A braquiterapia de baixas taxas de dose realizada com sementes de 125I tem sido amplamente usada por décadas em variados sítios anatômicos, com bons resultados clínicos. O advento de algoritmos para cálculo de dose baseados em modelos (MBDCAs) permitiu aprimorar oestudo de deposição da dose considerando heterogeneidades como diferentes tecidos, órgãos,aplicadores com composições diferentes da água, proporcionando a análise em geometriascomplexas. As simulações matemáticas realizadas através destes algoritmos possibilitam odesenvolvimento de modelos fisicamente mais acurados que estendem sua aplicabilidade àverificação de sistemas de planejamento em braquiterapia. Neste trabalho foram estudadasconfigurações de objetos simuladores confeccionados para medidas experimentais e simuladosatravés do código MCNP de Monte Carlo a fim de observar as diferenças ocasionadas pelaintrodução de heterogeneidades quando presentes fontes de 125I de baixa taxa de dose. Para estepropósito, distintas as vertentes do tema foram abordadas, entre elas o estudo da influênciaexercida pelos parâmetros de densidade e composição dos materiais tecido equivalentes. Osresultados obtidos demonstraram que, o efeito que a composição de cada um dos materiaisexerce sobre a deposição de dose é mais expressivo que o efeito de sua densidade. Em outroestudo, foi estabelecida uma relação para estimar, de maneira simples, a dose de atenuação detecidos heterogêneos a partir da aferição ou simulação da dose obtida num objeto simuladorconstituído por PMMA, metodologia que pode ser desenvolvida e implementada na rotina clínica.Para complementação das análises dos estudos dosimétricos com a presença deheterogeneidades, foi realizada a validação da geometria simulada da semente de 125I, onde sereproduziu a metodologia de cálculo dosimétrico presente no TG-43 da AAPM. Além disto, foirealizado o estudo teórico da dependência energética dos dosímetros termoluminescentes paraanalisar a variação de sua resposta conforme a energia. A metodologia desenvolvida para oestudo dos efeitos da heterogeneidade na deposição de dose é recomendada na avaliação desistemas de planejamento computadorizados que possuem algoritmos de cálculo de dosebaseados em modelos, quando utilizadas fontes de 125I com baixa taxa de dose, de forma acontribuir na incorporação de novas estimativas de doses com maior acurácia. / The low dose rate brachytherapy performed with 125I seeds has been widely used for decades in various anatomical sites with good clinical results. The advent of model-based dose calculation algorithms (MBDCAs) allowed improving the study of dose deposition considering patients heterogeneities such as tissues and organs with different compositions, patient contouring, and influence of applicators, providing the analysis in complex geometries. The mathematical simulations performed through algorithms enable the development of models physically much more accurate, extending its applicability to verify brachytherapy planning systems. In this work, different configurations of phantoms were confectioned for experimental studies and simulations using the Monte Carlo MCNP code to observe the differences caused by the introduction of heterogeneities for low dose rate brachytherapy using 125I sources. For this purpose, different aspects of the theme were discussed, among them the influence exerted by the density and composition parameters of the tissue equivalent materials. The results showed that each material composition effect in the dose deposition is more expressive than its density effect. In another study, a ratio was established to estimate the heterogeneous tissues attenuation from the dose measurement or simulation obtained using a PMMA phantom, this methodology can be developed and implemented in the clinical routine. In order to complement the analysis of the dosimetric studies with heterogeneities presence, the 125I seed simulated geometry was validated, showing the reproduction of the calculation methodology present in TG-43 of the AAPM. In addition, the theoretical study of the energy dependence of the thermoluminescent dosimeters was performed to analyze the variation its response according to energy. The methodology developed for the heterogeneity effects study on dose deposition is recommended for the evaluation of planning systems that use model-based dose calculation algorithms for low dose rate 125I sources, in order to contribute to the incorporation of dose estimates with greater accuracy.

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Thesis (MTech (Radiography))--Cape Peninsula University of Technology, 2012 / Introduction: Brachytherapy plays an essential role in the management of patients with cervical cancer. The high cervical cancer burden in Africa presents challenges with regard to provision and sustainability of these services. This study analysed treatment outcomes of two brachytherapy modalities, high dose rate (HDR) and low dose rate (LDR) intracavitary treatment for patients with cervical cancer, and evaluated the problems and challenges of the provision of these services within the African context. Methodology: The study was conducted using a case study approach with mixed methods at two sites in Africa, one in South Africa (Centre I) and the other in Kenya (Centre II). The study explored factors and issues affecting definitive radiotherapy of the patient with cervical cancer at the two sites with a focus on the brachytherapy treatment. The case study provided an opportunity to collect in-depth data consisting of quantitative and qualitative components that generated numeric and textual data. Treatment outcomes of one site treating with HDR and the other LDR intracavitary brachytherapy were retrospectively analysed for a maximum sample size of 193 (91%) patients in the HDR group and 49 (100%) patients in the LDR group. All patients were treated with external beam radiation therapy (EBRT) using parallel opposed beams (POP) for the patients that received LDR brachytherapy, and four field box technique or POP for those that received HDR brachytherapy. The linear quadratic formula was used to calculate the equivalent dose in 2 Gy fractions (EQD2) between the two groups.

