A sobrevida de crianças que foram submetidos a tratamento antineoplásico tem se acrescentado nos últimos anos devido às novas alternativas de tratamento. Os sobreviventes de câncer infantil com frequência podem apresentar efeitos tardios decorrentes do tratamento antineoplásico. Diferentes órgãos podem apresentar efeitos tardios incluindo os dentes. Algumas anomalias dentárias são associadas aos efeitos da quimioterapia e/ou radioterapia. O estudo da influência do tratamento antineoplásico sobre a ocorrência de anomalias dentárias, permite saber quais os possíveis desafios no tratamento odontológico nos sobreviventes de câncer infantil. Este estudo, avaliou as anomalias dentárias e a idade dentária através de radiografias panorâmicas em sobreviventes de câncer infantil e compará-la com radiografias panorâmicas de indivíduos saudáveis. Foram avaliadas 111 radiografias panorâmicas de sobreviventes de câncer infantil comparadas a 111 radiografias panorâmicas de indivíduos saudáveis pareadas por idade e gênero respeito ao grupo de estudo, com análise de tipo duplo cego. Foram avaliadas um total de 16 tipos de anomalias dentárias de forma, tamanho, número assim como anomalias do desenvolvimento da raiz dentária classificadas em 5 tipos diferentes. A idade dentária foi avaliada pelo método de Demirjiam. A microdontia, hipodontia e anomalias do desenvolvimento da raiz foram as anomalias dentárias que apresentaram maior ocorrência nos sobreviventes de câncer da infância quando comparado a indivíduos saudáveis (p=<0,05). A microdontia esteve associada à idade de diagnóstico menor a 5 anos de idade (p=<0,04). O dente não irrompido teve associação com indivíduos que foram submetidos a quimioterapia concomitante com radioterapia (p=<0,001). Anomalias dentárias com uma quantidade >10 estiveram presentes somente no grupo de estudo. A idade dentária não apresentou diferença significativa entre os grupos (p=>0,05). Conclui-se que Indivíduos submetidos a quimioterapia e/ou radioterapia durante a infância apresentaram maior ocorrência de desenvolver anomalias dentárias. Porém, a idade dentária sugere não ser afetada pela quimioterapia e/ou radioterapia. / Children who have been undergone antineoplastic treatment have increased the survival due to new treatment alternatives. The childhood cancer survivors may have frequently late effects from antineoplastic treatment. Different organs may have late effects including the teeth. Some dental anomalies are associated as late effects of chemotherapy and/or radiotherapy. To study the antineoplastic treatment influence on the occurrence of dental anomalies allows to know the possible challenges in dental care of childhood cancer survivors. This study evaluated dental abnormalities and the dental maturity by panoramic radiographs in childhood cancer survivors and to compare it with panoramic radiographs of healthy individuals. A total of 111 panoramic radiographs of childhood cancer survivors compared to 111 panoramic radiographs of healthy individuals were evaluated. They were matched for age and gender regarding the childhood cancer survivor, with a double-blind type analysis. A total of 16 types of dental anomalies of shape, size, number and developmental anomalies of the dental root were classified into 5 different types. Dental maturity was assessed by the Demirjian method. Microdontia, hypodontia, and root anomalies were the dental anomalies that presented a higher prevalence in CCS when compared to healthy individuals (p = <0.05). Microdontia was associated with a diagnosis age younger than 71 months of age (p = <0.04). The impacted tooth was associated with individuals who underwent chemotherapy concomitantly with radiotherapy (p <0.001). Individuals with an amount of 10 or > 10 dental anomalies were present only in the CCS group. Dental maturity did not present a significant statistical difference between CCS and healthy individuals. It was concluded that individuals undergoing chemotherapy and/or radiotherapy during childhood had a higher prevalence of dental. However, dental maturity suggests that it is not affected by chemotherapy and/or radiotherapy.

