Introdução: A Radioterapia é frequentemente utilizada no tratamento do câncer, seja como uma modalidade simples ou em combinação com outras modalidades, tais como a cirurgia e a quimioterapia. Com o objetivo de eliminar células não desejadas no organismo humano, utiliza-se de radiações ionizantes para provocar a destruição de células tumorais pela absorção da energia da radiação incidente. A principal dificuldade encontrada em radioterapia é que as células tumorais não são tratadas isoladamente, isto é, o dano da radiação não é restrito somente às células tumorais, mas afeta também as células normais. Assim sendo, é essencial que a dose de radiação liberada nos tecidos normais seja tão baixa quanto possível para minimizar o risco de efeitos colaterais provocados pelos tratamentos radioterápicos. Objetivos: O objetivo deste trabalho é a caracterização de dosímetros semicondutores e dosímetros termoluminescentes e suas aplicações em técnicas não convencionais de Radioterapia. A partir da caracterização será possível a implementação dos dosímetros como sistema de dosimetria in vivo em teleterapia com feixe de fótons, visando atender as necessidades prementes do Serviço de Radioterapia do HCFMRP em implantar a técnica de irradiação de corpo inteiro e em realizar o controle de dose administrada ao paciente. Metodologia e Resultados: Diodos semicondutores foram caracterizados de acordo com o fator campo, angulação, taxa de dose, temperatura e fator bandeja, para obtenção dos fatores de correção. Verificou-se que a variação da resposta dos diodos com a temperatura, angulação e taxa de dose não foi significativa. Fatores campo foram calculados e registrados para campos de 3x3 cm 2 a 40x40cm 2 , onde se observou aumento na leitura do diodo com o aumento no campo. A resposta com a taxa de dose apr esentou pouca variação (de 100cGy/min para 300cGy/min a variação foi menor que 1,2%). O fator bandeja encontrado foi de 0,95±0,01 demonstrando que a presença da bandeja provoca diminuição na resposta do detector. Após a caracterização, os diodos foram calibrados em setup TBI para determinação dos fatores de calibração para cada espessura simulada do paciente (DLL). A dosimetria in vivo foi realizada em 3 pacientes submetidos ao tratamento de TBI do HCFMRP. A diferença percentual máxima entre as medidas com diodo e o valor nominal de dose foi de 3,6%, o que está de acordo com o recomendado pelo ICRU (+/- 5%). Os resultados demonstram a viabilidade e confiabilidade da técnica de dosimetria com diodos semicondutores para Controle de Qualidade de dose em tratamento de TBI. Ainda, dosímetros termoluminescentes foram caracterizados quanto à homogeneidade do grupo e a linearidade. Os fatores de calibração individuais foram encontrados e os dosímetros foram aplicados em simulações em setup TBI. Os cálculos de dose das simulações realizadas com os termoluminescentes inseridos nos orifícios de um OSA demonstraram concordância com os valores nominais de dose. Para as regiões do tórax superior e inferior, onde os TLD receberam doses mais elevadas (>150cGy), recomendou-se a utilização de compensadores de dose, para a prática clínica.Uma câmara de ionização foi utilizada como dosímetro de referência em todas as etapas de calibração e caracterização dos diodos e termoluminescentes. Conclusões: Este estudo mostrou que, para tratamentos de irradiação de corpo inteiro, quando o paciente estiver sendo preparado para um transplante de medula óssea, e o planejamento necessitar de uma grande eficácia na distribuição de dose, a metodologia com aplicações de dosímetros semicondutores apresenta-se como uma alternativa viável, precisa e de grande importância para o controle dosimétrico. Assim, ficou evidenciada a importância da utilização do diodo para o Controle de Qualidade, na avaliação da dos e a ser ministrada ao paciente, pelo menos em toda primeira fração de tratamento de TBI. Além disso, ficou demonstrada a aplicabilidade dos dosímetros termoluminescentes para controle dosimétrico, demonstrando o valor da dosimetria termoluminescente como um sistema de verificação de dose e sua eficácia como parte de um programa de garantia de qualidade em Radioterapia. A caracterização dos termoluminescentes evidenciou a possibilidade de aplicação da técnica TL em dosimetria in vivo. / Introduction: Radiation therapy is often used in cancer treatment, either as a single modality or in combination with other modalities, such as surgery and chemotherapy. Aiming to eliminate unwanted cells in the human body, radiation therapy uses ionizing radiation to cause destruction of tumor cells by absorbing the energy of the incident radiation. The main difficulty in radiation therapy is that tumor cells are not separately treated. The radiation damage is not restricted solely to tumor cells, but also affects normal cells. Therefore, it is essential that the radiation dose released in normal tissues is as low as possible to minimize the risk of side effects caused by radiotherapy treatments. Objectives: The objective of this work is the characterization of semiconductor dosimeters and