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Orientador: Júlio Sérgio Marchini / Banca: Aureluce Demonte / Banca: Karina Pfrimer / Resumo: 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 / Abstract: 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 / Mestre

L’assurance qualité est un sujet clé en radiothérapie. En effet, la complexification des méthodes de traitements ont induit de nombreuses sources d’erreurs potentielles, et la vérification du bon déroulé du traitement est plus que jamais une tâche difficile. Un des objectifs de l’équipe de radiophysique est ainsi d’assurer que la dose délivrée au patient sera aussi conforme que possible à la prescription du médecin.Nombres d’outils ont été mis à disposition de ces équipes pour assurer des contrôles efficaces, réduisant les chances d’erreur. Une des solutions innovantes à l’épreuve dépend de l’utilisation de nouveaux détecteurs bidimensionnels, solidaires de la tête de l’accélérateur et placé en amont du patient, permettant ainsi de collecter des informations sur le flux de photons délivré par l’accélérateur.Ce type de détecteur présente plusieurs avantages. Il ne perturbe que très peu le faisceau de photons et permet donc une utilisation en simultané du traitement du patient. De plus, sa localisation en amont du patient ne permet pas d’ambiguïté sur l’origine des déviations en dose observées, une erreur de positionnement patient ne pouvant pas se confondre à une avarie sur l’accélérateur.Dans ce contexte, le groupe PHYSMED du LPSC, en collaboration avec le CHU de Grenoble développe TraDeRa, un détecteur 2D basé sur une chambre d’ionisation plane pixélisée. Embarquant une électronique de lecture dédiée conçue, il permet l’acquisition de carte de signal décrivant avec une bonne précision le flux de photons en provenance de l’accélérateur en temps réel et sans zone morte.Son portage vers la routine clinique passe en partie par la traduction de la carte de signal fournie par le détecteur en une carte de dose exploitable par les physiciens médicaux. Une des solutions envisagée tient dans le recours à des simulations Monte-Carlo complexes, afin d’associer la réponse du détecteur à un dépôt de dose calculé.La précision sur les différents calculs Monte-Carlo à fournir est très importante, aussi un modèle précis de l’accélérateur clinique nous a paru indispensable. Nous avons donc entrepris la modélisation d’un accélérateur clinique type Clinac 2100 pour le code Monte-Carlo PENELOPE, afin de reproduire le plus fidèlement possible l’accélérateur du CHU de Grenoble. Outre la géométrie complexe du dispositif, la fidélité de la reproduction vient aussi de la connaissance des caractéristiques du faisceau d’électrons utilisé pour produire ces photons. Nous avons élaboré une méthode de détermination de ces paramètres basée sur un ajustement de ces caractéristiques utilisant la comparaison de mesures avec des simulations de référence, présentant des avantages sur le processus essais-erreurs habituellement utilisé. L’objectif était de proposer une méthode applicable à n’importe quel accélérateur du même modèle, en n’exploitant qu’un jeu commun de simulations de référence, et permettre l’ajustement des caractéristiques en un minimum de temps. Cette méthode a fait ses preuves, notamment grâce à son application sur deux autres accélérateurs modèle Clinac 2100 que celui utilisé dans la conception du détecteur.Puis, nous avons modélisé le détecteur et son environnement d’exploitation à l’hôpital dans PENELOPE. Cette simulation nous a donné accès à des propriétés intrinsèques que des mesures réelles ne permettent pas de déterminer. Nous avons ainsi pu étudier la linéarité de sa réponse en dose et en débit de dose, caractériser l’atténuation qu’il oppose au faisceau, ou encore évaluer la diaphonie entre les différentes électrodes de la matrice pixélisée.Nous avons initié le travail de conversion du signal collecté par le détecteur en dose déposée dans le patient. Nous avons associé à la réponse d’électrodes choisies une distribution de dose en trois dimensions dans la cuve à eau. En décomposant un champ quelconque en une somme de réponses élémentaires, nous avons déterminé une procédure de reconstruction du dépôt de dose dans le patient. / Quality assurance is a key topic in radiation therapy. Indeed, the increasing complexity of the treatment methods led to many additional sources of potential errors, and the verification of treatment is more than ever a task that can be difficult. One of the objectives of the radiophysicists lies in the application of quality assurance procedures to ensure that the dose delivered to the patient is consistent with the oncologist’s prescription.Numerous tools are available to ensure controls that are both effective and reliable, reducing the chances of errors. However, zero risk is not achievable, and the use of new treatment techniques can make these errors difficult to