Intensity-modulated radiation therapy (IMRT) is an advanced mode of high- precision radiation therapy that utilizes computer-controlled x-ray accelerators to deliver precise radiation doses to malignant tumors. The radiation dose is designed to conform to the three-dimensional (3-D) shape of a tumor by modulating the intensity of the radiation beam to focus a higher radiation dose to the tumor while minimizing radiation exposure to surrounding normal tissue. One form of IMRT is known as tomotherapy. Tomotherapy achieves dose conformity to a tumor by modulating the intensity of a fan beam of radiation as the source revolves about a patient. Current available tomotherapy machines use x-ray linear accelerators (linacs) as a source of radiation. However, since linacs are technologically complex, the world- wide use of linac-based tomotherapy is limited. This thesis involves an investigation of Cobalt 60 (Co-60) based tomotherapy. The inherent simplicity of Co-60 has the potential to extend the availability of this technique to clinics throughout the world. The goal of this thesis is to generate two-dimensional (2-D) Co-60 tomotherapy con- formal dose distributions with a computer program and experimentally validate them on ¯lm using a ¯rst generation bench-top tomotherapy apparatus. The bench-top apparatus consists of a rotation-translation stage that can mimic a 2-D tomotherapy delivery by translating the phantom across a thin, "pencil- like" photon beam from various beam orientations. In this thesis, several random and clinical patterns are planned using an in-house inverse treatment planning system and are delivered on ¯lm using the tomotherapy technique. The delivered dose plans are compared with the simulated plans using the gamma dose comparison method. The results show a reasonably good agreement between the plans and the measurements, suggesting that Co-60 tomotherapy is indeed capable of providing state-of-the-art conformal dose delivery. / Thesis (Master, Physics, Engineering Physics and Astronomy) -- Queen's University, 2008-04-25 02:20:56.102 / Canadian Institutes of Health Research (CIHR) and the ORDCF’s Ontario Consortium for Image-guided Therapy and Surgery.

Le rêve ultime du radiothérapeute a toujours été d’avoir à disposition des technologies capables de délivrer avec une parfaite précision des doses élevées aux volumes tumoraux sans irradier les tissus sains avoisinants. Ce rêve ne deviendra jamais réalité, mais tous les efforts des physiciens, médecins et industriels doivent être combinés pour que la réalité s’approche le plus possible de cette utopie. Depuis le début des années 60 et l’avènement des accélérateurs linéaires d’électrons montés sur des unités de traitement, la technologie en thérapie par photons a évolué énormément. Aujourd’hui, les traitements les plus à la pointe incluent la radiothérapie par modulation d’intensité (« Intensity-Modulated Radiation Therapy » ou IMRT) avec l’aide d’outils d’imagerie hautement sophistiqués. L’IMRT est une technique complexe qui requiert un excellent contrôle de la précision dans toutes les étapes du processus du traitement. Ces étapes peuvent être résumées en trois catégories qui sont 1) l’étalonnage et la stabilité de l’unité de traitement, 2) le positionnement et la qualité des données associées au patient et 3) la précision du calcul de dose effectué lors de la planification du traitement. Pour améliorer l’incertitude globale d’un traitement donné, des efforts de recherche sont nécessaires dans les trois catégories. Cette thèse se concentre sur le processus de calcul de dose. Durant les dernières décennies, la complexité et la précision des algorithmes de dose ont augmenté fortement grâce aux énormes progrès de l’informatique. Malgré cela, l’immense majorité des algorithmes utilisent des méthodes analytiques impliquant des approximations importantes au niveau de la physique de transport des particules. Il est cependant possible de concevoir des algorithmes qui évitent ces approximations en se basant sur des méthodes dites de Monte Carlo (MC) qui simulent fidèlement la réalité physique et qui sont considérées aujourd’hui comme les plus précises de calcul de la dose dans les tissus humains. Malheureusement, jusqu’à récemment, la vitesse des simulations MC était trop lente pour être compatible avec les contraintes de temps liées à la routine clinique. Mais les progrès continus en puissance de calcul combinés avec l’introduction de simplifications pertinentes dans les codes MC permettent d’envisager l’introduction d’algorithmes MC en routine clinique, ce qui est déjà le cas pour plusieurs systèmes de planification de traitement commerciaux. L’objectif de cette thèse était d’évaluer la valeur ajoutée du MC comparé à des algorithmes analytiques modernes pour des traitements IMRT complexes de tumeurs entourées de nombreuses inhomogénéités de densité. Ces évaluations ont été effectuées pour deux techniques de traitement IMRT : « step-and-shoot » et tomothérapie hélicoïdale. Pour l’IMRT « step-and-shoot » délivrée par une unité de traitement Elekta SL25, des simulations MC avec BEAMnrc ont été comparées avec un algorithme commercialisé récemment par la firme Varian appelé « Anisotropic Analytical Algorithm » (AAA). Pour la tomothérapie, une étude similaire a été accomplie mais pour le code utilisé dans le système fourni par « Tomotherapy Incorporated » et basé sur un algorithme de type convolution/superposition utilisant l’approximation « collapsed-cone ». Durant cette seconde étude, la modélisation MC au moyen du code MC PENELOPE était un aspect très important étant donné que c’est la première fois qu’un code MC complet pour la tomothérapie était construit avec tous les détails techniques de la machine fournis par le constructeur. De plus, le modèle MC, appelé TomoPen, a été conçu en vue d’une introduction future dans le système clinique. La vitesse de la simulation était donc une contrainte importante. La stratégie utilisée pour la simulation et adoptée dans TomoPen consiste principalement à simplifier drastiquement le transport des photons dans le collimateur multilames et permet de calculer des distributions de dose dans une tumeur bilatérale de la sphère tête et cou en à peu près 10 heures sur un processeur de 2 GHz, sans perte de précision significative. En utilisant le groupe d’ordinateurs fourni avec chaque unité de traitement de tomothérapie, ce temps de simulation peut être réduit d’un facteur 32, correspondant au nombre de processeurs. Durant cette thèse, la correspondance entre algorithmes analytiques et MC était en général satisfaisante pour la majorité des cas cliniques et expérimentaux étudiés. Cependant, des différences ont pu être observées pour des situations critiques, comme des petites tumeurs pulmonaires ou des tumeurs ethmoïdes. Même si ces déviations n’étaient pas « dramatiques », elles ont pu démontrer clairement le potentiel des algorithmes MC dans la pratique clinique afin d’améliorer la qualité globale et la précision des traitements.

