Intensity modulated arc therapy is a novel treatment technique that has shown great potential to be superior to conventional intensity modulated radiotherapy, both in terms of treatment plan quality as well as treatment delivery. Based on previous literature, a simplified technique called two-step intensity modulated arc therapy (2-step IMAT) was implemented into a treatment planning system. In order to automatically generate treatment plans for this technique, a beam portal shaping method was developed to generate beam segments. A sensitivity analysis was carried out on a geometric phantom to determine optimal parameters for the 2-step IMAT implementation for that particular phantom. The segment weights were optimized using the dose-based and dose-volume-based objective functions. The optimal solution search was based on the gradient-descend algorithm. The dose-based objective function was implemented using a so-called lambda-value-dose-based objective function developed in this work in order to increase both speed and flexibility of the optimization. The successful implementation demonstrated the feasibility of automatic 2-step IMAT treatment planning. A comparison of conventional arc therapy and 2-step IMAT showed improvements in the target dose uniformity by about 50% for both geometric phantom and clinical paraspinal tumor case, whilst also improving the organ sparing. The comparisons between the lambda-value-dose-based and dose-volume-based optimizations showed a speed advantage of the former by a factor of over five in the phantom study. The current beam portal shaping approach can be improved by optimizing the segment width and including multiple organs-at-risk in the segment generation algorithm. Future work will also include the implementation of a stochastic optimization to minimize the chance of getting trapped in local minima during the segment weight optimization. In summary, the work of this research showed that the automatic 2-step IMAT planning is a viable technique that can result in highly conformal plans while keeping the treatment planning and delivery simple and straightforward.

Electron beam therapy planning and custom electron bolus design were identified as areas in which improvements in equipment and techniques could lead to significant improvements in treatment delivery and patient outcomes. The electron pencil beam algorithms used in conventional Treatment Planning Systems do not accurately model the dose distribution in irregularly shaped objects, near oblique surfaces or in inhomogeneous media. For this reason, at Christchurch Oncology Centre the TPS is not relied on for planning electron beam treatments. This project is an initial study of ways to improve the design of custom electron bolus, the planning of electron beam therapy, and other radiation therapy simulation tasks, by developing a system for the accurate assessment of dose distributions under irregular contours in clinically relevant situations. A shaped water phantom system and a diode array have been developed and tested. The design and construction of this water phantom dosimetry system are described, and its capabilities and limitations discussed. An EGS/BEAM Monte Carlo simulation system has been installed, and models of the Christchurch Oncology Centre linacs in 6MeV and 9MeV electron beam modes have been built and commissioned. A test was run comparing the EGS/BEAM Monte Carlo system and the CMS Xio conventional treatment planning system with the experimental measurement technique using the water phantom and the diode array. This test was successful as a proof of the concept of the experimental technique. At the conclusion of this project, the main limitation of the diode array system was the lack of data processing software. The array produces a large volume of raw data, but not enough processed data was produced during this project to match the spatial resolution of the computer models. An automated data processing system will be needed for clinical use of the array. It has been confirmed that Monte Carlo and pencil-beam algorithms predict significantly different dose distributions for an irregularly shaped object irradiated with megavoltage electron beams. The results from the diode array were consistent with the theoretical models. This project was an initial investigation. At the time of writing, the diode array and the water phantom systems were still at an early stage of development. The work reported here was performed to build, test and commission the equipment. Additional work will be needed to produce an instrument for clinical use. Research into electron beam therapy could be continued, or the equipment used to expand research into new areas.

