Thesis (doctoral)--University of Göteborg, 1997. / Added t.p. with thesis statement inserted.

The purpose of this work is to investigate the influence of possible patient movement and anatomy alteration on the quality of delivered prostate US based HDR-brachytherapy. The effect of patient movement and anatomy change (after the needle implantation and 3D image set acquisition) on catheter and organ dislocation and the consequences that this generated on the DVHs, conformity index and on radiobiological parameters. Materials and methods: This work is based on 3D image sets and treatment plans of 48 patients obtained right after the needle implantation (clinical plan is based on this 3D image set) and before and after the irradiation. In our institution the 3D-US based pre-planning, the transperineal implantation of needles using template and the intraoperative planning and irradiation is realized using the real-time dynamic planning system Oncentra Prostate. All pre-plans and all the inverse optimization of clinical plans were based on HIPO using the modulation restriction option. The patient body/OARs/catheters movement are generated from the clinical, pre- and post- irradiation plans and its influence on DVH-, COIN and radiobiological parameters of PTV and OARs are calculated and presented. Results: It is observed a slight decrease of treatment plan quality with increase of time between the clinical image set acquisition and the patient irradiation. Also, we show that the patient body movement/anatomy alteration and/or catheters dislocation results in decreased plan quality; change of values of the COIN, DVH- and radiobiological parameters. Conclusion: The measured mean shift of anatomy and needles (beams) is as low as 1.0mm that is lower by an order of magnitude to values known from external beam irradiation. For high modulated plans as those in HDR Brachytherapy such small shifts result in dosimetric changes which are in general lower than 5%. Our results demonstrate that quality assurance procedures have to be clinically implemented to guarantee anatomy and implant stability of the order of 1mm. This can only be realized without any manipulation of the implant and anatomy as done, for instance in the case of removing the US-probe before treatment delivery or moving the patient from one bed to another for the irradiation purposes / Σκοπός της εργασίας αυτής είναι να διερευνήσει την επιδραση που έχει η πιθανή μετακίνηση του ασθενούς και η αλλαγή της ανατομίας στην ποιότητα της Βραχυθεραπείας. Η μετακίνηση του ασθενούς, οι αλλαγές της ανατομίας ( μετά την εμφύτευση των βελονών και την συλλογή των τρισδιάστατων 3D εικόνων), η μετακίνηση των καθετήρων και των οργάνων επιφέρουν αλλαγές που παρουσιάζονται μέσα από τα ιστογράμματα δόσης - όγκου (DVH), δείκτη συμμορφίας (conformity index) και των ραδιοβιολογικών παραμέτρων. Υλικά και Μέθοδοι: Η μελέτη αυτή βασίζεται στην συλλογή τρισδιάστατων εικόνων υπερήχων (3D set) και στους σχεδιασμούς θεραπείας (treatment plans) από 48 ασθενείς που συλλέχθηκαν σε τρείς φάσεις: μετά την εμφύτευση των καθετήρων (κλινικός σχεδιασμός θεραπείας (clinical plan) βασίζεται σε αυτή την συλλογή 3D εικόνων), πριν την ακτινοβόληση και μετά την ακτινοβόληση.Στην κλινική μας ο προσχεδιασμός της θεραπείας (pre-planing) που βασίζεται στο τρισδιάστατο υπερηχογράφημα (3D-US), η διαπερινεϊκή εμφύτευση των καθετήρων με την βοήθεια του οδηγού template, ο διεγχειρητικός σχεδιασμός της θεραπείας (intraoperative planning) και η ακτινοβόληση πραγματοποιούνται με την χρήση του Real-time dynamic planning system Oncentra Prostate. Όλα τα pre-plans και όλα τα inverse optimization clinical plans βασίζονται στο HIPO χρησιμοποιώντας την επιλογή του modulation restriction. Οι μετακινήσεις του σώματος του ασθενούς/ των ευαίσθητων σε κίνδυνο οργάνων (OARs)/ και των καθετήρων αναπαράγονται από τα clinical, pre και post- irradiation plans. Κατόπιν υπολογίζεται και παρουσιάζεται η επίδρασή τους στο DVH, COIN και στις ραδιοβιολογικές παραμέτρους του όγκου στόχου σχεδιασμού (PTV) και των (OARs). Αποτελέσματα: Παρατηρείται μια ελαφρά μείωση της ποιότητας του σχεδιασμού θεραπείας με την αύξηση του χρόνου μεταξύ του κλινικού σχεδιασμού και της ακτινοβόλησης του ασθενούς. Επίσης παρουσιάζουμε ότι η μετακίνηση του ασθενούς/ η αλλαγή στην ανατομία ή/ και η μετακίνηση των καθετήρων έχει ως αποτέλεσμα στην μείωση της ποιότητας του σχεδιασμού. Έχουμε αλλαγή στις αλλαγές στις τιμές του COIN, του DVH και των ραδιοβιολογικών παραμέτρων. Συμπέρασματα: Η μέση τιμή των μετρούμενων μετακινήσεων της ανατομίας και των βελονών είναι ιδιαίτερα μικρή περίπου 1.0mm σε σύγκριση με τις γνωστές τιμές από την εξωτερική ακτινοθεραπεία. Για τους υψηλής διαμόρφωσης σχεδιασμούς, όπως αυτοί της HDR βραχυθεραπείας, μικρές μετακινήσεις οδηγούν σε δοσιμετρικές αλλαγές γενικά μικρότερες από 5%. Τα αποτελέσματα μας παρουσιάζουν ότι λαμβάνοντας υπόψη τις διαδικασίες εξασφάλισης ποιότητας επιτυγχάνεται η ακινητοποίηση του εμφυτεύματος της τάξης του 1mm. Αυτό μπορεί να επιτευχθεί μόνο με ακινητοποίηση του εμφυτεύματος και της ανατομίας, για παράδειγμα στην περίπτωση όπου μετακινούμε την κεφαλή της συσκευής υπερήχων (US- probe) πριν την ακτινοβόληση ή μετακινώντας τον ασθενή από ένα κρεβάτι σε ένα άλλο για τις ανάγκες τις ακτινοβόλησης.