thermoluminescent dosimeters and their applications in non -conventional radiotherapy techniques. After characterization it will be possible to implement the dosimeters as a system of in vivo dosimetry in radiotherapy with photon beam, to meet the pressing needs of the Radiotherapy Service of HCFMRP in deploying the technique of total body irradiation and make the control of dose administered to the patient . Methodology and Results: Semiconductor diodes were characterized according to the field factor, angle, dose rate, temperature and tray factor to obtain the correction factors. It was found that the variation of the response of the diodes with temperature, angle and dose rate was not significant. Field factors were calculated and recorded for fields from 3x3 cm 2 to 40x40cm 2 , wher e there was an increase in the reading of the diode with increasing field. The response with dose rate showed small variation (from 100cGy/min to 300cGy/min the variation was less than 1.2%). The tray factor was 0.95 ± 0.01 demonstrating that the tray decreases detector response. After characterization, the diodes were calibrated in TBI setup for determining the calibration factors for each simulated patient thickness (latero-lateral distance). The in vivo dosimetry was performed in 3 patients undergoing TBI treatment in HCFMRP. The maximum percentage difference between the measurements and the diode nominal dose was 3.6%, which is consistent with that recommended by ICRU (+ / - 5%). The results demonstrate the feasibility and reliability of the dosimetry technique with semiconductor diodes for dose quality control in TBI treatments. Still, dosimeters were characterized by group homogeneity and linearity. The calibration factors were found and individual dosimeters were applied in simulations with TBI setup. The dose calculation of simulations performed with the thermoluminescent inserted in holes of the phantom showed agreement with the nominal dose. For regions of the upper and lower thorax where TLD received higher doses (> 150cGy) it was recommended the use of compensating dose in clinic. An ionization chamber dosimeter was used as reference in all stages of calibration and characterization of diodes and thermoluminescents. Conclusions: This study showed that, for total body irradiation treatments, when the patient is being prepared for a bone marrow transplant, and planning requires a great effect on the dose distribution, the methodology with semiconductor dosimeters presented a viable alternative, and has great importance for the dosimetric control. The study proved the importance of diode semiconductors for quality control, for evaluation of the dose to be administered to the patient, at least throughout the first fraction of TBI treating. Furthermore, it was demonstrated the applicability of TLD for control quality, demonstrating the value of thermoluminescent dosimetry as a dose verification system and its effectiveness as part of a program of quality assurance in radiotherapy. The characterization of thermoluminescent showed the possibility of applying the TL technique in in vivo dosimetry.

L'efficacité des nanoparticules AGuIX a été démontré avec des irradiations précliniques ou monoénergétiques pour les cancers du cerveau, tête et cou, et poumon. L'irradiation préclinique de faible énergie (220 kV), et l'irradiation clinique (6 MV) sont adaptées pour activer les nanoparticules. L'effet radiosensibilisant des nanoparticules métalliques étant principalement causé par effet photoélectrique, il est nécessaire d'utiliser des photons d'énergie proche de la raie K du gadolinium (50.2 keV) afin de créer une interaction avec les électrons de l'atome dans le but d'amplifier localement la dose autour des nanoparticules aboutissant à des effets biologiques menant à une augmentation de la mort cellulaire. Dans le cadre de cette thèse, nous avons réalisé une preuve de concept sur le cancer du pancréas, connu pour son faible taux de survie, avec machines précliniques et cliniques. Afin de relever le défi du passage en clinique, nous avons proposé une méthode pour créer un adoucissement du faisceau d'irradiation et démontré la possibilité d'utiliser les nanoparticles AGuIX pour un essai clinique. Les travaux de recherche ont été réalisés en trois temps : un calcul analytique permettant d'obtenir une information sur l'influence des différents paramètres d'irradiation, une confirmation de l'efficacité des nanoparticules avec faisceaux précliniques, et enfin une preuve de concept avec faisceaux cliniques. Notre étude avec faisceaux cliniques est la première étude réalisée démontrant l'efficacité de nanoparticules de gadolinium passivement ciblées vers la tumeur, et démontre qu'il est possible d'obtenir des résultats cliniques similaires à ceux obtenus en préclinique / Previous studies demonstrated AGuIX ability to act as an efficient radiosensitizer under the presence of preclinical radiations or monoenergetic radiation beams for multiple cancer models. The preclinical irradiation (220 kV) has been shown effective in activating high atomic