Volumetric modulated arc therapy delivers highly conformal radiotherapy treatments to cancer patients in a continuous arc whilst dynamically varying the multi-leaf collimator (MLC) position, dose rate and rotational angular velocity. The present master’s thesis seeks to develop a better understanding of delivering treatment in this manner, ranging from progressive resolution inverse optimisation, class solutions, clinical application and the ability of dose calculation algorithms to model such a complex modality. A progressive resolution based class solution for inverse planning has been developed, outlining contouring, field set-up and optimisation. This class solution was then applied to 10 prostate patients and subjected to an inter-comparative planning study with static gantry intensity-modulated radiotherapy. The results of this justification study showed the presented class solution produces plans that are generally and directly comparable with previously published data. Following this result, the class solution was applied to a previously uninvestigated clinical site (treatment of prostate bed following radical prostatectomy) in an effort to solve persistent clinical problems involving target volumes and dose escalation. The results of this secondary study provisionally showed the feasibility of treating prostate beds with rotational intensity-modulated techniques whilst maintaining the integrity of the target volumes and escalating the delivered dose. The potential for improving the accuracy of the dose calculation analytic anisotropic algorithm for volumetric modulated plans was also investigated, through configuration of two independent algorithms containing beam data taken with either the linac jaws or MLCs defining the field. The two algorithms were inter-compared in virtual water phantoms and against physical verification measurements. The configuration process has shown to be sensitive to depth dose data but not beam profiles. Furthermore, the two algorithms show no significant difference and therefore it is recommended that beam be taken with the jaws defining the field.

External-beam radiotherapy is one of the primary methods for treating cancer. Typically a radiotherapy treatment course consists of radiation delivered to the patient in multiple daily treatment fractions over 6-8 weeks. Each fraction requires the patient to be aligned with the image acquired before the treatment course used in treatment planning. Unfortunately, patient alignment is not perfect and results in residual errors in patient setup. The standard technique for dealing with errors in patient setup is to expand the volume of the target by some margin to ensure the target receives the planned dose in the presence of setup errors. This work develops an alternative to margins for accommodating setup errors in the treatment planning process by directly including patient setup uncertainty in IMRT plan optimization. This probabilistic treatment planning (PTP) operates directly on the planning structure and develops a dose distribution robust to variations in the patient position. Two methods are presented. The first method includes only random setup uncertainty in the planning process by convolving the fluence of each beam with a Gaussian model of the distribution of random setup errors. The second method builds upon this by adding systematic uncertainty to optimization by way of a joint optimization over multiple probable patient positions. To assess the benefit of PTP methods, a PTP plan and a margin-based plan are developed for each of the 28 patients used in this study. Comparisons of plans show that PTP plans generally reduce the dose to normal tissues while maintaining a similar dose to the target structure when compared to margin-based plans. Physician assessment indicates that PTP plans are generally preferred over margin-based plans. PTP methods shows potential for improving patient outcome due to reduced complications associated with treatment.