detect. One of the innovative solutions studied in recent years depends on the use of new two-dimensional detectors, embedded on the head of the linear accelerator and placed upstream of the patient. These devices thus allow to collect information on the photon flux delivered by the accelerator.This type of detector has several advantages. Their attenuation is very light, and grant the possibility to use them while treating the patient. Moreover, their location does not give space to ambiguity about the origin of the observed dose deviations. Indeed, a patient positioning error cannot be confused with mechanical misbehavior of the linear accelerator.In this context, the PHYSMED group of the LPSC, in collaboration with the Grenoble Public Hospital, is developing TraDeRa, a detector based on a pixelated planar ionization chamber, embedding dedicated electronics specially designed by the lab. The detector is able to collect a signal map that accurately describes the incoming photon flux, for any clinical field, in real time and without dead zone.The portage of the detector towards clinical routine partially depends on the translation of the signal map supplied by the detector into a reliable dose map that can be used by medical physicists. To begin with, one of the considered solutions is the use of complex Monte Carlo simulations, in order to associate the detector response with a calculated dose deposition in a water tank.The precision to provide on the various Monte-Carlo calculations seemed very important. Therefore, a precise model of the clinical accelerator seemed essential. Thus, we have initiated the modeling of a type Clinac 2100 clinical accelerator for the Monte-Carlo code PENELOPE, in order to reproduce as accurately as possible the accelerator available for our measurements campaign. The knowledge of the primary electron beam characteristics is critical. We have thus developed an original method for adjusting these characteristics based on comparison of measurements with reference simulations. This method has interesting features compared with the usual trial and error process. The objective was to propose a method applicable to any accelerator of the same model, using only a set of reference simulations, thus allowing the faster adjustment (sometimes slightly less accurate than the trial and error method) of the beam characteristics. This method seems to have proved itself worth, and has been used on two other Clinac 2100 accelerators to test its reliability.Next, the full modeling of the detector in PENELOPE coupled and its environment granted us to describe some characteristics intrinsic to conception choices. Thus, we have been able to study the linearity response of the detector in terms of dose and dose rate, characterize the attenuation it opposes to the beam, and evaluate the cross-talk between the different electrodes of the pixelated matrix.In addition, we were able to initiate the work of converting the signal collected by TraDeRa into a dose deposited in the patient. We associated the response of selected electrodes with calculated dose distributions in a water tank model. By decomposing any field into a sum of elementary responses, we have determined a procedure allowing the reconstruction of the dose deposition in the patient.

O efeito da radiação ionizante sobre a tireóide vem sendo estudado há várias décadas. Os acidentes nucleares têm sido a maior fonte de estudos nessa área. A associação de hipotireoidismo, hipertireoidismo, nódulos e câncer de tireóide com a radiação é freqüentemente relatada, mas os limiares de dose de radiação para lesões, os mecanismos de lesão e alguns fatores de risco ainda não estão bem estabelecidos. As crianças apresentam maior risco para essas alterações de tireóide secundárias à radiação e necessitam de seguimento médico por longo período após a exposição. Este tema adquire maior relevância atualmente, uma vez que um grande número de pessoas tratadas com radioterapia para câncer na infância sobrevive e poderá apresentar seqüelas. Nesta revisão analisamos as diferentes alterações clínicas provocadas sobre a tireóide causadas por radiação interna e externa. / The effects of ionizing radiation on the thyroid have been studied for some time. Nuclear accidents are the major source of studies related to this matter. The association of hypothyroidism, hyperthyroidism, thyroid nodules and cancer is frequently reported, but the radiation dose injury thresholds, the mechanism of injury and some risk factors are not fully established. Children are at greater risk for developing thyroid injury secondary to radiation and need to be followed for a long time after exposure. This issue is especially relevant nowadays as many people treated by radiation for childhood cancer survive and may have squels. In this review we analyze the different clinical changes caused by internal and external radiation on the thyroid.