Tratamentos braquiterápicos são comumente realizados conforme o relatório da American Association of Physicists in Medicine (AAPM), Task Group report TG-43U1, o qual define o formalismo para cálculo de dose absorvida na água e não considera a composição dos materiais, densidades, dimensões do paciente e o efeito dos aplicadores. Estes efeitos podem ser significantes, conforme descrito pelo recente relatório da AAPM, Task Group report TG- 186, que define diretrizes para que sistemas de planejamento modernos, capazes de considerar as complexidades descritas acima, sejam implementados. Esta tese tem como objetivo contribuir para o aumento da exatidão dos planejamentos de tratamento braquiterápicos, seguindo as recomendações do TG-186 e indo além do mesmo. Um software foi desenvolvido para integrar planejamentos de tratamento e simulações pelo método de Monte Carlo (MC); modelos acurados, CAD-Mesh, foram utilizados para representar aplicadores braquiterápicos; Grandezas utilizadas para reportar dose absorvida, Dw,m (dose para água no meio) e Dm,m (dose para o meio no meio), foram calculadas para um tratamento de cabeça e pescoço, considerando a teoria para pequenas (SCT small cavity theory) e grandes cavidades (LCT large cavity theory); a componente da dose em razão do movimento da fonte foi avaliada para tratamentos de próstata e ginecológicos. Perfis de velocidade obtidos na literatura foram utilizados; medidas de velocidade de uma fonte braquiterapica foram realizadas com uma câmera de alta taxa de aquisição. Cálculos de dose obtidos usando MC (incluindo a composição e densidade dos tecidos, ar e o aplicador) mostram sobredoses de aproximadamente 5% dentro do volume alvo, em um tratamento ginecológico, quando comparados aos resultados obtidos com um meio homogêneo de água. Por sua vez, subdoses de aproximadamente 5% foram observadas ao considerar a composição dos tecidos e regiões com ar em um tratamento intersticial de braço. Um aplicador cilíndrico oco resultou na sobredose observada no caso ginecológico, ressaltando a necessidade de modelos acurados para representar os aplicadores. Os modelos CAD-Mesh utilizados incluem um aplicador Fletcher-Williamson, com blindagem, e um balão deformável para irradiação de mama. Os resultados obtidos com estes modelos são equivalentes aos obtidos com modelos geométricos convencionais. Este recurso pode ser conveniente para aplicadores complexos e/ou quando o projeto dos aplicadores for disponibilizado pelo fabricante. Cálculos de dose, com a composição real dos tecidos humanos, podem apresentar diferenças significativas em razão da grandeza adotada. Diferenças entre Dm,m e Dw,m (SCT ou LCT) chegam a 14% em razão da composição do osso. A metodologia adotada (SCT ou LCT) resulta em diferenças de até 28% para o osso e 36% para os dentes. A componente de dose de trânsito também pode levar a diferenças significativas, uma vez que baixas velocidades ou movimentos uniformemente acelerados foram descritos na literatura. Considerando a pior condição e sem incluir nenhuma correção no tempo de parada, a dose de trânsito pode chegar a 3% da dose prescrita para um caso ginecológico, com 4 cateteres, e até 11.1% da dose prescrita para um tratamento de próstata, com 16 cateteres. A dose de trânsito para a fonte avaliada (velocidade obtida experimentalmente) não é uniformemente distribuída e pode levar a sub ou sobredoses de até 1.4% das doses comumente prescritas (310 Gy). Os tópicos estudados são relevantes para tratamentos braquiterápicos e podem contribuir para o aumento de sua acurácia. Os efeitos estudados podem ser avaliados com o uso do software, associado a um código MC, desenvolvido. / Brachytherapy treatments are commonly performed using the American Association of Physicists in Medicine (AAPM) Task Group report TG-43U1 absorbed dose to water formalism, which neglects human tissue densities, material compositions, body interfaces, body shape and dose perturbations from applicators. The significance of these effects has been described by the AAPM Task Group report TG-186 in published guidelines towards the implementation of Treatment Planning Systems (TPS) which can take into account the above mentioned complexities. This departure from the water kernel based dose calculation approach requires relevant scientific efforts in several fields. This thesis aims to improve brachytherapy treatment planning accuracy following TG-186 recommendations and going beyond it. A software has been developed to integrate clinical treatment plans with Monte Carlo (MC) simulations; high fidelity CAD-Mesh geometry was employed to improve brachytherapy applicators modelling; different dose report quantities, Dw,m (dose to water in medium) and Dm,m (dose to medium in medium), were obtained for a head and neck case using small cavity theory (SCT) and large cavity theory (LCT); the dose component due to the source moving within the patient was evaluated for gynecological and prostate clinical cases using speed profiles from the literature. Moreover, source speed measurements were performed using a high speed camera. Dose calculations using MC showed overdosing around 5% within the target volume for a gynecological case comparing results obtained including