Le cancer de la prostate est le deuxième plus fréquent cancer chez les hommes. La France occupe le troisième rang du taux d’incidence. La curiethérapie bas-débit dose (LDR) est une option de traitement largement utilisée. Au cours de la curiethérapie LDR, des graines radioactives sont implantées en permanence dans la prostate afin de délivrer une dose thérapeutique de façon locale dans la zone cancéreuse tout en épargnant les organes voisins à risque (OAR). Malgré son taux de réussite élevé (75% à 91%), les effets secondaires restent élevés. La dose délivrée à la tumeur dépend des positions d’implantation des graines, ce qui implique que la planification est essentielle. Les systèmes cliniques de planification fournissent automatiquement les positions d’implantation. Cependant, cette prédiction est basée sur un modèle dosimétrique simplifié où le corps humain est considéré comme un volume d’eau. Un autre facteur des erreurs est l’apparition d’un oedème de la prostate impliquant un changement volumétrique. L’oedème peut entraîner une sous-estimation du D90 par exemple il est de 13.6% pour un changement volumétrique de 20%. De plus, l’oedème varie (10% à 96%) entre les patients. Aujourd’hui le mécanisme exact de l’apparition de cet oedème reste inconnu. Nous proposons un système de traitement inverse pour la curiethérapie prostate qui tient compte d’une personnalisation précise de la dosimétrie et de l’oedème. Ces travaux peuvent également être utilisés dans d’autres contextes cliniques, tel que la curiethérapie haut-débit, mais également être adapté pour traiter d’autres organes. Dans le futur, nos travaux porteront sur la personnalisation du modèle biomécanique de la prostate proposé à chaque patient en utilisant des mesures d’élasticité via l’élastographie. En raison des limitations inhérentes à la FEM, l’incorporation du modèle biomécanique de l’oedème dans le système de planification du traitement est coûteuse en temps de calcul. Une méthode alternative, serait de proposer un modèle sans maillage afin d’améliorer la simulation de l’oedème. / Prostate cancer is the second most common cancer in men. Two-thirds of the cases are diagnosed in developed countries and France is ranked third in incidence rate. Low-dose-rate (LDR) brachytherapy is a widely used treatment option. During LDR brachytherapy, radioactive seeds are implanted permanently in the prostate to deliver a therapeutic dose locally in the cancerous region while sparing the organs at risk (OARs). Despite its high success rate (75% to 91%), the side-effects (sexual and urinary problems) remain high. The dose delivered to the tumor depends on the implantation positions of the seeds, which implies that treatment planning is essential. Clinical inverse planning systems automatically provide optimal implantation positions. However, this prediction is based on a simplified dosimetric model where the human body is considered an infinite volume of water. Another important factor that induces treatment errors is the occurrence of prostate edema during brachytherapy that involves volumetric changes of the organ. Edema can lead to a significant underestimation of the D90, for example, by 13.6% for a volumetric change of 20%. Moreover, the edema magnitude varies considerably (10% to 96%) between patients. Today the exact mechanism of edema formation remains unknown. We propose in this thesis a system of inverse treatment for prostate brachytherapy which considers a precise personalization of the dosimetry but also of the prostate edema. This work can also be used in other clinical contexts, such as high-dose-rate brachytherapy, but also be adapted to treat other organs. In the future, our work will focus on the study of the ability to adapt the proposed prostate biomechanical model to each patient using elastic measurements via prostate elastography. Due to the inherent limitations of FEM, the incorporation of the biomechanical model of edema into the treatment planning system is costly in computation time. An alternative method would be to propose a new meshless model to improve the simulation of edema during intraoperative planning.

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.

L'hadronthérapie est une modalité d'irradiation récente particulièrement attractive. Les ions, par leur profil caractéristique de dépôt de dose dans la matière et leur efficacité biologique accrue, sont des particules parfaitement adaptées pour le traitement du cancer. C’est une modalité émergente et les travaux de recherche et de développement qui en font l'objet se poursuivent de manière soutenue. Cependant, il n'existe à ce jour aucun outil permettant de quantifier pour le patient le gain clinique associé aux améliorations proposées, comme l’apport d’une gantry par exemple. Nous proposons dans ce travail de concevoir un module de planification inverse du traitement pour un but prospectif. Détachée des contraintes usuelles de précision et de temps de calcul, notre méthode d'optimisation se base sur un algorithme génétique afin d'approcher d'une solution globale vis-à-vis d'un grand nombre de paramètres balistiques (champs d’irradiation libres) et en associant les diverses régions d'intérêt dosimétrique. La stratégie d'optimisation retenue est progressivement complexifiée afin de prendre en compte de manière efficace les différents enjeux de la planification. La robustesse du plan vis-à-vis des incertitudes inhérentes au traitement, primordiale en hadronthérapie, est évaluée. Dans toutes les situations testées, il apparaît que l'inclusion dans l'optimisation de paramètres habituellement fixés manuellement permet une amélioration de la qualité de traitement. Nous proposons au terme de cette étude un outil prospectif d'optimisation au réglage simple et capable de mener des études comparées sur la pertinence de nouvelles modalités d’irradiation. / Hadrontherapy is a recent and particularly attractive modality. Characterized by a specific dose deposition profile in matter and by a high biological effectiveness, ions are found to be very well-suited for cancer treatment. As an emergent modality, the research in hadrontherapy is extremely active and promises many improvements for the future. However, there is no tool to date to quantify the clinical benefit for the patient related to the proposed improvements, the use of a gantry for example. In this work, we propose to use the treatment planning system, usually dedicated to clinical practice, in a prospective purpose. Suppressing the classical constraints of precision and time, our optimization method is based on a genetic algorithm designed to approach a global solution including a high number of balistic parameters (free irradiation fields) for all regions of dosimetric interest. The optimization strategy is progressively complicated in order to efficientely take into account the main issues of the inverse planning problem. The robustness of plans towards the uncertainties related to the application of the treatment, essential in hadrontherapy, is evaluated. The results show that the inclusion, in the optimization, of parameters usually fixed by the human planner leads systematically to an improved treatment quality. The final product of this work is a prospective optimization tool characterized by an easy set-up system and the ability to perform comparative studies on the relevance of new irradiation modalities.

