O câncer de próstata é um problema de saúde pública no Brasil, sendo a segunda causa de óbitos por câncer em homens, superado apenas pelo câncer de pulmão. Entre os possíveis tratamentos disponíveis para o câncer de próstata encontra-se a braquiterapia, onde, pequenas sementes contendo o radioisótopo 125I são implantadas na próstata. A semente consiste de uma cápsula de titânio selada de 0,8 mm de diâmetro externo e 4,5 mm de comprimento, contendo um fio de prata com 125I adsorvido. A soldagem por arco plasma é uma das técnicas viáveis para selagem, o equipamento tem um custo menor que o de outros processos. Constituem os objetivos deste trabalho o desenvolvimento e a validação do procedimento de selagem utilizando processo de soldagem plasma e a elaboração de rotinas para selagem segundo as Boas Práticas de Fabricação. O desenvolvimento do trabalho apresentou as seguintes fases: corte e limpeza do material, determinação dos parâmetros de soldagem, desenvolvimento de dispositivos para fixação do tubo de titânio durante o processo de soldagem, ensaios de validação de fontes seladas conforme norma ISO 2919 Sealed Radioactive Sources General Requirements and Classification, ensaios de estanqueidade conforme norma ISO 9978 Sealed Radioactive Sources Leakage Test Methods e ensaio metalográfico. O procedimento desenvolvido para a selagem das sementes de 125I mostrou-se eficiente, atendendo a todos os requisitos estabelecidos na norma ISO 2919. Os resultados apresentados neste trabalho possibilitaram a elaboração de rotinas de fabricação segundo as orientações apresentadas na resolução RDC nº 59 Boas Práticas de Fabricação de Produtos Médicos da ANVISA - Agência Nacional de Vigilância Sanitária. / The prostate cancer, which is the second cause of death by cancer in men, overcome only by lung cancer, is a problem of public health in Brazil. Brachytherapy is among the possible available treatments for prostate cancer, in which small seeds containing 125I radioisotope are implanted in the prostate. The seed consists of a titanium sealed capsule with 0.8 mm external diameter and 4.5 mm length, containing a central silver wire with adsorbed 125I. The plasma arc welding is one of the viable techniques for the sealing process. The equipment used in this technique is less costly than in other processes. The main objective of this work was the development and the validation of the welding procedure using plasma welding process and the elaboration of a sealing routine according to Good Manufacturing Practices. The development of this work has presented the following phases: cut and cleaning of the titanium material, determination of the welding parameters, development of a device for holding the titanium tube during the welding process, validation of sealed sources according to ISO 2919 Sealed Radioactive Sources - General Requirements and Classification, leakage test according to ISO 9978 Sealed Radioactive Sources - Leakage Test Methods and metallographics assays. The developed procedure, to seal 125I seeds using plasma welding process, has shown to be efficient, satisfying all the established requirements of ISO 2919. The results obtained in this work have given the possibility to establish a routine production process according to the orientations presented in resolution RDC nº 59 - Good Manufacturing Practices to Medical Products of the ANVISA - National Agency of Sanitary Surveillance.

La curiethérapie électronique, également appelée radiothérapie de contact, est une technique de traitement du cancer utilisant des rayons X de faible énergie (≤ 50 keV) générés par des tubes à rayons X miniaturisés et positionnés au contact des tissus à irradier. La miniaturisation des générateurs à rayons X a conduit au développement de nouveaux systèmes de traitement, dont le plus répandu dans le monde et le seul utilisé en France est le système INTRABEAM® commercialisé par la société Zeiss. Au-delà du bénéfice médical, les avantages potentiels de la curiethérapie électronique sont une diminution drastique de l'inconfort du patient combinée à un moindre coût de traitement. Ainsi, dans le cadre du cancer du sein qui correspond à l’application principale de l’INTRABEAM, cette technique remplace la trentaine de séances de radiothérapie externe classiquement prescrite suite à l’exérèse du volume tumoral par une seule et unique séance délivrée en 20 à 50 minutes au bloc opératoire directement après l’acte chirurgical alors que la patiente est encore sous anesthésie. Cette radiothérapie peropératoire (RTPO) associe au mini générateur de rayons X des applicateurs qui, en sénologie, correspondent à des sphères de différents diamètres conçues pour épouser au mieux la cavité tumorale résultant de l’exérèse. La dose délivrée en RTPO est classiquement de l'ordre de 20 Gy en surface du lit tumoral et diminue rapidement avec la profondeur afin de préserver les tissus sains voisins (< 1 Gy après quelques cm). En France, le 1er traitement par RTPO a eu lieu à Nantes fin 2011. Aujourd’hui, une dizaine de centres hospitaliers français propose des traitements par RTPO au moyen de la technique INTRABEAM®. Très rapidement, plusieurs physiciens médicaux ont exprimé au laboratoire français de métrologie de la dose (LNHB), leur besoin de raccordement dosimétrique à une référence indépendante du constructeur. Ce