tissue, air and applicator effects against a homogeneous water phantom. On the other hand, the same comparison showed underdosing around 5% when including tissue and air composition for an interstitial arm case. A hollow cylinder applicator was responsible for the overdosing observed for the gynecological case highlighting the importance of accurate applicator modelling. The evaluated CAD-Mesh applicators models included a Fletcher- Williamson shielded applicator and a deformable balloon used for accelerated partial breast irradiation. Results obtained were equivalent to ones obtained with conventional constructive solid geometry and may be convenient for complex applicators and/or when manufacturer CAD models are available. Differences between Dm,m and Dw,m (SCT or LCT) are up to 14% for bone in a evaluated head and neck case. The approach (SCT or LCT) leads to differences up to 28% for bone and 36% for teeth. Differences can also be significant due to the source movement since some speed profiles from literature show low source speeds or uniform accelerated movements. Considering the worst case scenario and without include any dwell time correction, the transit dose can reach 3% of the prescribed dose in a gynecological case with 4 catheters and up to 11.1% when comparing the average prostate dose for a case with 16 catheters. The transit dose for a high speed (measured with a video camera) source is not uniformly distributed leading to over and underdosing, which is within 1.4% for commonly prescribed doses (310 Gy). The main subjects evaluated in this thesis are relevant for brachytherapy treatment planning and can improve treatment accuracy. Many of the issues described in here can be assessed with the software, coupled with a MC code, developed in this work.

O sucesso de uma radioterapia depende do correto planejamento da dose a ser entregue ao volume alvo. Na braquiterapia, modalidade da radioterapia onde um radioisótopo selado é implantado intracavitariamente ou intersticialmente no paciente, há menos avanços em sistemas de planejamento de tratamento computacionais do que na teleterapia, amplamente mais utilizada nos serviços típicos. Porém, a braquiterapia, quando aplicável, é preferível por poupar tecidos sadios vizinhos de uma dose desnecessária. O AMIGOBrachy, um sistema de planejamento para braquiterapia de interface amigável, compatibilidade com outros sistemas comerciais em uso e integrado ao código MCNP6 (Monte Carlo N-Particle Transport Code v. 6) foi desenvolvido no Centro de Engenharia Nuclear do Instituto de Pesquisas Energéticas e Nucleares (CEN-IPEN) e atualmente está em processo de validação. Este trabalho contribuiu para este processo, avaliando três diferentes casos clínicos através do AMIGOBrachy com o formalismo do TG43 da AAPM (Associação Americana de Física Médica), protocolo que rege a dosimetria em braquiterapia, e comparando seus resultados com as distribuições de dose calculadas por outros sistemas comerciais consagrados: Varian BrachyVision TM (Varian Medical Systems; Palo Alto, CA, EUA) e Nucletron Oncentra® (Elekta; Estocolmo, Suécia). Os resultados obtidos estão dentro de uma faixa de concordância de ±10%, estando mais discrepantes em regiões muito próximas do aplicador, onde os sistemas de planejamento comerciais e o AMIGOBrachy divergem devido aos diferentes métodos de cálculo. Em pelo menos dois terços da região de interesse, porém, a dose concordou em uma faixa de ±3% para os três casos. Também foram realizadas simulações utilizando o formalismo do TG186 da AAPM, que considera heterogeneidades no tecido, para avaliar o impacto dos mesmos na dose. Em adição ao processo de validação, também foi realizado um estudo em braquiterapia oftálmica para posterior inserção de um módulo adicional ao AMIGOBrachy; para isso, um modelo de olho humano foi desenvolvido utilizando geometria UM (Unstructured Mesh), para validação com o código MCNP6, que apenas nesta versão demonstra um novo recurso capaz de simular uma geometria híbrida: parcialmente analítica, parcialmente UM. O modelo considera dez diferentes estruturas no olho humano: esclera, coroide, retina, corpo vítreo, córnea, câmara anterior, lente, nervo óptico, parede do nervo óptico, e um tumor definido de forma arbitrária crescendo da superfície externa do globo ocular em direção ao seu centro. Os resultados foram comparados com um modelo de olho puramente analítico modelado com o MCNP6 e tomado como referência. Os resultados foram satisfatórios em todas as simulações desenvolvidas, exceto para as estruturas do nervo óptico e sua parede, que devido ao seu pequeno tamanho e distância da fonte, mostraram erros relativos maiores, mas ainda menores que 10%, e não representam problema de preocupação clínica uma vez que recebem doses muito pequenas. Discutiu-se também a eficácia e problemas encontrados nessa nova capacidade do código MCNP de simular geometrias híbridas, uma vez que é recente e ainda apresenta deficiências, que tiveram que ser contornadas no presente trabalho. / The success of a radiotherapy depends on the correct planning of the dose to be delivered to the target volume. In brachytherapy which is a radiotherapy mode where intracavitary or interstitial implants of a sealed