The Leksell Gamma Knife® is an instrument designed for high precision treatment of tumours and lesions located in the brain and upper spine. Today, the radioactive cobalt-60 sources can only move linearly along the radiation unit, but the machine could be modified to include rotational motion as well. We extend an existing linear programming approach to inverse planning for the Gamma Knife by examining the benefits from rotational degrees of freedom. The improvements offered from rotations are limited, but easy to make use of. We investigate the model in four patient cases, and find that an upper bound on the improvement of the optimization cost function is between 4.5% and 7.0% depending on case. With a total of four angles distributed uniformly over a 45 degree interval, one can in each case achieve a solution that performs up to within 1% of this bound. The average maximal improvements in terms of clinical metrics are 0.5% selectivity and 1.9% gradient index, at the cost of 5.9% worse beam-on time. No statistically significant change in coverage is found. A dynamic model based on column generation is proposed, which allows treatment during constant velocity angular motion and can achieve practically the same plan quality as the model with uniformly distributed angles at a significantly lower problem size. A similar algorithm can be designed to locate the most effective angles in a non-uniform manner that achieves better plans with fewer added rotational degrees of freedom. Trade-offs between memory and solution times are used to successively reduce the RAM occupation by around 90% and make significantly larger models computationally feasible to solve. A voxel clustering approach with emphasis on surface voxels, adapted to the radiosurgical framework, can significantly reduce the problem size while still producing competitive plans. / Strålkniven Leksell Gamma Knife® är ett instrument designat för högprecisionsbestrålning av tumörer och lesioner i hjärnan och övre delen av ryggraden. Idag kan de radioaktiva källorna endast förflyttas linjärt under behandlingen, men maskinen skulle kunna modifieras för att även tillåta rotationsrörelser. Vi utvidgar ett ramverk för inversplanering, formulerat som ett linjär-programmeringsproblem, genom att undersöka fördelarna med nya rotationsfrihetsgrader. Förbättringarna som rotationer möjliggör är begränsade, men kan relativt enkelt tas till vara. Vi undersöker de potentiella förändringarna i fyra patientfall och finner att den övre gränsen av förbättringarna för målfunktionsvärdet i optimeringsproblemet är mellan 4.5% och 7.0% beroende på fall. Genom att tillåta rotation av källorna till fyra jämnt fördelade vinklar över 45 grader kan man i samtliga fall hitta en lösning som är inom 1% från det bästa målfunktionsvärdet. De genomsnittliga förbättringarna i form av kliniska metriker är 0.5% selektivitet och 1.9% gradient-index, dock på bekostnad av en försämring av bestrålningstiden med 5.9%. Ingen tydlig förändring av täckningen kunde påvisas. En modell baserad på kolumngenerering, som tillåter behandling under rotation av kollimator-kroppen med konstant hastighet, föreslås. I denna modell kan praktiskt taget lika bra lösningar uppnås som för likformigt fördelade vinklar, men med betydligt mindre problemstorlek. En liknande algoritm kan lokalisera de mest effektiva vinklarna och åstadkomma samma plankvalitet med färre, men olikformt fördelade, rotationsfrihetsgrader. RAM-användningen kan reduceras med cirka 90% genom avvägningar mellan minne och beräknings-tider, vilket möjliggör lösning av probleminstanser som tidigare var beräkningsmässigt omöjliga. Klustringsmetoder av voxlar anpassade till strålkniven kan minska problemstorleken betydelsefullt medan de resulterande behandlingsplanerna är fortsatt konkurrenskraftiga.