La radiochirurgie par Gamma Knife constitue une modalité thérapeutique reconnue de certaines affections cérébrales. Le traitement se base sur l’administration d’un rayonnement focalisé au niveau d’une cible intracrânienne. L’efficacité de ce traitement repose sur la délivrance d’une dose d’irradiation efficace au sein d’un volume-cible associé à la délivrance d’une dose d’irradiation négligeable à l’extérieur de ce même volume-cible. En pratique, la dose d’irradiation administrée à l’intérieur du volume-cible n’est pas distribuée de manière homogène, et la dose d’irradiation reçue par les tissus situés en-dehors du volume-cible n’est pas nécessairement faible. Notre travail est basé sur l’hypothèse que l’imperfection de la distribution de la dose d’irradiation au sein du volume-cible et en-dehors de celui-ci peut être responsable des échecs et des complications rencontrées en radiochirurgie. Dans deux modèles cliniques de traitement radiochirurgical, le schwannome vestibulaire et la névralgie du trijumeau, nous avons montré qu’il existait une relation entre les paramètres de distribution de dose d’irradiation et certains résultats du traitement radiochirurgical par Gamma Knife de ces pathologies. Nous avons développé deux modèles expérimentaux d’irradiation radiochirurgicale de rats, l’un ciblé sur le striatum et l’autre sur le nerf trijumeau, permettant d’analyser les conséquences histologiques des variations de la distribution de dose à l’intérieur du volume-cible ainsi qu’à distance de celui-ci. Nous avons démontré que la réponse radiobiologique des tissus irradiés était fortement dépendante de ce paramètre dosimétrique, et que ce dernier constituait une donnée de la planification chirurgicale aussi importante que la dose de prescription. Nous avons corrélé ces résultats avec certaines observations réalisées dans d’autres indications de traitement radiochirurgical ainsi que dans l’analyse histologique de tumeurs traitées par Gamma Knife. Ces études mettent en évidence le rôle important joué par l’optimalisation de la distribution de la dose d’irradiation dans l’amélioration des résultats cliniques du traitement radiochirurgical. Les valeurs optimales de la distribution de dose dans les différentes indications de traitement radiochirurgical doivent être recherchées, et les différentes méthodes mises à notre disposition lors de la planification dosimétrique pour améliorer la distribution de dose doivent être utilisées avec discernement pour obtenir la dosimétrie radiochirurgicale la plus parfaite possible.

Made available in DSpace on 2014-10-09T12:33:22Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:06:31Z (GMT). No. of bitstreams: 0 / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Made available in DSpace on 2014-10-09T12:33:22Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:06:31Z (GMT). No. of bitstreams: 0 / Atualmente a radioterapia de intensidade modulada (IMRT) está sendo implementada em um número crescente de centros no Brasil. Como conseqüência disto, muitas instituições estão enfrentando o problema de executar um programa de controle de qualidade antes e durante a execução do IMRT na prática da rotina clínica. O objetivo deste trabalho é avaliar e propor uma metodologia para o controle de qualidade de tratamentos com IMRT. Uma câmara de ionização e um detector bidimensional foram utilizados para avaliar a dose absoluta total de todos os campos em um determinado ponto. A distribuição de dose relativa total de todos os campos foi medida com filmes radiocrômicos e um detector bidimensional em uma profundidade no objeto simulador. Uma comparação entre as distribuições de dose medidas e calculadas foi realizada usando o método do índice gama, avaliando o percentual de pontos que satisfazem os critérios de diferença dose de ±3% e distância de concordância de ±3 mm. Como resultado da dosimetria absoluta de 113 feixes de IMRT medidos com uma câmara de ionização e 81 feixes usando o detector bidimensional, foi proposto um nível de ação de cerca de ± 5% em relação ao sistema de planejamento e de tratamento para a verificação da dose em um único ponto na região de baixo gradiente de dose. A análise das medições com o detector bidimensional mostrou que o valor da função gama foi <1 para 97,7% dos dados e, para o filme, o valor da função gama foi <1 para 96,6% dos dados. Neste trabalho pode-se concluir que para uma entrega exata de dose em IMRT sliding-window com um colimador micro multilâminas, os parâmetros de dose total absoluta e distribuição de dose total relativa devem ser verificados por dosimetria absoluta e relativa respectivamente. / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

No description available.