radioisotope are used, there are less computational advances in treatment planning systems than in teletherapy, more widely used in typical medical services. However, brachytherapy, where applicable, is preferable for sparing neighboring healthy tissues from unnecessary dose. The AMIGOBrachy is a treatment planning system (TPS) with an user-friendly interface for brachytherapy, compatible with other commercial systems, and integrated with MCNP6 code (Monte Carlo N-Particle Transport Code v. 6). It was developed in the Nuclear Engineering Center of the Instituto de Pesquisas Energéticas e Nucleares (CEN-IPEN), São Paulo, Brasil, and is currently in a validation process. This work contributed to this process, evaluating three different clinical cases with the TG43 formalism by AAPM (American Association of Medical Physics), a protocol for dosimetry in brachytherapy, and comparing their results with the dose distributions calculated by other well-known commercial systems: Varian BrachyVision TM (Varian Medical Systems; Palo Alto, CA, USA) and Nucletron Oncentra® (Elekta; Stockholm, Sweden). The results obtained are within a ±10% range of agreement, being more discrepant in regions very near to the applicator, where commercial planning systems and AMIGOBrachy differ due to different calculation methods. However, the dose agreed in a range of ±3% for at least two thirds of the region of interest, for all three cases. Also, simulations were performed using the TG186 formalism of AAPM, which considers heterogeneities in the tissue, to assess their impact on the dose. In addition to the validation process, a study in ophthalmic brachytherapy for future insertion of an additional module to AMIGOBrachy was performed; for this, a human eye model was developed using UM (Unstructured Mesh) geometry, for validation with MCNP6 code, that only in this version shows a new resource capable of simulating a hybrid geometry: partly analytical, partly UM. Ten different structures of the human eye were modeled: sclera, choroid, retina, vitreous body, cornea, anterior chamber, lens, optic nerve, optic nerve wall, and a tumor defined arbitrarily growing from the external surface of the eyeball toward its center. The results were compared with a purely analytical model eye modeled with MCNP6 and used as a reference. The results were satisfactory in all performed simulations, except for the optic nerve and its wall, mainly because of their small size and distance from the source, showing larger relative errors, but still lower than 10%, which, however, does not represent clinical concern problem since they receive very small doses. The problems encountered in this new resource of MCNP code to simulate hybrid geometries were also discussed, since it was implemented recently and still display deficiencies that were overcome in the present work.

Low and middle-income countries (LMICs) around the world are experiencing a global cancer crisis. For treatable disease, cancer specific mortality in LMICs is much higher than in high-income countries. Botswana is a middle-income country in Sub-Saharan Africa that had its population decimated by the AIDS epidemic. In the aftermath and due to the successful implementation of an anti-retroviral program, patients are living longer and are developing cancer. Cervical cancer is one of the leading causes of death in women around the world, but it is curable. Patients in Botswana live far from treatment centers and therefore often present with locally advanced disease that can be cured with a combination of chemotherapy, external beam radiation therapy and brachytherapy. The goal of this present study is to describe the challenges and implementation of brachytherapy in the country of Botswana in 2012 and to report its uses within the cervical cancer population between 2012 and 2014. The government of Botswana recognized that there was a need for in country brachytherapy to help reduce the cervical cancer burden. A public-private partnership was negotiated through the government of Botswana in order to bring brachytherapy into the country. In March 2011, a Nucletron HDR-Brachytherapy unit that uses Ir-192 was installed at Gaborone Private Hospital. Longitudinal support from international partners provided instruction in insertion, dosimetry, physics and management of complications. The initial burden of patients presented with severe cervical fibrosis and vaginal stenosis due to late presentation of disease. This resulted in numerous complications in the first treatments, which included failed insertions, perforations and bleeding. Following training and support from international partners, complications have been reduced. There are about 45 insertions performed each month, with an average of 3 insertions per patient. Introduction of HDR Brachytherapy to Botswana has led to decreased treatment time, reduced complications, increased patient compliance and projected improved survival. Implementation of brachytherapy was facilitated by a public-private partnership and onsite mentorship by expert clinicians. Further research is needed to evaluate impact on patient quality of life and survival, and whether this experience can be replicated for other tumor sites.