BACKGROUND:To evaluate the feasibility of image-guided radiotherapy based on helical Tomotherapy to spare the contralateral parotid gland in head and neck cancer patients with unilateral or no neck node metastases.METHODS:A retrospective review of 52 patients undergoing radiotherapy for head and neck cancers with image guidance based on daily megavoltage CT imaging with helical tomotherapy was performed.RESULTS:Mean contralateral parotid dose and the volume of the contralateral parotid receiving 40Gy or more were compared between radiotherapy plans with significant constraint (SC) of less than 20Gy on parotid dose (23 patients) and the conventional constraint (CC) of 26Gy (29 patients). All patients had PTV coverage of at least 95% to the contralateral elective neck nodes. Mean contralateral parotid dose was, respectively, 14.1Gy and 24.7Gy for the SC and CC plans (p<0.0001). The volume of contralateral parotid receiving 40Gy or more was respectively 5.3% and 18.2% (p<0.0001)CONCLUSION:Tomotherapy for head and neck cancer minimized radiotherapy dose to the contralateral parotid gland in patients undergoing elective node irradiation without sacrificing target coverage.

BACKGROUND:In this study the feasibility of intensity-modulated radiotherapy (IMRT) and tomotherapy-based image-guided radiotherapy (IGRT) for locally advanced esophageal cancer was assessed.METHODS:A retrospective study of ten patients with locally advanced esophageal cancer who underwent concurrent chemotherapy with IMRT (1) and IGRT (9) was conducted. The gross tumor volume was treated to a median dose of 70Gy (62.4-75Gy).RESULTS:At a median follow-up of 14months (1-39 months), three patients developed local failures, six patients developed distant metastases, and complications occurred in two patients (1 tracheoesophageal fistula, 1 esophageal stricture requiring repeated dilatations). No patients developed grade 3-4 pneumonitis or cardiac complications.CONCLUSIONS:IMRT and IGRT may be effective for the treatment of locally advanced esophageal cancer with acceptable complications.