besoin a été réaffirmé par la Haute Autorité de Santé (HAS) dans un rapport sur l’évaluation de la RTPO dans le cancer du sein, édité en avril 2016. Le présent travail vise à renforcer la sécurité d’emploi d’appareils de RTPO par rayons X de basse énergie (< 50 keV). Cependant, afin de répondre aux physiciens médicaux français et du fait de contraintes temporelles, l’étude est ici limitée au système INTRABEAM associé au seul applicateur sphérique de 4 cm de diamètre. Le travail a été articulé autour de trois axes. Le premier a concerné l’établissement et le transfert d’une référence primaire en termes de dose absorbée dans l’eau à 1 cm de profondeur. La méthodologie a été développée et ensuite appliquée pour le système INTRABEAM® associé à un applicateur sphérique de 4 cm, pour lequel, la référence primaire a été réalisée. Le deuxième axe a eu pour objet la détermination de la distribution spatiale de dose autour de la source considérée par l’utilisation de gels dosimétriques et par calcul de type Monte Carlo. L’hydrogel à base de Fricke, utilisé ici, est lu par imagerie par résonance magnétique à l’hôpital d’Orsay. Ce gel a été étalonné en dose pour des photons d’énergie inférieure à 50 keV puis utilisé pour déterminer les profils de doses autour de la source INTRABEAM® associée à l’applicateur sphérique de 4 cm de diamètre dans les plans axial et transverse incluant le centre de la source INTRABEAM®. Quant au dernier axe, il s’est agi de confronter des données dosimétriques fournies par la société Zeiss, concernant l’INTRABEAM® en utilisation à l’hôpital St-Louis à Paris, à celles obtenues au cours de la présente étude pour le même système. Des différences significatives ont été trouvées entre les doses délivrées par Zeiss et celles obtenues dans la présente étude. Une étude indépendante menée par le PTB pour une autre configuration de source INTRABEAM® a conduit à des observations comparables. L’approche adoptée par Zeiss a ainsi été investiguée dans le présent travail et une cause de divergence a été proposée. / Electronic Brachytherapy (eBT), also called contact radiotherapy, is a cancer treatment technique using low energy X-Rays (≤ 50 keV) generated by X-Ray tubes which are placed in close contact with the treated lesions. The latest evolutions of miniaturized X-Ray tubes led to the development of new treatment systems, such as the INTRABEAM® system of the ZEISS Company which is the most available eBT system and the only one currently used in France. Beside its medical benefit, the potential major advantages of treatment by eBT are the drastic decrease in patient discomfort and treatment cost. In the case of breast cancer treatment with such technique, the treatment is given in a single session that lasts 20 to 50 minutes where a high dose, in the order of 20 Gy, is delivered to the tumor bed surface in contact with spherical applicators associated to the X-Ray source. The delivered dose decreases rapidly with depth (< 1 Gy after a few centimeters) enabling to preserve neighboring healthy tissues. In France, the first IORT treatment performed was in Nantes in 2011. Today, ten medical centers offer IORT treatment using the INTRABEAM® system. Consequently, several medical physicists addressed to the French national metrology laboratory for ionizing radiation (LNHB) their need for a dosimetric traceability with a reference independent from the manufacturer. This need was reaffirmed by the French Authority for Health (HAS), in their report on the evaluation of the IORT for breast cancer treatment published in April 2016. This thesis work is a contribution to the metrological work initiated by LNHB for enhancing the safety of employing IORT by eBT systems. It was limited, within the thesis period, to the INTRABEAM® system associated with a 4 cm diameter spherical applicator. The thesis work was oriented towards three main objectives. The first one concerned the establishment and the transfer of a primary dosimetric standard, in terms of absorbed dose to water at 1 cm depth in water. The methodology was developed and applied on the INTRABEAM® system with 4 cm spherical applicator, for which, the dosimetric reference was established. The second objective was to use a dosimetric gel and the Monte Carlo method to assess the 3D spatial distribution of the relative absorbed dose delivered by such a system. The dosimetric gel system used was a Fricke-based hydrogel read by Magnetic Resonance Imaging at Service Hospitalier Frédéric Joliot in Orsay (SHFJ). The gel reading was calibrated, in terms of absorbed dose for low energy X-Rays (< 50 keV), and then used to define the relative dose distributions of the INTRABEAM® X-Ray source associated with the 4 cm spherical applicator in the axial and transverse planes of the X-Ray source probe tip. The last objective was to compare the dosimetric data delivered by Zeiss, for the INTRABEAM® system used at St. Louis hospital in Paris, by the ones obtained in the current study for the same system. Significant discrepancies were found from this comparison between the doses delivered by Zeiss and those obtained in the current study. Discrepancies were also observed in a separate work conducted by the PTB under a different INTRABEAM® configuration. Some reasons of these discrepancies are outlined and discussed in this study.