O tratamento de câncer possui diversas modalidades. Uma delas é a utilização de fontes de radiação como principal protagonista do tratamento. A radioterapia e a medicina nuclear são exemplos desse tipo de tratamento. Por utilizarem a radiação ionizante como principal ferramenta para a terapia, há a necessidade de se efetuar diversas simulações do tratamento a fim de maximizar a dose nos tecidos tumorais sem ultrapassar os limites de dose nos tecidos sadios circunvizinhos. Os sistemas utilizados na simulação desses tipos de terapia recebem o nome de Sistemas de Planejamento Dosimétrico. A medicina nuclear e a radioterapia possuem seus próprios sistemas de planejamento dosimétricos devido a grande diversidade das informações necessárias às suas simulações. Os sistemas de planejamento em radioterapia são mais consolidados do que os de medicina nuclear e por tal motivo um sistema que aborde tanto os casos de radioterapia como de medicina nuclear contribuiria para significativos avanços na área de medicina nuclear. Dessa forma, o objetivo do trabalho foi modelar um Sistema de Planejamento Dosimétrico com o uso do código de Monte Carlo MCNP6 Monte Carlo N-Particle Transport Code que permitisse incorporar os casos de radioterapia e medicina nuclear e que fosse extensível a novos tipos de tratamentos. A modelagem desse sistema resultou na construção de um Framework, orientado a objetos, nomeado IBMC o qual auxilia no desenvolvimento de sistemas de planejamento que necessitam interpretar grandes quantidades de informações com o objetivo de escrever o arquivo base do MCNP6. O IBMC permitiu desenvolver de maneira rápida e prática sistemas de planejamento para radioterapia e medicina nuclear e os resultados foram validados com sistemas já consolidados. Ele também mostrou alto potencial para desenvolver sistemas de planejamento de novos tipos de tratamentos que utilizam a radiação ionizante. / Cancer therapy has many branches and one of them is the use of radiation sources as treatment leading method. Radiotherapy and nuclear medicine are examples of these treatment types. For using the ionization radiation as main tool for the therapy, there is the need of crafting many treatment simulation in order to maximum the tumoral tissue dose without throught the dose limit in health tissue surrounding. Treatment planning systems (TPS) are systems which have the purpose of simulating these therapy types. Nuclear medicine and radiotherapy have many distinct features linked to the therapy mode and consequently they have different TPS destined for each. The radiotherapy TPS is more developed than the nuclear medicine TPS and by that reason the development of a TPS that was similar to the radiotherapy TPS, but enough generic for include other therapy types, it will contribute with significant advances in nuclear medicine and in others therapy types with radiation. Based on this, the goal of work was to model a TPS that utilizes the Monte Carlo N-Particle Transport code (MCNP6) in order to simulate radiotherapy therapy, nuclear medicine therapy and with potential for simulating other therapy types too. The result of this work was the creation of a Framework in Java language, objectoriented, named IBMC which will assist in the development of new TPS with MCNP6 code. The IBMC allowed to develop rapidly and easily TPS for radiotherapy and nuclear medicine and the results were validated with systems already consolidated. The IBMC showed high potential for developing TPS by new therapy types.

Earlier studies show that when psychiatric out- and in-patient care units work together the risk for hospitalization decreases, leads to increased flexibility and shorter in-patient periods. At a psychiatric clinic in western Sweden there are routines in place regarding the transfer of patients from in-patient to out-patient care. The aim of this study was to describe nurses' experience of how out-and in-patient clinics collaborate during patients in-patient care. This is a qualitative study with an inductive approach. Ten nurses participated through semi structured interviews. The result ended up in two domains and eight subthemes and one theme, the diffuse responsibility – makes us not understand each other. Nurses in both out- and in-patient care experience uncertainty as to who has the responsibility for patients' treatment-plans and also uncertainty in how communication between the two parties works. Nurses in in-patient care experience that the out-patient care are uninterested, and nurses in out-patient care experience that in-patient care does not follow treatment-plans. In Conclusion both nurses in out- and in-patient care describe a need for an improved partnership. Some find that they are unsure of their role and their responsibility in the partnership. Structures for an improved partnership need to be implemented from the staff leadership, to be able to live up to the national guidelines and ensure that patients receive the treatment which serious psychiatric illness needs.

Emotional regulation may be an underaddressed therapeutic target in sex offender treatment. This article presents a case report of “Adam,” a Caucasian male referred to a prison-based sex offender treatment program. Adam’s social anxiety was recognized as an antecendent to his sexual offending, and treatment of such, as a critical adjunct to sex offender treatment, is discussed herein. Adam’s individualized treatment included aspects of rational emotive behavior therapy and time-limited dynamic psychotherapy. Adam showed an increased understanding of his anxiety and improvement in his social interactions, both in the context of treatment groups and with female staff, and was willing to continue follow-up care in the community. This case provides support for the individualized treatment of incarcerated offenders as opposed to exclusively utilizing manualized psychoeducational interventions.