number (Z) nanoparticles. The energy peak is close to the k-edge of the different high-Z elements used (50.2 keV for the gadolinium), leading to a strong photoelectric effect. Auger electrons generation and biological effects occur afterwards creating a local dose enhancement. However, clinical treatments use a higher energy beam (>6 MV). At these energy ranges, the photoelectric probability is less important, decreasing the direct interaction of the nanoparticles with the incoming photons. We performed a proof of concept on a pancreatic tumor model, known for its low survival rates, with preclinical and clinical radiation beams to evaluate the efficacy of the AGuIX. To increase the efficacy of the clinical radiation beam without modifying the nanoparticle structure in order to obtain a dose enhancement close to the one observed with the preclinical beam, we evaluated key clinical beam parameters to understand and increase the mechanisms of interaction between the incident photons and the high-Z nanoparticles. Hence, we evaluated analytically the impact of the radiation beam under different conditions of irradiation, confirming the potential of the AGuIX with a preclinical beam, and finally shown their significant efficacy under a clinical setup. This study is the first to evaluate the potential of a high-Z nanoparticle to act as radiosensitizer following low dose intravenous injections

La radiothérapie interne sélective est une thérapie émergente très peu invasive du carcinome hépatocellulaire, quatrième cause de décès par cancer dans le monde. Des millions de microsphères chargées en Yttrium 90 sont injectées dans l'artère hépatique par un cathéter. Actuellement, leur distribution lors d'une injection est estimée par l'injection préliminaire d'un radiomarqueur, ce qui peut se révéler trop approximatif. Un traitement personnalisé permettrait une concentration des radiations à la tumeur tout en épargnant le tissu sain environnant. Dans ce travail je me suis intéressée au développement d'un modèle numérique, pour une simulation spécifique à chaque patient des trajectoires des microsphères, dans le but d'optimiser le traitement. Le protocole clinique d'imagerie a été exploité et optimisé pour l'extraction de données spécifiques patients telles que le foie, les tumeurs, l'artère hépatique et le flux sanguin. Les tissus et l'artère hépatique (jusqu'à un diamètre de 0.05 mm) sains et malins ont été simulés. Cela nous permet de simuler la distribution des microsphères dans le tissue hépatique, validée grâce à la scintigraphie post-traitement. Il est supposé ici que les microsphères se distribuent de façon proportionnelle au flux sanguin, lequel est modélisé par la loi de Poiseuille. Des simulations plus approfondies en mécanique de fluides numérique du flux sanguin ont ensuite été réalisées dans l'artère hépatique du patient. Pour cela nous avons utilisé et comparé les méthodes des Volumes Finis (Ansys Fluent) et de Lattice Boltzmann (programme développé dans le laboratoire). Le transport des microsphères a été simulé dans l'artère hépatique du patient avec la méthode des volumes finis, et dans une géométrie simplifiée avec la méthode de Lattice Boltzmann. Une séquence IRM de contraste de phase a aussi été optimisée pour l'extraction de la vitesse du sang dans l'artère hépatique, dans le but de valider le modèle numérique. / Selective internal radiation therapy using Yttrium-90 loaded glass microspheres injected in the hepatic artery is an emerging, minimally invasive therapy of hepatocellular carcinoma, which is the fourth cause of mortality in the world. Currently, microspheres distribution can be only approximately predicted by the injection of a radiotracer, whose behaviour may be different. A personalised intervention can lead to high concentration dose in the tumour, while sparing the surrounding parenchyma. This work is concerned with the development of a patient-specific numerical model for the simulation of microspheres trajectories and treatment optimisation. Clinical imaging protocol is utilised and optimised in order to extract patient’s specific data such as liver, tumours, hepatic artery and blood flow. Normal and malignant hepatic arterial vasculature and tissues are simulated down to a vessels diameter of 0.05 mm. A preliminary simulation of microspheres distribution in liver tissue is proposed and validated against post-treatment scintigraphy. Microspheres are here supposed to distribute proportionally to blood flow, which is computed based on Poiseuille’s law. More precise computational fluid dynamics (CFD) simulations of blood flow in the patient’s segmented arteries are performed. The Finite Volume Method (Ansys Fluent) and the Lattice Boltzmann Method (in-house developed software) are used to this purpose and their efficacy is compared. Microspheres transport is simulated in the patient’s hepatic artery using the FVM, and in a representative geometry using the LBM method. A phase contrast MRI sequence has been optimised in order to extract blood velocity from the hepatic artery and validate CFD simulations.

