesti se značajno pobolj&scaron;ala poslednjih godina XX veka, ali nedovoljno u odnosu na očekivano. U najvećem broju slučajeva, bolest se otkriva u uznapredovalom stadijumu, kada je radikalno hirur&scaron;ko lečenje kao optimalan vid lečenja nemoguće. Neodjuvantna terapija kod bolesnika sa lokalno uznapredovalim karcinomom pluća i zahvaćenim N2 limfnim čvorovima jedan je od modusa multimodalnog lečenja bolesnika sa nemikrocelularnim karcinomima pluća (NSCLC) u cilju pobolj&scaron;anja ishoda njihovog lečenja. Ovakav pristup podrazumeva prevođenje pacijenta iz vi&scaron;eg u niži stadijum bolesti - &bdquo;downstaging&rdquo;. Na taj način pacijent postaje potencijalno resektabilan u smislu daljeg hirur&scaron;kog lečenja koji bi mogao da obezebedi sveukupni onkolo&scaron;ki benefit. Osnovni ciljevi ove doktorske disertacije su bili: procena odgovora na neoadjuvantnu terapiju kod bolenika sa IIIA stadijumom nemikrocelularnog karcinoma bronha u odnosu na T faktor i N faktor, procena TNM klasifikacije pre i posle primenjene neoadjuvantne terapije kod bolesnika sa IIIA stadijumom nemikrocelularnog karcinoma bronha, određivanje stepena tumorske regresije patohistolo&scaron;kom analizom hirur&scaron;kog resekata nemikrocelularnog karcinoma bronha operisanih bolesnika nakon primenjene neoadjuvantne terapije, kao prognostički faktor za period bez bolesti i ukupnog preživljavanja i određivanje stepena regresije tumora u maligno izmenjenim limfnim čvorovima nakon primenjene neoadjuvantne terapije kod bolesnka sa IIIA stadijumom nemikrocelularnog karcinoma bronha, kao prognostički faktor za period bez bolesti i ukupnog preživljavanja.Rezultati su pokazali da neoadjuvantna terapija prema RECIST kriterijumima dovodi značajnog smanjenja veličine tumora, T faktora, kao i do znčajnog downstaging&ldquo;-a nodalnog statusa, N faktora, u terapiji bolesnika sa IIIA stadijumom nemikrocelularnog karcinoma bronha. Neoadjuvantna terapija prema RECIST kriterijumima dovodi značajnog smanjenja klinikog stadijuma bolesti, u terapiji bolesnika sa IIIA stadijumom nemikrocelularnog karcinoma bronha Nakon primenjene neoadjuvantne terapije nema značajne razlike u T faktoru koji je određen radiolo&scaron;ki prema RECIST kriterijumima (ycT) i patohistolo&scaron;ki (ypT) na hirur&scaron;kom materijalu. Nakon primenjene neoadjuvantne terapije prisutna je značajna razlika u N faktoru koji je određen radiolo&scaron;ki prema RECIST kriterijumima (ycN) i patohitolo&scaron;ki (ypN) na hirur&scaron;kom materijalu. Nakon primenjene neoadjuvantne terapije prisutna je značajna razlika u kliničkom stadijumu bolesti koji je određen radiolo&scaron;ki prema RECIST kriterijumima (yc) i patohitolo&scaron;ki (yp) na hirur&scaron;kom materijalu. Gradusi tumorske regresije su usko povezani sa procentom očuvanog tumorskog tkiva. Stepen tumorske regresije u resekatu primarnog tumora nije u korelaciji sa ukupnim preživljavanjem i procenom perioda bez bolesti kod pacijenata sa IIIA stadijumom nemikrocelularnog karcinoma bronha.</p> / <p>Lung cancer is the most common cause of death among malignant diseases in the world. In the twentieth century was a significant increase in both incidence and mortality of lung cancer in most countries. Median survival in all stages of the disease has improved significantly in recent years of the twentieth century, but not as we expected. In most cases, the disease is detected at an advanced stage, when the radical surgical treatment is considered impossible. Neoadjuvant therapy, in patients with locally advanced carcinoma of the lung, and with affected the lymph nodes N2, is one of the modes of multimodal treatment of patients with non-small cell lung cancer (NSCLC) in order to improve the outcome of their treatment. This involves translating the patient from a higher to a lower stage of the disease - &quot;downstaging&quot;. In this way the patient is considered for further surgical treatment that could provide him overall oncology benefit. Main objectives of this PhD dissertation are: evaluation of response to neoadjuvant therapy in stage IIIA NSCLC patients in relation to T factor and N factor; evaluation of TNM classification before and after use of neoadjuvant therapy in stage IIIA NSCLC patients; determination of degree of tumor regression with pathohistologic analysis of resection specimen of NSCLC obtained from patients after application of neoadjuvant therapy, as a prognostic factor for disease-free period and overall survival rate; and determination of degree of tumor regression in malignant lymph nodes after application of neoadjuvant therapy in stage IIIA NSCLC patients, as a prognostic factor for disease-free period and overall survival rate. Results have shown that neoadjuvant therapy according to RECIST criteria leads to significant reduction of tumor size, T factors, as well as significant downstaging of nodal status, N factor, in treatment of stage IIIA NSCLC patients. Furthermore, neoadjuvant therapy according to RECIST criteria leads to significant reduction of clinical stage of the disease in treatment of stage IIIA NSCLC patients. However, after neoadjuvant therapy is applied there is no significant difference in T factor determined radiologically according to RECIST criteria (ycT) and by pathohistologic analysis (ypT) of resected specimen. Neoadjuvant therapy leads to significant difference in N factor which is determined radiologically according to RECIST criteria (ycN) and by pathohistologic analysis (ypN) of resection specimen. After neoadjuvant therapy is applied there is significant difference in clinical stage of the disease determined radiologically according to RECIST criteria (yc) and by pathohistologic analysis (yp) of resection specimen. Tumor regression grading is closely linked to the percentage of preserved tumor tissue. Degree of tumor regression in surgical resection of primary tumor does not correlate to the overall survival rate and estimation of disease-free period in stage IIIA NSCLC patients.</p>

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