Cancer is the leading cause of death in Canada. Many cancer treatments are using chemotherapy, surgery and radiotherapy. In radiotherapy, photons are the most used ionizing radiation, however alpha particles have higher radiobiological impact which increases the efficiency of patient treatment delivery. Alpha Tau Medical Ltd. (Tel Aviv, Israël) has developed a new brachytherapy method using radioactive seeds. The seeds called DaRT, for Diffusing alpha emitters Radiation Therapy, are composed of 224-Ra atoms which come from 228-Th generator. Currently, these seeds are characterized by an alpha-spectrometer and Geiger-Muller counter or well chamber for quality control. This project offers a new characterization of DaRT seeds using liquid scintillation. Liquid scintillation allows alpha and beta particles detection with the help of liquid cocktail and employing a scintillation counter. The characterization with liquid scintillation allows establishing and quantifying 228-Th trace contamination on the DaRT seeds. Also, it provides a method for seed quality control before they are used on patients by estimating their activity from spectrums established with the liquid scintillation counter. The spectrums obtained also give the possibility of dose estimation using either mass or mass stopping power in water. The results of the dose are compared to expected values from the literature and to simulations. / Le cancer est la première cause de mortalité au Canada. De nombreuses techniques de traitement du cancer existent utilisant la chimiothérapie, la chirurgie et la radiothérapie. En radiothérapie, les photons sont les rayonnements ionisants les plus fréquemment utilisés, cependant les particules alpha présentent des propriétés radiobiologiques intéressantes augmentant l'efficacité des résultats du traitement prodigué au patient. Une nouvelle technique de curiethérapie ayant recourt à des grains a été développée par Alpha Tau Medical Ltd.(Tel Aviv, Israël). Pour ce faire les grains appelés DaRT, pour Radiothérapie par émetteurs-alpha diffusant, sont constitués d'atomes 224-Ra issu d'un processus de fabrication à l'aide d'un générateur de 228-Th. Ces grains sont actuellement caractérisés par spectromètre-alpha et compteur Geiger-Muller ou chambre à puit dans le cas du contrôle de qualité. Ce projet vise à proposer une nouvelle caractérisation des grains DaRT en recourant à la scintillation liquide. La scintillation liquide permet la détection des particules alpha et beta à l'aide de liquide scintillant et d'un compteur de scintillation. La caractérisation des grains avec la scintillation liquide permet d'établir et de quantifier la présence de trace de contamination de 228-Th. Cette technique de mesure de la radioactivité donne aussi la possibilité de réaliser le contrôle de qualité des grains avant son utilisation sur les patients en évaluant l'activité de ces derniers à partir des spectres obtenus par le compteur de scintillation liquide. Les spectres obtenus offrent la réalisation d'une estimation de la dose soit par la masse soit par le pouvoir d'arrêt massique des alpha dans l'eau. Les résultats de la dose sont comparés à des valeurs attendues de la littérature et de simulation.

Jamaican males are a high-risk population for aggressive prostate cancer (PrCa) due to genetic influences, and identifying empirical data on treatments, which provide survival benefits is a prime challenge for clinicians who manage Jamaican PrCa patients. Thus, the purpose of this investigation was to elucidate treatment effects of brachytherapy and ERBT in the survival of a Jamaican PrCa cohort. Differences in survival outcomes of brachytherapy and ERBT treated Jamaican, and White U.S.-born PrCa patients with localized PrCa were compared. The mechanism of radiation programmed cell death in PrCa carcinogenesis explained in the oxidative stress theory, was the theoretical base for interpreting the research questions. A retrospective cohort design was used, and included survival analysis of secondary data from the Surveillance Epidemiology and End Results database. The sample size was 10,752 Jamaican and White U.S.-born prostate cancer patients diagnosed between 1992 and 2011. Kaplan-Meier and Cox proportional hazard regression models confirmed that brachytherapy resulted in enhanced survival benefits to the Jamaicans, HR 0.63, 95% CI [0.55, 0.73], p < .001, but ERBT did not, HR 1.6, 95% CI [1.38, 1.84] p < .001. Hence, brachytherapy may be an appropriate treatment option for Jamaican PrCa patients. Clinicians and health care planners can utilize the results for policy decisions aimed at increasing access to brachytherapy treatments to Jamaicans. Improving access to efficient PrCa treatments could reduce the morbidity and mortality rates of PrCa among Jamaicans, decrease years of potential life lost from PrCa, and enhance the life expectancy of the Jamaican male population.