Este trabalho visa estudar as margens necessárias para definir o volume de planejamento do alvo (PTV) requeridas para tratar adequadamente tumores móveis como os localizados na próstata ou tumores localizados em áreas com pouca mobilidade como os da região da cabeça e pescoço, na ausência de localização do alvo por imagem. Também tem como objetivo avaliar o impacto causado pelo PTV, em termos de dose, nas estruturas críticas ao seu redor e sua influência quando planejamento inverso é utilizado na radioterapia com modulação de feixe (IMRT). Dados de 387 pacientes de próstata foram analizados retrospectivamente. Todos os pacientes receberam localização pré-tratamento com ultra-som 2D resultando em 10.327 localizações, cada uma com deslocamento de isocentro em três direções: antero-posterior (AP), lateral direitaesquerda (DE), e superior-inferior (SI). O deslocamento médio e desvio padrão (SD) para cada direção foi estimado a partir dos dados de tratamento gravados diariamente. As incertezas (SD) na posição do alvo foram 4,4 mm (AP), 3,6 mm (DE), e 4,5 mm (SI). O estudo das incertezas no posicionamento diário de 78 pacientes com tumores de cabeça e pescoço que utilizaram máscaras termoplásticas como imobilizadores, avaliados com equipamento de portal com imagem eletrônica (EPID), mostrou variações (SD) na posição do isocentro de tratamento de 3,1 mm (AP), 1,5 mm (DE), 4,5 mm (SI). Aplicando estes desvios num simulador antropomórfico estudou-se os histogramas de dose-volume resultantes do deslocamento do isocentro no tratamento diário. Os resultados mostraram a importância de se colocar margens no volume clínico do alvo para garantir um tratamento adequado e também mostraram que a variação diária do isocentro de tratamento pode causar um aumento de dose maior que o nível de tolerância dos órgãos críticos. / This work intends to study the margins required to define a planning target volume (PTV) for adequate treatment of the mobile tumors such as prostate or those located in areas with less mobility as the ones in head and neck region, in the absence of daily localization imaging based. It is also intends to evaluate the impact caused by the PTV, in terms of dose, to the critical structures surrounding the PTV and its influence when inverse planning is used in the intensity-modulated radiation therapy (IMRT). Data from 387 prostate patients were analyzed retrospectively. Every patient in the study received daily pre-treatment localization with 2D ultrasound resulting in a total of 10,327 localizations, each comprising of an isocenter displacement in 3 directions: anterior-posterior (AP), right-left lateral (RL), and superior-inferior (SI). The mean displacement and standard deviation (SD) for each direction for each patient was computed from daily treatment records. The uncertainties (SD) in the target position were 4.4 mm (AP), 3.6 mm (RL), and 4.5 mm (SI). A study of the uncertainties in the daily positioning of 78 head and neck patients who used thermoplastic mask to immobilize them, evaluated with electronic portal imaging device (EPID), showed variations (SD) in the isocenter treatment position of 3.1 mm (AP), 1.5 mm (RL), and 4.5 mm (SI). By applying these shifts in an anthropomorphic phantom it was studied the dose-volume histograms resultant of the isocenter displacement in the daily treatment. The result showed the importance of putting margins in the clinical target volume to assure an adequate treatment and also showed that isocenter daily variation can cause an increase to the dose greater than the tolerance level to the critical organs.

Dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science in Medicine. Johannesburg, 2014 / Background: The causes of renal dysfunction in children treated for childhood cancers are multifactorial and clinical manifestations of dysfunction include hypertension, proteinuria and varying degrees of renal insufficiency. This study aimed to determine the different residual effects of cancer therapy on the renal system and factors associated with the residual effects in children treated for childhood cancers. Patients and Methods: The study was a descriptive cross sectional study that assessed 130 children, between the age of 1 and 18 years, who had completed treatment at Charlotte Maxeke Johannesburg Academic Hospital and were being followed up at the paediatric oncology clinic of the hospital. Results: After a median follow-up post treatment of 2 years, the various manifestations of renal dysfunction identified in the survivors included; decreased GFR, hypomagnesaemia, hypophosphataemia, proteinuria, haematuria and hypertension. In total, 34 survivors (26.15%) had at least one manifestation of renal dysfunction after completing treatment. The most prevalent manifestation of renal dysfunction detected was decreased GFR (17.69%). Hypomagnesaemia and hypophosphataemia were present in 8 (6.15%) and 6 (4.62%) of the survivors respectively. Patients who had renal dysfunction pre-treatment were three times more likely to have renal dysfunction post-treatment. Ifosfamide, Carboplatinum, and nephrectomy were significantly associated with a reduction in GFR Conclusion: A significant number of the survivors had a decreased GFR while some of them had hypomagnesaemia and hypophosphataemia. There was a strong association between pre-treatment and post-treatment renal dysfunction. These findings are very important in terms of decision making for individual patients with respect to selecting treatment modalities and dosages and also with respect to instituting nephro-protective measures to avoid further damage to the kidneys during and after treatment.

