Dissertations / Theses on the topic 'High dose rate brachytherapy'

Cancer is a widespread type of diseases that each year affects millions of people. It is mainly treated by chemotherapy, surgery or radiation therapy, or a combination of them. One modality of radiation therapy is high dose-rate brachytherapy, used in treatment of for example prostate cancer and gynecologic cancer. Brachytherapy is an invasive treatment in which catheters (hollow needles) or applicators are used to place the highly active radiation source close to or within a tumour. The treatment planning problem, which can be modelled as a mathematical optimization problem, is the topic of this thesis. The treatment planning includes decisions on how many catheters to use and where to place them as well as the dwell times for the radiation source. There are multiple aims with the treatment and these are primarily to give the tumour a radiation dose that is sufficiently high and to give the surrounding healthy tissue and organs (organs at risk) a dose that is sufficiently low. Because these aims are in conflict, modelling the treatment planning gives optimization problems which essentially are multiobjective. To evaluate treatment plans, a concept called dosimetric indices is commonly used and they constitute an essential part of the clinical treatment guidelines. For the tumour, the portion of the volume that receives at least a specified dose is of interest while for an organ at risk it is rather the portion of the volume that receives at most a specified dose. The dosimetric indices are derived from the dose-volume histogram, which for each dose level shows the corresponding dosimetric index. Dose-volume histograms are commonly used to visualise the three-dimensional dose distribution. The research focus of this thesis is mathematical modelling of the treatment planning and properties of optimization models explicitly including dosimetric indices, which the clinical treatment guidelines are based on. Modelling dosimetric indices explicitly yields mixedinteger programs which are computationally demanding to solve. The computing time of the treatment planning is of clinical relevance as the planning is typically conducted while the patient is under anaesthesia. Research topics in this thesis include both studying properties of models, extending and improving models, and developing new optimization models to be able to take more aspects into account in the treatment planning. There are several advantages of using mathematical optimization for treatment planning in comparison to manual planning. First, the treatment planning phase can be shortened compared to the time consuming manual planning. Secondly, also the quality of treatment plans can be improved by using optimization models and algorithms, for example by considering more of the clinically relevant aspects. Finally, with the use of optimization algorithms the requirements of experience and skill level for the planners are lower. This thesis summary contains a literature review over optimization models for treatment planning, including the catheter placement problem. How optimization models consider the multiobjective nature of the treatment planning problem is also discussed.

Für die Therapie maligner intranasaler Neoplasien beim Hund existieren nur mäßig be-friedigende Behandlungsstrategien. Als Therapiemodalität der Wahl wird die Radiothe-rapie angesehen, die gegenwärtig v.a. in Form einer perkutanen Bestrahlung (Telethe-rapie) mit aufwendigen, bis zu 20 Fraktionen umfassenden Protokollen kurativer Intenti-on angewendet wird. Die erreichbaren Überlebenszeiten sind meist limitiert durch das Auftreten eines Rezidivs des Nasentumors innerhalb des Bestrahlungsfeldes, sodass eine Erhöhung der applizierten Gesamtdosis nötig erscheint. Dies ist jedoch im Rahmen einer Teletherapie aufgrund nicht vertretbarer akuter Nebenwirkungen nicht möglich. Alternativ steht die Brachytherapie zur Verfügung, die aufgrund ihrer physikalischen Charakteristika zur besseren Schonung des umliegenden Normalgewebes beiträgt. Ge-genwärtig existieren keine anderen Untersuchungen zur Anwendung der fraktionierten High-Dose-Rate-Brachytherapie bei Nasentumoren des Hundes. Ziel dieser Studie war es daher, die Durchführbarkeit dieser Therapiemodalität beim Hund erstmals zu unter-suchen und die akuten und chronischen Nebenwirkungen sowie die erzielbare progres-sionsfreie Zeit und die Überlebenszeit zu dokumentieren. Im Zeitraum von 2001 bis 2007 gingen 18 Hunde in die Studie ein. Das diagnostische Vorgehen beinhaltete neben einer klinischen Untersuchung und der Röntgenuntersu-chung von Nase und Thorax auch die kernspintomographische Beurteilung der Nasen-höhlen und eine nachfolgende Rhinoskopie inklusive Biopsie. Die Therapie bestand aus zwei wöchentlichen Fraktionen, bei denen in Vollnarkose über einen in der Nasenhöhle applizierten Katheter mithilfe des Radioisotops 192Iridium jeweils 5 Gy appliziert wurden. Die damit über vier Wochen erreichte Gesamtdosis lag bei 40 Gy, und entsprach damit der biologischen Effizienz einer perkutan applizierten konventionell fraktionierten Ge-samtdosis von circa 60 Gy. Im Anschluss an die Therapie wurden die Hunde monatlich klinisch untersucht und die auftretenden Nebenwirkungen anhand des Radiation Morbi-dity Scores der VRTOG beschrieben. Es wurden außerdem weiterführende Untersu-chungen in Form von MRT, Rhinoskopie und Biopsie durchgeführt. Die aufgetretenen Nebenwirkungen waren mit denen in der Literatur nach Teletherapie beschriebenen vergleichbar, beziehungsweise fielen im Bereich von Augen und Maulschleimhaut ge-ringer aus. Nebenwirkungen im Bereich der Haut traten in Form von Alopezie, Hyper-pigmentation oder Leukotrichie auf. Im Bereich der Nasenschleimhaut zeigten fast alle Hunde eine leichte chronische Rhinitis. Als problematische Nebenwirkungen traten bei drei Patienten Osteoradionekrosen auf, die einer aufwendigeren chirurgischen Versor-gung bedurften. Die mediane progressionsfreie Zeit lag bei 13 Monaten, die mediane Überlebenszeit bei 17 Monaten. Die Adenokarzinome wiesen die längste Überlebens-zeit auf, dies war jedoch aufgrund der insgesamt kleinen Patientenzahl nicht signifikant. Ein Zusammenhang zwischen dem Tumorstadium und der progessionsfreien Zeit oder Überlebenszeit bestand nicht. Bei dem beschriebenen Protokoll handelt es sich um eine unter klinischen Bedingungen praktikable Therapieform, die mit ihren insgesamt acht Fraktionen für Besitzer und Tier wesentlich weniger belastend ist als teletherapeutische kurative Protokolle mit 12-20 Fraktionen. Gleichzeitig gelingt es, eine Gesamtdosis von verhältnismäßig hoher biolo-gischer Effizienz zu applizieren, ohne jedoch stärkere Nebenwirkungen in Kauf nehmen zu müssen. Im Bereich von Auge und Maulschleimhaut sind die Nebenwirkungen sogar geringer. Bei einem kleinen Teil der Patienten treten jedoch auch hier, ebenso wie nach teletherapeutischen Protokollen, problematische chronische Nebenwirkungen auf, die die Lebensqualität der betroffenen Tiere beeinträchtigen und die einer aufwendigeren Therapie zwingend bedürfen. Die mit diesem Protokoll erreichten Remissions- und Ü-berlebenszeiten sind mit denen aus der Literatur vergleichbar bis tendenziell besser. Aufgrund der oben genannten Vorteile erscheint die vorgestellte Therapie daher als Al-ternative zu Teletherapie bei der Behandlung kaniner Nasentumoren durchaus geeig-net. Weitere Studien mit größeren Patientenzahlen unter Einbeziehung einer anders therapierten Kontrollgruppe sind jedoch notwendig