Le cancer de la prostate est le cancer le plus fréquent chez l'homme en France et aux pays occidentaux. Il est la troisième cause de décès liés au cancer, étant responsable d'environ 10% des morts. La curiethérapie, une technique de radiothérapie, est liée à une meilleure qualité de vie après le traitement, par rapport aux autres méthodes de traitement. La curiethérapie de la prostate consiste à insérer des sources radioactives dans la prostate afin de délivrer une dose d'irradiation localisée à la tumeur tout en protégeant les tissus sains environnants. L'imagerie multimodale est utilisée afin d'améliorer la précision du traitement. Les images Tomodensitométriques préopératoires, appelées Computed Tomography (CT), peuvent être utilisées pour calculer une distribution personnalisée et plus précise de dose. Pendant l'intervention, le chirurgien utilise un système de guidage temps-réel par l'Ultrason Transrectale, Transrectal Ultrasound (TRUS), pour placer correctement les sources radioactives dans leurs positions souhaitées. Par conséquent, si les positions des sources sont déterminées sur l'image CT, elles doivent être transférées à l'image US. Cependant, un recalage US/CT direct et robuste est difficilement envisageable parce que les tissus mous, telle que la prostate, offrent peu de contraste en CT et en US. En revanche, l'Imagerie par Résonance Magnétique (IRM) fournit un meilleur contraste et peut, potentiellement, améliorer le traitement en améliorant la visualisation. Donc, ces trois modalités (IRM, CT et US) doivent être correctement alignées. Pour compenser les déformations de la prostate, due au changement de taille et forme entre les différentes acquisitions, un recalage non-rigide est nécessaire. Une méthode de recalage entièrement automatique est nécessaire, afin de faciliter son intégration au bloc opératoire. Nous proposons dans un premier temps un recalage IRM/CT basé sur la maximisation de l'information mutuelle en combinaison avec un champ de déformation paramétré par B-Splines. Nous proposons de contraindre le recalage sur des volumes d'intérêt (VOIs) afin d'améliorer la robustesse et le temps de calcul. L'approche proposée a été validée sur des jeux de données cliniques. Une évaluation quantitative a montré que l'erreur de recalage est égale à 1.15±0.20 mm; qui répond à la précision clinique souhaitée. Ensuite, nous proposons un deuxième recalage US/IRM, où nous utilisons une approche multi-résolution pour éviter les minima locaux et améliorer le temps de calcul. Un critère de similarité, qui met en corrélation l'intensité de l'image US avec l'intensité ainsi que le gradient de l'image IRM, a été utilisé afin de trouver la transformation qui aligne les deux images. Cette méthode a été validée sur un fantôme de prostate dans un premier temps pour évaluer sa faisabilité. Ensuite, elle a été validée sur des jeux de données cliniques en utilisant des critères qualitatives et quantitatives. La distance Hausdorff a montré que l'erreur de recalage est égale à 1.44±0.06 mm. L'approche proposée dans ce travail permet d'aller vers un protocole de curiethérapie guidée par l'imagerie multimodale qui puisse améliorer la précision globale de cette procédure. Malgré ces résultats plutôt encourageants, les travaux futurs impliqueront une évaluation plus approfondie sur plus de jeux de données afin d'évaluer la fiabilité et l'efficacité de cette méthode avant de l'intégrer au bloc opératoire. / Prostate cancer is the most common cancer in men in France and western countries. It is the third leading cause of death from cancer, being responsible for around 10% of deaths. Brachytherapy, a radiotherapy technique, is associated with a better health-related quality of life after the treatment, compared to other treatment techniques. Prostate brachytherapy involves the implantation of radioactive sources inside the prostate to deliver a localized radiation dose to the tumor while sparing the surrounding healthy tissues. Multi-modal imaging is used in order to improve the overall accuracy of the treatment. The pre-operative Computed Tomography (CT) images can be used to calculate a personalized and accurate dose distribution. During the intervention, the surgeon utilizes a real-time guiding system, Trasnrectal Ultrasound (TRUS), to accurately place the radioactive sources in their desired pre-planned positions. Therefore, if the positions of the sources were determined on CT, they need to be transferred to US. However, a robust and direct US/CT registration is hardly possible since they both provide low soft tissue contrast. Magnetic Resonance Imaging (MRI), on the other hand, has a superior contrast and can potentially improve the treatment planning and delivery by providing a better visualization. Thus, these three modalities (MRI, US and CT) need to be accurately registered. To compensate for prostate deformations, caused by changes in size and form between the different acquisitions, non-rigid registration is essential. Fully automatic registration methodology is necessary in order to facilitate its integration in a clinical workflow. At first, we propose a registration between pre-operative MR and CT images based on the maximization of the mutual information in combination with a deformation field parameterized by cubic B-Splines. We propose to constrain the registration to volumes of interest (VOIs) in order to improve the robustness and the computational efficiency. The proposed approach was validated on clinical patient datasets. Quantitative evaluation indicated that the overall registration error was of 1.15±0.20 mm; which satisfies the desired clinical accuracy. Then, we propose a second intra-operative US/MRI registration, where a multi-resolution approach is implemented to reduce the probability of local minima and improve the computational efficiency. A similarity measure, which correlates intensities of the US image with intensities and gradient magnitude of the MRI, is used to determine the transformation that aligns the two images. The proposed methodology was validated on a prostate phantom at first to assess its feasibility. Subsequently, the method was validated on clinical patient datasets and evaluated using qualitative and quantitative criteria, resulting in a registration error of 1.44±0.06 mm. The approach proposed in this work allows going towards a multimodal protocol for image-guided brachytherapy which can improve the overall accuracy of this procedure. Despite such encouraging results, future work will involve further evaluation on a larger number of datasets in order to assess the reliability and the efficiency of this methodology before integrating it in a clinical workflow.

