Made available in DSpace on 2014-06-11T19:23:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-11-12Bitstream added on 2014-06-13T18:50:47Z : No. of bitstreams: 1 duarte_psf_me_arafcf.pdf: 881250 bytes, checksum: 0243bb612ab8c3253bf8e99a55fd6441 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Universidade Estadual Paulista (UNESP) / Um dos tratamentos mais utilizados no câncer é a radioterapia. Esta, ao lado dos benefícios inerentes da terapia pode cursar com efeitos colaterais indesejados. Um destes efeitos diz respeito ao comprometimento do estado nutricional, tanto devido a doença em si, como da radioterapia. Conseqüentemente, a subnutrição destes pacientes é multifatorial e potencializa a morbi-mortalidade. No entanto, não há um consenso sobre o dano e nem sobre a sua relação temporal com intensidade, freqüência e estado nutricional. Objetivo: Avaliar prospectivamente a evolução do estado nutricional, do gasto energético e dos níveis corporais dos minerais, zinco, ferro, cálcio, magnésio e estrôncio antes e após a radioterapia em pacientes portadores de câncer de cabeça e pescoço. Métodos: Foram monitorados, utilizando as técnicas espectrofotométricas os minerais, zinco, ferro, cálcio, magnésio e estrôncio (plasmático, eritrocitário e urinário). Os pacientes foram avaliados quanto a ingestão dietética (questionário de freqüência do consumo alimentar), estimou-se a massa corpórea (antropometria e bioimpedância) e o gasto energético (calorimetria indireta). Resultados: Não foi verificada diferença significativa nos valores dos minerais (plasmático, eritrocitário e urinário), no gasto energético de repouso, na ingestão de macronutrientes e dos minerais analisados. Foram observadas alterações nas medidas antropométricas com valor significativo da porcentagem de gordura corporal, no volume expirado de gás carbono, na oxidação de carboidratos e no quociente respiratório. Conclusão: Apesar das alterações corporais ocorridas, são necessários mais estudos para limitar as variações corporais e bioquímicas dos pacientes com câncer de cabeça e pescoço submetidos à radioterapia e encontrar observações estatísticas mais definidas / One of the most used treatments for cancer is radiation therapy. This, along with the inherent benefits of therapy may be associated with unwanted side effects. One of these effects with respect to impairment of nutritional status, both because the disease itself, such as radiotherapy. Consequently, the malnutrition of these patients is multifactorial and enhances the morbidity and mortality. However, there is no consensus about the damage and not on its temporal relation to intensity, frequency and nutritional status. Objective: To evaluate prospectively the evolution of nutritional status, energy expenditure and body levels of minerals, zinc, iron, calcium, strontium and magnesium before and after radiotherapy in patients with head and neck cancer. Methods: We monitored using the spectrophotometric techniques minerals, zinc, iron, calcium, magnesium and strontium (plasma, erythrocyte and urinary). Patients were assessed for dietary intake (food frequency questionnaire of food consumption), we estimated body mass (anthropometry and bioimpedance) and energy expenditure (indirect calorimetry). Results: There was no significant difference in the values of minerals (plasma, erythrocyte and urinary) in resting energy expenditure, intake of nutrients and minerals analyzed. Have been changes in anthropometric measures with a significant value of the percentage of body fat, the volume of gas exhaled carbon in carbohydrate oxidation and respiratory quotient. Conclusion: Although the body changes that occur, more studies are needed to limit the variation in physical and biochemical characteristics of patients with head and neck cancer undergoing radiotherapy and find more definite statistical observations