L’objectif général de cette thèse est d’utiliser les connaissances en physique de la radiation, en programmation informatique et en équipement informatique à la haute pointe de la technologie pour améliorer les traitements du cancer. En particulier, l’élaboration d’un plan de traitement en radiothérapie peut être complexe et dépendant de l’utilisateur. Cette thèse a pour objectif de simplifier la planification de traitement actuelle en curiethérapie de la prostate à haut débit de dose (HDR). Ce projet a débuté à partir d’un algorithme de planification inverse largement utilisé, la planification de traitement inverse par recuit simulé (IPSA). Pour aboutir à un algorithme de planification inverse ultra-rapide et automatisé, trois algorithmes d’optimisation multicritères (MCO) ont été mis en oeuvre. Suite à la génération d’une banque de plans de traitement ayant divers compromis avec les algorithmes MCO, un plan de qualité a été automatiquement sélectionné. Dans la première étude, un algorithme MCO a été introduit pour explorer les frontières de Pareto en curiethérapie HDR. L’algorithme s’inspire de la fonctionnalité MCO intégrée au système Raystation (RaySearch Laboratories, Stockholm, Suède). Pour chaque cas, 300 plans de traitement ont été générés en série pour obtenir une approximation uniforme de la frontière de Pareto. Chaque plan optimal de Pareto a été calculé avec IPSA et chaque nouveau plan a été ajouté à la portion de la frontière de Pareto où la distance entre sa limite supérieure et sa limite inférieure était la plus grande. Dans une étude complémentaire, ou dans la seconde étude, un algorithme MCO basé sur la connaissance (kMCO) a été mis en oeuvre pour réduire le temps de calcul de l’algorithme MCO. Pour ce faire, deux stratégies ont été mises en oeuvre : une prédiction de l’espace des solutions cliniquement acceptables à partir de modèles de régression et d’un calcul parallèle des plans de traitement avec deux processeurs à six coeurs. En conséquence, une banque de plans de traitement de petite taille (14) a été générée et un plan a été sélectionné en tant que plan kMCO. L’efficacité de la planification et de la performance dosimétrique ont été comparées entre les plans approuvés par le médecin et les plans kMCO pour 236 cas. La troisième et dernière étude de cette thèse a été réalisée en coopération avec Cédric Bélanger. Un algorithme MCO (gMCO) basé sur l’utilisation d’un environnement de développement compatible avec les cartes graphiques a été mis en oeuvre pour accélérer davantage le calcul. De plus, un algorithme d’optimisation quasi-Newton a été implémenté pour remplacer le recuit simulé dans la première et la deuxième étude. De cette manière, un millier de plans de traitement avec divers compromis et équivalents à ceux générés par IPSA ont été calculés en parallèle. Parmi la banque de plans de traitement généré par l’agorithme gMCO, un plan a été sélectionné (plan gMCO). Le temps de planification et les résultats dosimétriques ont été comparés entre les plans approuvés par le médecin et les plans gMCO pour 457 cas. Une comparaison à grande échelle avec les plans approuvés par les radio-oncologues montre que notre dernier algorithme MCO (gMCO) peut améliorer l’efficacité de la planification du traitement (de quelques minutes à 9:4 s) ainsi que la qualité dosimétrique des plans de traitements (des plans passant de 92:6% à 99:8% selon les critères dosimétriques du groupe de traitement oncologique par radiation (RTOG)). Avec trois algorithmes MCO mis en oeuvre, cette thèse représente un effort soutenu pour développer un algorithme de planification inverse ultra-rapide, automatique et robuste en curiethérapie HDR.
L’objectif général de cette thèse est d’utiliser les connaissances en physique de la radiation, en programmation informatique et en équipement informatique à la haute pointe de la technologie pour améliorer les traitements du cancer. En particulier, l’élaboration d’un plan de traitement en radiothérapie peut être complexe et dépendant de l’utilisateur. Cette thèse a pour objectif de simplifier la planification de traitement actuelle en curiethérapie de la prostate à haut débit de dose (HDR). Ce projet a débuté à partir d’un algorithme de planification inverse largement utilisé, la planification de traitement inverse par recuit simulé (IPSA). Pour aboutir à un algorithme de planification inverse ultra-rapide et automatisé, trois algorithmes d’optimisation multicritères (MCO) ont été mis en oeuvre. Suite à la génération d’une banque de plans de traitement ayant divers compromis avec les algorithmes MCO, un plan de qualité a été automatiquement sélectionné. Dans la première étude, un algorithme MCO a été introduit pour explorer les frontières de Pareto en curiethérapie HDR. L’algorithme s’inspire de la fonctionnalité MCO intégrée au système Raystation (RaySearch Laboratories, Stockholm, Suède). Pour chaque cas, 300 plans de traitement ont été générés en série pour obtenir une approximation uniforme de la frontière de Pareto. Chaque plan optimal de Pareto a été calculé avec IPSA et chaque nouveau plan a été ajouté à la portion de la frontière de Pareto où la distance entre sa limite supérieure et sa limite inférieure était la plus grande. Dans une étude complémentaire, ou dans la seconde étude, un algorithme MCO basé sur la connaissance (kMCO) a été mis en oeuvre pour réduire le temps de calcul de l’algorithme MCO. Pour ce faire, deux stratégies ont été mises en oeuvre : une prédiction de l’espace des solutions cliniquement acceptables à partir de modèles de régression et d’un calcul parallèle des plans de traitement avec deux processeurs à six coeurs. En conséquence, une banque de plans de traitement de petite taille (14) a été générée et un plan a été sélectionné en tant que plan kMCO. L’efficacité de la planification et de la performance dosimétrique ont été comparées entre les plans approuvés par le médecin et les plans kMCO pour 236 cas. La troisième et dernière étude de cette thèse a été réalisée en coopération avec Cédric Bélanger. Un algorithme MCO (gMCO) basé sur l’utilisation d’un environnement de développement compatible avec les cartes graphiques a été mis en oeuvre pour accélérer davantage le calcul. De plus, un algorithme d’optimisation quasi-Newton a été implémenté pour remplacer le recuit simulé dans la première et la deuxième étude. De cette manière, un millier de plans de traitement avec divers compromis et équivalents à ceux générés par IPSA ont été calculés en parallèle. Parmi la banque de plans de traitement généré par l’agorithme gMCO, un plan a été sélectionné (plan gMCO). Le temps de planification et les résultats dosimétriques ont été comparés entre les plans approuvés par le médecin et les plans gMCO pour 457 cas. Une comparaison à grande échelle avec les plans approuvés par les radio-oncologues montre que notre dernier algorithme MCO (gMCO) peut améliorer l’efficacité de la planification du traitement (de quelques minutes à 9:4 s) ainsi que la qualité dosimétrique des plans de traitements (des plans passant de 92:6% à 99:8% selon les critères dosimétriques du groupe de traitement oncologique par radiation (RTOG)). Avec trois algorithmes MCO mis en oeuvre, cette thèse représente un effort soutenu pour développer un algorithme de planification inverse ultra-rapide, automatique et robuste en curiethérapie HDR.
The overall purpose of this thesis is to use the knowledge of radiation physics, computer programming and computing hardware to improve cancer treatments. In particular, designing a treatment plan in radiation therapy can be complex and user-dependent, and this thesis aims to simplify current treatment planning in high dose rate (HDR) prostate brachytherapy. This project was started from a widely used inverse planning algorithm, Inverse Planning Simulated Annealing (IPSA). In order to eventually lead to an ultra-fast and automatic inverse planning algorithm, three multi-criteria optimization (MCO) algorithms were implemented. With MCO algorithms, a desirable plan was selected after computing a set of treatment plans with various trade-offs. In the first study, an MCO algorithm was introduced to explore the Pareto surfaces in HDR brachytherapy. The algorithm was inspired by the MCO feature integrated in the Raystation system (RaySearch Laboratories, Stockholm, Sweden). For each case, 300 treatment plans were serially generated to obtain a uniform approximation of the Pareto surface. Each Pareto optimal plan was computed with IPSA, and each new plan was added to the Pareto surface portion where the distance between its upper boundary and its lower boundary was the largest. In a companion study, or the second study, a knowledge-based MCO (kMCO) algorithm was implemented to shorten the computation time of the MCO algorithm. To achieve this, two strategies were implemented: a prediction of clinical relevant solution space with previous knowledge, and a parallel computation of treatment plans with two six-core CPUs. As a result, a small size (14) plan dataset was created, and one plan was selected as the kMCO plan. The planning efficiency and the dosimetric performance were compared between the physician-approved plans and the kMCO plans for 236 cases. The third and final study of this thesis was conducted in cooperation with Cédric Bélanger. A graphics processing units (GPU) based MCO (gMCO) algorithm was implemented to further speed up the computation. Furthermore, a quasi-Newton optimization engine was implemented to replace simulated annealing in the first and the second study. In this way, one thousand IPSA equivalent treatment plans with various trade-offs were computed in parallel. One plan was selected as the gMCO plan from the calculated plan dataset. The planning time and the dosimetric results were compared between the physician-approved plans and the gMCO plans for 457 cases. A large-scale comparison against the physician-approved plans shows that our latest MCO algorithm (gMCO) can result in an improved treatment planning efficiency (from minutes to 9:4 s) as well as an improved treatment plan dosimetric quality (Radiation Therapy Oncology Group (RTOG) acceptance rate from 92.6% to 99.8%). With three implemented MCO algorithms, this thesis represents a sustained effort to develop an ultra-fast, automatic and robust inverse planning algorithm in HDR brachytherapy.
The overall purpose of this thesis is to use the knowledge of radiation physics, computer programming and computing hardware to improve cancer treatments. In particular, designing a treatment plan in radiation therapy can be complex and user-dependent, and this thesis aims to simplify current treatment planning in high dose rate (HDR) prostate brachytherapy. This project was started from a widely used inverse planning algorithm, Inverse Planning Simulated Annealing (IPSA). In order to eventually lead to an ultra-fast and automatic inverse planning algorithm, three multi-criteria optimization (MCO) algorithms were implemented. With MCO algorithms, a desirable plan was selected after computing a set of treatment plans with various trade-offs. In the first study, an MCO algorithm was introduced to explore the Pareto surfaces in HDR brachytherapy. The algorithm was inspired by the MCO feature integrated in the Raystation system (RaySearch Laboratories, Stockholm, Sweden). For each case, 300 treatment plans were serially generated to obtain a uniform approximation of the Pareto surface. Each Pareto optimal plan was computed with IPSA, and each new plan was added to the Pareto surface portion where the distance between its upper boundary and its lower boundary was the largest. In a companion study, or the second study, a knowledge-based MCO (kMCO) algorithm was implemented to shorten the computation time of the MCO algorithm. To achieve this, two strategies were implemented: a prediction of clinical relevant solution space with previous knowledge, and a parallel computation of treatment plans with two six-core CPUs. As a result, a small size (14) plan dataset was created, and one plan was selected as the kMCO plan. The planning efficiency and the dosimetric performance were compared between the physician-approved plans and the kMCO plans for 236 cases. The third and final study of this thesis was conducted in cooperation with Cédric Bélanger. A graphics processing units (GPU) based MCO (gMCO) algorithm was implemented to further speed up the computation. Furthermore, a quasi-Newton optimization engine was implemented to replace simulated annealing in the first and the second study. In this way, one thousand IPSA equivalent treatment plans with various trade-offs were computed in parallel. One plan was selected as the gMCO plan from the calculated plan dataset. The planning time and the dosimetric results were compared between the physician-approved plans and the gMCO plans for 457 cases. A large-scale comparison against the physician-approved plans shows that our latest MCO algorithm (gMCO) can result in an improved treatment planning efficiency (from minutes to 9:4 s) as well as an improved treatment plan dosimetric quality (Radiation Therapy Oncology Group (RTOG) acceptance rate from 92.6% to 99.8%). With three implemented MCO algorithms, this thesis represents a sustained effort to develop an ultra-fast, automatic and robust inverse planning algorithm in HDR brachytherapy.

In high-dose-rate iridium-192 brachytherapy, the radiation dose received by the patient is calculated according to the AAPM Task Group 43 (TG-43) formalism. This table-based dose superposition method uses dosimetry parameters derived with the radioactive iridium source centered in a water phantom. It neglects the dose perturbations caused by inhomogeneities, such as the patient anatomy, applicators, shielding, and radiographic contrast solution.
In this work, we evaluated the dosimetric characteristics of a shielded rectal applicator with an endocavitary balloon injected with contrast solution. The dose distributions around this applicator were calculated by the GEANT4 Monte Carlo (MC) code and measured by ionization chamber and GAFCHROMIC EBT film. A patient-specific dose calculation study was then carried out for 40 rectal treatment plans. The PTRAN_CT MC code was used to calculate the dose based on computed tomography (CT) images. This study involved the development of BrachyGUI, an integrated treatment planning tool that can process DICOM-RT data and create PTRAN_CT input initialization files. BrachyGUI also comes with dose calculation and evaluation capabilities.
We proposed a novel scatter correction method to account for the reduction in backscatter radiation near tissue-air interfaces. The first step requires calculating the doses contributed by primary and scattered photons separately, assuming a full scatter environment. The scatter dose in the patient is subsequently adjusted using a factor derived by MC calculations, which depends on the distances between the point of interest, the iridium source, and the body contour. The method was validated for multicatheter breast brachytherapy, in which the target and skin doses for 18 patient plans agreed with PTRAN_CT calculations better than 1%.
Finally, we developed a CT-based analytical dose calculation method. It corrects for the photon attenuation and scatter based upon the radiological paths determined by ray tracing. The scatter dose is again adjusted using our scatter correction technique. The algorithm was tested using phantoms and actual patient plans for head-and-neck, esophagus, and MammoSite breast brachytherapy. Although the method fails to correct for the changes in lateral scatter introduced by inhomogeneities, it is a major improvement over TG-43 and is sufficiently fast for clinical use.
En curiethérapies à haut débit de dose, la dose aux patients est évaluée selon le protocole AAPM Task-Group 43 (TG43), qui utilise des paramètres dosimétriques obtenues avec une source dans l'eau. Cependant, le patient, l'applicateur et le contraste ont des propriétés radiologiques différentes de l'eau; ces inhomogénéités sont donc négligées dans TG43.
Dans ce travail, nous utilisons le programme Monte Carlo (MC) GEANT4 pour évaluer les propriétés dosimétriques d'un applicateur rectal muni d'un blindage radio-protecteur et d'un ballon intra-cavitaire. Ces résultats sont confirmés par des mesures d'une chambre d'ionisation et des films GAFCHROMIC EBT. Une étude des calculs de dose a été faite avec le programme PTRAN_CT avec l'aide des images scanner de 40 patients de cancer rectal. Ceci a conduit au développement de BrachyGUI, un programme de planification de curiethérapie, capable de traiter les données DICOM-RT des patients et générer les paramètres d'entrée pour PTRAN_CT. BrachyGUI dispose d'outils de calcul, d'extraction et d'analyse de dose.
Nous proposons une nouvelle méthode de calcul qui tient compte des effets de diffusion au voisinage des interfaces tissus-air. Cette méthode calcule séparément la dose due aux photons primaires et diffusés, ensuite la composante diffusée est ajustée par un paramètre extrait des calculs MC incluant les contours du patient, la source et sa position. Nos résultats s'accordent avec une incertitude inferieure à 1% avec les calculs de dose à la surface et dans la cible effectués avec PTRAN_CT pour 18 patients en curiethérapie du sein.
Enfin, nous avons conçu une méthode analytique de calcul de dose qui incorpore l'atténuation et la diffusion des photons, et qui est basée sur les chemins radiologiques déterminées par traçage des trajectoires. Cet algorithme est validé par l'utilisation de fantômes, des données de patients traités pour divers cancers (oesophage, tête et cou), et par la curiethérapie MammoSite du sein. Bien que cette méthode ne reproduise pas bien les diffusions latérales induites par les inhomogénéités, elle représente une amélioration majeure par-rapport-à TG43 et est rapide pour une implémentation clinique.