Uma das modalidades de tratamento para mulheres acometidas pelo câncer ginecológico é a radioterapia interna, também conhecida como braquiterapia. Caracteriza-se pela colocação de materiais radioativos junto ao tumor. No caso daquele tipo de câncer, para se efetuar a irradiação, é necessário introduzir um aplicador dentro da vagina. Este tratamento pode ser bastante desconfortável para a mulher, tanto no momento da aplicação, quanto após a mesma. Neste sentido, estudos sobre o tema apontam não apenas para efeitos colaterais físicos, mas também para conseqüências psicológicas na qualidade de vida de pacientes tratadas por braquiterapia. Entretanto, tais estudos são ainda incipientes, tendo maior concentração na área de Enfermagem. É quase inexistente uma produção de caráter psicológico que aprofunde o conhecimento a respeito de questões emocionais em mulheres submetidas a esse procedimento invasivo. Sendo assim, esta pesquisa qualitativa objetivou compreender aspectos psicológicos em mulheres com câncer ginecológico submetidas a essa modalidade radioterápica. Para tanto, foram realizadas sete entrevistas abertas com mulheres em tratamento junto ao Serviço de Radioterapia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo. As entrevistas foram áudio-gravadas, transcritas na íntegra e submetidas à análise de acordo com o método clínico-qualitativo, utilizando-se a psicanálise como marco teórico para a interpretação dos dados. Foi elaborado um diário de campo como instrumento auxiliar de pesquisa. Após realização das leituras flutuantes e análise do material, observou-se que a braquiterapia é sentida pelas mulheres como uma agressão, gerando intensa angústia, desespero e raiva. A manipulação na região vaginal, com entradas e saídas de objetos (aplicador, sonda, etc.), desencadeia vivências e efeitos físicos desagradáveis, como dor, ardência urinária, sensação de queimação. Em uma perspectiva psicanalítica, o tratamento é vivido como um objeto hostil e persecutório que é introduzido na intimidade sexual, afetando a mulher em sua feminilidade. A posição física em que as mulheres permanecem para receber a irradiação acarretou sensação de submissão, vergonha e exposição de sua intimidade. Ainda com relação a este tratamento, foram feitas associações e comparações com a experiência anterior de gravidez/parto, possivelmente pela existência de conflitos e questões inconscientes relacionadas ao nascimento, mas também à morte concretizada pela doença grave. As mulheres atribuíram significados ao surgimento do câncer ginecológico relacionados à vivência de depressão, à sexualidade e à gravidez/parto, sendo que se evidenciou uma culpa inconsciente pela doença. Para enfrentarem as vicissitudes do tratamento, as mulheres tiveram que se basear mais no princípio de realidade - buscar a remissão da doença através do tratamento e da confiança na equipe - do que no princípio de prazer (ou evitação do desprazer), mas com considerável sofrimento psíquico. Neste sentido, considera-se relevante pensar numa assistência psicológica às pacientes, com o intuito de minimizar possíveis efeitos psicológicos adversos associados à braquiterapia. / One of the treatment modes for women affected by gynecological cancer is internal radiotherapy, also known as brachytherapy. It is characterized by the placement of radioactive material near the tumor. For that type of cancer, the irradiation requires the introduction of an applicator inside the vagina. This treatment can be quite uncomfortable for the women, both during and after the application. In this sense, research on the theme appoints not only physical collateral effects, but also psychological consequences for the quality of life of patients treated with brachytherapy. However, these studies are still incipient, with a greater concentration in the Nursing area. Production of psychological nature, which deepens knowledge about emotional issues in women submitted to this invasive procedure, almost does not exist. Thus, this qualitative research aimed to understand psychological aspects in women with psychological cancer submitted to this radiotherapeutic modality. Therefore, seven open interviews were held with women under treatment at the Radiotherapy Service of the University of São Paulo at Ribeirão Preto Medical School Hospital das Clínicas. The interviews were tape-recorded, fully transcribed and submitted to analysis according to the clinical-qualitative method, using psychoanalysis as a theoretical framework for data interpretation. A field diary was elaborated as an auxiliary research instrument. After floating reading and analysis of the material, it was observed that the women feel brachytherapy as an aggression, generating intense anguish, despair and rage. Manipulation in the vaginal region, with insertions and withdrawals of objects (applicator, probe, etc.), causes unpleasant experiences and effects, such as pain, urinary burning and a burning feeling. In a psychoanalytical perspective, treatment is experienced as a hostile and persecutory object, which is introduced in the sexual intimacy, affecting the woman in her femininity. The physical position in which women remain to receive the irradiation caused a feeling of submission, shame and exposure of their intimacy. Moreover, with respect to this treatment, associations and comparisons were made with previous experiences of pregnancy/delivery, possibly due to the existence of conflicts and unconscious questions related to birth, but also to death made real by the severe disease. The women attributed meanings to the appearance of gynecological cancer, related to the experience of depression, sexuality and pregnancy/delivery, evidencing an unconscious feeling of guilt about the disease. In order to face the vicissitudes of treatment, the women had to base themselves more on the reality principle - seeking the remission of the disease through treatment and confidence in the team - than on the principle of pleasure (or avoidance of displeasure), but accompanied by considerable mental suffering. In this sense, it is considered relevant to think of psychological care delivery to these patients, with a view to minimizing possible adverse psychological effects associated with brachytherapy.