En radiothérapie, le niveau de précision de la dose délivrée au patient au cours de son traitement est d’une importance essentielle dans l’évolution vers une amélioration de la qualité et de la cohérence des données de suivi. L’une des premières étapes vers un système de support à la décision clinique (Clinical-Decision Support System CDSS) est la reconstruction précise de cette dose délivrée, en prenant en compte les nombreux facteurs pouvant générer des déviations significatives entre la dose planifiée visualisée à l’écran par l’utilisateur et la dose réellement accumulée lors des séances de traitement. Ces facteurs incluent les variations de débit de l’accélérateur, les incertitudes d’étalonnage, de calcul de dose, les mouvements du patient et des organes, etc.L’objectif de cette étude est d’implémenter et tester une plate-forme de calcul Monte Carlo pour la validation des systèmes Cyberknife et Tomothérapie installés au Centre Oscar Lambret. L’étude d’un détecteur dédié aux petits faisceaux (la chambre d’ionisation microLion) est également incluse, ce détecteur étant particulièrement adapté aux mesures sur le système Cyberknife.Le contexte et les concepts théoriques sont introduits dans les deux premiers chapitres. Dans le troisième chapitre, la modélisation Monte Carlo du Cyberknife et du détecteur microLion est détaillée. La quatrième partie inclut la description de la plate-forme Moderato et de son module d’évaluation. Dans le dernier chapitre, la modélisation du dernier modèle de Cyberknife (M6) équipé d’un collimateur multi-lames est décrite. Une nouvelle technique est également introduite dans le but d’accélérer la recherche des paramètres du faisceau d’électrons pour un modèle Monte Carlo, permettant une intégration plus simple et automatisée de nouveaux appareils dans Moderato. / In radiation therapy, the accuracy of the dose delivered to the patient during the course of treatment is of great importance to progress towards improved quality and coherence of the outcome data. One of the first steps to evolve towards a Clinical-Decision Support System (CDSS) is to be able to accurately reconstruct that delivered dose, taking into account the range of factors that can potentially generate significant differences between the planned dose visualized on the screen of the dosimetrist, and the actually delivered dose accumulated during the treatment sessions. These factors include accelerator output variations, commissioning uncertainties, dose computation errors, patient and organ movement, etc.The objective of this work is to implement and test a Monte Carlo platform for the validation of the Cyberknife and Tomotherapy systems installed at Centre Oscar Lambret. A study of a small field-dedicated detector (the microLion ionization chamber) is also included, this detector being particularly suited for measurements on the Cyberknife system.The context and theoretical concepts are introduced in the first two chapters. In the third chapter, the Monte Carlo modelling of the Cyberknife and microLion detector is detailed. The fourth part includes the description of the Monte Carlo platform Moderato and its evaluation module. In the final chapter, the modelling of the latest MLC-equipped Cyberknife model (the M6) is described. A new technique is also introduced to accelerate the optimization of the beam electron parameters of a Monte Carlo model, thus allowing for an easier and more automated use of the Moderato system. / Doctorat en Sciences biomédicales et pharmaceutiques (Médecine) / info:eu-repo/semantics/nonPublished