Brachytherapy is a form of radiotherapy in which radioactive sources are placed at short distances from, or even inside the target volume. The use of high dose rate brachytherapy is a widely accepted and clinically proven treatment for some stages of prostate cancer. The aim of this project was to investigate potential improvements on two of the most important aspects of high dose rate (HDR) and pulsed dose rate (PDR) prostate brachytherapy - prostate definition and treatment delivery verification. The use of magnetic resonance (MR) imaging in addition to the conventional computed tomography (CT) imaging methods currently used routinely for brachytherapy planning may provide some benefit in accurately defining the prostate and surrounding critical structures. The methods used in this project involved analysis of data sets provided by two Radiation Oncologists. The results presented showed inter-observer and intra-observer variations in the size and shape of the prostate, as well as analysis of the dosimetric differences that may be reported due to the differences in prostate size and shape. The results also included analysis of critical structure dosimetry - dose to the surrounding radio-sensitive rectum and urethra. In summary, the results showed that the prostate was defined to be smaller using MR imaging than CT, however the consistency between Oncologists was not significantly improved using MR imaging. MR imaging may be useful in reducing the dose to normal tissue surrounding the prostate and in obtaining better coverage of the smaller target volume, without compromising the critical structures. The use of LiF:Mg,Ti thermoluminescent dosimeters (TLDs) is a potential avenue for in vivo dose verification of an HDR or PDR prostate brachytherapy treatment plan. This project included a phantom study of these TLDs with the aim to determine their feasibility for clinical use. Cylindrical TLD rods (6 mm length x 1 mm diameter) were used, as these fit inside the brachytherapy needles implanted into the prostate, and therefore had potential to be used clinically to verify the dose delivered in the prostate. This study was extended to include determination of a correction factor to allow an independent radiation source (6 MV photon beam from a linear accelerator) to be used to obtain control readings for this relative dosimetric method. The results showed these TLDs to be a promising in vivo dosimeter for prostate brachytherapy with potential errors in the order of 4%. Their potential lies in the fact that they could detect and flag significant calculation errors in treatment plans, and they utilise equipment used routinely for external beam radiotherapy dosimetry in many treatment facilities, reducing the cost of implementing such a procedure.

In radiation therapy, accurate dose determination and precise dose delivery to the tumour are directly associated with better treatment outcomes in terms of higher tumour control and lower post radiation therapy complications. In the past, film dosimetry was developed into a powerful tool for external beam radiotherapy treatment verification and quality assurance. The objective of this thesis was the development and clinical application of the EBT-3GafChromicTMfilm model patient specific based quality assurance (QA) procedures in brachytherapy. The lack of clinical measurements and patient specific QA procedures (similar to that in intensity modulated radiotherapy (IMRT) delivery) in high dose rate brachytherapy (HDRBT) were the motivation to improve both the QA program of delivery and patient safety during brachytherapy procedures.Patient specific QA tools for pre-operative brachytherapy in rectal cancer developed in this thesis use a radiochromic film dosimetry system together with gamma function evaluation method to compare calculated and measured dose distributions. We also created a dedicated phantom for a brachytherapy applicator used for treatment of rectal cancer patients, which enabled us to compare calculated dose distributions to measured ones in high and low dose gradient regions. Starting from the same passing criteria used for external IMRT QA (3%, 3 mm), passing criteria for high and low dose regions were subsequently discussed. Finally, we investigated the QA system's sensitivity to source positional errors by introducing intentional and controlled mistakes on selected patient plans.Results presented in this thesis demonstrated that radiochromic film dosimetry based QA for brachytherapy can be used not only for patient specific quality assurance, but as a part of the commissioning process and periodic QA as well.
En radiothérapie, la détermination de la dose exacte et la livraison de dose précise de la tumeur sont directement associés à de meilleurs résultats de traitement en termes de contrôle de la tumeur et à une baisse des complications de thérapie post- irradiation. Dans le passé, le film dosimétrie a été développé dans un outil puissant pour la radiothérapie externe de faisceau (CDE) vérification du traitement et de l'assurance de la qualité. L'objectif de cette thèse est le développement et l'application clinique de la BAI - 3 GafChromicTM modèle de film spécifique au patient d'assurance de la qualité basé (AQ) procédures en Brachythérapie. L'absence de mesures cliniques et les procédures d'assurance qualité spécifiques au patient (similaire à celle de la livraison IMRT) en haute curiethérapie de débit de dose (HDRBT) étaient la motivation pour améliorer à la fois le programme d'AQ de livraison et la sécurité des patients pendant les procédures de Brachythérapie.Outils d'assurance qualité spécifiques au patient pour curiethérapie préopératoire dans le cancer du rectum développé dans cette thèse utilise un système de dosimétrie du film Radiochromique avec la méthode d'évaluation de la fonction gamma pour comparer des distributions de dose calculées et mesurées. Nous avons également créé un fantôme dédié pour un applicateur de curiethérapie utilisé pour le traitement des patients atteints de cancer du rectum, ce qui nous a permis de comparer les distributions de dose calculées à celles mesurées dans les régions de gradient doses élevées et faibles. A partir de même critère de passage utilisé pour externe IMRT QA (3 %, 3 mm), en passant critères pour les régions hautes et basses doses ont ensuite été discuté. Enfin, nous avons étudié la sensibilité du système d'assurance qualité à la source des erreurs de position en introduisant des erreurs intentionnelles et contrôlées sur les plans de patients sélectionnés.Les résultats présentés dans cette thèse ont démontré que l'AQ sur film Radiochromique dosimétrie pour curiethérapie peut être utilisée non seulement pour l'assurance qualité spécifique au patient, mais comme une partie du processus de mise en service et AQ périodique ainsi.

Pre-operative radiotherapy for patients with locally advanced rectal carcinoma has been shown to improve survival rates and local tumour control. The ability to identify tumours most likely to undergo a complete or partial response would improve the selection of patients for radiotherapy and potentially modify post-treatment planning. The aim of this study was to develop a multi-marker model of tumour response to pre-operative high-dose rate endorectal brachytherapy (HDREB). Immunohistochemistry (IHC) for p53, Bcl-2, VEGF, APAF-1 and EGFR was carried out on 104 pre-treatment rectal tumour biopsies from patients undergoing a pre-operative HDREB protocol. Immunoreactivity was scored by at least three pathologists using a semi-quantitative scoring method. The reproducibility of the scoring system was evaluated. Receiver operating characteristic curve (ROC) analysis was performed for each protein to determine clinically relevant cutoff scores for defining tumour positivity. Multivariate logistic regression analysis was carried out to identify independent predictive factors of tumour response. Both the semi-quantitative scoring system and ROC curve analysis were found to be reproducible. In addition, the combined analysis of VEGF and EGFR was highly predictive of complete pathologic response to radiotherapy. EGFR was found to independently predict complete or partial tumour regression but only with low sensitivity and specificity. A large-scale prospective study is necessary to confirm these findings. Moreover, the novel methodology proposed and validated in this study to assess immunoreactivity could significantly enhance the value of IHC findings in colorectal cancer as well as other tumour types.

Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2015-12-10T16:54:22Z No. of bitstreams: 0
Made available in DSpace on 2015-12-10T16:54:22Z (GMT). No. of bitstreams: 0
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Tese (Doutorado em Tecnologia Nuclear)
IPEN/T
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP
FAPESP:11/01913-4

Current brachytherapy dosimetry protocols assume that a physical source may be approximated by a point source. A new brachytherapy dosimetry protocol, recently proposed by the American Association of Physicists in Medicine Task Group 43, has the advantage of using functions derived solely from measurements performed in the medium and uses a more realistic source geometry than the point source approximation. The aim of this work is to obtain the dosimetric functions required by this new protocol for both a low and a high dose-rate Iridium-192 brachytherapy source through dose measurements in a water-equivalent phantom.
Dose measurements have been performed using lithium fluoride thermoluminescent detectors positioned in a polystyrene phantom at distances from the source that vary from 1 cm to 10 cm, with 1-cm intervals, and at angles that vary from 0$ sp circ$ to 170$ sp circ$ with 10$ sp circ$ intervals.
Our experimental results have clearly shown that the point-source approximation model can overestimate the dose to water, especially for the high dose-rate source, where we have found that differences between point-source estimates and exact measured values can differ by almost 30% for points along the longitudinal axis of the source.

A braquiterapia de alta taxa de dose é uma das modalidades mais utilizadas em braquiterapia para o tratamento de câncer. Os diversos avanços tecnológicos, bem como a evolução das técnicas de tratamento tornaram a braquiterapia de alta taxa de dose uma das modalidades de estado da arte para o tratamento de alguns cânceres. Parte deste avanço é creditada à melhoria na acurácia e na prescrição de dose absorvida recomendada ao paciente, ao longo dos anos. Este avanço permite que atualmente seja possível realizar os cálculos dosimétricos, por meio de sistemas de planejamento computadorizado, considerando as heterogeneidades dos pacientes, tais como: tecidos e órgãos com composições diferentes da água (meio de referência em radioterapia), contorno do paciente individualizado, introdução de aplicadores, dentre outros. Tais avanços demandam o controle de qualidade destas ferramentas, com objetivo de assegurar que todo o processo de tratamento seja satisfatório e acurado. Até o momento, a comunidade carece de um sistema experimental capaz de avaliar, considerando os níveis de incerteza, se os sistemas de planejamento computadorizados são aptos a considerar a heterogeneidade dos tratamentos. Neste trabalho, apresentamos o desenvolvimento de medidas experimentais em um objeto simulador, com capacidade de mensurar as diferenças introduzidas pela heterogeneidade por meio de três técnicas dosimétricas experimentais: termoluminescência, filmes radiocrômicos e ionométrica. Os resultados experimentais foram comparados com as simulações de Monte Carlo e com um sistema de planejamento computadorizado comercial, apto a realizar correções de heterogeneidade em braquiterapia. Discutimos as principais etapas de desenvolvimento deste objeto simulador, seus resultados experimentais e as comparações com os demais sistemas. As conclusões e as etapas futuras deste projeto também são apresentadas.
High dose rate brachytherapy is one of the most widely used modalities in brachytherapy for cancer treatment The various technological advances and the development of treatment techniques have made high dose rate brachytherapy as one of the state of the art methods for the treatment of some cancers. Part of this progress is credited to the improvement in the accuracy and absorbed dose prescription recommended to patients over the years. This advance currently allows the possibility of performing dosimetric calculations, by means of computerized planning systems, considering the heterogeneity of patients, such as: tissues and organs with different water compositions (reference medium in radiotherapy), individualized patient\'s contour and introduction of applicators, among others. Such advances require quality control of these tools, in order to ensure that the entire treatment process is satisfactory and accurate. Nowadays, the community needs an experimental system capable of evaluating, since the uncertainty levels if the computerized planning systems are able to consider the heterogeneity of treatments. In this project, we present the development of experimental measurements into a phantom, capable of measuring the differences introduced by heterogeneity through three experimental dosimetric techniques: thermoluminescence, radiochromic films and ionometric. The experimental results were compared with the Monte Carlo simulations and a commercial treatment planning system able to perform correction of heterogeneity in brachytherapy. We discuss the main stages of development of this phantom, their experimental results and comparisons with other systems. The conclusions and future steps to complete this project are also presented.