Em radioterapia externa, uma nova técnica chamada terapia de radiação de intensidade modulada - IMRT - permite delinear a dose de radiação em imagens de 2 ou 3 dimensões, delimitando de forma bastante precisa e não necessariamente uniforme a região a ser irradiada. Assim, ao mesmo tempo que o tumor é irradiado, é possível evitar a irradiação aos tecidos vizinhos íntegros (sãos), limitando os efeitos secundários do tratamento. Para que a radioterapia externa tenha sucesso usando a técnica IMRT, é fundamental delinear previamente de forma precisa o tumor e os órgãos sãos que devem ser protegidos da radiação, garantindo assim a dose exata de radiação nos volumes alvos. O objetivo desta tese é fornecer ferramentas que sejam adequadas ao delineamento automático de estruturas de interesse e à radioterapia adaptativa para tumores da região da cabeça e do pescoço. Atualmente, a segmentação de estruturas de interesse, tais como os órgãos em risco e as regiões de propagação tumoral, é feita manualmente. Esta é uma tarefa que demanda bastante tempo de um especialista, além de ser tediosa. Além do mais, o planejamento em radioterapia é feito baseado na imagem adquirida na semana do pré-tratamento, onde é calculada a dose. Normalmente o tratamento ocorre em várias semanas, porém a dose estimada no início do tratamento é a mesma para todas as outras semanas do tratamento. Calcular a dose e mantê-la nas demais semanas é uma simplificação que não corresponde à realidade, já que ocorrem mudanças anatômicas no paciente ao longo do tratamento. Estas mudanças ocorrem devido ao encolhimento do tumor e ao possível emagrecimento do paciente, provocando alterações anatômicas locais e globais. As contribuições desta tese visam solucionar e avançar nestes problemas e são apresentadas em dois eixos. No primeiro eixo, é proposta uma metodologia para escolher uma anatomia que seja representativa da população, anatomia esta chamada de atlas. O registro do atlas na imagem do paciente permite que estruturas de interesse sejam segmentadas automaticamente, acelerando o processo de delineamento e tornando-o mais robusto. A segunda contribuição desta tese é voltada à radioterapia adaptativa. Para que a dose estimada na primeira semana seja adaptada às modificações anatômicas, é necessária a utilização de métodos de registro não-rígidos. Portanto, nesta etapa é feita uma avaliação e adaptação dos métodos de registros de forma que a região do tumor esteja bem alinhada. / Intensity Modulated Radiotherapy (IMRT) is a new technique enabling the delineation of the 3D radiation dose. It allows to delineate a radiation zone of almost any shape and to modulate the beam intensity inside the target. If IMRT enables to constrain the radiation plan in the beam delivery as well as in the protection of important functional areas (e.g. spinal cord), it also raises the issues of adequacy and accuracy of the selection and delineation of the target volumes. The purpose of this thesis is to provide tools to automatic delineation of the regions of interest and also to adaptive radiotherapy treatment for tumors located in the head and neck region. The delineation in the patient computed tomography image of the tumor volume and organs to be protected is currently performed by an expert who delineates slice by slice the contours of interest. This task is highly time-consuming and requires experts’ knowledge. Moreover, the planning process in radiotherapy typically involves the acquisition of a unique set of computed tomography images in treatment position on which target volumes (TVs) and normal structures are delineated, and which are used for dose calculation. Restricting the delineation of these regions of interest based solely on pre-treatment images is an oversimplification as it is only a snapshot of the patient´s anatomy at a given time. Shrinkage of the tumor and modification of the patient anatomy at large (e.g. due to weight loss) may indeed occur within the several weeks’ duration of a typical treatment. The main contributions of this thesis aim to advance in the solution to these issues and are presented in two axes. In the first one, it is proposed a methodology to choose an image with the most representative anatomy of a population; such image is called Atlas. The registration of the atlas into a new image of the patient allows to automatically segment the structures of interest, speeding up the delineation process and making it more robust. The second contribution of this thesis is focused on the adaptive radiotherapy. In order to adjust the estimated dose to the anatomical modifications, it is fundamental to have non-rigid registration algorithms. So, the evaluation and adaptation of non-rigid registration methods are required, addressing especially the alignment of the tumor’s region among different moments of the treatment.