Radioimmunotherapy consists in the use of beta radioactive labeled monoclonal antibodies as selective carriers of radiation to tumors. Internal spatially distributed sources created at the disease sites would deliver high radiation doses to tumors while the normal tissues would not be exposed to the intense radiation as in conventional forms of cancer treatments. A rapid and accurate estimation of the spatial dose distribution from nonuniform sources is essential for the optimization of this form of cancer therapy. The method used for such calculations is based on the knowledge of dose distributions around a unit source, quantities referred to as dose kernels. Thus far, the Monte Carlo technique is the most accurate way of the dose kernel determinations. However, for routine dosimetry simpler and less time consuming methods of adequate accuracy may appear more preferable. The "scaling factor" method is used to determine the depth dose distribution in a medium based on data about the dose distribution in an arbitrary reference medium (e.g. air, water). The transformation of the dose distribution curves from the reference medium to the desired new medium is done using a constant, known as scaling factor or relative dose attenuation, and a closely related renormalization factor imposed by the energy conservation. This work investigates the accuracy of the scaling factor method using a statistical approach (generalized chi-squared test), focusing on a particular case of potential practical interest, the scaling factor water to bone. The work also investigates a procedure for extending the applicability of the scaling factor method to dosimetry in dissimilar media, as a first step, a planar interface. / Thesis / Master of Science (MS)

<p>Since 1986 patients with ocular malignant melanoma have been treated with Ru-106 plaques at S:t Erik Eye Hospital. In 1998 I-125 radioactive seed plaques was presented as an alternative to Ru-106 when treating tumors with an apical height greater than 7 mm. Until June 2005 the doseplanning of these plaques was based on a depth-dose curve made in the dose planning system Cadplan supplied by Varian Medical Systems. In the recent years the capabilities of computerized 3D dose planning system has increased greatly. The number of types of seeds on the market has also increased.</p><p>In order to implement the modern 3D dose planning system Brachy Vision 7.3.10 in planning the I-125 plaques, a review of the dose planning process have been done.</p><p>The ultra sound equipment used by the ophthalmologist to determine the apical height of the tumor has been investigated in terms of accuracy. A phantom has been developed for this task.</p><p>As new seeds entered the market a comparision have been made comparing the Amersham 6711 seed with the Bebig I25.S06 seed. A method for measuring the activity of the single seeds has also been developed.</p><p>The dose planning system Brachy Vision 7.3.10 have been compared to the old dose planning method, and an implementation of the plaques into Brachy Vision have been made.</p><p>The ultra sound equipment was accurate in the regions of interest. It was also discovered that the Bebig I25.S06 seed gave slightly higher dose compared to the Amersham 6711 with the same activity. The difference between the seeds is however small. The results indicate that the old dose planning method gave a slight underdosage.</p>

Since 1986 patients with ocular malignant melanoma have been treated with Ru-106 plaques at S:t Erik Eye Hospital. In 1998 I-125 radioactive seed plaques was presented as an alternative to Ru-106 when treating tumors with an apical height greater than 7 mm. Until June 2005 the doseplanning of these plaques was based on a depth-dose curve made in the dose planning system Cadplan supplied by Varian Medical Systems. In the recent years the capabilities of computerized 3D dose planning system has increased greatly. The number of types of seeds on the market has also increased. In order to implement the modern 3D dose planning system Brachy Vision 7.3.10 in planning the I-125 plaques, a review of the dose planning process have been done. The ultra sound equipment used by the ophthalmologist to determine the apical height of the tumor has been investigated in terms of accuracy. A phantom has been developed for this task. As new seeds entered the market a comparision have been made comparing the Amersham 6711 seed with the Bebig I25.S06 seed. A method for measuring the activity of the single seeds has also been developed. The dose planning system Brachy Vision 7.3.10 have been compared to the old dose planning method, and an implementation of the plaques into Brachy Vision have been made. The ultra sound equipment was accurate in the regions of interest. It was also discovered that the Bebig I25.S06 seed gave slightly higher dose compared to the Amersham 6711 with the same activity. The difference between the seeds is however small. The results indicate that the old dose planning method gave a slight underdosage.