Introduction : Rapporter le développement et les expérimentations d'un nouveau système robotisé destiné à la curiethérapie prostatique possédant un système de suivi de la prostate et une possibilité de fusion écho-IRM. Matériel et méthodes : Un robot d'implantation d'aiguilles transpérinéales guidé par échographie transrectale avec suivi peropératoire des mouvements et de la déformation de la prostate a été crée. Les expériences ont été conduites sur 90 cibles réalisées dans 9 fantômes conçus pour être mobiles et déformables. Les expériences ont été ensuite conduites chez 2 cadavres. Le robot a cherché à déposer des billes de verre simulant des grains de curiethérapie aussi près que possible des cibles dans des fantômes évaluables par différentes modalités d'imagerie dont le scanner et dans des prostates de cadavre. Les résultats étaient mesurés en segmentant les cibles et les billes de verre sur des volumes tomodensitométriques des fantômes et des cadavres. Résultats : Le robot était capable d'atteindre les cibles choisies dans les fantômes avec une précision médiane de 2.73 mm, avec un déplacement médian de la prostate de 5.46 mm. La précision était meilleure à la base qu'à l'apex (2.28 mm vs 3.83 mm, p<0.01) et n'était pas significativement différente pour les implantations horizontales et obliques (2.7 vs 2.82 mm, p=0.18). Les tests sur cadavre ont montré la faisabilité et l'ergonomie du robot en salle d'opération mais des expérimentations plus poussées sont nécessaires. Conclusion : Ce robot destiné à la curiethérapie prostatique est le premier système utilisant le suivi de la prostate intra-opératoire pour guider des aiguilles dans la prostate. Les expériences préliminaires montrent sa capacité à atteindre des cibles malgré les mouvements de la prostate. Les applications pourraient être élargies à la thérapie focale et aux biopsies guidées compte-tenu de sa possibilité à fusionner l'imagerie IRM et l'échographie. / Purpose: To report on the development and the initial experience with a new 3D ultrasound robotic system for prostate brachytherapy assistance and focal therapy. MRI-TRUS fusion as well as its ability to track prostate motion intra-operatively allows it to manage motions and guide needles to MRI enhanced tumor foci. Materials and methods: A robotic system for TRUS-guided needle implantation combined with intraoperative prostate tracking was created. Experiments were conducted on 90 targets embedded in 9 mobile and deformable synthetic prostate phantoms. A preliminary feasibility study on 2 cadavers was also carried out. The experiments involved trying to insert glass beads as close as possible to targets in multimodal imaging phantoms and in cadaver prostates. The results were measured by segmenting the inserted beads in CT scan volumes of the phantoms and of the cadaver's radical prostatectomy specimens. Results: The robot was able to reach the chosen targets in phantoms with a median accuracy of 2.73 mm, with a median prostate motion of 5.46 mm. Accuracy was better in apex than in base (2.28 vs 3.83 mm, p<0.001) and was similar for horizontal and angled needle inclinations (2.7 vs 2.82 mm, p=0.18). Cadaver tests showed the feasibility of the robot's ergonomics in the operating room but further in vivo assessments are needed. Conclusion: This robot for prostate focal therapy and brachytherapy is the first system using intraoperative prostate motion tracking to guide needles into the prostate. The preliminary experiments described show its ability to reach targets in spite of the motion of the prostate.