External Beam Radiation Therapy (EBRT) is a common treatment option for patients with prostate cancer. When treating the prostate with EBRT, a geometric volume (PTV margin) is added around the prostate to account for uncertainties in treatment planning and delivery. Current methods for estimating PTV margins rely on the analysis of population-based inter- and intra-fraction motion data. These methods do not consider the patient-to-patient differences in demographic or clinical presentation of patient specific factors (PSFs), such as age, weight, body-mass index, health and performance status, prostate-specific antigen levels, Gleason scores, presence of bowel problems, or other health conditions. The purpose of this thesis is to investigate the feasibility using regression-based predictive algorithms to predict the extent of prostate motion for the purpose of personalizing the PTV margin using PSFs as inputs. Benchmarking simulations of Linear, Ridge, LASSO, SVR, kNN, and MLP algorithms were performed by simulating prostate intra-fraction motion and realistic variations in PSFs. Sample sizes ranged from n=20 to 800, with varying levels of noise into the motion data (0-10mm). Leave-one-out cross validation was used to train and validate algorithm performance. The results suggest that algorithm performance improves significantly within the first 50 – 100 patients, and this rate of improvement is independent of noise in prostate motion. The Ridge regression algorithm predicted intra-fraction motion to the lowest mean absolute error in simulated motion, performing especially well in small datasets. To evaluate the clinical utility of this approach, pre- and post-treatment prostate motion data, treatment time data, and rectal distension data was recorded in 21 patients, along with a variety of PSFs. In the analysis of patient data, the LASSO algorithm out-performed the Ridge algorithm, predicting the mean and standard deviation of an individual prostate cancer patient’s intra-fraction motion to within 0.8mm and 0.4 mm mean absolute error, respectively. However, prostate motion predictions did not correlate with PSFs, possibly due to the small sample size. This work demonstrates the feasibility of using regression-based algorithms for predicting prostate motion, and hence the opportunity to personalize PTV margins in prostate cancer patients. / Graduate / 2018-08-22

New radiation therapy (RT) techniques for treating cancer are continually under development. Our ability to demonstrate the safe and accurate implementation of new RT treatment techniques is dependent on the information provided by current dosimetric tools. Advanced dosimetric tools will become increasingly necessary as treatments become more complex. This work examines the readout of an advanced dosimeter --- the polyacrylamide, gelatin, and tetrakis (hydroxymethyl) phosphonium chloride (PAGAT) dosimeter --- using a prototype fan-beam optical computed tomography (CT) scanner. A number of developments sought to improve the performance of the optical CT device. A new fan-creation method (laser diode module) and new matching tank were introduced. Artefact removal techniques were developed to remove flask seam artefacts and ring artefacts via sinogram space. A flask registration technique was established to achieve reproducible placement of flasks in the optical CT scanner. A timing-correction technique was implemented to allow for the scanning of continuously rotating samples. A number of experiments examined factors related to the PAGAT dosimeter. Comparisons of post-irradiation scans to pre-irradiation scans improved dosimeter readout quality. Changes to the PAGAT dosimeter cooling/scanning routine provided further improvements to dosimeter readout. Evaluations of calibration curves showed that a linear calibration curve was less capable of describing PAGAT dose response than a quadratic calibration curve. Intra-gel calibration using another dose distribution was shown to be no less accurate than self calibration, but inter-gel calibrations saw a statistically significant increase in absolute readout errors. A set of investigations examined how optical CT scanning protocols affected readout quality for PAGAT dosimeters. Doubling the dose delivered to the dosimeter doubled the signal-to-noise ratio. Acquiring and averaging additional light profiles at each projection angle provided only slight reductions in readout noise. Sampling a higher number of projection angles provided substantial reductions in readout noise. Those reductions in readout noise were not lost when sinograms with many projections were encapsulated into sinograms