INTRODUÇÃO: Braquiterapia de alta taxa de dose (BATD) para o câncer de próstata pode ser uma boa opção para escalonamento de dose, como um reforço de dose, associada à radioterapia externa, principalmente se não há disponibilidade de radioterapia tridimensional conformada ou tecnologia mais avançada. OBJETIVOS: Neste trabalho, analisaram-se os resultados e as toxicidades de um reforço de dose com BATD prévio à radioterapia externa convencional ou tridimensional conformada em pacientes portadores de câncer localizado da próstata. Fatores prognósticos relacionados à sobrevida livre de doença, além de toxicidade do tratamento também foram estudados. MÉTODOS: Estudo retrospectivo de 403 pacientes com adenocarcinoma localizado da próstata tratados entre dezembro de 2000 e março de 2004, que receberam 3 esquemas de fracionamento distintos de BATD de acordo com o seu grupo de risco: três frações de 5,5 a 6 Gy, 6 a 6,5 Gy ou 6,5 a 7 Gy, para baixo, médio ou alto risco, respectivamente, em um único implante, no decorrer de 24h de internação. A radioterapia externa convencional ou conformada compreendeu dose de 45 Gy na próstata e vesículas seminais. Foram realizadas análises uni e multivariada para avaliação dos fatores prognósticos relacionados à sobrevida livre de falha bioquímica e toxicidades. RESULTADOS: A idade mediana dos pacientes foi de 68 anos, com PSA médio de 9g/ml, peso prostático médio de 35 cc. Grau histológico de Gleason igual a 6 ocorreu em 43% dos casos, estádio menor do que T2c em 97%, presença de nódulo prostático em 49%; 11% dos pacientes apresentaram história de ressecção transuretral e 16% obstrução urinária prévias. No grupo de baixo risco foram classificados 36.1% dos pacientes, 42.8% no grupo de risco intermediário e 21.1% foram considerados de alto risco. Hormonioterapia neoadjuvante por até 6 meses foi utilizada em 64% dos casos e teleterapia conformada em 19%. O seguimento médio foi de 50 meses (mediano de 48,4 meses), variando de 24 a 113 meses. Nove (2,2%) pacientes não responderam ao tratamento e 4,5% evoluíram a óbito por neoplasia prostática em um tempo médio de 22 meses. Falha bioquímica, tanto pelo critério ASTRO, quanto PHOENIX ocorreu em 9,6% dos pacientes. Entretanto, o tempo médio para falha foi de 13 meses pelo critério ASTRO e 26 meses pelo PHOENIX. O único fator preditivo de falha bioquímica pela análise multivariada por ambos os critérios ASTRO e PHOENIX foi a presença de nódulos prostáticos, mas pacientes com menos de 60 anos apresentaram maior chance de falha apenas pela definição de PHOENIX. Toxicidades urinárias agudas como retenção e hematúria ocorreram em 2,8% e 1,3% dos casos, respectivamente; sendo 23,7% grau 1, 15,1% grau 2 e 2% grau 3. Estenose uretral tardia foi observada em 8,5% dos pacientes e as toxicidades urinárias tardias foram grau 1 em 8,8%, grau 2 em 3,9%, grau 3, em 7,7% e grau 4, em 0,3% dos casos. Toxicidade urinária aguda foi relacionada a obstrução urinária prévia e maior dose de braquiterapia na uretra. Estenose uretral tardia também foi relacionada à maior dose uretral pela braquiterapia e com maior idade. Toxicidade retal precoce ocorreu como grau 1 em 14,8% dos pacientes; como grau 2, em 10,5%; e como grau 3, em 1,3%. Toxicidade retal tardia ocorreu como grau 1 em 3,4% dos pacientes; como grau 2, em 1,5%; como grau 3, em 0,3%; e como grau 4, em 0,3%. O risco para toxicidades retais agudas e tardias foi maior quando teleterapia conformada foi utilizada. Foi observada dor na glande em 4,9% dos pacientes e 71% apresentaram disfunção erétil tardiamente. O uso de Sildenafil foi eficiente em 59%. Pacientes mais velhos, ou com uma ou mais comorbidades, comprometimento prévio da ereção, ou que receberam radioterapia externa conformada apresentaram maior incidência de disfunção erétil. CONCLUSÕES: a associação de BATD como um reforço de dose para teleterapia mostrou ser um método viável e seguro apresentando boa eficácia e toxicidade aceitável. Os fatores relacionados à sobrevida e toxicidade podem colaborar na melhor seleção e tratamento de pacientes com câncer de próstata localizado. / INTRODUCTION: high dose-rate brachytherapy (HDR) for prostate cancer may be a nice treatment option for dose escalation as a boost, when associated to external beam irradiation, mainly if 3D conformal or more advanced technology is not available. PURPOSE: this study analyzes the results and toxicities of HDR brachytherapy boost prior to external beam radiotherapy with 2D or 3D conformal irradiation in patients with localized prostate cancer. Prognostic factors associated to overall and disease-free survival, as well as to treatment related toxicity were also studied. METHODS: A retrospective study of 403 patients with localized prostate adenocarcinoma treated between December 2000 and March 2004 was performed. According to the risk group, three fractions of HDR brachytherapy were delivered in the course of 24 hours, with a single implant: 5.5 to 6 Gy per fraction for low risk, 6 to 6.5 Gy per fraction for intermediate risk, and 6.5 to 7 Gy per fraction for high risk patients. The interval between fractions was of at least 6 hours. Conventional 2D or 3D conformal external beam irradiation was delivered to the prostate and