La curiethérapie constitue 25% à 30% des opérations de traitement utilisées sur les 40.000 cas de cancer de prostate par an en France. Elle consiste à mettre manuellement une trentaine d'aiguilles creuses dans la prostate, à travers le périnée, en utilisant des images échographiques pour localiser la prostate et les aiguilles. Au moyen de ces aiguilles, des grains radioactifs sont insérés dans la prostate à des endroits précis pré-planifiés grâce à l'imagerie. Le succès de l'opération est étroitement lié à la répartition et l'homogénéité de la dose radioactive répartie dans la prostate, donc à la précision avec laquelle les grains y sont placés. Cette précision est affectée par plusieurs facteurs. Premièrement, la prostate bouge et se déforme pendant l'insertion des aiguilles et lors des déplacements de la sonde échographique pour les acquisitions d'images. Deuxièmement, la taille de la prostate est susceptible d'augmenter pendant l'opération à cause des saignements occasionnés. Enfin, les aiguilles sont très minces et susceptibles de se courber pendant leur insertion.Le laboratoire TIMC-IMAG (équipe GMCAO) a mis au point un système robotisé d'insertion d'aiguilles transpérinéale, guidé par échographie 3D avec le but d'améliorer la précision, la fiabilité et l'efficacité de la pose des grains. Ces travaux ont montré une première faisabilité globale de l'approche avec un premier prototype de laboratoire. Cependant l'approche actuelle permet de corriger seulement en partie les bougés et déformations de la prostate en cours de geste grâce au couplage avec des méthodes d'imagerie 3D. La correction ne tire pas parti des informations très riches issues de l'imagerie : seule la profondeur d'insertion est modifiée pendant le geste. Le LIRMM (équipe DEXTER) a développé récemment une approche de planification adaptative pour le guidage d'aiguille flexible lors de leur insertion dans des procédures percutanées. La technique proposée permet la mise à jour du chemin suivi par l'aiguille en intégrant des informations obtenues en ligne par un retour visuel. Cette stratégie de planification et de contrôle est définie dans une architecture en boucle fermée et permet ainsi de compenser les incertitudes du système et les perturbations (déformations des organes, inhomogénéité des tissus, etc) auxquelles il est soumis.Le but de ces travaux de thèse est donc de coupler les savoir-faire de chacun des deux laboratoires afin d’apporter une solution de guidage d’aiguilles flexibles pour la curiethérapie de prostate. La réalisation de cet objectif passe, dans un premier temps, par l’élaboration d’un algorithme de suivi d’aiguille sous échographie 3D. Cet algorithme est confronté à la faible visibilité des aiguilles offerte par cette modalité d’imagerie, associée à diverses sources de bruit. Ces conditions rendent très difficile la détection de l’aiguille. Dans le but d’améliorer la robustesse de cet algorithme, la zone de recherche de l’aiguille dans le volume est déterminée par un modèle prédictif, qui constitue une première contribution de ce manuscrit. Le contrôle de l’aiguille par planification en boucle fermée a été adapté aux spécificités de l’imagerie échographique 3D ainsi qu’à celles du robot développé précédemment. Ce contrôle est couplé au retour visuel de l’aiguille donné par l’algorithme de détection. Ce dispositif a, par la suite, été testé sur fantômes puis sur pièce anatomique afin de déterminer la viabilité et la pertinence du système proposé.Ce travail constitue donc une première étape vers une future application clinique du guidage d’aiguilles flexibles. Si voir un système robotique insérer seul une aiguille flexible en clinique est encore un rêve lointain, l’idée d’un système d’assistance à l’insertion d’aiguille, où le clinicien et le robot travaillent de pairs, est une solution envisageable dès maintenant. / In France, 25% to 30% of the 40,000 prostate cancer cases per year are treated with brachytherapy. During this procedure, about thirty needles are manually inserted into the prostate through the perineum using ultrasound images to locate the prostate and needles. Radioactive seeds are then inserted into the prostate specific pre-planned locations using needle cannula. The success of the operation is closely related to the distribution and homogeneity of the radioactive dose distribution in the prostate, therefore the precision with which the seeds are positioned. This accuracy is affected by many factors. Firstly, the prostate moves and deforms due to the insertion of the needles and to the movements of the ultrasonic probe. Secondly, the size of the prostate increases due to tissue inflammation and bleeding. Finally, the needles are very thin and could bend during insertion.The TIMC-IMAG laboratory (CAMI team) has developed a robotic system for transperineal needle insertion. This system is guided by 3D ultrasound to improve the precision, reliability and efficiency of the radioactive source positioning. These works showed a first proof of concept using a laboratory prototype. However the current approach can only partially correct prostate movements and deformations using 3D imaging methods. The correction does not take advantage of the rich information of this imaging modality: only the insertion depth is changed during the gesture. LIRMM (DEXTER team) recently developed an adaptive planning approach to guide a flexible needle during its insertion in percutaneous procedures. The proposed technique allows to update the path followed by the needle using online information from the visual feedback. This planning and control approach forms a closed-loop architecture and allows to compensate system disturbances (organ deformities, tissue inhomogeneity, etc.).The purpose of this thesis is to combine the expertise of the two laboratories to provide a flexible needle steering system for prostate brachytherapy purposes. This objective is achieved first by developing a needle tracking algorithm in 3D ultrasound. This algorithm deals with low visibility of the needles offered by this imaging modality, combined with various noises. These conditions complicate the detection of the needle. In order to improve the robustness of our algorithm, a search area is defined to detect the needle in the volume. This area is then determined by a predictive model, which is a first contribution of this manuscript. Control of the closed-loop planning needle is adapted to the specifications of the 3D ultrasound imaging system as well as those of the previously developed robot. This control is coupled to the needle visual feedback given by the detection algorithm. This device is tested on phantoms then on anatomical specimen to assess the viability and relevance of the proposed system.This work is therefore a first step towards a future clinical application of flexible needle steering. The entirely automatic insertion of flexible needle in clinic is a distant dream. However, the idea of an assistance system for needle insertion, where the clinician and the robot work together, is reachable from now.