O sarcoma de Ewing é uma neoplasia maligna agressiva que acomete ossos e tecidos moles com maior frequência em crianças e adolescentes. O tratamento consta de quimioterapia de indução, seguida pelo controle local da doença (cirurgia, cirurgia associada à radioterapia, ou apenas radioterapia), e quimioterapia de consolidação. A introdução da quimioterapia possibilitou aumento significativo na sobrevida dos pacientes nas últimas décadas. Por outro lado, o impacto da modalidade de controle local ainda não está bem estabelecido. Estudos observacionais têm demonstrado superioridade do tratamento cirúrgico em relação à radioterapia isolada, no entanto, são limitados os estudos prospectivos que confirmam esta diferença. O objetivo deste estudo é avaliar o impacto da modalidade de tratamento local nos desfechos oncológicos, bem como descrever o perfil clínico-epidemiológico de portadores de sarcoma de Ewing ósseo não-metastático. Os dados foram coletados em 15 instituições no período entre 2003 e 2010 e fazem parte do primeiro estudo do Grupo Colaborativo Brasileiro para Tratamento dos Tumores da Família Ewing (EWING I). Dos 73 pacientes incluídos, 47 foram tratados com cirurgia isolada, 13 receberam cirurgia associada à radioterapia, e 13 apenas radioterapia. O seguimento médio foi de 4,5 anos (2,3 até 6,7 anos) e a sobrevida geral e livre de eventos foi de 63,3 e 62,1 por cento em 5 anos, respectivamente. A falha do tratamento local foi de 0 (zero) por cento para a modalidade de cirurgia associada à radioterapia, 6,5 por cento para cirurgia isolada, e 10 por cento para radioterapia (p=0,5). A sobrevida dos pacientes submetidos à radioterapia isolada foi significativamente inferior à sobrevida dos tratados com cirurgia e com cirurgia associada a radioterapia (30,8 versus 71,7 versus 64,1 por cento, respectivamente). Concluiu-se que não houve diferença em termos de falha local de acordo com a modalidade de tratamento empregada, no entanto houve diferença significativa em termos de sobrevida. Apesar dos resultados cirúrgicos superiores, a radioterapia isolada ainda apresenta papel fundamental no tratamento de casos selecionados. / Ewing sarcoma is a small round cell malignancy of bone and soft tissue that usually occurs in children and adolescents. Current treatment includes induction chemotherapy, local control of the primary tumor (surgery, surgery plus radiotherapy, or radiotherapy) and consolidation chemotherapy. The introduction of chemotherapy has improved significantly the oncologic outcomes in Ewing sarcoma. On the other hand, the impact of the local control modality has not been established. Surgery alone or in combination with radiation has traditionally been considered a good choice for resectable ES, while unresectable tumors have been treated with definitive radiotherapy. Despite the results from a few trials and observational studies, there is no consistent knowledge about the local control modality in ES outcomes. The present study aims to evaluate the impact of the local control modality in the oncologic outcomes, as well as to describe the clinical features of the patients with localized Ewing sarcoma of the bone. The data were collected between 2003 and 2010 in 15 hospitals and were part of the first Brazilian Collaborative Group for the Treatment of the Ewing Sarcoma Family Tumors (EWING 1). From 73 patients (median age 12.8 years old), 47 were treated with surgery, 13 with surgery plus radiotherapy, and 13 with definitive radiotherapy. Median follow up was 4.5 years (2.3 to 6.7 years) and the overall and event-free survival 63.3 and 62.1 percent in 5 years, respectively. The local control failure was 0 percent for surgery plus radiotherapy, 6.5 percent for surgery, and 10 percent for radiotherapy (p=.5). The survival of the patients treated with radiotherapy was significantly worse than those treated with surgery and surgery plus radiotherapy (30.8 versus 71.7 versus 64.1 percent, respectively). In conclusion, there was no significant difference in local failure according to the modality of treatment, but there was significant difference in survival rates. Despite the better outcomes in individuals treated with surgery, the radiotherapy modality has still an important role in selected patients.