La curiethérapie par diffusion d’émetteurs alpha (DaRT) est un nouveau type de grain interstitiel dont le potentiel thérapeutique pour les tumeurs solides est élevé en raison de l’utilisation de particules alpha. Cette modalité se distingue de la curiethérapie conventionnelle par une contamination des tissus à un niveau thérapeutique. Les radionucléides filles pénètrent la tumeur grâce à l’énergie de recul acquise lors de l’émission d’une particule alpha, puis ils se dispersent par diffusion dans les tissus avoisinants créant un nuage d’émetteurs alpha. Présentement, le \(^{224}\)Ra est la source radioactive utilisée par la modalité car la synergie de ses descendants de courte demi-vie permettent de produire une zone où la mort cellulaire est élevée. De plus, sa longue demie-vie permet de produire des sources thérapeutiques de faible activité. Le modèle de planification dosimétrique Diffusion-Leakage ne permet pas de déterminer la dose livrée à une zone qui seraient étanche aux radionucléides diffusants. Les particules possédant une longue portée, comme les particules beta et gamma, ne sont pas évaluées par le modèle. Pourtant, ces particules secondaires sont les seules qui déposent de l’énergie dans les zones non-traitées par les particules alpha. Le projet cadre est de simuler la distribution de la dose livrée par ces particules à l’aide de la méthode Monte Carlo. Deux distributions sont recherchées. Une première est la dose associée aux descendants du \(^{224}\)Ra qui se sont dispersés autour du grain et la deuxième est associée au \(^{224}\)Ra et à ses descendants distribués quelques nanomètres sous la surface du grain. Ce mémoire présente une méthode permettant de modéliser la distribution interne de la source de \(^{224}\)Ra sous la surface d’un grain DaRT. Des mesures de spectrométrie alpha ont permis de tester le diagramme de flux de travail et de confirmer la faisabilité de l’extraction de la distribution interne pour trois émetteurs alpha. Les distributions permettront d’évaluer la dose provenant exclusivement du grain en plus d’aider à concevoir des simulations du taux de désorption par recul atomique. Ce travail pourrait permettre d’aider à la conception de nouveaux grains et à l’évaluation de la dose beta et gamma entourant un grain DaRT au \(^{224}\)Ra. / Diffusion alpha-emitter Radiation Therapy (DaRT) is a new type of interstitial brachytherapy seed with high therapeutic potential for solid tumors due to the use of alpha particles. This modality differs from conventional brachytherapy by contaminating tissues to a therapeutic level. The daughters penetrate the tumor using the recoil energy acquired when an alpha particle is emitted and they then scatter by diffusion into the surrounding tissue, creating a cloud of alpha emitters. Currently, \(^{224}\)Ra is the radioactive source used by the modality because the synergy of its short half-life progeny allow to produce a zone where cell death is significant. In addition, its long half-life allows the production of therapeutic sources of low activity. The dosimetric planning model Diffusion-Leakage does not allow the determination of the dose delivered to an area that would be impenetrable by diffusing radionuclides. Particles with a long range, such as beta and gamma particles, are not evaluated by the model. However, these secondary particles are the only ones that deposit energy in areas not treated by alpha particles. The framework project is to simulate the dose distribution delivered by these particles using the Monte Carlo method. Two distributions are pursued. The first is the dose associated with the \(^{224}\)Ra progeny that are dispersed around the seed and the second is associated with radium and its progeny distributed a few nanometers below the surface of the seed. This thesis presents a method enabling the modelisation of the internal distribution of the \(^{224}\)Ra source below the surface of a DaRT seed. Alpha spectrometry measurements were used to test the workflow diagram and confirm the feasibility of extracting the internal distribution for three alpha emitters. The distributions will enable an assessment of the dose coming exclusively from the seed, in addition to helping in designing simulations of the desorption rate by atomic recoil. This work could assist in the design of new seeds and in the evaluation of the beta and gamma dose surrounding a \(^{224}\)Ra DaRT seed.