Cobalt-60 (Co-60) units played an integral role in radiation therapy from the mid-1950s to the 1970s. Although they continue to be used to treat cancer in some parts of the world, their role has been significantly reduced due to the invention of medical linear accelerators. A number of groups have indicated a strong potential for Co-60 units in modern radiation therapy. The Medical Physics group at the Cancer Center of the Southeastern Ontario and Queen’s University has shown the feasibility of Intensity Modulated Radiation Therapy (IMRT) via simple conformal treatment planning and dose delivery using a Co-60 unit. In this thesis, initial Co-60 tomotherapy planning investigations on simple uniform phantoms are extended to actual clinical cases based on patient CT data. The planning is based on radiation dose data from a clinical Co-60 unit fitted with a multileaf collimator (MLC) and modeled in the EGSnrc Monte Carlo system. An in house treatment planning program is used to calculate IMRT dose distributions. Conformal delivery in a single slice on a uniform phantom based on sequentially delivered pencil beams is verified by Gafchromic film. Volumetric dose distributions for Co-60 serial tomotherapy are then generated for typical clinical sites that had been treated at our clinic by conventional 6MV IMRT using Varian Eclipse treatment plans. The Co-60 treatment plans are compared with the clinical IMRT plans using conventional matrices such as dose volume histograms (DVH). Dose delivery based on simultaneously opened MLC leaves is also explored and a novel MLC segmentation method is proposed. In order to increase efficiency of dose calculations, a novel convolution based fluence model for treatment planning is also proposed. The ion chamber measurements showed that the Monte Carlo modeling of the beam data under the MIMiC MLC is accurate. The film measurements from the uniform phantom irradiations confirm that IMRT plans from our in-house treatment planning system are deliverable. Comparing the Co-60 dose distributions and DVHs to the IMRT plans from the clinic indicates that Co-60 is able to provide similar dose conformality to targets and dose sparing to critical organs. The results of the novel MLC segmentation algorithm and the photon fluence model proposed in this work compared well with the Monte Carlo calculations. In summary, the investigations presented in this thesis confirm that Co-60 tomotherapy is indeed capable of providing state-of-the-art conformal dose delivery. We have shown that the perceived beam limitations often identified with Co 60 (e.g., lower penetration, source size artifacts under small field collimation, and larger penumbra) are negligible when using intensity modulated techniques. / Thesis (Ph.D, Physics, Engineering Physics and Astronomy) -- Queen's University, 2013-08-22 11:34:14.861

Cobalt-60 (Co-60) units played an integral role in radiation therapy from the mid-1950s to the 1970s. Although they continue to be used to treat cancer in some parts of the world, their role has been significantly reduced due to the invention of medical linear accelerators. A number of groups have indicated a strong potential for Co-60 units in modern radiation therapy. The Medical Physics group at the Cancer Center of the Southeastern Ontario and Queen’s University has shown the feasibility of Intensity Modulated Radiation Therapy (IMRT) via simple conformal treatment planning and dose delivery using a Co-60 unit. In this thesis, initial Co-60 tomotherapy planning investigations on simple uniform phantoms are extended to actual clinical cases based on patient CT data. The planning is based on radiation dose data from a clinical Co-60 unit fitted with a multileaf collimator (MLC) and modeled in the EGSnrc Monte Carlo system. An in house treatment planning program is used to calculate IMRT dose distributions. Conformal delivery in a single slice on a uniform phantom based on sequentially delivered pencil beams is verified by Gafchromic film. Volumetric dose distributions for Co-60 serial tomotherapy are then generated for typical clinical sites that had been treated at our clinic by conventional 6MV IMRT using Varian Eclipse treatment plans. The Co-60 treatment plans are compared with the clinical IMRT plans using conventional matrices such as dose volume histograms (DVH). Dose delivery based on simultaneously opened MLC leaves is also explored and a novel MLC segmentation method is proposed. In order to increase efficiency of dose calculations, a novel convolution based fluence model for treatment planning is also proposed. The ion chamber measurements showed that the Monte Carlo modeling of the beam data under the MIMiC MLC is accurate. The film measurements from the uniform phantom irradiations confirm that IMRT plans from our in-house treatment planning system are deliverable. Comparing the Co-60 dose distributions and DVHs to the IMRT plans from the clinic indicates that Co-60 is able to provide similar dose conformality to targets and dose sparing to critical organs. The results of the novel MLC segmentation algorithm and the photon fluence model proposed in this work compared well with the Monte Carlo calculations. In summary, the investigations presented in this thesis confirm that Co-60 tomotherapy is indeed capable of providing state-of-the-art conformal dose delivery. We have shown that the perceived beam limitations often identified with Co 60 (e.g., lower penetration, source size artifacts under small field collimation, and larger penumbra) are negligible when using intensity modulated techniques. / Thesis (Ph.D, Physics, Engineering Physics and Astronomy) -- Queen's University, 2013-08-22 11:34:14.861