of fewer projection angles. Detector element binning (sinogram space) and pixel binning (image space) also provided substantial reductions in readout noise. None of these elements of the scanning protocol had statistically significant effects on readout errors. Finally, distinct imaging artefacts seen throughout this work were shown to be caused by radiation-induced refractive index changes in PAGAT dosimeters. Radiation-induced refraction (RIR) artefacts result when dose gradients caused the refraction of fan-beam raylines towards high dose regions. A filtering technique was developed to remove RIR artefacts in sinogram space, but this technique caused substantial blurring to the measured dose distribution. / Graduate / 0760 / 0756 / 0752 / warreng1983@gmail.com

Abstract THE CHARACTERIZATION OF CHIMERIC CHAPERONE FLAGRP170 AS A NOVEL RADIOPROTECTANT By Tyler Nguyen, M.S. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. Virginia Commonwealth University, 2017 Major Director: Dr. Xiang-Yang (Shawn) Wang, Ph.D., Professor, Department of Human and Molecular Genetics Radiation therapy (RT) is restricted by toxic effects on adjacent normal tissue, which limits RT efficacy in cancer treatment. Damage to normal tissue, such as radiosensitive intestine and bone marrow compartments, results in acute radiation damage. To reduce normal tissue injury in the setting of RT, we examine the potential radioprotectant, Flagrp170, a chimeric protein. Flagrp170 is comprised of glucose-regulated protein-170 (Grp170) and a NF-κB activating sequence derived from flagellin. We show that Flagrp170 can protect normal tissues post irradiation, indicated by TUNEL and clonogenic assays. However, treatment with Flagrp170 does not influence tumor response to RT. Studies indicate that Flagrp170 activates the transcription factor NF-κB, a strong pro-survival signal. In addition, Flagrp170 can induce production of radioprotective cytokines as well. Data suggests that Flagrp170 has potential as a novel radioprotectant in the setting of RT. The combination of Flagrp170 therapy and RT may lead to improved treatment outcomes.

Cancer is one of the deadliest diseases today, and with increasingly larger and older populations, cancer constitutes an enormous contemporary and future challenge. Luckily, advances in technology and medicine are continuously contributing to a decrease in cancer mortality, and to the reduction of treatment side effects. The aim of this Master's thesis is to be a part of these advances, thereby increasing the survival chances and well-being of future cancer patients. The thesis regards specifically the improvement of radiation therapy, a form of treatment utilized in both curative and palliative cancer care. In radiation therapy, ionizing radiation is directed at cancerous cells in the body. The radiation prevents the further proliferation of malignant cells by damaging their DNA. However, the radiation is also harmful to healthy cells. It is therefore of utmost importance that the irradiation of the patient is done in such a way to spare the critical organs in the vicinity of the tumor. To obtain the best possible treatment, mathematical optimization algorithms are utilized. Using physical models of how radiation travels in the body, it is possible to calculate what effect the irradiation of the patient will have. To quantify the quality of the treatment, mathematical functions are used, which evaluate the radiation dose under certain criteria. Once these functions are defined, algorithms can be applied that find the optimal treatment with regard to the given criteria. The formulation of these functions and their properties is the main focus of this thesis. Using clinical evaluation criteria previously used to assess treatments, a framework for optimizing functions that directly correlate to the clinical goals is constructed. The framework is examined and used to generate radiation therapy plans for three cancer patients. In each of the cases, the constructed treatment plans demonstrate high quality, often better than or comparable to the plans created by experienced dose planners using existing tools. A particularly interesting application of the developed framework is the automatic generation of treatments. This relies on the clinician giving the clinical goals as input to the algorithm. A plan is then generated with maximal goal fulfillment. This eliminates the tedious and time consuming process of parameter tuning to achieve a satisfactory plan. Several studies have demonstrated the ability of automatic planning to retain the plan quality while substantially improving planning efficiency.