Published Article
Worldwide, uterine cervical cancer is one of the most frequently occurring cancers in women, with more than 80% of these cases occurring in developing countries. The South African screening policy and screening program, implemented in 2001, attempt to reduce this incidence of cervical cancer in South Africa. It is essential to treat these women with the best modalities available. This retrospective study focused specifically on the curative potential of radiotherapy administered to patients at the Oncology Department, Bloemfontein, since a new modality of high dose-rate intracavitary brachytherapy was implemented in 1994. Late radiation complications were also investigated.

This work is concerned with physics-aspects of safety, quality control (QC) and dosimetry audit in high dose rate (HDR) gynaecological brachytherapy. A survey of brachytherapy QC practice across the UK was conducted. Areas of least consistency were addressed, including test method development and establishment of clinical performance requirements. ‘End to end’ dosimetry auditing was not being utilised and its implementation was the main focus of this work. Three candidate dosimeters were evaluated for use in audit: Fibre optic thermoluminescence detector, Gafchromic EBT3® radiochromic film, and Presage® radiochromic plastic. Film dosimetry was selected, fully characterised, triple-channel dosimetry evaluated, and uncertainty reduction methods implemented. A novel ‘end to end’ audit methodology was developed, the BRachytherapy Applicator Dosimetry (BRAD) system, to measure dose distributions around clinical brachytherapy applicators and compare to treatment planning system calculations. MCNP5 Monte Carlo code was used to support the design of the BRAD system and validate the use of film dosimetry. 46 radiotherapy centres in the UK were audited. Delivery of the intended prescription dose was confirmed to be within clinically acceptable levels at all centres, mean difference 0.6% for plastic and 3.0% for metal applicators (±3.0% k=1). The intended dose distribution was faithfully delivered to the film-measured dose planes with a mean gamma passing rate of 97.8% at 3% (local) 2 mm criteria. Two audits had results that required follow-up and both were resolved. Each audit included a review of local brachytherapy physics practice and opportunities for improvement were reported, including imaging, applicator reconstruction, planning procedures, QC tests, and staff training. The brachytherapy audit provided the first comprehensive validation of ‘end to end’ clinical brachytherapy dosimetry, from applicator imaging to treatment delivery, combined with a review of clinical physics practice. The BRAD system is retained in the Institute of Physics and Engineering in Medicine (IPEM) phantom library.

A number of QA procedures have been developed for Breast Brachytherapy treatments, yet none guarantee accurate dose delivery or allow conformation of the actual source position leading to errors sometimes going unnoticed. The objective of this study is to track the exact path the HDR source would follow in real time. The exit radiation of the HDR source was used to image a well defined matrix of markers. The images were acquired using FPD and were processed to obtain projection coordinates while an x-ray calibration image was processed to obtain marker coordinates. Each marker along with its projection represents a line in 3D. A mathematical solution for the ‘near-intersection’ of two 3D lines was implemented and used to determine the ‘true’ 3D source position. A matrix with N markers will produce N*(N-1)/2 points of intersection and their mean will result in a more accurate source position. This study has proved that the accuracy of source position detection using a FPD is sub-millimeter.

A novel optical calorimetry approach is proposed for the dosimetry of therapeutic radiation, based on the optical technique of Digital Holographic Interferometry (DHI). This detector determines the radiation absorbed dose to water by measurement of the refractive index variations arising from radiation induced temperature increases. The output consists of a time series of high resolution, two dimensional images of the spatial distribution of the projected dose map across the water sample. This absorbed dose to water is measured directly, independently of radiation type, dose rate and energy, and without perturbation of the beam. These are key features which make DHI a promising technique for radiation dosimetry. A prototype DHI detector was developed, with the aim of providing proof-of-principle of the approach. The detector consists of an optical laser interferometer based on a lensless Fourier transform digital holography (LFTDH) system, and the associated mathematical reconstruction of the absorbed dose. The conceptual basis was introduced, and a full framework was established for the measurement and analysis of the results. Methods were developed for mathematical correction of the distortions introduced by heat di usion within the system. Pilot studies of the dosimetry of a high dose rate Ir-192 brachytherapy source and a small eld proton beam were conducted in order to investigate the dosimetric potential of the technique. Results were validated against independent models of the expected radiation dose distributions. Initial measurements of absorbed dose demonstrated the ability of the DHI detector to resolve the minuscule temperature changes produced by radiation in water to within experimental uncertainty. Spatial resolution of approximately 0.03 mm/pixel was achieved, and the dose distribution around the brachytherapy source was accurately measured for short irradiation times, to within the experimental uncertainty. The experimental noise for the prototype detector was relatively large and combined with the occurrence of heat di usion, means that the method is predominantly suitable for high dose rate applications. The initial proof-of-principle results con rm that DHI dosimetry is a promising technique, with a range of potential bene ts. Further development of the technique is warranted, to improve on the limitations of the current prototype. A comprehensive analysis of the system was conducted to determine key requirements for future development of the DHI detector to be a useful contribution to the dosimetric toolbox of a range of current and emerging applications. The sources of measurement uncertainty are considered, and methods suggested to mitigate these. Improvement of the signal-to-noise ratio, and further development of the heat transport corrections for high dose gradient regions are key areas of focus highlighted for future development.

Introduction Treating localized prostate cancer with combination radiotherapy consisting ofexternal beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) has beenproven to result in better disease outcome than EBRT only. There is, however, a decreasingtrend in utilization of combination therapy, partially due to concerns for elevated toxicityrisks. Aim To determine which parameters correlate to acute and late (≤ 6 months) urinary toxicity(AUT and LUT) and acute and late rectal toxicity (ART and LRT), and thereafter createpredictive models for rectal toxicity. Methods Data on toxicity rates and 32 patient, tumor and treatment parameters were collectedfrom 359 patients treated between 2008 and 2018 with EBRT (42 Gy in 14 fractions) andHDR-BT (14.5 Gy in 1 fraction) for localized prostate cancer at Örebro University Hospital.Bivariate analyses were conducted on all parameters and the outcome variables AUT, LUT,ART and LRT grade ≥ 1, graded according to the RTOG-criteria. Parameters correlating toART and LRT in this and previous studies were included in multivariate logistic regressionanalyses for creation of predictive models. Results Most toxicities, 86%, were of grade 0 or 1, only 9% of patients had grade 2 – 3toxicity. Only 2 – 4 parameters correlated to the respective toxicities in bivariate analyses.Logistic regressions generated no significant predictors of ART or LRT. Therefore, nopredictive models were obtained. Conclusion None of the included parameters have enough discriminative abilities regardingrectal toxicity. Predictive models can most probably be obtained by including otherparameters and more patients.