Ce mémoire présente l’étude de la faisabilité de la planification de traitements pour la curiethérapie interstitielle du sein en utilisant l’imagerie par résonance magnétique (IRM) seule au lieu de l’imagerie par tomodensitométrie (CT). L'imagerie CT étant la référence, la mesure des différences observables sur la distribution de doses provenant des deux types d’imagerie a été effectuée. Des fantômes de seins ont été fabriqués et utilisés, ainsi que l’imagerie de patients. La taille des fantômes en fonction du positionnement dans l’appareil d’IRM et la longueur reconstruite des cathéters ont été analysées. Les différences dans les distributions de doses de fantômes et de patients ont été calculées en s’assurant que la reconstruction des cathéters provenant des images CT et IRM est la seule variable. La différence dans les critères de doses à respecter est plus grande lorsque la taille du fantôme et/ou un déplacement latéral dans l’IRM sont plus grands. La longueur reconstruite des cathéters est comparable entre les deux techniques d’imagerie. Pour le petit fantôme des différences <2% ont été observées pour tous les critères de dose. Pour le grand fantôme et pour les patients, une valeur maximale de 5% est observée pour les critères sur la cible, mais peut atteindre 19% pour le critère Externe V150%/V100% pour le grand fantôme et 33% pour les patients. Par contre, le seuil clinique de ce critére est toujours respecté. Ceci nous indique que pour la plupart des patients, la zone à traiter serait bien couverte en utilisant les images IRM uniquement pour planifier. / This dissertation presents the study of the feasibility of planning for interstitial breast brachytherapy treatments using only magnetic resonance imaging (MRI) instead of computed tomography (CT) imaging. CT imaging being the reference, the measurement of observable differences on dose distributions from the two types of imaging has been done. Breast phantoms has been fabricated and used, as imaging of patients. Size of the phantoms according to the positioning inside the MRI device and catheters reconstructed length has been analysed. Differences in dose distributions of phantoms and patients have been calculated by ensuring that catheters reconstruction from CT and MRI images is the only variable. The difference in respecting the dose’s criteria is bigger when the size and/or the lateral shift into the MRI are bigger. The catheters’ reconstructed length is similar between the two imaging techniques. For the small phantom, differences <2% has been observed for all dose criteria. For the large phantom and for patients, a maximum value of 5% is observed for targets criteria, but can reach 19% for External V150/V100 criterion for the large phantom and 33% for patients. However, clinical threshold for this criterion is still respected. This tells us that for most patients, the treatment region would be covered by using MRI images only for planning.

INTRODUÇÃO: Nos pacientes com câncer de próstata considerados de baixo risco, a braquiterapia de baixa taxa de dose (BBTD) utilizando sementes de 125I é uma excelente opção, com seguimento após o tratamento, devendo ser feito por meio de medidas seriadas de PSA. A avaliação de falha bioquímica após radioterapia, definida por elevação do PSA, tem sido feita pelo critério da ASTRO (American Society for Therapeutic Radiology and Oncology) e, mais recentemente, pelo critério do consenso de Phoenix. OBJETIVOS: Avaliar a sobrevida livre de falha bioquímica (SLFB) de pacientes submetidos à BBTD pelos critérios ASTRO e Phoenix e as relações entre eles com as falhas clínicas. Correlacionar essas sobrevidas com idade, grau histológico de Gleason, estadiamento clínico, PSA inicial, porcentagem de fragmentos positivos na biópsia, invasão perineural, volume prostático na ultra-sonografia diagnóstica, hormonioterapia neoadjuvante, bounce e D90 (dose recebida por 90% do volume de próstata). MÉTODO: Estudo retrospectivo de 329 pacientes tratados, entre julho de 1998 e dezembro de 2002, no serviço de Radioterapia do Hospital Sírio-Libanês, São Paulo. Foram excluídos 18 pacientes que tinham recebido braquiterapia associada à RT externa, 18 pacientes classificados como de alto risco, 61 casos com menos de dois anos de seguimento mínimo e 12, com dados incompletos nos prontuários. Portanto, 220 pacientes formaram a base desta análise. RESULTADOS: Cento e vinte e um (55%) pacientes foram classificados como de baixo risco e 99 (45%) de risco intermediário. O seguimento mediano foi de 53,5 meses (24 a 116); 74 pacientes (33,6%) fizeram algum tipo de bloqueio hormonal por um tempo mediano de 90 dias e 66 pacientes (30%) apresentaram bounce. O tempo médio para o aparecimento do bounce foi de 15 meses, com um nadir médio de 0,30ng/mL. A SLFB em cinco anos pelo critério ASTRO foi de 83% e de 88,3% pelo Phoenix (p < 0,05). Para os pacientes de risco baixo e intermediário, respectivamente, 86,7% e 78,4% pela definição ASTRO (p = 0,069) e 88,5% e 77,9% de acordo com Phoenix (p = 0,016). Na análise multivariada, PSA inicial < 10 ng/mL e porcentagem de fragmentos positivos < 50% foram fatores prognósticos favoráveis em relação à falha (p < 0,05) pelo critério ASTRO. De acordo com o critério Phoenix, PSA inicial < 10 ng/mL, grau histológico de Gleason < 7, porcentagem de fragmentos positivos < 50% e grupo de baixo risco foram os fatores independentes favoráveis, preditivos de falha bioquímica (p < 0,05). CONCLUSÕES: Os dados de sobrevida livre de falha bioquímica em cinco anos para pacientes de risco baixo e intermediário desta análise foram comparáveis aos da literatura. Nesta análise, não houve diferença entre as definições ASTRO e Phoenix de falha. PSA, escore de Gleason, porcentagem de fragmentos positivos na biópsia e grupo de risco foram os fatores prognósticos independentes para falha bioquímica. / INTRODUCTION: Patients with low-risk prostate adenocarcinoma may be very well treated by low dose-rate brachytherapy (LDR) using 125I seeds. Follow-up with periodical serum prostate specific antigen (PSA) dosages is used to determine the effectiveness of treatment. Biochemical relapse may be defined either by the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, or, more recently, by the Phoenix Consensus criteria. PURPOSE: To evaluate and compare biochemical failure-free survival (BFFS) of patients treated with LDR brachytherapy using ASTRO and Phoenix criteria. Also, to correlate BFFS with age, Gleason score, clinical stage, initial PSA, percentage of positive prostate biopsies, perineural invasion, prostate volume at diagnostic ultrasound, neoadjuvant hormone therapy, bounce, and D90 (dose received by 90% of the prostate). METHODS: A cohort of 329 patients who received LDR brachytherapy for prostate cancer, between 1998 and 2002 at Hospital Sírio-Libanês, São Paulo, was retrospectively studied. Eighteen patients who received external beam irradiation were excluded, together with another 18 high-risk patients, 61 with less than 2 years minimal followup, and 12 with incomplete record data. So, 220 patients were the basis of this study. RESULTS: One hundred and twenty one (55%) were low-risk patients and 99 (45%) were intermediate-risk. Median follow-up was 53.5 months (24-116); 74 (33.6%) patients received neoadjuvant hormone therapy during a median period of 90 days, and 66 (30%) presented bounce. Mean time till bounce was 15 months, with mean nadir of 0,30ng/mL. The 5-year BFFS was 83% using ASTRO criteria, and 88.3% using Phoenix (p > 0,05). Low and intermediate-risk patients presented, respectively, 86.7% and 78.4% 5-year BFFS using ASTRO definition (p = 0,069), and 88.5% and 77.9%, considering Phoenix criteria (p = 0,016). In multivariate analysis, initial PSA < 10 ng/mL, and percentage of positive prostate biopsies < 50% were favorable prognostic factors, regarding biochemical relapse using ASTRO criteria (p < 0,05), while initial PSA < 10 ng/mL, Gleason score < 7, percentage of positive prostate biopsies < 50%, and low-risk group were detected as independent favorable prognostic factors using Phoenix definition (p < 0,05). CONCLUSIONS: The 5-year estimates of BFFS using both criteria, for low and intermediate-risk patients, were similar to previous published data, with no significant difference between them. Initial PSA, Gleason score, percentage of positive prostate biopsies, and risk group were independent prognostic factors for biochemical relapse.

INTRODUÇÃO: Nos pacientes com câncer de próstata considerados de baixo risco, a braquiterapia de baixa taxa de dose (BBTD) utilizando sementes de 125I é uma excelente opção, com seguimento após o tratamento, devendo ser feito por meio de medidas seriadas de PSA. A avaliação de falha bioquímica após radioterapia, definida por elevação do PSA, tem sido feita pelo critério da ASTRO (American Society for Therapeutic Radiology and Oncology) e, mais recentemente, pelo critério do consenso de Phoenix. OBJETIVOS: Avaliar a sobrevida livre de falha bioquímica (SLFB) de pacientes submetidos à BBTD pelos critérios ASTRO e Phoenix e as relações entre eles com as falhas clínicas. Correlacionar essas sobrevidas com idade, grau histológico de Gleason, estadiamento clínico, PSA inicial, porcentagem de fragmentos positivos na biópsia, invasão perineural, volume