A common co-pathology of large lung tumors located near the central airways is collapse of portions of lung due to blockage of airflow by the tumor. Not only does the lung volume decrease as collapse occurs, but fluid from capillaries also fills the space no longer occupied by air, greatly altering tissue appearance. During radiotherapy, typically administered to the patient over multiple weeks, the tumor can dramatically shrink in response to the treatment, restoring airflow to the lung sections which were collapsed when therapy began. While return of normal lung function is a positive development, the change in anatomy presents problems for future radiation sessions since the treatment was planned on lung geometry which is no longer accurate. The treatment must be adapted to the new lung state so that the radiation continues to accurately target the tumor while safely avoiding healthy tissue. However, to account for the dose delivered previously, correspondences of anatomy between the former image when the lung was collapsed and the re-expanded lung in a current image must be obtained. This process, known as deformable image registration, is performed by registration software. Most registration algorithms assume that identical anatomy is contained in the images and that intensities of corresponding image elements are similar; both assumptions are untrue when collapsed lung re-expands. This work was to develop an algorithm which accurately registers images in the presence of lung expansion. The lung registration method matched CT images of patients aided by vessel enhancement and information of individual lobe boundaries. The algorithm was tested on eighteen patients with lung collapse using physician-specified correspondences to measure registration error. The image registration algorithm developed in this work which was designed for challenging lung patients resulted in accuracy comparable to that of other methods when large lung changes are absent.

Le cancer de la prostate est le cancer le plus fréquemment diagnostiqué en France chaque année. Il est responsable d’environ 10 % des morts liées au cancer. Les principaux traitements sont la chirurgie et la radiothérapie. Cette dernière concerne environ 60 % à 70 % des patients pris en charge en oncologie. La radiothérapie consiste à délivrer la dose la plus élevée possible à une cible tumorale, via des rayonnements ionisants, tout en limitant au maximum la dose délivrée aux tissus sains et organes à risque (OAR) environnants. Cette pratique requiert un contrôle sans faille de la dose délivrée au patient car une déviation de la prescription médicale peut réduire l’efficacité du traitement des volumes tumoraux. Elle peut également avoir des conséquences graves sur le patient dues à l’irradiation excessive des tissus sains. Un moyen pour évaluer de façon précise la dose délivrée est de simuler l’interaction rayonnement matière à l’intérieur du patient par simulation Monte-Carlo (SMC). Ceci exige une capacité de calcul importante notamment pour simuler les milliards de particules nécessaires à l’évaluation de la dosimétrie. Le temps nécessaire pour obtenir un résultat satisfaisant peut varier de quelques heures à plusieurs jours. Dans ce contexte, le moteur de simulation Monte-Carlo GGEMS (GPU GEant4-based Monte-Carlo Simulation), basé sur l’utilisation de cartes graphiques (GPUs), a pu être développé. Les effets physiques modélisés se basent sur le code Monte-Carlo générique Geant4 réputé et validé. Ce logiciel tient compte de différents types de simulations comme la radiothérapie externe ou les techniques de curiethérapie bas débit et haut débit de dose. Ces exemples ont nécessité la modélisation précise et l’utilisation de plusieurs types de géométries comme des volumes voxélisés, analytiques ou maillés. Concernant la radiothérapie, il n'existait pas de code Monte-Carlo utilisant les architectures GPUs prenant en considération l'ensemble de l'appareil de traitement. Dans ce contexte, nous avons développé un modèle de source paramétrée reproduisant scrupuleusement le faisceau d'émission et permettant une utilisation sur GPU. Nous avons modélisé analytiquement les géométries des mâchoires. Le collimateur multi-lames est quant à lui formé par un ensemble de triangles (maillage). La navigation des électrons dans un volume voxélisé a également été développée. Nous avons utilisé comme exemple l'accélérateur Novalis TrueBeam® Stx. Nous pouvons ainsi effectuer des simulations Monte-Carlo reproduisant fidèlement cet accélérateur linéaire. L’ensemble de l’appareil a été validé à l’aide de comparaisons avec des mesures expérimentales ou avec des simulations Monte-Carlo de référence. Finalement, nous avons développé une plateforme de simulation Monte-Carlo utilisant les architectures GPUs pour des applications de curiethérapie et de radiothérapie externe. Cette plateforme comprend la navigation des photons et des électrons. Elle gère également les volumes voxélisés, analytiques (cylindre, pavé) et maillés. Les sources d'émission des particules sont modélisées pour reproduire fidèlement leur modèle de référence. Les facteurs d'accélération par rapport à Geant4 sont compris entre 40 et 568 selon l'application. Des applications de GGEMS dans des conditions cliniques, notamment en curiethérapie, sont la prochaine étape du développement. / Prostate cancer is the most frequently diagnosed cancer in France each year. It is responsible for about 10% of deaths related to cancer. The main treatments are surgery and radiation therapy. The latter concerns about 60 % to 70 % of patients treated in