Orientador: Luis Otavio Zanatta Sarian
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-11-07T13:22:12Z (GMT). No. of bitstreams: 1 Oliveira_AntonioCarlosZulianide_D.pdf: 2312185 bytes, checksum: 6a45c1be8238c13c3a584fdc2ef426e4 (MD5) Previous issue date: 2013
Resumo: Introdução: Ensaios clínicos das últimas duas décadas do século XX demonstraram a superioridade da radioterapia associada à quimioterapia na abordagem do carcinoma espinocelular do colo do útero (CEC). Contudo, tais estudos abordaram todos os estádios clínicos e para o subgrupo de mulheres com CEC estádio IIIB e os benefícios da quimioterapia não foram totalmente comprovados. Objetivos: Esta tese divide-se em dois estudos: 1) uma comparação histórica de sobrevida livre de doença (SLD), sobrevida total (ST) e toxicidade de tratamento em mulheres com CEC IIIB submetidas à braquiterapia de baixa taxa de dose (BBTD) versus braquiterapia de alta taxa de dose exclusiva (BATD) versus braquiterapia de alta taxa de dose associada à quimioterapia (BATD-QT) e 2) um ensaio clínico aleatorizado comparando esses mesmos parâmetros em mulheres submetidas à BATD versus BATD-QT. Métodos: Na comparação histórica de tratamentos, foram levantados os dados de evolução de pacientes admitidas entre 1985 e 2005 no CAISM-UNICAMP e seguidas até 2007, totalizando 230 pacientes com CEC IIIB que receberam BBTD (42 pacientes), BATD (155 pacientes) ou BATD-QT (33 pacientes). As SLD e ST das mulheres nos três grupos foram comparadas usando curvas de sobrevida tipo Kaplan-Meyer e testes de log-rank. Já o ensaio clínico aleatorizado foi realizado entre setembro de 2003 e julho de 2010. Foram incluídas no estudo 147 mulheres com CEC IIIB. Após aceitarem participar e assinarem o termo de consentimento, as mulheres foram randomizadas para BATD ou BATD-QT através de planilha de aleatorização criada pelo programa SAS e trazida ao conhecimento de pacientes e médicos através de envelopes opacos. Todas as mulheres receberam teleterapia com dose de 45Gy para a região pélvica em 25 frações, 14,4Gy de reforço no(s) paramétrio(s) comprometido(s) e BATD em quatro frações semanais de 7Gy, prescritos no ponto A. O grupo BATD-QT recebeu cisplatina concomitante semanal (40mg/m2) durante a teleterapia pélvica. O follow-up durou até janeiro de 2013, (72 pacientes do grupo com cisplatina e 75 no grupo-controle), com o seguimento médio de 54,9 meses (intervalo interquartil = 55,4 meses). Comparações de SLD e ST foram realizadas usando curvas de Kaplan-Meyer, testes de log-rank e modelos multivariados de Riscos Proporcionais de Cox, os quais englobaram características clínicas das mulheres como variáveis de controle. Resultados: Na comparação histórica, a SLD média para o grupo BATD foi de 60%, para BBTD 45% e para BATD-QT foi de 65% (p = 0,02). Já a ST foi de 65% para o grupo BATD, 49% para BBTD e a ST em dois anos para o grupo BATD-QT foi de 86% (p = 0,02). A toxicidade retal de grau II foi de 7% para o grupo que recebeu BBTD, de 4% para BATD e 7% para o grupo BATD-QT, que teve um caso de toxicidade retal grau IV. No ensaio clínico aleatorizado, mulheres alocadas no grupo BATD-QT tiveram SLD significativamente melhor (RR = 0,52, 95% CI 0,28-0,98, p = 0,04), porém não houve diferença em relação a ST (RR = 0,67, 95% CI 0,37-1,183, p = 0,16). Mulheres com Karnofsky <90 tiveram uma SLD significativamente pior (RR = 2,52, 95% CI 1,23-4,78, p = 0,01). O mesmo ocorreu para as mulheres com invasão parametrial bilateral até a parede óssea (RR = 2,93, 95% CI 1,21-7,13, p = 0,02), e a hemoglobina média durante o tratamento <10mg/dL (RR = 2,22, 95% CI 1,01-4,93, p = 0,04). A ST também foi menor em mulheres com Karnofsky <90 (RR = 2,75, 95% CI 1,29-5,87, p <0,01), e hemoglobina média durante o tratamento <10mg/dL (RR = 2,82, 95% CI 1,27-6,29, p = 0,01). Conclusões: Na revisão da série histórica, as pacientes que receberam braquiterapia de alta taxa de dose tiveram melhores SLD e ST, e as taxas de toxicidade não foram diferentes entre os três grupos. O ensaio clínico, que é o único estudo controlado randomizado comparando a BATD-QT e BATD para CEC IIIB, sugere que há um pequeno, mas significativo, benefício na SLD com a adição de cisplatina à BATD, com uma toxicidade aceitável
Abstract: Introduction: Clinical trials of the last two decades of the twentieth century demonstrated the superiority of radiotherapy combined with chemotherapy in the management of squamous cell carcinoma of the cervix (SCC). However, such studies have addressed all clinical stages and for the subgroup of women with stage IIIB SCC the benefits of chemotherapy have not been fully proven. Objectives: This thesis is divided into two studies: 1) a historical comparison of disease-free survival (DFS), overall survival (OS) and toxicity of treatment in women with SCC IIIB undergoing low-dose rate brachytherapy (LDR) brachytherapy versus high dose rate exclusive (HDR) brachytherapy versus high dose rate associated with chemotherapy (CHT) and 2) a randomized clinical trial comparing these parameters in women undergoing HDR versus CHT. Methods: In the historical comparison of treatments, data on the outcomes of patients admitted between 1985 and 2005 in CAISM-Unicamp and followed until 2007 were collected, totaling 230 patients with SCC stage IIIB who received either LDR (42 patients), HDR (155 patients) or CHT (33 patients). The DFS and OS of women in the three groups were compared using Kaplan-Meyer survival curves and the "log-rank" test. The randomized clinical trial was conducted between September 2003 and July 2010. A total of 147 with SCC stage IIIB were included. After accepting to participate and signing the consent form, women were randomized to HDR or CHT through a randomization spreadsheet created by SAS program and concealment allocation of patients through opaque envelopes. Patients of either the CHT or HDR groups received external-beam radiation (45 Gy) to the entire pelvic region in 25 fractions over a 5-week period. Compromised parametria were treated with 14.4 Gy boost. High-dose rate brachytherapy consisted of four weekly fractions of 7 Gy prescribed to point A. Patients in the CHT group also received concomitant weekly cisplatin (40mg/m2) during the pelvic external beam radiotherapy. The follow-up lasted until January 2013 (72 patients in the cisplatin group and 75 in the control group), with a mean follow-up of 54.9 months (interquartile range = 55.4 months). Comparisons of DFS and OS were performed using Kaplan-Meyer log-rank tests and multivariate models of Cox proportional hazards model, which encompassed the clinical characteristics of women as control variables. Results: In the historical comparison, the DFS for the group HDR was 60% , 45% for LDR and 65% for CHT (p = 0.02). The OS was 65% for the HDR group, 49% for LDR and 86% for CHT (p = 0.02). The Grade II rectal toxicity was 7% for LDR, 4% in HDR patients and 7% in CHT group, which had a case of rectal toxicity grade IV. In the randomized clinical trial, women in the CHT group had significantly better DFS (RR = 0.52, 95% CI from 0.28 to 0.98, p = 0.04), but there was no difference in OS (RR = 0.67, 95% CI 0.37 to 1.183, p = 0.16). Women with Karnofsky <90 had a significantly worse DFS (RR = 2.52, 95% CI 1.23 to 4.78, p = 0.01). The same was true for women with bilateral parametrial invasion to the bone wall (RR = 2.93, 95% CI 1.21 to 7.13, p = 0.02), and mean hemoglobin during treatment <10mg/dL (RR = 2.22, 95% CI 1.01 to 4.93, p = 0.04). The OS was also lower in women with Karnofsky <90 (RR = 2.75, 95% CI 1.29 to 5.87, p <0.01), and mean hemoglobin during treatment <10mg/dL (RR = 2, 82, 95% CI 1.27 to 6.29, p = 0.01). Conclusions: Patients who received HDR had better DFS and OS, and toxicity rates were not different among the three groups. The randomized trial, which is the only randomized controlled study comparing HDR and CHT for CEC IIIB, suggests that there is a small but significant DFS benefit with the addition of cisplatin to HDR, with acceptable toxicity
Doutorado
Oncologia Ginecológica e Mamária
Doutor em Ciências da Saúde

Po radikalaus gydymo 20–50 proc. pacientų, kuriems nustatytas galvos–kaklo srities vėžys lokoregioninis atkrytis nustatomas per pirmus dvejus metus. Literatūroje paskelbtų tyrimų rezultatai taikant pakartotinę nuotolinę spindulinę terapiją dėl galvos-kaklo vėžio atkryčio prasti: 2-jų metų bendras išgyvenimas siekė 15,2–40 proc., vėlyvųjų 3-4 laipsnio komplikacijų dažnis buvo 1,4–47 proc., 5 laipsnio - 7,6 proc. Retrospektyvinių ir II fazės tyrimų rezultatai naudojant didelės dozės galios brachiterapiją galvos-kaklo srities vėžio atkryčiui gydyti: 2-jų metų bendras išgyvenimas siekė 19–63 proc., vėlyvųjų 3-4 laipsnio komplikacijų dažnis buvo 4–22,2 proc. Tyrimų metu skirtos 3–4 Gy frakcijos iki 30–40 Gy suminės dozės. Iki šiol neatlikti tyrimai lyginantys nuotolinės spindulinės terapijos ir didelės dozės galios brachiterapijos gydymo veiksmingumą ir saugumą. Šioje disertacijoje palyginti skirtingi spindulinio gydymo metodai gydant galvos-kaklo srities vėžio atkrytį: kontrolinei grupei taikytas nuotolinis konforminis spindulinis gydymas (25 frakcijos po 2 Gy, suminė dozė 50 Gy), tiriamajai grupei - hipofrakcionuota didelės dozės galios brachiterapija skiriant naują frakcionavimo režimą – po 2,5 Gy per frakciją po dvi frakcijas per dieną, iki 30 Gy suminės dozės. Toks frakcionavimo režimas pasirinktas siekiant sumažinti spindulinių reakcijų dažnį ir sunkumo laipsnį, o suminė dozė yra biologiškai ekvivalentiška suminėms dozėms, kurios buvo naudotos ankstesniuose tyrimuose.
After radical treatment of head and neck cancer 20–50% of patients are diagnosed with the locoregional recurrence during first two years. In the literature the results of studies, using reirradiation by three-dimensional radiotherapy for head and neck cancer recurrence, according to a 2-year overall survival and toxicity, are poor: overall survival reached 15.2–40%, the grade 3 - 4 toxicity reached 1.4–47% and grade 5 - 7.6%. The results of phase II and retrospective studies using the high-dose-rate brachytherapy for treatment of head and neck cancer relapse were: 2-year overall survival was 19–63%; grade 3 - 4 late toxicity 4–22.2%. In these studies 3–4 Gy per fraction up to 30–40 Gy total dose were administered. So far, the randomized study, comparing the high-dose-rate brachytherapy with the three-dimensional radiotherapy, treating head and neck cancer relapse, hasn’t been conducted. We compared different radiotherapy methods: three-dimensional conformal radiotherapy was administered to the control group (25 fractions of 2 Gy, total dose of 50 Gy); the hypofractionated high-dose-rate brachytherapy was administered to the experimental group, while applying a new regime of fractionation: 2.5 Gy per fraction, two fractions per day, up to 30 Gy total dose. Such fractionation regimen was selected in order to reduce the rate and grade of toxicity, while the total dose is biologically equivalent to the total doses, which have been used in previous studies.

Submitted by SBI Biblioteca Digital (sbi.bibliotecadigital@puc-campinas.edu.br) on 2018-02-07T13:06:22Z No. of bitstreams: 1 ANA CAROLINA MASSAROTTO.pdf: 924874 bytes, checksum: 09a1ac55208a09df27e003db121d89d6 (MD5)
Made available in DSpace on 2018-02-07T13:06:22Z (GMT). No. of bitstreams: 1 ANA CAROLINA MASSAROTTO.pdf: 924874 bytes, checksum: 09a1ac55208a09df27e003db121d89d6 (MD5) Previous issue date: 2017-12-15
Breast cancer is the second most common type of cancer in the world, and the most common among women, affecting men who account for 1% of all cases of the disease. The risk factors of the disease are related to age, endocrine / reproductive history, behavioral / environmental factors, and genetic / hereditary factors. The prognosis of the disease depends on its extension (staging), with greater curative potential when diagnosed at baseline.Among the types of treatment of breast cancer stand out surgery, radiotherapy, chemotherapy, hormone therapy and biological therapy. It is highlighted in the radiotherapy modality, Brachytherapy, which is the application of radiation in a more precise and localized way in the tumor. In this work we will focus on high-grade interstitial brachytherapy dose rate, partial and accelerated breast irradiation (IPAM), which has been shown to have better esthetic results, lower risk of injury from radiation from healthy adjacent tissues, shorter duration of treatment, and low recurrence rates. This is a retrospective, longitudinal, descriptive, analytical study, with a review of medical records of patients diagnosed with breast cancer, stages 0-I-II, between the years 2004 and 2013 who received IPAM using brachytherapy after conservative surgery of the breast at the Radium Institute of Campinas, Campinas-SP, Brazil.This work aims to report and evaluate the viability, acute and chronic toxicity, aesthetic aspects, efficacy and factors related to the use of Partial and Accelerated Breast Irradiation with high dose rate brachytherapy for patients with early stage of breast cancer. In addition to assessing recurrence rates and local control of the disease.
O c?ncer de mama ? o segundo tipo de c?ncer mais comum no mundo,e o mais frequente entre as mulheres, acometendo tamb?m homens que representam 1% do total de casos da doen?a. Os fatores de risco da doen?a est?o relacionados com idade, fatores end?crinos/hist?ria reprodutiva, fatores comportamentais/ambientais e fatores gen?ticos/heredit?rios. O progn?stico da doen?a depende da sua extens?o (estadiamento), com maior potencial curativo quando diagnosticada no in?cio. Entre os tipos de tratamento do c?ncer de mama destacam-se a cirurgia, radioterapia , quimioterapia, hormonioterapia e terapia biol?gica. Apresenta destaque na modalidade radioter?pica, a Braquiterapia, que trata-se da aplica??o de radia??o de forma mais precisa e localizada no tumor. Neste trabalho teremos como enfoque a braquiterapia intersticial de alta taxa de dose, irradia??o parcial e acelerada da mama (IPAM), que vem apresentando melhores resultados est?ticos, menor risco de les?o pela radia??o de tecidos adjacentes saud?veis, menor dura??o do tratamento, e baixas taxas de recorr?ncia. Trata-se de um estudo retrospectivo, longitudinal, descritivo, anal?tico, com revis?o de prontu?rios de pacientes com diagn?stico de c?ncer de mama, est?dios 0-I-II , entre os anos de 2004 e 2013 que receberam IPAM utilizando braquiterapia ap?s a cirurgia conservadora da mama no Instituto do Radium de Campinas, Campinas-SP, Brasil. Tal trabalho objetiva relatar e avaliar a viabilidade, toxicidade aguda e cr?nica, aspectos est?ticos, efic?cia e fatores relacionados com utiliza??o de Irradia??o Parcial e Acelerada da Mama com braquiterapia de alta taxa de dose para pacientes com est?dio inicial de c?ncer de mama. Al?m de avaliar as taxas de recorr?ncia e controle local da doen?a.