L'objectif principal de cette thèse est de développer et optimiser les algorithmes caractérisant les propriétés physiques et biologiques des mini-faisceaux de protons pour la réalisation des traitements avec modulation d'intensité. Un modèle basé sur la superposition et décomposition des mini-faisceaux en faisceaux élémentaires a été utilisé. Un nouveau modèle de description des mini-faisceaux primaires a été développé à partir de la sommation de trois fonctions gaussiennes. Les algorithmes ont été intégrés dans un logiciel de planification de traitement, puis validés expérimentalement et par comparaison avec des simulations Monte Carlo. Des approximations ont été réalisées et validées afin de réduire les temps de calcul en vue d'une utilisation clinique. Dans un deuxième temps, un travail en collaboration avec les équipes de radiobiologie de l'institut Curie a été réalisé afin d'introduire des résultats radiobiologiques dans l'optimisation biologique des plans de traitement. En effet, les faisceaux balayés sont délivrés avec des débits de dose très élevés (de 10 à 100 Gy/s) et de façon discontinue, et l'efficacité biologique des protons est encore relativement méconnue vue la diversité d'utilisation de ces faisceaux : les différents modèles disponibles et notamment leur dépendance avec le transfert d'énergie linéique ont été étudiés. De bons accords (écarts inférieurs à 3 % et 2 mm) ont été obtenus entre calculs et mesures de dose. Un protocole d'expérimentation pour caractériser les effets des hauts débits pulsés a été mis en place et les premiers résultats obtenus sur une lignée cellulaire suggèrent des variations d'efficacité biologique inférieures à 10 %, avec toutefois de larges incertitudes. / The main objective of this thesis is to develop and optimize algorithms for intensity modulated proton therapy, taking into account the physical and biological pencil beam properties. A model based on the summation and fluence weighted division of the pencil beams has been used. A new parameterization of the lateral dose distribution has been developed using a combination of three Gaussian functions. The algorithms have been implemented into a treatment planning system, then experimentally validated and compared with Monte Carlo simulations. Some approximations have been made and validated in order to achieve reasonable calculation times for clinical purposes. In a second phase, a collaboration with Institut Curie radiobiological teams has been started in order to implement radiobiological parameters and results into the optimization loop of the treatment planning process. Indeed, scanned pencil beams are pulsed and delivered at high dose rates (from 10 to 100 Gy/s), and the relative biological efficiency of protons is still relatively unknown given the wide diversity of use of these beams: the different models available and their dependence with linear energy transfers have been studied. A good agreement between dose calculations and measurements (deviations lower than 3 % and 2 mm) has been obtained. An experimental protocol has been set in order to qualify pulsed high dose rate effects and preliminary results obtained on one cell line suggested variations of the biological efficiency up to 10 %, though with large uncertainties.