Les références actuelles, pour les rayons X de moyenne énergie en radiothérapie, sont établies au LNHB en termes de kerma dans l’air. La dose absorbée dans l’eau, grandeur d’intérêt pour la radiothérapie, est déduite de ces valeurs par transfert conformément aux protocoles internationaux. Ce travail de thèse a permit d’établir les références en termes de dose absorbée dans l’eau dans les conditions de référence des protocoles en utilisant la méthode de calorimétrie dans l’eau. La calorimétrie est la mesure de la dose absorbée à partir de l’élévation de température. Un « calorimètre-eau » a été conçu et réalisé afin d’effectuer des mesures à 2 cm de profondeur : conditions de référence définies par le protocole AIEA TRS-398. Les débits de dose absorbée dans l’eau ainsi déterminés ont été comparés aux valeurs issues de l’application des protocoles fondés sur le kerma dans l’air. Un écart maximum inférieur à 2.1 % a été trouvé par rapport à la calorimétrie. L’incertitude type associée aux valeurs calorimétriques étant inférieure à 0.8 % et celle associée aux valeurs issues des protocoles étant de l’ordre de 3.0 %, les résultats sont compatibles aux incertitudes des méthodes près. Grâce à ces nouvelles références, la détermination de la dose absorbée dans l’eau dans ce type de faisceau pourra désormais être réalisée en appliquant le protocole AIEA TRS-398, conduisant ainsi à une forte réduction des incertitudes (facteur 3 par rapport au protocole AIEA TRS-277). Actuellement, aucun autre laboratoire primaire ne possède un tel instrument permettant l’établissement direct de ces références dans les conditions recommandées par les protocoles. / LNE-LNHB current references for medium energy X-rays are established in terms of air kerma. Absorbed dose to water, which is the quantity of interest for radiotherapy, is obtained by transfer dosimetric techniques following a methodology described in international protocols. The aim of the thesis is to establish standards in terms of absorbed dose to water in the reference protocol conditions by water calorimetry. The basic principle of water calorimetry is to measure the absorbed dose from the rise in temperature of water under irradiation. A calorimeter was developed to perform measurements at a 2 cm depth in water according to IAEA TRS-398 protocol for medium energy x-rays. Absorbed dose rates to water measured by calorimetry were compared to the values established using protocols based on references in terms of air kerma. A difference lower than 2.1% was reported. Standard uncertainty of water calorimetry being 0.8%, the one associated to the values from protocols being around 3.0%, results are consistent considering the uncertainties. Thanks to these new standards, it will be possible to use IAEA TRS-398 protocol to determine absorbed dose to water: a significant reduction of uncertainties is obtained (divided by 3 by comparison with the application of the IAEA TRS-277 protocol). Currently, none of the counterparts’ laboratories own such an instrument allowing direct determination of standards in the reference conditions recommended by the international radiotherapy protocols.