Submitted by SBI Biblioteca Digital (sbi.bibliotecadigital@puc-campinas.edu.br) on 2018-02-15T12:50:05Z No. of bitstreams: 1 VANDERLEI JOSE JUNIOR.pdf: 1351825 bytes, checksum: 599d050ec951a6a8e7497a0cea5d2e17 (MD5)
Made available in DSpace on 2018-02-15T12:50:05Z (GMT). No. of bitstreams: 1 VANDERLEI JOSE JUNIOR.pdf: 1351825 bytes, checksum: 599d050ec951a6a8e7497a0cea5d2e17 (MD5) Previous issue date: 2017-12-15
Introduction: Prostate cancer is one of the most prevalent diseases in the male population, occupying the second position among malignant neoplasms. There are several therapeutic options for the treatment of localized prostate cancer, ranging from conservative behaviors to interventional treatments such as radical prostatectomy or external radiotherapy, associated or not with brachytherapy. Objective: To identify the factors that can predict biochemical recurrence and to evaluate treatment toxicity. METHOD: This is a retrospective and longitudinal study of 162 patients diagnosed with prostate cancer treated with conformational external radiotherapy associated with high dose rate brachytherapy (BTATD) between 2005 and 2014. The database was used of the Radium ? Campinas Oncology Institute, collected prospectively. Results: The mean follow-up time was 57 months. No grade 3 late toxicity was observed in the gastrointestinal tract, with only 1 patient (0.6%) genitourinary tract. The only categorical variable that presented statistical significance for biochemical relapse was the Nadir PSA <1 ng / ml (p = 0.018). The biochemical recurrence rate found was 96.3%, based on the Phoenix criteria (PSA nadir + 2 ng / ml). Conclusions: This study demonstrated that in the treatment of localized prostate cancer, the association of external radiotherapy with BATD is a safe therapeutic option, with a low degree 3 late toxicity and a biochemical recurrence of only 3.7% (with HF = 95 %).
Introdu??o: O c?ncer de pr?stata ? uma das doen?as mais prevalentes na popula??o masculina, ocupando a segunda posi??o entre as neoplasias malignas. H? v?rias op??es terap?uticas para o tratamento do c?ncer de pr?stata localizado, podendo variar de condutas conservadoras ? tratamentos intervencionistas como a prostatectomia radical ou a radioterapia externa, associada ou n?o ? braquiterapia. Objetivo: Identificar os fatores que possam predizer recidiva bioqu?mica e avaliar a toxicidade do tratamento. M?todo: Tratase de um estudo retrospectivo e longitudinal, com 162 pacientes diagnosticados com c?ncer de pr?stata, tratados com radioterapia externa conformacional associada ? braquiterapia de alta taxa de dose (BATD), entre 2005 e 2014. Utilizou-se o banco de dados do Radium - Instituto de Oncologia de Campinas, coletados prospectivamente. Resultados: O tempo m?dio de seguimento foi de 57 meses. N?o foi observada toxicidade tardia grau 3 no trato gastrointestinal, sendo apenas 1 paciente (0,6%) trato genitourin?rio. A ?nica vari?vel categ?rica que apresentou signific?ncia estat?stica para recidiva bioqu?mica foi o PSA Nadir <1 ng/ ml (p = 0,018). A taxa de recidiva bioqu?mica encontrada foi de 96,3%, baseando-se nos crit?rios de Phoenix (PSA nadir + 2 ng/ml). Conclus?es: Esse estudo demonstrou que, no tratamento de c?ncer de pr?stata localizado, a associa??o de radioterapia externa com BATD ? uma op??o terap?utica segura, com baixa taxa de toxicidade tardia grau 3 e recidiva bioqu?mica de apenas 3,7% (com I.C = 95%).

The aim of this study is to develop an intraoperative dose assessment procedure that can be performed after an I-125 prostate seed implantation, while the patient is still under anaesthesia. To accomplish this, we reconstruct the 3D position of each seed and co-register it with the prostate contour acquired with a transrectal ultrasound (TRUS) probe. Our seed detection method involves a tomosynthesis-based filtered reconstruction of the volume of interest requiring 7 projections acquired over an angle of 60o with an isocentric imaging system. The co-registration between the tomosynthesis-based seed positions and the TRUS-based prostate contour is based on the planned position. A phantom and a clinical study (25 patients) were carried out to validate the technique. In the patient study, the automatic tomosynthesis-based reconstruction yields a seed detection rate of 96.7% and less than 2.6% false-positive. The seed localization error obtained with a phantom study is 0.4 ± 0.4 mm. The co-registration method based on planned seed position has proved to be not accurate enough for dosimetric purposes. We believe that this technique may be used to discover considerable underdosage and to improve the dosimetric coverage by potentially reimplanting additional seeds.
L'objectif de ce projet est de développer une procédure d'évaluation dosimétrique intra-opératoire en implantation prostatique de grains d'iode 125. Pour y arriver, la position 3D des grains doit être reconstruite et recalée avec les contours de la prostate imagée en échographie endorectale. La reconstruction des grains est basée sur une technique de tomosynthèse requérant 7 projections acquises entre -30o et 30o. Le recalage entre la position 3D des grains et les contours utilise comme cible la position planifiée des grains. Notre technique de reconstruction dosimétrique a été testée sur un mannequin et dans une étude clinique incluant 25 patients. Notre méthode permet de reconstruire la position 3D des grains avec une précision de 0.4 ± 0.4 mm. De plus, l'étude clinique a démontré un taux de détection de 96.7% des grains et incluant moins de 2.6% de faux-positifs. La méthode de recalage n'a pas permis d'atteindre une précision acceptable pour une application clinique. La technique développée permet de repérer la présence de sous-dosage considérable et ouvre la porte vers la réimplantation de grains additionnels afin d'améliorer la couverture dosimétrique de la prostate.

Permanent Low Dose Rate (LDR) brachytherapy is mostly used for the treatment of prostate cancer and is also used for breast cancer treatment. The dosimetry is made using the TG-43 protocol in which the interseed and the tissue-composition effects are ignored. The interseed effect is the impact of the presence of the seeds on the dosimetry. By ignoring that effect, the Dose Volume Histogram (DVH) is right-shifted and dose analysis parameters such as the D90 are overestimated. The tissue-composition effect is due to the presence of materials different from water around the seeds. In prostate tissue, the DVH is right shifted when this effect is ignored and the dosimetry is made using the TG-43 formalism. In breast tissue the DVH is left shifted when the tissue-composition effect is ignored. The tissue-composition effect is more important in breast tissue than in prostate tissue, so that parameters like the D90 are greatly underestimated by doing the dosimetry for a breast permanent LDR brachytherapy treatment using the TG-43 protocol.
La curiethérapie permanente à faible débit de dose est surtout utilisée pour traiter le cancer de la prostate et est aussi utilisée pour le traitement du cancer du sein. La dosimétrie est faite en utilisant le formalisme du TG-43 dans lequel l'effet intergrain et l'effet de composition sont ignorés. L'effet intergrain est l'impact de la présence des grains sur la dosimétrie. Quand cet effet est ignoré, le DVH (Dose Volume Histogram) est décalé vers la droite et les paramètres dosimétriques comme la D90 sont surestimés. L'effet de composition est dû à la présence de matériel différent de l'eau autour des grains. Dans du tissus prostatique, le DVH est décalé vers la droite quand cet effet est ignoré et que la dosimétrie est faite avec le protocole TG-43. Dans le sein, le DVH est décalé vers la gauche quand l'effet de composition est ignoré. L'effet de composition est plus important pour le sein que pour la prostate. Conséquemment, les paramètres comme la D90 sont grandement sous-estimés en faisant la dosimétrie pour un traitement du sein en curiethérapie permanente à faible débit avec le protocole TG-43.

Introduction I Low dose-rate brachytherapy is an accepted treatment for early prostate cancer in the UK. This thesis reports studies of clinical outcome from this treatment in a UK centre. Patients and Methods Prospective observational study in three areas of outcome for patients undergoing low' dose-rate (LDR) seed brachytherapy implants: . 1. Quality of life questionnaires were used to prospectively assess toxicity of 3 LDR brachytherapy treatments: monotherapy+l- androgen deprivation+lexternal beam radiotherapy in a longitudinal study. ii. Post-implant catheter use was correlated with preoperative variables (prostate volume, androgen deprivation, urodynamic obstruction status and IPSS score) and treatment indices (prostate D90, Urethral DIO, D25, and D50). 1lI. Bicalutamide and goserelin for pre-brachytherapy prostate volume reduction. Results General health related quality of life was 'a little' to 'moderately' decreased 6weeks after brachytherapy, but unchanged by clinically significant amounts >9 months after any brachytherapy treatment. Permanent problematic urinary incontinence «4%) and significant bother from use of incontinence aids «3%) were rare after any - 4- brachytherapy subtype. Urinary problems, principally frequency and urgent micturition worsened after brachytherapy with peak 'very much' worsened symptoms at 6-weeks post treatment and improvements to 'a little' worse than baseline at 1-2 years. Sexual function declined significantly in potent men with partners who underwent brachytherapy. By 2 years post brachytherapy, almost half of men who were potent before brachytherapy as monotherapy started using phosphodiesterase inhibitors (e.g. Viagra®). Despite this medication, at least 47% rep'orted moderatesevere erectile dysfunction. Postoperative need for catheterisation was predicted by elevated prostate volume (>35cc), raised IPSS score (>7 vs. <7), and urodynamic obstruction (vs. equivocal or unobstructed patients). Bicalutamide produced smaller reductions in prostate volume than Goserelin (-8 vs. -26% reduction in volume). Conclusions Clinically significant changes in HRQOL were present at >12m but they were of small magnitude except for sexual side effects which continued to be common and marked. Use of an IPSS score, prostate volume and urodynamic assessment may improve selection of patients for brachytherapy. Bicalutamide is superior to goserelin for prostate cytoreduction prior to brachytherapy.