Au-delà des techniques conventionnelles de diagnostic et de suivi du cancer, l’analyse radiomique a pour objectif de permettre une médecine plus personnalisée dans le domaine de la radiothérapie, en proposant une caractérisation non invasive de l’hétérogénéité tumorale. Basée sur l’extraction de paramètres quantitatifs avancés (histogrammes des intensités, texture, forme) issus de l’imagerie multimodale, cette technique a notamment prouvé son intérêt pour définir des signatures prédictives de la réponse aux traitements. Dans le cadre de cette thèse, des signatures de la récidive des cancers du col utérin ont notamment été développées, à partir de l’analyse radiomique seule ou en combinaison avec des biomarqueurs conventionnels, apportant des perspectives majeures dans la stratification des patients pouvant aboutir à une adaptation spécifique de la dosimétrie.En parallèle de ces études cliniques, différentes barrières méthodologiques ont été soulevées, notamment liées à la grande variabilité des protocoles et technologies d’acquisition des images, qui entraîne un biais majeur dans les études radiomiques multicentriques. Ces biais ont été évalués grâce à des images de fantômes et des images multicentriques de patients pour l’imagerie TEP, et deux méthodes de correction de l’effet de stratification ont été proposées. En IRM, une méthode de standardisation des images par harmonisation des histogrammes a été évaluée dans les tumeurs cérébrales.Pour aller plus loin dans la caractérisation de l’hétérogénéité intra-tumorale et permettre la mise en œuvre d’une radiothérapie personnalisée, une méthode d’analyse locale de la texture a été développée. Adaptée particulièrement aux images IRM de tumeurs cérébrales, ses capacités à différencier des sous-régions de radionécrose ou de récidive tumorale ont été évaluées. Dans ce but, les cartes paramétriques d’hétérogénéité ont été proposées à des experts comme des séquences IRM additionnelles.À l’issue de ce travail, une validation dans des centres extérieurs des modèles développés, ainsi que la mise en place d’essais cliniques intégrant ces méthodes pour personnaliser les traitements seront des étapes majeures dans l’intégration de l’analyse radiomique en routine clinique. / Beyond the conventional techniques of diagnosis and follow-up of cancer, radiomic analysis allows to personalize radiotherapy treatments, by proposing a non-invasive characterization of tumor heterogeneity. Based on the extraction of advanced quantitative parameters (histograms of intensities, texture, shape) from multimodal imaging, this technique has notably proved its interest in determining predictive signatures of treatment response. During this thesis, signatures of cervical cancer recurrence have been developed, based on radiomic analysis alone or in combination with conventional biomarkers, providing major perspectives in the stratification of patients that can lead to dosimetric treatment plan adaptation.However, various methodological barriers were raised, notably related to the great variability of the protocols and technologies of image acquisition, which leads to major biases in multicentric radiomic studies. These biases were assessed using phantom acquisitions and multicenter patient images for PET imaging, and two methods enabling a correction of the stratification effect were proposed. In MRI, a method of standardization of images by harmonization of histograms has been evaluated in brain tumors.To go further in the characterization of intra-tumor heterogeneity and to allow the implementation of a personalized radiotherapy, a method for local texture analysis has been developed. Specifically adapted to brain MRI, its ability to differentiate sub-regions of radionecrosis or tumor recurrence was evaluated. For this purpose, parametric heterogeneity maps have been proposed to experts as additional MRI sequences.In the future, validation of the predictive models in external centers, as well as the establishment of clinical trials integrating these methods to personalize radiotherapy treatments, will be mandatory steps for the integration of radiomic in the clinical routine.

京都大学 / 新制・課程博士 / 博士(人間健康科学) / 甲第24539号 / 人健博第110号 / 新制||人健||8(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 木下 彩栄, 教授 中尾 恵, 教授 中山 健夫 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

Radiation therapy accounts for treatment of over one million cancer patients each year in the United States alone, and its use will continue to grow rapidly in the coming years. Recently, many important advancements have been developed that greatly improve the outcomes and effectiveness of this treatment technique, the most notable being Intensity Modulated Radiation Therapy (IMRT). IMRT is a sophisticated treatment technique where the radiation dose is conformed to the tumor volume, thereby sparing nearby healthy tissue from excessive radiation dose. While IMRT is a valuable tool in the planning of radiation treatments, it is not without its difficulties. This research has created, developed, and tested an innovative approach to IMRT treatment planning, coined Direct Compensator Profile Optimization (DCPO), which is shown to eliminate many of the difficulties typically associated with IMRT planning and delivery using solid compensator based treatment. The major innovation of this technique is that it is a direct delivery parameter optimization approach which has adopted a parameterized surface representation using Non-Uniform Rational B-Splines (NURBs) to replace the conventional beamlet weight optimization approach. This new approach brings with it three key advantages: 1) a reduced number of parameters to optimize, reducing the difficulty of numerical optimization; 2) the ability to ensure complete equivalence of planned and actual manufactured compensators; and 3) direct inclusion of delivery device effects during planning with no performance penalties, eliminating the degrading fluence-to-delivery parameter conversion process. Detailed research into the affects of the DCPO approach on IMRT planning has been completed and a thorough analysis of the developments is provided herein. This research includes a complete description of the DCPO surface representation scheme, inverse planning process, as well as quantification of the manufacturing constraint control procedure. Results are presented which demonstrate the performance and innovation offered by this new approach and show that the resulting compensator shapes can be manufactured to nearly 100 percent of the designed shape.

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