Quando se utiliza feixes de radiação ionizante de fótons e elétrons com altas energias, a região mais perto da superfície do paciente, região de não-equilíbrio, pode ter o comportamento das doses absorvidas comprometido devido a vários fatores como a presença de materiais auxiliares na radioterapia, exemplo o \"bolus\" (para superficializar a dose absorvida) e materiais imobilizadores como a máscara termoplástica. Dependendo da significância da incerteza no valor da dose absorvida, medidas devem ser tomadas para que esta seja mais próxima possível daquela prescrita. O objetivo desse trabalho é o de avaliar a capacidade do FXG para medidas de dose absorvida na região de não-equilíbrio e o comportamento dessas. Os objetivos específicos foram: (1) o de avaliar e comparar os (µ/?) experimentais e simulados (X-COM e GEANT-4) para diversos materiais, incluindo o FXG, (2) avaliar a influência da máscara termoplástica na dose absorvida prescrita e (3) determinar o ponto de equilíbrio eletrônico, R100, em função das energias dos feixes de fótons e elétrons para diversos materiais. Dos resultados obtidos tem-se que o (µ/?) relativo ao FXG é próximo daquele do tecido mole (TM), o material da máscara influencia a distribuição da dose absorvida na região de não-equilíbrio e os valores obtidos experimentalmente e por simulação MathLab® e PENELOPE® , indicam equivalência entre os materiais da câmara de ionização (CI) e Água, diferentes da equivalência do FXG eTM. Esse último resultado corrobora aquele obtido no experimento para determinação do (µ/?) , levando a concluir a adequabilidade do FXG para medidas na região de não-equilíbrio. / When one uses high energies photons and electrons ionizing radiations beam, the region closer to the surface of the patient, non-equilibrium region, can obtain the absorbed dose behavior compromised due to several factors such as the presence of auxiliary materials in radiotherapy, like the \"bolus\" (used to superficialize the absorbed dose) and immobilizing material as the thermoplastic mask. Depending on the significance of the uncertainty in the dose absorbed value, measurements must be taken in order the measured value be as close as possible to that prescribed. The aim of this paper is to evaluate the ability of FXG for the measurements of the absorbed dose in the region of non-equilibrium and their behavior. The specific object ives are: (1) to evaluate and compare the µ/? experimental and simulated (X-COM and GEANT-4) for various materials, including the FXG; (2) to evaluate the influence of the therm oplastic mask in the prescribed absorbed dose, and (3) to determine the equilibrium electronic point, R100, depending on the photon and electron beam energies for various materials. The results present that the FXG µ/? is close to that of the soft tissue (TM); the mask material influences the absorbed dose distribution in the non-equilibrium region, and the values obtained experimentally and also through MatLab® and Penelope® simulation indicate equivalence between the materials of ionization chamber (IC) a nd water, different from the equivalence between the FXG and TM. This last result corroborates the obtained one in the experiment for the µ/? determination, suggesting the adequacy of FXG for measurements in the non-equilibrium region.

abstract: The challenge of radiation therapy is to maximize the dose to the tumor while simultaneously minimizing the dose elsewhere. Proton therapy is well suited to this challenge due to the way protons slow down in matter. As the proton slows down, the rate of energy loss per unit path length continuously increases leading to a sharp dose near the end of range. Unlike conventional radiation therapy, protons stop inside the patient, sparing tissue beyond the tumor. Proton therapy should be superior to existing modalities, however, because protons stop inside the patient, there is uncertainty in the range. “Range uncertainty” causes doctors to take a conservative approach in treatment planning, counteracting the advantages offered by proton therapy. Range uncertainty prevents proton therapy from reaching its full potential. A new method of delivering protons, pencil-beam scanning (PBS), has become the new standard for treatment over the past few years. PBS utilizes magnets to raster scan a thin proton beam across the tumor at discrete locations and using many discrete pulses of typically 10 ms duration each. The depth is controlled by changing the beam energy. The discretization in time of the proton delivery allows for new methods of dose verification, however few devices have been developed which can meet the bandwidth demands of PBS. In this work, two devices have been developed to perform dose verification and monitoring with an emphasis placed on fast response times. Measurements were performed at the Mayo Clinic. One detector addresses range uncertainty by measuring prompt gamma-rays emitted during treatment. The range detector presented in this work is able to measure the proton range in-vivo to within 1.1 mm at depths up to 11 cm in less than 500 ms and up to 7.5 cm in less than 200 ms. A beam fluence detector presented in this work is able to measure the position and shape of each beam spot. It is hoped that this work may lead to a further maturation of detection techniques in proton therapy, helping the treatment to reach its full potential to improve the outcomes in patients. / Dissertation/Thesis / Doctoral Dissertation Physics 2019