Le cancer est la deuxième cause de décès dans le monde, représentant environ un décès sur six en 2018. Parmi les techniques employées de nos jours dans la lutte contre le cancer, l’une des plus utilisées et prometteuses est la radiothérapie, technique consistant en l’utilisation de rayonnements ionisants afin de déposer de l’énergie dans la tumeur pour la traiter. Or, puisque les cellules saines sont également endommagées par les rayonnements, le but de la radiothérapie est d’augmenter la sélectivité du traitement en épargnant autant que possible les tissus sains. L’optimisation de la sélectivité repose sur plusieurs aspects, comprenant l’optimisation spatiale de la dose, la précision de l’imagerie et de la dosimétrie, le type de rayonnement et la structure temporelle utilisée pour délivrer la dose. En particulier, le rôle du débit de dose et du temps d’irradiation n’a pas encore été explorés en détail.Les accélérateurs cliniques délivrent la dose avec un débit de dose d’environ quelques Gy/min, ce qui entraîne des temps d’irradiation de l’ordre de quelques minutes. Si, d’une part, l’effet d’une réduction du débit de dose de l’ordre de cGy/min sur la réponse biologique est bien connu, d’autre part l’effet d’un débit de dose élevé doit encore être éclairci. Recemment, des études in vivo réalisées avec des électrons et des photons produits par des prototypes d’accélérateurs ont montré que l’administration de la dose dans un temps court (<500 ms) et à un débit de dose élevé (>40 Gy/s) augmente la sélectivité du traitement en réduisant le risque d’effets secondaires sur les tissus sains. Bien que les causes de ce phénomène soient encore à l’étude, le protocole FLASH a été testé avec succès sur le premier patient en 2019. Ces résultats soulignent l’importance de la structure temporelle de l’irradiation et les avantages potentiels que les protocoles d’irradiation à haut débit de dose peuvent apporter en clinique. Or, l’utilisation de ces protocoles demande une compréhension plus approfondie des processus physico-chimiques et biologiques déclenchés par un dépôt de dose rapide.Dans ce contexte, les faisceaux de particules accélérées par laser représentent un outil unique pour jeter de la lumière sur les processus qui régissent la réponse biologique suite à une irradiation à haut débit de dose. Ces faisceaux sont produits en focalisant une impulsion laser ultra-courte (~fs) et ultra-intense (1019 W/cm2) sur une cible mince solide ou gazeuse (~μm), ce qui produit des faisceaux de particules ayant une durée de l’impulsion allant de la picoseconde à la femtoseconde. Ces caractéristiques permettent d’atteindre un débit de dose dans l’impulsion de l’ordre de ~109 Gy/s, c’est-à-dire des conditions d’irradiation extrêmement différentes par rapport aux protocoles de traitement conventionnels et FLASH. Pour cette raison, les faisceaux de particules accélérées par laser ont reçu une grande attention au cours des dernières années, mais leur effet biologique est toujours en discussion et d’autres études plus approfondies sont nécessaires.Cette thèse décrit les atouts des Protons Accélérés par Laser (PAL) et des Électrons Accélérés par Laser (EAL) produits par différents types de laser à haute puissance disponibles dans le commerce. En particulier, elle présente des études expérimentales et théoriques réalisées avec trois types de faisceaux permettant différentes modalités temporelles d’administration de la dose. L’objectif est de traiter certains des principaux problèmes liés à l’application de ces sources de particules à la biologie des rayonnements et de montrer des solutions et des techniques viable pour mener des études de radiobiologie systématique. Cela demande une caractérisation précise de ces faisceaux, l’optimisation de la distribution de la dose dans la cible biologique à travers la conception de lignes de transport adaptées et, enfin, l’étude de la réponse des instruments de dosimétrie utilisés en clinique à haut débit de dose
Cancer is the second leading cause of death globally, accounting for an estimated 9.6 million deaths, or one in six deaths, in 2018. Besides surgery and chemotherapy, radiotherapy is one of the major treatment modality. It consists in the use of ionising radiation to kill cancerous cells by depositing energy into the tumour and destroying the genetic material that controls how cells grow and divide. While both cancerous and healthy cells are damaged by radiation, the goal of radiotherapy is to increase the treatment selectivity by sparing as much as possible the healthy tissues. Optimisation of the selectivity reposes on several aspects, including spatial optimisation of the dose, precision of imaging techniques and dosimetry instruments, use of different radiations and temporal structures of dose delivery. In particular, the role of the dose-rate and the total irradiation time has not been extensively explored yet.Clinical accelerators typically deliver the dose with a dose rate around few Gy/min, leading to exposure times in the order of few minutes to deliver a therapeutic dose. While the effect of a reduction of the dose rate in the order of cGy/min is well known, the effect of high-dose rate, fast irradiation on living cells still need to be elucidated. Evidences of an effect of the high dose-rate on the biological response have been recently observed in many studies. In particular, in-vivo studies performed with electrons and photons produced by accelerator prototypes have shown that delivering the prescribed dose in a short exposure time (<500ms) and at a high dose-rate (>40Gy/s) increases the treatment selectivity by reducing the occurrence of secondary effects on healthy tissues compared to conventional treatments with the same total dose. Although theoretical explanations underpinning such phenomenon are still under discussion, the so-called FLASH protocol has been successfully tested with the first human patient in 2019, paving the way for further research in this domain. These important results point out the importance of the dose delivery modality on the treatment selectivity and the potential benefit that high dose-rate protocols may bring to clinics, asking for a deeper understanding of the physico-chemical and biological processes following fast dose deposition.In this scenario, Laser-Driven Particle (LDP) beams represent a unique tool to shed some light on the radiobiological response following high-dose rate irradiation. LDP sources are produced by focusing an ultra-short (~fs) and ultra-intense (1019 W/cm2) laser pulse on a solid or gaseous thin target (~μm), producing proton and electron bunches with duration of respectively a few picoseconds and a few femtoseconds. These characteristics allow the reach of extremely high peak dose-rate in the pulse of the order of ~109 Gy/s in comparison with conventional and FLASH treatment protocols. For this reason, LDP sources have been receiving great attention in the last decade, but their radiobiological effect is still debated and further systematic studies are required.This thesis discusses the potential of both Laser-Accelerated Protons (LAP) and Laser-Accelerated Electrons (LAE) produced by different types of commercially available high-power lasers systems. In particular, it presents experimental and theoretical studies carried out with three different types of LDP beams, i.e. Hz LAPs, single-shot LAPs and kHz LAEs, enabling different temporal modalities of dose delivery. The goal is to address some of the main issues related to the application of such sources to radiation biology and show viable solutions and irradiation protocols to perform systematic radiobiology studies. Such issues include accurate characterisation of the source, optimisation of the dose distribution at the biological target through the design of adapted transport beamlines and investigation of the behaviour of dosimetric instruments for high dose-rate dosimetry

Recently a powerful electron accelerator, 50 MeV race-track microtron, has been taken into clinical use. This gives the opportunity to treat patients with higher x-ray and electron energies than before. Furthermore, treatments can be performed were the entire fractional dose can be delivered in parts of a second. The relative biological effectiveness (RBE) of high energy photons (up to 50 MV) was studied in vitro and in vivo. Oxygen enhancement ratio (OER) of 50 MV photons and RBE of 50 MeV electrons were investigated in vitro. Single-fraction experiments, in vitro, using V-79 Chinese hamster fibroblasts showed an RBE for 50 MV x-rays of approximately 1.1 at surviving fraction 0.01, with reference to the response to 4 MV x- rays. No significant difference in OER could be demonstrated. Fractionation experiments were carried out to establish the RBE at the clinically relevant dose level, 2 Gy. The RBE calculated for the 2 Gy/fraction experiments was 1.17. The RBEs for 20 MV x-rays and 50 MeV electrons were equal to one. In order to investigate the validity of these results, the jejunal crypt microcolony assay in mice was used to determine the RBE of 50 MV x-rays. The RBE for 50 MV x-rays in this case was estimated to be 1.06 at crypt surviving fraction 0.1. Photonuclear processes are proposed as one possible explanation to the higher RBE for 50 MV x-rays. Several studies of biological response to ionizing radiation of high absorbed dose rates have been performed, often with conflicting results. With the aim of investigating whether a difference in effect between irradiation at high dose rates and at conventional dose rates could be verified, pulsed 50 MeV electrons from a clinical accelerator were used for experiments with ultra high dose rates (mean dose rate: 3.8 x 10^ Gy/s) in comparison to conventional (mean dose rate: 9.6 x 10"^ Gy/s). V-79 cells were irradiated in vitro under both oxic and anoxic conditions. No significant difference in relative biological effectiveness (RBE) or oxygen enhancement ratio (OER) was observed for ultra high dose rates compared to conventional dose rates. A central issue in clinical radiobiological research is the prediction of responses to different radiation qualities. The choice of cell survival and dose response model greatly influences the results. In this context the relationship between theory and model is emphasized. Generally, the interpretations of experimental data are dependent on the model. Cell survival models are systematized with respect to their relations to radiobiological theories of cell kill. The growing knowledge of biological, physical, and chemical mechanisms is reflected in the formulation of new models. This study shows that recent modelling has been more oriented towards the stochastic fluctuations connected to radiation energy deposition. This implies that the traditional cell survival models ought to be complemented by models of stochastic energy deposition processes at the intracellular level.

S. 1-44: sammanfattning, s. 47-130: 5 uppsatser

digitalisering@umu

A dose rate measurement survey was performed at various locations inside the radiation chamber of the Cobalt-60 gamma irradiation facility located in Room 130, Building 20 at the University of Arizona. TLDs were used for the dose rate measurements. It was observed that the dose rates decrease rapidly with increasing distance from the source. Also, dose rates decreased with increased distance away from the centerline of the radiation chamber which is indicative of the position of the effective center of the source. Percent dose rates with respect to the dose rate of the calibration position were tabulated.

Previous research 1 on this subject tracked the presumed exact path the HDR source would follow in real-time, during breast brachytherapy treatments in other to ensure accurate dose delivery and effectively confirm actual source position. As a continuation, this research has three objectives. Firstly, we will extract information from patient DICOM file which will be used to perform evaluations, then we will establish communication between our C program and the new Varex Paxscan flat panel detector (FPD). Finally, we will try to embed our C codes into a MATLAB graphical user interface (GUI) This research will attempt to improve the overall existing system in several ways including, code optimization and trying a sample simulation of the process in MATLAB guide app, to check the quality of the new design. Finally, all the algorithms will be integrated into the user-friendly GUI, such that its operation can be implemented easily. The FPD is used to obtain images resulting from the exit radiation of the HDR source, emerging from an organized matrix of markers. The images are processed using in-built functions in MATLAB to obtain projection coordinates, and marker coordinates. Each marker along with its projection constitutes a line in 3D. Using the mathematical solution for near intersection of two 3D lines, N-markers will produce N*(N-1)/2 points of intersection and their mean will produce a more precise source position. The changes in this position as well as the time interval between these changes will be used to confirm the accuracy of our treatment system using the standalone monitoring system built in this research. In the previous study the accuracy of source position detection using the FPD was found to be in sub-millimeter. This study which uses a new FPD with improved features is used to confirm that, but our focus here is improvement of the previous work, as stated earlier.