Made available in DSpace on 2014-10-09T12:28:49Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:57:12Z (GMT). No. of bitstreams: 0 / A utilização da técnica braquiterapia com sementes de iodo-125 para o tratamento do câncer de próstata têm sido utilizada por décadas com bons resultados clínicos. Para atender as necessidades da população brasileira, o IPEN-CNEN/SP desenvolveu o protótipo para as sementes de iodo-125 com tecnologia nacional. Os objetivos deste trabalho são o desenvolvimento e estudo dos processos dosimétricos associados à obtenção experimental dos parâmetros úteis à caracterização das sementes de iodo-125 e avaliar se os procedimentos desenvolvidos, por este trabalho, possuem as condições necessárias para a determinação das análises dosimétricas, fundamentais para o sucesso dos procedimentos clínicos. Os dosímetros escolhidos para as análises são os TLD-100 (LiF:Mg,Ti), inicialmente estes dosímetros foram submetidos por duas etapas de seleção, com o objetivo de escolher os dosímetros mais reprodutíveis para as análises dosimétricas. As duas etapas foram à seleção por medidas de massa e a reprodutibilidade após quatro séries de irradiações por um irradiador de Cobalto-60 (CTR-IPEN). Após estas etapas, os dosímetros foram irradiados em um acelerador linear com energia de 6 MV (Serviço de Radioterapia Hospital Israelita Albert Einstein) para gerar os fatores de calibração individuais para cada dosímetro. Posteriormente, os dosímetros foram utilizados para as irradiações com a semente de iodo-125, modelo 6711 (GE-Healthcare). As irradiações com a semente de iodo-125 e demais análises renderam os valores necessários para a determinação dos parâmetros sugeridos pela AAPM (American Association of Physicists in Medicine): constante de taxa de dose, função de geometria, função de dose radial e função de anisotropia. Os resultados obtidos mostram boa concordância com os valores publicados pela literatura, para o mesmo modelo de semente de iodo-125, ratificando que os parâmetros realizados poderão ser utilizados para a dosimetria e controle de qualidade das sementes de iodo- 125 que irão ser produzidas pelo IPEN-CNEN/SP. / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

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Permanent breast seed implant brachytherapy (PBSI) is a recently developed form of treatment for early-stage breast cancer which can be completed in a single day procedure. Due to the reduced treatment burden, PBSI has the potential to benefit many women. However the technique has not been widely implemented, potentially related to the lack of a standardized, reproducible procedure and a high level of operator dependence. Challenges relating to target visualization uncertainties and the reliance on free-hand 2D ultrasound (US) guidance potentially inhibit adoption of the technique. This work aims to evaluate the current PBSI procedure to identify uncertainties and potential sources of errors in the current technique and develop methods to ameliorate these issues to potentially increase treatment accuracy, standardize the procedure, and reduce user-dependence. A comprehensive assessment of the current PBSI procedure was performed to identify any trends or systematic errors in the placement of seeds and establish the effects of seed placement accuracy on the treatment. Baseline seed placement accuracy, assessed in a 20 patient cohort was observed to be 9(5) mm. Random displacements of seeds from their planned position contributed significantly to the overall accuracy. No trends or systematic errors were observed across the aggregate population, however intra-patient systematic offsets were observed. The potential effects of visualization of the post-lumpectomy cavity (seroma) on treatment delivery was investigated using spatially registered CT and 3DUS images. Planning the treatment on CT, as is standard practice, resulted in less than optimal coverage to target volumes defined on US in the majority of cases. The effects of intra-operative adjustments relating to the visualization differences on the two modalities was assessed by shifting the CT-based treatment plan to centre on the US-defined seroma. Such shifts were shown to potentially contribute to the systematic displacements observed in PBSI delivery, and also had significant dosimetric effects on the planned target volumes. The impact of seroma visualization on PBSI implant accuracy was further assessed through the evaluation of CT and 3DUS images acquired for PBSI patients. Correlations were observed between the seed placement accuracy and the inter-user variability of