Accurate tumor tracking remains as a major challenge in radiation therapy. Large margins are added to the clinical target volume (CTV) to ensure the treatment of tumor in presence of patient setup uncertainty and that caused by intra-motion. Fiducial seeds and calypso markers are commonly implanted into the disease sites to further reduce the dose delivery error due to tumor motion. For more accurate dose delivery and improved patient comfort, the use of radioactive tracers in positron emission tomography (PET) as non-invasive tumor markers has been proposed - a concept called emission-guided radiation therapy (EGRT). Instead of using images obtained from a stand-alone PET scanner for treatment guidance, we mount a positron imaging system on a radiation therapy machine. Such an EGRT system is able to track the tumor in real time based on the lines of response (LOR) of the tumor positron events, and perform radiation therapy simultaneously. In this work, we illustrate the EGRT concept using computer simulations and propose a typical treatment scheme. EGRT's advantage on increased dose delivery accuracy is demonstrated using a pancreas tumor case and a lung tumor case without the setup margin and motion margin. The emission process is simulated by Geant4 Application for Tomographic Emission package and Linac dose delivery is simulated using a voxel-based Monte Carlo algorithm. The tumor tracking error can be controlled within 2 mm which indicates margins can be significantly reduced. The dose distributions show that the proposed EGRT can accurately deliver the prescribed dose to the CTV with much less margins. Although still in a preliminary research stage, EGRT has the potential to substantially reduce tumor location uncertainties and to greatly increase the performance of current radiation therapy.

The topic of this thesis is the analysis of export opportunities for the tomotherapy irradiator TOMOS. The first part of the thesis addresses new emerging methods of radiation therapy focusing on the research and development of tomotherapy irradiator in particular and the availability of radiation therapy in the world in general. The second part of the thesis provides financial analysis of the tomotherapy research and development project which is executed to evaluate the effectiveness of the project as an investment. Finally, the thesis concludes with the proposition of the most convenient export strategy indicating the perspective territories for trading the tomotherapy irradiator together with the most influential factors for each territory considered.

L’objectif principal de notre travail était d’évaluer deux nouvelles technologies, l’arcthérapie par la technique Rapid’Arc de chez Varian Medical System® et l’irradiation hélicoïdale avec Tomotherapy Hi-Art de chez Accuray® dans les tumeurs des Voies Aéro-Digestives Supérieures. Dans un premier temps, nous avons montré que ces 2 techniques étaient équivalentes du point de vue de la délivrance de la dose à partir de cas théoriques (30 cas) mais également in vivo à partir d’une population de patients analysée de façon prospective dans le cadre de l’étude nationale ARTORL (115 cas). Puis, nous avons cherché à augmenter le ratio thérapeutique en combinant l’une de ces 2 techniques avec des nouvelles techniques d’irradiation en conditions stéréotaxiques (Cyberknife d’Accuray® et Vero de Brainlab®). Nous avons étudié ensuite la toxicité radio-induite la plus fréquente dans notre population, à savoir la xérostomie. Aucun facteur prédictif de toxicités n’a pu être mis en évidence. Toutefois, nous avons pu créer un modèle prédictif de la fonction de récupération de la glande sous maxillaire, celles-ci étant souvent moins bien protégées. L’ensemble de ces résultats confirme les capacités « conformationnelles » de ces 2 nouvelles techniques innovantes et de leurs équivalences d’un point de vue dosimétrique et surtout clinique. Par ailleurs, cette équivalence dosimétrique de ces deux machines a également été retrouvée dans l’irradiation de tumeur pelvienne, dans le cadre de l’étude prospective ARTPELVIS. Le suivi ultérieur de ces populations permettra de confirmer l’équivalence clinique de ces 2 techniques d’un point de vue carcinologique. / The main objectif of our work was to assess two new technologies, arctherapy by Rapid'Arc technology from Varian Medical System® and helical irradiation with Tomotherapy Hi-Art, Accuray® in Head and Neck cancer. First, we showed that these 2 techniques were equivalent in terms of dose delivery from theoretical cases (30 cases), but also in vivo from a population of patients analyzed prospectively included in the national study ARTORL (115 cases). Then, we tried to increase the therapeutic ratio by combining one of these 2 techniques with new techniques for stereotactic irradiation (Cyberknife of Accuray® and Vero Brainlab®). We then studied the most common toxicity in our population, ie xerostomia. No predictif factor could be highlighted. However, we were able to create a predictive model of the recovery function of the sub-mandibular gland, they tend to be less well protected. All these results confirm the "conformational" capacity of these two new innovative techniques, their equivalences dosimetric and especially clinically. These results were confirmed in an another location in the prospective study ARTPELVIS. Subsequent monitoring of these populations will confirm the clinical equivalence of these new technologies.