This thesis mainly focuses on proposing a 4D (three spatial dimensions plus time) tissue-volume preserving non-rigid image registration algorithm for pulmonary 4D computed tomography (4DCT) data sets to provide relevant information for radiation therapy and to estimate pulmonary ventilation. The sum of squared tissue volume difference (SSTVD) similarity cost takes into account the CT intensity changes of spatially corresponding voxels, which is caused by variations of the fraction of tissue within voxels throughout the respiratory cycle. The proposed 4D SSTVD registration scheme considers the entire dynamic 4D data set simultaneously, using both spatial and temporal information. We employed a uniform 4D cubic B-spline parametrization of the transform and a temporally extended linear elasticity regularization of deformation field to ensure temporal smoothness and thus biological plausibility of estimated deformation. A multi-resolution multi-grid registration framework was used with a limited-memory Broyden Fletcher Goldfarb Shanno (LBFGS) optimizer for rapid convergence rate, robustness against local minima and limited memory consumption. The algorithm was prototyped in Matlab and then fully implemented in C++ in Elastix package based on the Insight Segmentation and Registration Toolkit (ITK). We conducted experiments on 2D+t synthetic images to demonstrate the effectiveness of the proposed method. The 4D SSTVD algorithm was also tested on clinical pulmonary 4DCT data sets in comparison with existing 3D pairwise SSTVD algorithm and 4D sum of squared difference (SSD) algorithm. The mean landmark error and mean landmark irregularity were calculated based on manually annotated landmarks on publicly available 4DCT data sets to evaluate the accuracy and temporal smoothness of the registration results. A 4D landmarking software tool was also designed and implemented in Java as an ImageJ plug-in to help facilitate the landmark labeling process in 4DCT data sets.

Cancer (CA) is the second leading cause of death in the United States preceded only by cardiovascular disease (CVD). Over the past 30 years, the 5-year survival rate for all cancers combined has increased by more than 20%. This improved survival rate is due to early diagnosis and advances in treatment involving a multimodality treatment approach that includes radiotherapy [RT] with about half of all CA patients receiving some type of RT sometime during the course of their treatment. Cardiotoxicity is one of the most important adverse reactions of RT and leads to a meaningful risk of CVD-related morbidity and mortality. Radiotherapy-related cardiotoxicity is a heterogeneous clinical syndrome characterized by symptoms related to impaired cardiac function due to radiation-injury to one or more cardiac structures. Furthermore, the relative risk of CVD increases with increasing incidental radiation dose to the heart. There is not a unified consensus on the definition of CA-related cardiotoxicity although most trials have focused on changes in resting systolic function, and/or development of cardiac symptoms.Commonly used tools to assess cardiac function are insensitive to minor injury hence subtle changes may go unnoticed for many years. Cardiotoxicity definitions should include a dynamic functional assessment of the CV system. This may allow detection of latent CV abnormalities before the precipitous decline of resting myocardial function or the development of CV symptomology that may impact quality of life. Cardiopulmonary exercise testing (CPET) including measurement of peak oxygen consumption (VO2) is the gold standard for the assessment of cardiorespiratory fitness (CRF). Cardiorespiratory fitness is a strong, independent predictor of mortality, CVD-related mortality, HF-related morbidity and mortality, CA-related mortality and may be involved in the pathophysiologic link between anti-CA related treatments and the increased risk of late CVD events. Emerging evidence indicates CRF may be reduced in CA survivors and have utility to detect subclinical cardiotoxicity, but this has not been evaluated in CA survivors treated with RT with significant heart involvement. This dissertation consists of one literature review and one comprehensive paper that will examine the ability of CPET to detect subclinical cardiotoxicity.