Background: Growing numbers of patients with cancer are surviving following treatment with pelvic radiotherapy. Eighty per cent will experience acute gastrointestinal (GI) toxicity during treatment and 50% will subsequently have a change in their bowel habit which will affect their quality of life. The main project in this thesis aims to determine whether delivery of a gastrointestinal bundle of care will decrease GI acute toxicity and late effects of pelvic chemoradiotherapy. Additional work in the thesis evaluated the newer technique of Volumetric Modulated Arc Therapy (VMAT) which delivers decreased dose to the organs at risk on planning scans. We aimed to determine outcomes of this technique in terms of patient-reported acute toxicity and late effects. There is no internationally accepted patient reported outcome measure to capture this toxicity data and this issue was addressed using Rasch analysis in a third project. Methods: A randomised controlled trial was performed. Patients who were scheduled to undergo potentially curative chemoradiotherapy for cervix and bladder cancers were recruited and randomised. The treatment group received dietetic input and if they developed lower GI symptoms they underwent investigations and treatment for bile acid malabsorption, small bowel bacterial overgrowth and lactose intolerance. The control group received standard care. Patients who were to undergo VMAT to treat gynaecological malignancy completed patient-reported outcomes at baseline, end of treatment and one year. The rates of patient-reported toxicity were compared with those of a historical cohort and were correlated with the volume of small bowel which was irradiated. Thirdly the technique of Rasch analysis was used to evaluate the Common Terminology Criteria for Adverse Events derived patient reported outcome to measure pelvic toxicity of gynaecological cancer treatments. Results: It was feasible and acceptable to deliver a GI care bundle to patients undergoing chemotherapy and pelvic radiotherapy. All patients' data were available for analysis for the primary outcome and 29 patients' data were available at the 1 year time point. GI toxicity at 6 weeks was predicted by the trial group, suggesting that the intervention benefited the patients in terms of GI toxicity at 6 weeks. It is not yet clear whether this benefit is maintained at the 1 year time point. The frequencies of acute and late GI toxicity reported by patients undergoing VMAT were similar to that of a historical cohort who received conformal therapy. There was not a strong association between the volume of small bowel which was irradiated and the toxicity which was reported suggesting that other factors are involved in the development of toxicity. Rasch analysis of the pelvic symptom questionnaire demonstrated the main issue to be response dependency. When this was accounted for by grouping items into sub-tests the questionnaire could be made to be unidimensional and showed high reliability in a symptomatic population. Conclusion: GI intervention holds promise as a measure to reduce the acute toxicity and late effects of pelvic radiotherapy. Although newer radiotherapy techniques appear to decrease the dose delivered to the small bowel this does not translate to a reduction in patient-reported toxicity. The measurement of toxicity is complex and patient-reported outcome measures should be developed with techniques such as Rasch analysis to ensure meaningful data is available to guide further developments to reduce GI toxicity secondary to pelvic radiotherapy.

Em radioterapia externa, uma nova técnica chamada terapia de radiação de intensidade modulada - IMRT - permite delinear a dose de radiação em imagens de 2 ou 3 dimensões, delimitando de forma bastante precisa e não necessariamente uniforme a região a ser irradiada. Assim, ao mesmo tempo que o tumor é irradiado, é possível evitar a irradiação aos tecidos vizinhos íntegros (sãos), limitando os efeitos secundários do tratamento. Para que a radioterapia externa tenha sucesso usando a técnica IMRT, é fundamental delinear previamente de forma precisa o tumor e os órgãos sãos que devem ser protegidos da radiação, garantindo assim a dose exata de radiação nos volumes alvos. O objetivo desta tese é fornecer ferramentas que sejam adequadas ao delineamento automático de estruturas de interesse e à radioterapia adaptativa para tumores da região da cabeça e do pescoço. Atualmente, a segmentação de estruturas de interesse, tais como os órgãos em risco e as regiões de propagação tumoral, é feita manualmente. Esta é uma tarefa que demanda bastante tempo de um especialista, além de ser tediosa. Além do mais, o planejamento em radioterapia é feito baseado na imagem adquirida na semana do pré-tratamento, onde é calculada a dose. Normalmente o tratamento ocorre em várias semanas, porém a dose estimada no início do tratamento é a mesma para todas as outras semanas do tratamento. Calcular a dose e mantê-la nas demais semanas é uma simplificação que não corresponde à realidade, já que ocorrem mudanças anatômicas no paciente ao longo do tratamento. Estas mudanças ocorrem devido ao encolhimento do tumor e ao possível emagrecimento do paciente, provocando alterações anatômicas locais e globais. As contribuições desta tese visam solucionar e avançar nestes problemas e são apresentadas em dois eixos. No primeiro eixo, é proposta uma metodologia para escolher uma anatomia que seja representativa da população, anatomia esta chamada de atlas. O registro do atlas na imagem do paciente permite que estruturas