prostático na ultra-sonografia diagnóstica, hormonioterapia neoadjuvante, bounce e D90 (dose recebida por 90% do volume de próstata). MÉTODO: Estudo retrospectivo de 329 pacientes tratados, entre julho de 1998 e dezembro de 2002, no serviço de Radioterapia do Hospital Sírio-Libanês, São Paulo. Foram excluídos 18 pacientes que tinham recebido braquiterapia associada à RT externa, 18 pacientes classificados como de alto risco, 61 casos com menos de dois anos de seguimento mínimo e 12, com dados incompletos nos prontuários. Portanto, 220 pacientes formaram a base desta análise. RESULTADOS: Cento e vinte e um (55%) pacientes foram classificados como de baixo risco e 99 (45%) de risco intermediário. O seguimento mediano foi de 53,5 meses (24 a 116); 74 pacientes (33,6%) fizeram algum tipo de bloqueio hormonal por um tempo mediano de 90 dias e 66 pacientes (30%) apresentaram bounce. O tempo médio para o aparecimento do bounce foi de 15 meses, com um nadir médio de 0,30ng/mL. A SLFB em cinco anos pelo critério ASTRO foi de 83% e de 88,3% pelo Phoenix (p < 0,05). Para os pacientes de risco baixo e intermediário, respectivamente, 86,7% e 78,4% pela definição ASTRO (p = 0,069) e 88,5% e 77,9% de acordo com Phoenix (p = 0,016). Na análise multivariada, PSA inicial < 10 ng/mL e porcentagem de fragmentos positivos < 50% foram fatores prognósticos favoráveis em relação à falha (p < 0,05) pelo critério ASTRO. De acordo com o critério Phoenix, PSA inicial < 10 ng/mL, grau histológico de Gleason < 7, porcentagem de fragmentos positivos < 50% e grupo de baixo risco foram os fatores independentes favoráveis, preditivos de falha bioquímica (p < 0,05). CONCLUSÕES: Os dados de sobrevida livre de falha bioquímica em cinco anos para pacientes de risco baixo e intermediário desta análise foram comparáveis aos da literatura. Nesta análise, não houve diferença entre as definições ASTRO e Phoenix de falha. PSA, escore de Gleason, porcentagem de fragmentos positivos na biópsia e grupo de risco foram os fatores prognósticos independentes para falha bioquímica. / INTRODUCTION: Patients with low-risk prostate adenocarcinoma may be very well treated by low dose-rate brachytherapy (LDR) using 125I seeds. Follow-up with periodical serum prostate specific antigen (PSA) dosages is used to determine the effectiveness of treatment. Biochemical relapse may be defined either by the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, or, more recently, by the Phoenix Consensus criteria. PURPOSE: To evaluate and compare biochemical failure-free survival (BFFS) of patients treated with LDR brachytherapy using ASTRO and Phoenix criteria. Also, to correlate BFFS with age, Gleason score, clinical stage, initial PSA, percentage of positive prostate biopsies, perineural invasion, prostate volume at diagnostic ultrasound, neoadjuvant hormone therapy, bounce, and D90 (dose received by 90% of the prostate). METHODS: A cohort of 329 patients who received LDR brachytherapy for prostate cancer, between 1998 and 2002 at Hospital Sírio-Libanês, São Paulo, was retrospectively studied. Eighteen patients who received external beam irradiation were excluded, together with another 18 high-risk patients, 61 with less than 2 years minimal followup, and 12 with incomplete record data. So, 220 patients were the basis of this study. RESULTS: One hundred and twenty one (55%) were low-risk patients and 99 (45%) were intermediate-risk. Median follow-up was 53.5 months (24-116); 74 (33.6%) patients received neoadjuvant hormone therapy during a median period of 90 days, and 66 (30%) presented bounce. Mean time till bounce was 15 months, with mean nadir of 0,30ng/mL. The 5-year BFFS was 83% using ASTRO criteria, and 88.3% using Phoenix (p > 0,05). Low and intermediate-risk patients presented, respectively, 86.7% and 78.4% 5-year BFFS using ASTRO definition (p = 0,069), and 88.5% and 77.9%, considering Phoenix criteria (p = 0,016). In multivariate analysis, initial PSA < 10 ng/mL, and percentage of positive prostate biopsies < 50% were favorable prognostic factors, regarding biochemical relapse using ASTRO criteria (p < 0,05), while initial PSA < 10 ng/mL, Gleason score < 7, percentage of positive prostate biopsies < 50%, and low-risk group were detected as independent favorable prognostic factors using Phoenix definition (p < 0,05). CONCLUSIONS: The 5-year estimates of BFFS using both criteria, for low and intermediate-risk patients, were similar to previous published data, with no significant difference between them. Initial PSA, Gleason score, percentage of positive prostate biopsies, and risk group were independent prognostic factors for biochemical relapse.