Orientador: Rubens Nisie Tango / Banca: Estevão Tomomitsu Kimpara / Banca: Rogério de Lima Romeiro / Resumo: A radioterapia é o uso da aplicação de radiação ionizante em áreas específicas, visando tratamento de tumores. Porém, a área irradiada e os tecidos normais circundantes estão sujeitos a danos agudos e crônicos. As injúrias no tecido ósseo variam desde osteopenia até osteorradionecrose e, devido a estas alterações, pacientes irradiados portadores de implantes vêm demonstrando maior taxa de insucesso. O objetivo deste estudo foi avaliar os efeitos da radioterapia, simulando uma dose total de um tratamento radioterápico convencional para pacientes oncológicos, na neoformação óssea e na osseointegração de implantes em fêmures de ratos. Foram utilizados neste estudo 66 ratos que receberam implantes cilíndricos de titânio comercialmente puro (TiCp) nos fêmures direito e esquerdo. Os animais foram divididos em 3 grupos: a) Grupo controle (C): cirurgia de colocação dos implantes (tecido sadio sem irradiação); b) Grupo irradiação precoce (Ip): cirurgia de colocação dos implantes seguido de irradiação após 24h; c) Grupo irradiado (I): irradiação e após 4 semanas, cirurgia de colocação dos implantes. Os animais dos grupos Ip e I foram submetidos a irradiação em 02 sessões de 15 Gy, totalizando a dose de 30 Gy. Os animais foram eutanasiados nos períodos de 2 e 7 semanas após o tratamento. Durante o experimento, os animais foram cuidadosamente monitorados quanto as alterações clínicas. Em cada período, 06 animais foram submetidos à análise histomorfométrica, visando avaliar a neoformação ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The radiotherapy is ionizing radiation proceeding in specific areas, aiming at the treatment of tumors. However, the irradiated area and the surrounding normal tissue can develop acute and chronic damage. In bone tissue, injuries ranging from osteopenia to osteroadionecrosis and due to these changes patients irradiated with implants have shown higher failure rate. The objective of this study was to evaluate the effects of radiation, simulating a total dose of a conventional radiotherapy treatment for cancer, bone regeneration and osseointegration of implants in femurs of rats. It was used in this study 66 mice that receive cylindrical implants of commercially pure titanium (cpTi) on the right and left femurs. The animals were divided into 3 groups: a) control group (C): implant placement surgery (control group - healthy tissue without irradiation); b) Group early irradiation (Ip): placement of implants surgery followed by radiation after 24h; c) Group irradiated (I): irradiation and after 4 weeks of surgery implant placement. The animals of the Ip and I groups were subjected to irradiation in a double step at a dose of 15 Gy each, totalizing dose of 30 Gy. The animals were euthanized at periods of 2 and 7 weeks after treatment. During the experiment, the animals were carefully monitored for clinical changes. In each period 06 animals were submitted to histomorphometric analysis, to evaluate the bone formation and boneimplant interface. The other 05 animals, in periods of 2 an... (Complete abstract click electronic access below) / Mestre

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