Um conceito central na dosimetria da terapia fotodinâmica (TFD) é o limiar de dose (Dth do inglês threshold dose). O Dth é definido como a quantidade mínima de luz que deve ser absorvida pelas moléculas de fotossensibilizador (FS) dentro das células malignas a serem tratadas para que ocorra a morte celular por necrose ou apoptose. Os resultados do estudo da captação de FS por células Hep G2 demonstraram que uma população celular de linhagem, cultivada em monocamada, apresenta captação de Photogem (PG) heterogênea, ou seja, algumas células têm maior capacidade de captar moléculas de PG, outras células captam o PG em menor quantidade. A captação heterogênea de PG pode ser a causa para fenômenos de seleção de células mais resistentes à TFD. É razoável supor que as subpopulações celulares de uma mesma massa de células malignas possam apresentar diferentes valores de Dth. Definiu-se uma função de distribuição das doses limiares (g()) como uma função de distribuição gaussiana, e para a sua parametrização desenvolveu-se um método para o cultivo in vitro de culturas tridimensionais (culturas 3D), mais fidedignas ao tecido neoplásico maligno que as culturas tradicionais. Utilizando-se o método de levitação magnética (MLM) e o método de impressão magnética (MIM) para a dosimetria da TFD, foi possível parametrizar a g(Dth), investigar a resistência celular à TFD. O MLM demonstrou ser facilmente manuseável na rotina experimental, e consistente para o teste in vitro de novos FS. Comparando-se as culturas MDA-MB-231e Hep G2, obtidas por MLM por mais de 185 horas de levitação, pode-se concluir que as células Hep G2 formaram uma estrutura celular mais densa e que ofereceu mais resistência ao dano causado pela TFD. É notável como as células Hep G2 retomaram o crescimento, e restabeleceram-se em cultura de modo semelhante ao grupo controle, por meio da reconstrução da matriz extracelular (MEC). Enquanto isso, no caso das células MDA-MB-231, a integridade da cultura não foi restabelecida após a aplicação da TFD, formando uma cultura fragmentada. O dano mais evidente, para ambas as culturas, foi observado nas margens dos tumores, evidenciando que os componentes importantes da reação fotodinâmica, como o fotossensibilizador, a luz e o oxigênio, estavam presentes em maiores quantidades na superfície da cultura, em comparação às outras regiões tumorais. Os resultados obtidos demonstram que para o Photogem (PG) é necessária uma fluência de luz da ordem de 40 J.cm-2, para que o efeito fotodinâmico promova morte celular nas culturas 3D obtidas pelo MLM. O resultado da combinação de dois tipos celulares, o maligno (MDA-MB-231) e o sadio (HPF), demonstrou que o efeito fotodinâmico é efetivo quando se tem controle adequado da entrega dos agentes da terapia, independentemente do tipo celular. Algumas células sobreviveram ao tratamento, e existe um forte indicativo de que a presença de fibroblastos HPF esteja relacionada a esta pequena parcela de células que receberam dose de luz inferior ao seu Dth. Os resultados demonstraram que quanto maior a fluência de luz, menor é o IC50 do PG. Para a fluência de luz de 60 J.cm-1 obteve-se um IC50 de 3,1 &mu;g.mL-1, e para a fluência de luz de 30 J.cm-1 obteve-se um IC50 de 18,0 &mu;g.mL-1. / Photodynamic therapy (PDT) dosimetry includes a central concept: the threshold dose (Dth), which is the minimum amount of light to be absorbed by the photosensitizer (PS) molecules to induce irreversible oxidative damage, and hence to cause cell death by necrosis or apoptosis. It is reasonable to assume that cells subpopulation in one individual tumor cell mass may present different Dth values, which implies the existence of a distribution of Dth values defined by a Gauss distribution function (g(Dth)). Developing methods for more realistic tissue emulation with in vitro cultures, such as three-dimensional (3D) cultures, have been encouraged aiming to avoid the above-mentioned dissimilarities. A 3D cell culture is preferable compared to monolayer cell cultures, because it provides cell-cell and cell-substrate interaction, and makes evaluating a culture