Submitted by SBI Biblioteca Digital (sbi.bibliotecadigital@puc-campinas.edu.br) on 2018-02-15T12:50:05Z No. of bitstreams: 1 VANDERLEI JOSE JUNIOR.pdf: 1351825 bytes, checksum: 599d050ec951a6a8e7497a0cea5d2e17 (MD5) / Made available in DSpace on 2018-02-15T12:50:05Z (GMT). No. of bitstreams: 1 VANDERLEI JOSE JUNIOR.pdf: 1351825 bytes, checksum: 599d050ec951a6a8e7497a0cea5d2e17 (MD5) Previous issue date: 2017-12-15 / Introduction: Prostate cancer is one of the most prevalent diseases in the male population, occupying the second position among malignant neoplasms. There are several therapeutic options for the treatment of localized prostate cancer, ranging from conservative behaviors to interventional treatments such as radical prostatectomy or external radiotherapy, associated or not with brachytherapy. Objective: To identify the factors that can predict biochemical recurrence and to evaluate treatment toxicity. METHOD: This is a retrospective and longitudinal study of 162 patients diagnosed with prostate cancer treated with conformational external radiotherapy associated with high dose rate brachytherapy (BTATD) between 2005 and 2014. The database was used of the Radium ? Campinas Oncology Institute, collected prospectively. Results: The mean follow-up time was 57 months. No grade 3 late toxicity was observed in the gastrointestinal tract, with only 1 patient (0.6%) genitourinary tract. The only categorical variable that presented statistical significance for biochemical relapse was the Nadir PSA <1 ng / ml (p = 0.018). The biochemical recurrence rate found was 96.3%, based on the Phoenix criteria (PSA nadir + 2 ng / ml). Conclusions: This study demonstrated that in the treatment of localized prostate cancer, the association of external radiotherapy with BATD is a safe therapeutic option, with a low degree 3 late toxicity and a biochemical recurrence of only 3.7% (with HF = 95 %). / Introdu??o: O c?ncer de pr?stata ? uma das doen?as mais prevalentes na popula??o masculina, ocupando a segunda posi??o entre as neoplasias malignas. H? v?rias op??es terap?uticas para o tratamento do c?ncer de pr?stata localizado, podendo variar de condutas conservadoras ? tratamentos intervencionistas como a prostatectomia radical ou a radioterapia externa, associada ou n?o ? braquiterapia. Objetivo: Identificar os fatores que possam predizer recidiva bioqu?mica e avaliar a toxicidade do tratamento. M?todo: Tratase de um estudo retrospectivo e longitudinal, com 162 pacientes diagnosticados com c?ncer de pr?stata, tratados com radioterapia externa conformacional associada ? braquiterapia de alta taxa de dose (BATD), entre 2005 e 2014. Utilizou-se o banco de dados do Radium - Instituto de Oncologia de Campinas, coletados prospectivamente. Resultados: O tempo m?dio de seguimento foi de 57 meses. N?o foi observada toxicidade tardia grau 3 no trato gastrointestinal, sendo apenas 1 paciente (0,6%) trato genitourin?rio. A ?nica vari?vel categ?rica que apresentou signific?ncia estat?stica para recidiva bioqu?mica foi o PSA Nadir <1 ng/ ml (p = 0,018). A taxa de recidiva bioqu?mica encontrada foi de 96,3%, baseando-se nos crit?rios de Phoenix (PSA nadir + 2 ng/ml). Conclus?es: Esse estudo demonstrou que, no tratamento de c?ncer de pr?stata localizado, a associa??o de radioterapia externa com BATD ? uma op??o terap?utica segura, com baixa taxa de toxicidade tardia grau 3 e recidiva bioqu?mica de apenas 3,7% (com I.C = 95%).

En dosimétrie, la distribution énergétique des photons émis par une source constitue un paramètre incontournable. Dans la gamme des basses et moyennes énergies (i.e. E<150 keV ici), le LNHB possède 5 tubes à rayons X ainsi que des grains de curiethérapie à l’iode 125, présentant des hauts débits de fluence. La détermination du spectre émis par calcul (déterministe ou Monte-Carlo) est limitée, dans la gamme d’énergie considérée, par les incertitudes élevées sur les bases de données ainsi que par les approximations du modèle. La mesure directe avec un détecteur au germanium ultra-pur a donc été retenue, bien que nécessitant de lourds moyens. De plus, le spectre mesuré est le produit de convolution du spectre émis recherché par la réponse du système. Une fois la réponse du détecteur modélisée, il est possible de « déconvoluer» la mesure, i.e. de remonter au spectre réellement émis en corrigeant (par stripping, model-fitting, inférence bayésienne…) les déformations spectrales induites par le processus de détection. Pour la curiethérapie, le modèle de grain-source a ainsi pu être ajusté. Pour les tubes à rayons X, les résultats obtenus avec différents codes Monte-Carlo et 4 logiciels déterministes ont été comparés à un spectre dit de référence obtenu par mesure et déconvolué. Ainsi l’impact sur certaines grandeurs dosimétriques de la méthode utilisée a pu être quantifié. / In the field of dosimetry, the knowledge of the whole photon fluence spectrum is an essential parameter. In the low-to-medium energy range (i.e. E<150 keV), the LNHB possess 5 X-ray tubes and iodine-125 brachytherapy seeds, both emitting high fluence rates. The performance of calculation (either Monte Carlo codes or deterministic software) is flawed by increasing uncertainties on fundamental parameters at low energies, and modelling issues. Therefore, direct measurement using a high purity germanium is preferred, even though it requires a time-consuming set-up and mathematical methods to infer impinging spectrum from measured ones (such as stripping, model-fitting or Bayesian inference…). Concerning brachytherapy, the knowledge of the seed’s parameters has been improved. Moreover, various calculated X-ray tube fluence spectra have been compared to measured ones, after unfolding. The results of all these methods have then be assessed, as well as their impact on dosimetric parameters.