oncology. The aim of radiation therapy is to deliver the highest possible dose to the tumor target, via ionizing radiation, while minimizing the dose delivered to surrounding healthy tissues and organs at risk (OAR). This practice requires a flawless dose control for patient safety as far as a deviation from the medical prescription could reduce treatment efficiency This could also lead to an excessive irradiation of healthy tissues and cause serious damage to the patient. A way to evaluate the dose delivered to the patient is to track particles in the matter using Monte Carlo simulations (MCS). This requires a large computation time specially to simulate billion of particles and to evaluate the associated dosimetry. The time required to obtain a satisfactory result may vary from hours to days. In this context, the Monte Carlo simulation engine GGEMS (GPU Geant4-based Monte Carlo Simulation), based on the use of graphics cards (GPUs), has been developed. Physics effects are based on the generic and validated Monte Carlo code Geant4. This software is able to handle various types of simulations such as external beam radiation therapy and low dose rate or high dose rate brachytherapy. These examples need an accurate modelling and the use of several types of geometries such as for voxelised, analytical or meshed volumes. We analytically modeled jaw geometries. The multi-leaf collimator was formed by a set of triangles (mesh). Electron navigation in a voxelised volume was also developed. We used the example of the Novalis TrueBeam® Stx accelerator. We can then perform Monte Carlo simulations reproducing the linear accelerator. The entire device was validated using comparisons with experimental measurements or with Monte Carlo simulations from Geant4 Finally, we have developed a Monte Carlo simulation platform using GPU architectures for applications of brachytherapy and external beam radiotherapy. This platform includes photons and electrons navigation. It also manages voxelised, analytical (cylinder, cube) and mesh volumes. The particle emission sources are modelled to accurately reproduce their reference model. The acceleration factors from Geant4 are between 40 and 568 depending on the application. GGEMS Applications under clinical conditions, including brachytherapy, are the next development step.

A study was done at Steve Biko Academic hospital to determine the influence that respiratory gating will have on target volumes used in radiotherapy treatment planning. The primary objective was to compare target volumes of respiratory gated scans to ungated scans and to determine whether it will be meaningful to permanently implement a 4D respiratory gating system on CT scanners in the South African public health sector and to use these images for target volume delineation in radiotherapy planning. The study consisted of three sections. In the first section, 4D respiratory gated CT images were obtained and delineated with 4D software. The full-inspiration and full-expiration phases of the gated scans were then fused to obtain ungated images which were also delineated. The gross tumor volumes (GTVs) of the gated phases were compared to the ungated GTVs, and found that on average the volumes decreased by 14.63% with a standard deviation of 7.96% when gating was applied. Yet another aim was to determine the influence that 4D imaging will have on radiotherapy treatment planning. One of the 4D study sets was imported to the XIO treatment planning system where IMRT treatment plans were created on both the gated and ungated scans. The plans conformed to the treatment aims and restrictions when clinical parameters such as DVHs were used to evaluate it. The planned target volume coverage differed by less than 1% between the gated and the ungated plans, but significant dose reductions to the OARs of up to 32.65% to the contralateral lung were recorded on the gated plan. In the second section of this study, respiratory gated CT scans were simulated by applying the breath-hold technique to lung cancer patients. The technique was applied during full-inspiration which fundamentally represents the maximum peak of the sinusoidal respiratory waveform. An ungated scan was also acquired during normal respiration. The clinical target volumes (CTVs) were identified on both scans by three oncologists and the average CTVs were compared. It was found that the CTVs decreased significantly by an average of 14.33%. Palliative patients receive parallel opposing field therapy which is planned from 2D films. It is very unlikely that these opposing field sizes will differ when gating is applied. It was therefore concluded that only radical lung patients, which was estimated to be a mere 0.03% of the total radiation therapy patient population, will benefit by implementing respiratory gating or any motion-reduction technique. For the third section of the study, respiratory gated PET scans were acquired on a PET/CT scanner to evaluate external, non-technical parameters that will influence respiratory gating. The results indicated that time and patient participation were not limiting factors. The biggest concerns however were the effectiveness of the gating system, software limitations and the gated results. These problems might be minimized with thorough training on the system. All three sections as well as the financial implications were considered to conclude that it will not be meaningful to implement 4D respiratory gating techniques in the South African public health sector Copyright / Dissertation (MSc)--University of Pretoria, 2013. / Medical Oncology / unrestricted