and its volumetric dimension (which resembles the tumor morphology) possible. This study also includes the development of a 3D model, using the magnetic levitation method (MLM) and the magnetic printing method (MIM, from Portuguese método de impressão magnetic) for PDT dosimetry. The aim is to define parameters for g(Dth), to investigate cell resistance to PDT, and to achieve a fast and consistent method for new PS in vitro tests. By comparing cultures from the different cell types studied, the ones obtained by MLM for more than 185 hours were found to present a denser cellular structure, which provided improved resistance to PDT-induced damage. Hep G2 cells showed a remarkable behavior by being able to recover culture integrity; meanwhile MDA-MB-231 cells were not able to do so. The most evident damage, for both cell culture types, was observed on tumor margins, showing that the main elements to play a role in PDT reaction (PS, light and oxygen) were present in larger quantities, at culture surface, when compared with internal regions of the cell culture. Results obtained for PG show that a light fluence of about 40 J.cm-2 is required to induce cell death by photodynamic effect on 3D cells obtained by MLM. A combination of two different cell types - a tumor cell line and a healthy cell line - shows clearly that there is no difference for the photodynamic outcome if one holds enough control on the therapeutic parameters. The results presented in this thesis show that even a strain cell population, grown in a monolayer cell culture, results in a non-homogeneous PG uptake, which means that part of the cells seems to be able to collect PG molecules more efficiently than other cells. This difference in collection among cells may be the cause of a selection of cells that are more \"resistant\" to PDT. There were cells that survived treatment, and the presence of HPF fibroblasts might be the cause of these surviving cells, since their Dth might have not been achieved. The results showed that as higher is the light fluence, as lower is the IC50 of PG. The fluence of 60 and 30 J.cm-1 resulted in IC50 of 3.1 and 18.0 &mu;g.mL-1, respectively.

Les faisceaux de photons de petites dimensions utilisés en radiothérapie stéréotaxique sont caractérisés par de forts gradients de dose et un manque important d’équilibre électronique latéral, ce qui rend les techniques dosimétriques conventionnelles inadaptées. L’objectif de la thèse est de permettre une meilleure évaluation de la dose délivrée aux patients traités par radiothérapie stéréotaxique. D’une part, les données dosimétriques de base utilisées pour l’étalonnage du système de planification de traitement (TPS) ont été déterminées numériquement. Pour cela, deux installations de radiothérapie de type CyberKnife ont été modélisées avec le code Monte Carlo PENELOPE. Des mesures de rapport d’ouverture du collimateur ont également été réalisées à l’aide de plusieurs détecteurs actifs et de deux dosimètres passifs (film radiochromique et micro-LiF) et comparées aux facteurs d’ouverture du collimateur calculés par simulation. Six détecteurs ont été modélisés afin d’étudier les phénomènes physiques impliqués dans la réponse des détecteurs en petits champs. Parmi les détecteurs étudiés, seuls les films radiochromiques sont en accord avec la simulation, ils peuvent être utilisés sans facteur correctif. La perturbation induite par les autres détecteurs a pu être expliquée, soit par l’effet volume dû à la taille trop importante du volume actif par rapport au diamètre du faisceau, soit par la masse volumique des matériaux utilisés dans la conception du détecteur qui est trop éloignée de celle de l’eau. Les facteurs correctifs, permettant de corriger la non-équivalence-eau et/ou la mauvaise résolution spatiale de chaque détecteur, ont été déterminés pour les deux systèmes CyberKnife.D’autre part, un protocole de mesure de distributions de dose 2D pour les mini-faisceaux, basé sur l’utilisation des films radiochromiques, a été établi et un programme sous MatLab permettant l’analyse entre les distributions de doses mesurées et