seminal vesicles with 25 fractions of 1.8Gy (45Gy), about 2 weeks after brachytherapy. Multivariate analysis was done to evaluate unfavorable prognostic factors for biochemical failure free survival (BFFS). RESULTS: Patients presented a median age of 68 years, mean PSA of 9g/ml, and average prostate weight of 35 cc. Gleason score was equal to 6 in 43% of the cases, and 97% of the cases were at a stage lower than T2c. Prostate nodules were present in 49% of the patients; prior history of transurethral resection or urinary obstruction was present in 11% and 16% of the patients, respectively. There were 36.1% patients in the low risk group, 42.8% in the intermediate, and 21.1% in the high risk groups, respectively. Up to six months of neoadjuvant hormone therapy was used in 64% of the cases. External beam radiation was delivered with 3D conformal radiation in 19% of patients. The mean follow-up was 50 months ranging from 24 to 113 months (median 48,4 months). Nine patients (2.2%) did not respond to treatment. Death from prostate cancer occurred in 4.5% of the cases in a mean period of 22 months. Biochemical failure occurred in 9.6% according to both ASTRO and Phoenix consensus criteria. However, the mean time to relapse was 13 months using the ASTRO criteria and 26 months with the Phoenix definition. The five-year BFFS using the ASTRO criteria was 94.3%, 86.9% and 86.6% for the low, intermediate and high risk groups, respectively. Using the Phoenix criteria, 92.4%, 88.0% and 85.3% for the low, intermediate and high risk groups, respectively (p = 0.109). The only feature predicting biochemical failure (BF) in the multivariate analysis by both ASTRO and Phoenix criteria was the presence of prostate nodules, but patients younger than 60 years presented higher chance of BF using Phoenix criteria only. Acute urinary toxicities as urinary retention and hematúria occurred respectively in 2.8% and 1.3% of the patients. They presented as grade 1 in 23.7%, grade 2 in 15.1% and grade 3 in 2%. Late urethral stenosis was observed in 8.5% and late urinary toxicity was grade 1 in 8.8% of the patients, grade 2 in 3.9%, grade 3 in 7.7% and grade 4 in 0.3%. Acute urinary toxicity was related to previous urinary obstruction and higher brachytherapy dose to the urethra. Late urethral stenosis was related to older age and higher brachytherapy dose. Grade 1 early rectal toxicity occurred in 14.8% of the patients, grade 2 in 10.5% and grade 3 in 1.3%. Late rectal toxicity occurred as grade 1 in 3.4% of patients, as grade 2 in 1.5%, grade 3 in 0.3% and grade 4 in 0.3%. The risk of acute and late rectal toxicity was higher when 3D conformal irradiation was used. Glans pain was observed in 4.9% of the patients. Late sexual impotence occurred in 71% of cases. Sildenafil was effective in 59%. Sexual impotence presented a higher incidence in older patients with one or two co-morbidities, previous sexual impairment, or 3D conformal irradiation. CONCLUSIONS: the association of HDR brachytherapy as a boost for external beam irradiation seems to be a feasible and safe procedure, with good efficacy and acceptable toxicity. Factors related to survival and toxicity can help to better select and manage patients with localized prostate carcinoma.

A braquiterapia é a modalidade de tratamento radioterápico que utiliza fontes radioativas seladas a uma distância curta do tumor, diminuindo o risco de aplicação de uma dose indesejável em tecidos sadios adjacentes. Para que a braquiterapia seja confiável, é necessário estabelecer um programa de práticas dosimétricas visando a determinação da dose ideal de radiação para esta prática radioterápica. Neste trabalho apresenta a aplicação de duas metodologias destinadas à dosimetria utilizando filmes radiocrômicos. Medidas experimentais foram realizadas com filmes EBT3 em objetos simuladores composto de material homogêneo e heterogêneo (pulmão, osso e tecidos moles) construídos especialmente para medidas de dose em braquiterapia. Os processamentos e analises das imagens resultantes do procedimento experimental foram realizados com o software IMAGEJ e MATLAB. Os resultados foram avaliados a partir de comparações medidas experimentais de dose e obtidas por simulações pelo Método de Monte Carlo. / Brachytherapy is a radiotherapy treatment modality using radioactive sealed sources within walking distance of the tumor, reducing the risk of applying an unwanted dose to adjacent healthy tissues. For brachytherapy is reliable, it is necessary to establish a dosimetric practices program aimed at determining the optimal dose of radiation for this radiotherapy practice. This paper presents the application of two methodologies for the dosimetry using radiochromic movies. Experimental measurements were performed with EBT3 movies phantoms consisting of homogeneous and heterogeneous material (lung, bone and soft tissue) built especially for dose measurements in brachytherapy. The processing and analysis of the resulting images of the experimental procedure were performed with ImageJ software and MATLAB. The results were evaluated from comparisons dose of experimental measurements and simulations obtained by the Monte Carlo method.

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