de interesse sejam segmentadas automaticamente, acelerando o processo de delineamento e tornando-o mais robusto. A segunda contribuição desta tese é voltada à radioterapia adaptativa. Para que a dose estimada na primeira semana seja adaptada às modificações anatômicas, é necessária a utilização de métodos de registro não-rígidos. Portanto, nesta etapa é feita uma avaliação e adaptação dos métodos de registros de forma que a região do tumor esteja bem alinhada. / Intensity Modulated Radiotherapy (IMRT) is a new technique enabling the delineation of the 3D radiation dose. It allows to delineate a radiation zone of almost any shape and to modulate the beam intensity inside the target. If IMRT enables to constrain the radiation plan in the beam delivery as well as in the protection of important functional areas (e.g. spinal cord), it also raises the issues of adequacy and accuracy of the selection and delineation of the target volumes. The purpose of this thesis is to provide tools to automatic delineation of the regions of interest and also to adaptive radiotherapy treatment for tumors located in the head and neck region. The delineation in the patient computed tomography image of the tumor volume and organs to be protected is currently performed by an expert who delineates slice by slice the contours of interest. This task is highly time-consuming and requires experts’ knowledge. Moreover, the planning process in radiotherapy typically involves the acquisition of a unique set of computed tomography images in treatment position on which target volumes (TVs) and normal structures are delineated, and which are used for dose calculation. Restricting the delineation of these regions of interest based solely on pre-treatment images is an oversimplification as it is only a snapshot of the patient´s anatomy at a given time. Shrinkage of the tumor and modification of the patient anatomy at large (e.g. due to weight loss) may indeed occur within the several weeks’ duration of a typical treatment. The main contributions of this thesis aim to advance in the solution to these issues and are presented in two axes. In the first one, it is proposed a methodology to choose an image with the most representative anatomy of a population; such image is called Atlas. The registration of the atlas into a new image of the patient allows to automatically segment the structures of interest, speeding up the delineation process and making it more robust. The second contribution of this thesis is focused on the adaptive radiotherapy. In order to adjust the estimated dose to the anatomical modifications, it is fundamental to have non-rigid registration algorithms. So, the evaluation and adaptation of non-rigid registration methods are required, addressing especially the alignment of the tumor’s region among different moments of the treatment.

Made available in DSpace on 2014-06-11T19:25:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-08Bitstream added on 2014-06-13T18:53:14Z : No. of bitstreams: 1 ciesielski_fin_me_araca.pdf: 340364 bytes, checksum: 27a652e37436beb5112aa9fdd7fb42ce (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O objetivo deste estudo foi avaliar a ocorrência de microrganismos exógenos e oportunistas (bactérias entéricas, pseudomonados, leveduras e Helicobacter pylori) na cavidade bucal de pacientes submetidos à radioterapia para tratamento de câncer de cabeça e pescoço. Cincoenta pacientes que iria receber radioterapia foram examinados antes, durante e 30 dias após radioterapia. Amostras de saliva, mucosa e biofilme foram coletadas e os microrganismos foram detectados por cultura e Reação em Cadeia da Polimerase (PCR). Candida albicans, C. tropicalis, C. krusei, C. glabrata e C. parapsilosis foram as leveduras mais prevalentes nos pacientes submetidos a radioterapia. Gêneros Citrobacter, Enterobacter, Enterococcus, Klebsiella, Proteus, e Pseudomonas forma as bactérias mais frequentemente cultivadas. As bactérias alvo foram cultivadas de 77.8% dos pacientes edêntulos e 46.9% dos pacientes dentados 30 dias após a radioterapia. Por PCR, estes microrganismos foram detectados em todos os pacientes edêntulos e 78.1% dos pacientes dentados. Bactérias não orais e espécies de Cândida foram mais prevalentes nestes pacientes. Modificações no meio ambiente oral devido a radioterapia parecem facilitar a colonização por estes microrganismos. / The aim of this study was to evaluate the occurrence of opportunistic and exogenous microrganisms (enteric bacteria, pseudomonads, yeasts and Helicobacter pylori) in the oral cavity of patients undergoing radiotherapy (RT) for treatment of head and neck cancer. Fifty patients receiving RT were examined before, during and 30 days after RT. Saliva, mucosa, and biofilm samples were collected and microorganisms were detected by culture and Polymerase Chain Reaction (PCR). Candida albicans, C. tropicalis, C. krusei, C. glabrata and C. parapsilosis were the most prevalent yeasts in patients submitted to RT. Genera Citrobacter, Enterobacter, Enterococcus, Klebsiella, Proteus, and Pseudomonas were the most frequently cultivated bacteria. Targeted bacteria were cultivated from 77.8% edentulous and 46.9% dentate patients 30 days after RT. By PCR, these microorganisms were detected from all edentulous patients and from 78.1% of dentate patients. Non-oral bacteria and Candida species were prevalent in these patients. Modifications of the oral environment due to RT seem to facilitate the colonization of these microorganisms.

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