calculées a été développé. Des plans de traitement stéréotaxique en milieu hétérogène ont ensuite été réalisés pour un fantôme afin d’évaluer les algorithmes de calcul de dose implémentés dans le TPS MultiPlan (TPS associé au système CyberKnife). L’analyse des distributions de dose 2D des plans de traitement a montré que l’algorithme de type « Pencil Beam » implémenté dans MultiPlan est performant en milieu homogène équivalent-eau mais n’est pas adapté pour les milieux à faible densité électronique tels que le poumon. En effet, celui-ci surestime la dose dans le champ (jusqu’à 40%) ce qui peut conduire à diminuer l’efficacité du traitement de la tumeur et la sous-estime hors du champ ce qui risque de sous-évaluer la dose reçue par les organes à risques à proximité. En milieu hétérogène, l’algorithme Monte Carlo implémenté dans MultiPlan est globalement en accord avec la mesure et est par conséquent l’algorithme à privilégier pour estimer la dose délivrée au patient lorsque des milieux à faible densité sont présents. / Dosimetry of small beams is challenging given their small size compared to the detectors, high dose gradient and the lack of lateral electronic equilibrium. The Ph.D. thesis aims to improve the accuracy of the dose delivered to the patient in stereotactic radiotherapy.On the one hand, dosimetric data used to calibrate the treatment planning system (TPS) were determined using numerical simulations. To achieve this, two CyberKnife radiotherapy facilities were modelled using the PENELOPE Monte Carlo code. Output ratios measurements were performed with several active detectors and with two passive dosimeters (radiochromic film and micro-LiF) and compared with output factors calculated by simulation. Six detectors were modeled in order to study the detectors response in small beams. Among the detectors studied, only the radiochromic films were in agreement with the simulations, they can be used without correction factors. The disturbance of the detectors response in small beams was explained either by the volume effect induced by the active volume, which is too high compared to the beam size, or by the mass density effect induced by the detector body materials which are too far from water mass density. The correction factors, required to correct the disturbance caused by the non-water-equivalence and/or the low spatial resolution of each detector, were calculated for the two CyberKnife systems.On the other hand, a 2D dose measurement protocol using radiographic films and a MatLab program were developed. Stereotactic treatment plans were then performed for a phantom in order to assess the calculation algorithms implemented in the MultiPlan TPS (associated with the CyberKnife system). The analysis of the 2D dose distributions related to the stereotactic treatment plans has shown that the “Pencil Beam” based algorithm implemented in MultiPlan is suitable for dose calculation in homogeneous water-equivalent media but not in low electronic density media such as the lung. Indeed, the dose is overestimated (up to 40%) inside the field and may lead to reduce the tumor treatment efficiency while it is underestimated outside the field which can underestimate the dose to critical organs within proximity of the tumor. Regarding the Monte Carlo algorithm implemented in MultiPlan, calculated and measured dose distributions are consistent and, as a consequence, it is the most suitable algorithm available in MultiPlan to estimate the dose received by a patient when low density media are involved.

Die Nephrotoxizität ist die wichtigste Nebenwirkung bei Applikation von Radioimmunkonjugaten zur Konditionierung des Knochenmarks bei der Leukämiebehandlung. Die Auswirkungen der Unsicherheiten bei der Dosisbestimmung der Niere, insbesondere durch individuelle Nierenmasse und regionale Aktivitätsunterschiede, wurden untersucht. Die biologische Strahlenwirkung wurde als Biologisch Effektive Dosis unter Berücksichtigung des Zeitverlaufs der Dosisapplikation quantifiziert. Berechnungen wurden neben 188Rhenium auch für andere therapierelevante Radionuklide durchgeführt.