seroma definition on CT (r = 0.74, p = 0.01) and the volume difference of the seroma on the two modalities (r = 0.65, p = 0.04), indicating that discrepancies in target delineation can impact treatment accuracy. The systematic displacements of the implants were observed to be correlated with the visualization metrics, however random displacements were independent of seroma delineation. Deviations in needle positioning during insertion may not be realized until the implant is complete, thus contributing to the random inaccuracies in seed placement. A purpose built 3DUS scanning system was investigated for its use in guiding needle insertion. Registration of the treatment template with the imaging system was validated to provide accurate target localization for needle insertion. Adjustments and re-insertion of needles under 3DUS guidance provided significant improvements to the needle positioning accuracy. A simulated implant with the guidance system indicated that overall treatment accuracy may be improved through the clinical implementation of such a system. Efforts to improve seroma definition during treatment planning and image guidance during the delivery can significantly increase seed placement accuracy and reduce the need for subjective intra-operative adjustments to the setup and needle positioning. Standardization of such advanced imaging techniques can greatly benefit the PBSI procedure by reducing user dependence and help to promote implementation. / Graduate / 2018-09-22

BACKGROUND High dose rate Intraluminal Brachytherapy (HDRILBT) is one of the most used palliative treatment options for advanced esophageal cancer. The present study evaluates the role of additional chemotherapy in improving dysphagia free survival (DFS) and overall survival (OS) in patients with inoperable advanced esophageal cancer treated with brachytherapy. MATERIAL and METHODS 132 patients with advanced metastatic esophageal cancer with total or near total dysphagia were given HDRILBT to a dose of 18 Gray (Gy) in 3 fractions on alternate days. Intraluminal brachytherapy alone was performed on 98 patients. 34 patients received Epirubicin, 5-Fluorouracil, and Cisplatin (ECF) chemotherapy regimen after HDRILBT. The mean age of the whole group was 65 years (HDRILBT-71.41, HDRILBT+ECF-59.98; p<0.0001). Male: Female was 101:31 (HDRILBT 72:26; HDRILBT +ECF 29:5; p>0.05). The location incidence was GEJ: Lower Esophagus: Mid Esophagus: Cervical Esophagus 24:81:17:5 respectively; for the whole group HDRILBT- 17:57:16:4; HDRILBT+ECF-7:24:1:1; p>0.05. 78 patients presented with co-morbidities (cardiac) (HDRILBT- 59; HDRILBT+ECF- 19; p>0.05). 74 patients presented with distant metastasis (54 with HDRILBT and 20 with HDRILBT+ECF; p>0.05). The ECOG scores were as follows 0:1:2:3:4 15:52:51:12:2 (HDRILBT- 10:35:41:10:2; HDRILBT+ECF- 5:17:10:2:0; p=0.0014). All patients completed 3 fractions of HDRILBT. 34 patients received additional chemotherapy with ECF regimen. Selection of patients was done by the medical oncologist. Statistical analysis of data was done using the SAS statistical analysis software system. Univariate and multivariate analysis was done using the log rang test. RESULTS Patients who received additional ECF were younger (p< 0.001) and with a better performance status than those who received HDRILBT alone (p=0.0014). Mean DFS was higher for patients who had further chemotherapy treatment (232 days) vs. patients who had HDRILBT only (155 days) (p>0.05). The mean OS for HDRILBT + ECF was 266 days (p = 0.0010) compare with HDRILBT alone which was 155 days, when the effect of 10 prognostic factors was analyzed for DFS and OS. Only additional ECF after brachytherapy impacted on DFS while age (p<0.001) and performance status (p=0.0014) impacted on overall survival on univariate analysis. On multivariate analysis tumor length and nodal presentation (p<0.000) impacted on OS. The incidence of stricture and fistulae were similar. Chemotherapy related side effects: gastrointestinal tract (25 patients), neurotoxicities (2) and nephrotoxicities (2) were seen as a result of 5-FU and Cisplatin respectively. 18 patients completed at least 3 cycles of ECF. CONCLUSION Additional chemotherapy with ECF after HDRILBT improves the DFS and OS in selected patients with advanced esophageal cancer. These patients tend to be younger with better performance status, small tumor length and nodal metastasis. The incidence of complications is similar with more than 50% patients completing at least 3 cycles of chemotherapy. / Thesis / Master of Science (MSc)

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