Breast cancer patients undergoing radiotherapy often experience severe levels of anxiety and depression. There is a gap in the research literature from Africa, particularly from Ghana, with few studies focusing on the assessment of anxiety and depression among breast cancer patients undergoing radiation treatment. A better understanding was essential to promote efforts to help breast cancer patients cope with their diagnosis and treatment and increase their overall quality of life. This mixed method study examined breast cancer patients in Ghana undergoing radiotherapy and their responses related to anxiety and depression through a concurrent triangulation involving an interview with selected professional participants and a detailed patient survey. Patients completed 2 modified scales, the Patient Health Questionnaire and Depression Anxiety Stress Scale. The sample consisted of 100 patients between the ages of 20-89. Individual interviews were held with 6 professionals with a minimum of 5 years of work experience. Themes were generated through open coding of the interview data, while multiple regression was performed to determine the relationship between depression and anxiety with the independent variables . Findings of this study indicated the need intervene through counseling and education on behalf of patients in Ghana as they undergo breast cancer treatment. Age and monthly income of patients were statistically significant in predicting the anxiety and depression among the patients. The study's implications will lead to positive change when all stakeholders take on the responsibility of implementing measures to promote coping strategies for breast cancer patients in Ghana.

Ce travail de thèse a pour but d'améliorer la précision de mesure de la dosimétrie basée sur le transducteur en Nitrure de Gallium (GaN) et de développer son application en radiothérapie. L'étude comprend des phases de modélisation, de simulation et de caractérisation de cette réponse pour la radiothérapie externe et la curiethérapie. En modélisation, nous avons proposé deux approches pour modéliser la réponse du transducteur GaN en radiothérapie externe. Dans la première approche, un modèle a été construit à partir de données expérimentales et en séparant les composantes primaires et diffusées du faisceau. Pour la deuxième approche, nous avons adapté un modèle initialement proposé pour les diodes silicium pour l'adapter au transducteur radioluminescent GaN. Nous avons également proposé un concept original de dosimétrie bi-média qui permet à partir des réponses mesurées des deux média de remonter à la dose dans les tissus, sans connaissance à priori des conditions d'irradiation. Ce concept a été démontré par des simulations Monte Carlo. Par ailleurs GaN pour la curiethérapie à Haut Débit de Dose, la réponse du transducteur GaN sous irradiation des sources d'iridium 192 et de cobalt 60 a été évaluée par simulation Monte Carlo et confirmée par des mesures. Des études de caractérisation des propriétés du transducteur radioluminescent GaN ont été réalisées avec ces sources. Un prototype de fantôme instrumenté avec des sondes GaN a été développé pour le contrôle qualité en curiethérapie HDR. Il permet de vérifier en temps réel les paramètres physiques du traitement (position de la source, le temps d'exposition, activité de la source) / The work in this thesis has the objective to increase the measurement precision of the dosimetry based on the Gallium Nitride (GaN) transducer and develop its applications on radiotherapy. The study includes the aspects of modeling, simulation and characterization of this response in external radiotherapy and brachytherapy. In modeling, we have proposed two approaches to model the GaN transducer’s response in external radiotherapy. For the first approach, a model has been built based on experimental data, while separating the primary and scattering component of the beam. For the second approach, we have adopted a response model initially developed for the silicon diodes for the GaN radioluminescent transducer. We have also proposed an original concept of bi-media dosimetry which evaluates the dose in tissue according to different responses from two media without prior information on the conditions of irradiation. This concept has been shown by Monte Carlo simulation. Moreover, for High Dose Rate brachytherapy, the response of GaN transducer irradiated by iridium 192 and cobalt 60 sources has been evaluated by Monte Carlo simulation and confirmed by the measurements. Studies on the property characterization of GaN radioluminescent transducer has been carried out with these sources as well. An instrumented phantom prototype with GaN probe has been developed for the HDR brachytherapy quality control. It allows a real-time verification of the physics parameters of a treatment (source dwell position, source dwell time, source activity)