Submitted by Pedro Silva Filho (pfsilva@ipen.br) on 2017-11-23T09:59:05Z No. of bitstreams: 0
Made available in DSpace on 2017-11-23T09:59:05Z (GMT). No. of bitstreams: 0
A braquiterapia de baixas taxas de dose realizada com sementes de 125I tem sido amplamente usada por décadas em variados sítios anatômicos, com bons resultados clínicos. O advento de algoritmos para cálculo de dose baseados em modelos (MBDCAs) permitiu aprimorar oestudo de deposição da dose considerando heterogeneidades como diferentes tecidos, órgãos,aplicadores com composições diferentes da água, proporcionando a análise em geometriascomplexas. As simulações matemáticas realizadas através destes algoritmos possibilitam odesenvolvimento de modelos fisicamente mais acurados que estendem sua aplicabilidade àverificação de sistemas de planejamento em braquiterapia. Neste trabalho foram estudadasconfigurações de objetos simuladores confeccionados para medidas experimentais e simuladosatravés do código MCNP de Monte Carlo a fim de observar as diferenças ocasionadas pelaintrodução de heterogeneidades quando presentes fontes de 125I de baixa taxa de dose. Para estepropósito, distintas as vertentes do tema foram abordadas, entre elas o estudo da influênciaexercida pelos parâmetros de densidade e composição dos materiais tecido equivalentes. Osresultados obtidos demonstraram que, o efeito que a composição de cada um dos materiaisexerce sobre a deposição de dose é mais expressivo que o efeito de sua densidade. Em outroestudo, foi estabelecida uma relação para estimar, de maneira simples, a dose de atenuação detecidos heterogêneos a partir da aferição ou simulação da dose obtida num objeto simuladorconstituído por PMMA, metodologia que pode ser desenvolvida e implementada na rotina clínica.Para complementação das análises dos estudos dosimétricos com a presença deheterogeneidades, foi realizada a validação da geometria simulada da semente de 125I, onde sereproduziu a metodologia de cálculo dosimétrico presente no TG-43 da AAPM. Além disto, foirealizado o estudo teórico da dependência energética dos dosímetros termoluminescentes paraanalisar a variação de sua resposta conforme a energia. A metodologia desenvolvida para oestudo dos efeitos da heterogeneidade na deposição de dose é recomendada na avaliação desistemas de planejamento computadorizados que possuem algoritmos de cálculo de dosebaseados em modelos, quando utilizadas fontes de 125I com baixa taxa de dose, de forma acontribuir na incorporação de novas estimativas de doses com maior acurácia.
Dissertação (Mestrado em Tecnologia Nuclear)
IPEN/D
Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP

Radiotherapy (RT) has recently evolved with the emergence of heavy ion radiations or new fractionation schemes of photon therapy, which modify the dose rate of treatment delivery. The aim of the present study was then to evaluate the in vitro influence of a ultra-high dose rate comparing them with standard dose rate. In this regard, a radioresistant SK-MEL-28 cell line were irradiated with x-ray in order to have a total dose of 2 and 4 Gy, at two different dose rate. The ultra-high dose rate is a specific property of the dense plasma focus (DPF) device, which has pulsed operation and thus gives short and highly energetic pulses of multiple types of rays and particles, in this case, we focused our study on the influence of X-rays. While a low dose rate is obtained with conventional X-ray tube. In this study it results that a ultra-high dose rate enhances radiosensitivity of melanoma cells while reducing the adhesion, proliferation and migration ability of cells.

Irradiadores comerciais de grande porte são projetados para processarem grandes quantidades de produtos com altas doses, por exposição à radiação gama. A irradiação em escala industrial é efetuada de forma dinâmica, em que os produtos percorrem um caminho em torno de uma fonte de radiação, geralmente de 60Co, cuja atividade é da ordem de TBq a PBq (kCi a MCi). A dose será diretamente proporcional ao tempo transcorrido pelo material para percorrer este trajeto em torno da fonte. Entretanto, em algumas situações, principalmente para pesquisas ou processos de validação de clientes seguindo a norma ISO 11137, se faz necessário irradiar pequenas amostras com doses fracionadas na posição de irradiação estática. Nesta posição as amostras são colocadas dentro da sala de irradiação a uma distância fixa da fonte e as doses recebidas são determinadas utilizando-se dosímetros. Portanto, a dose somente será conhecida depois da irradiação, pela leitura dos mesmos. Entretanto, em irradiadores industriais, diferentes tipos de produtos com diferentes densidades atravessam o caminho entre a fonte e a posição de irradiação estática, onde estão as amostras. Conseqüentemente, a taxa de dose variará dependendo da densidade do produto, que está sendo irradiado dinamicamente. Uma metodologia adequada seria monitorar a dose recebida pelas amostras em tempo real, medindo a dose por meio de um detector de radiação, com uma melhor precisão e exatidão. Neste trabalho foi desenvolvida uma câmara de ionização cilíndrica de 0.9 cm3, para monitorar as altas doses recebidas por amostras em tempo real, na posição de irradiação estática de um irradiador gama de 60Co. Os gases de nitrogênio e de argônio a pressão de 10exp5 Pa (1 bar) foram utilizados para preencherem a câmara de ionização e determinar uma configuração de trabalho apropriada, para o detector ser utilizado em medidas de altas doses. Cabos de isolação mineral foram soldados diretamente ao corpo da câmara de ionização, para a transmissão do sinal gerado pelo detector até a eletrônica associada, distante cerca de 20 m. O sinal obtido foi cerca de 100 vezes maior do que o ruído de fundo. Este sistema dosimétrico foi testado em um irradiador gama de categoria I e na posição de irradiação estática de um irradiador de grande porte, em que diferentes taxas de dose foram obtidas utilizando materiais absorvedores. Foi encontrada uma boa linearidade do detector entre a dose e a carga, independentemente das diferentes taxas de dose. As incertezas de todas as curvas ficaram abaixo dos +/- 5 %, valor de incerteza máxima recomendada para um sistema dosimétrico de rotina. A câmara de ionização desenvolvida se mostrou adequada para ser utilizada como um dosímetro em tempo real, independente da degradação do espectro causada pela absorção dos fótons da fonte de 60Co, pelo material em irradiação dinâmica.
Industrial gamma irradiators facilities are designed for processing large amounts of products, which are exposed to large doses of gamma radiation. The irradiation, in industrial scale, is usually carried out in a dynamic form, where the products go through a 60Co gamma source with activity of TBq to PBq (kCi to MCi). The dose is estimated as being directly proportional to the time that the products spend to go through the source. However, in some situations, mainly for research purposes or for validation of customer process following the ISO 11137 requirements, it is required to irradiate small samples in a static position with fractional deliver doses. The samples are put inside the irradiation room at a fixed distance from the source and the dose is usually determined using dosimeters. The dose is only known after the irradiation, by reading the dosimeter. Nevertheless, in the industrial irradiators, usually different kinds of products with different densities go through between the source and the static position samples. So, the dose rate varies in function of the product density. A suitable methodology would be to monitor the samples dose in real time, measuring the dose on line with a radiation detector, which would improve the dose accuracy and avoid the overdose. A cylindrical ionization chamber of 0.9 cm3 has been developed for high-doses real-time monitoring, during the sample irradiation at a static position in a 60Co gamma industrial plant. Nitrogen and argon gas at pressure of 10exp5 Pa (1bar) was utilized to fill the ionization chamber, for which an appropriate configuration was determined to be used as a detector for high-dose measurements. To transmit the signal generated in the ionization chamber to the associated electronic and processing unit, a 20 m mineral insulated cable was welded to the ionization chamber. The signal to noise ratio produced by the detector was about 100. The dosimeter system was tested at a category I gamma irradiator and at an industrial irradiation plant in static position, using different absorbing materials. A good linearity of the detector was found between the dose and the accumulated charge, independently of the different dose rates caused by absorbing materials. The uncertainties for all curves were less than 5%, which is recommended for a dosimetric system routine. The developed ionization chamber showed to be suitable as a dosimeter on line, independently of the spectrum degradation caused by the absorption of the 60Co photons in the material under dynamic irradiation.

Brahiterapija visokim brzinama doze (HDR–BT) predstavlja efikasan modalitet zračenja kod pacijenata sa lokalizovanim karcinomom prostate (CaP) svih rizika. Za razliku od transkutane radioterapije i brahiterapije niskim brzinama doze (LDR–BT), kod ove grupe pacijenata u intersticijalnoj HDR–BT još uvek nisu jednoznačno definisane ukupne doze zračenja, način frakcionisanja kod pacijenata sa lokalizovanim CaP različitih rizika. U periodu od 2009–2018.god. HDR–BT kao jedinim načinom lečenja (monoterapija) u Opštoj bolnici Medicinski sistem Beograd, lečeno je 35 pacijenata (6 (17,1%) pacijenata niskog rizika, 21 (60%) pacijent srednjeg rizika i 8 (22,9%) pacijenata visokog rizika) sa lokalizovanim CaP različitih rizika od relapsa i progresije bolesti. Grupe pacijenata sa srednjim i visokim rizikom spojene su u jednu grupu (grupa sa višim rizikom). Tehnika sprovođenja HDR–BT, osim u pojedinačnim specifičnim detaljima, bila je slična kao i kod LDR–BT. Aplikacija igala, segmentacija, delineacija i planiranje HDR–BT vršeno je korišćešem transrektalnog ultrazvuka (TRUS) i izocetričnog radioskopskog C–luka, a zračenje je sprovedeno na uređaju Microselectron HDR sa zatvorenim radioaktivnim izvorom 192Ir početne aktivnosti 370 GBq. Aplikovane terapijske doze (TD), u opsegu od 30–57 Gy frakcionisane su u 3–4 nezavisne frakcije sa razmakom od 2–3 nedelje između frakcija, a individualizovane su prema nivou rizika, stanju organa u riziku (OAR) i kvalitetu aplikacije (indeksu prekrivanja CTV sa planiranom terapijskom dozom (CI100%) i mogućnošću zaštite OAR). Uspešnost terapije ocenjivana je postignutom biohemijskom kontrolom (BFS – biochemical–free–survival), prema ASTRO i Phoenix kriterijumima, kao i ukupnim preživljavanjem u periodu od 5 godina (2–9 godina) posle sprovedene terapije. U niskorizičnoj grupi pacijenata lečenih HDR–BT, BFS je postignuta kod svih pacijenata kao i ukupno preživljavanje. U grupi pacijenata sa višim rizikom BFS je postignuta kod 95,8% lečenih pacijenata, a ukupno 5–to godišnje preživljavanje je 96,4%. BFS u ovom istraživanju se pokazala statistički značajnije bolja nego ona koju su prikazali drugi autori. Na osnovu rizika, nivoa PSA, TD i indeksa pokrivenosti CTV sa TD, izvršeno je modelovanje terapijskih parametara korišćenjem MANN (multilauyer artificial neural network). Određena optimalna doza zračenja (TD) u HDR–BT lokalizovanog CaP niskog rizika je 40,7 Gy za CI100% = 1,01. Kod viših rizika TD = 50,9 Gy za CI100% = 1,6. TD se frakcioniše u 4 nezavisne frakcije sa razmakom od 2–3 nedelje. Ovakav izbor parametara HDR–BT (TD, CI100%, i način frakcionisanja), uz individualizaciju i kontrolu u toku svake aplikacije, obezbedio bi prihvatljiv nivo kasnih postiradijacionih komplikacija gradusa G1–G3 na uretri (< 17% ukupnog broja lečenih pacijenata), uz minimimalne komplikacije na rektumu (pretežno G1–G2) i zanemarljive komplikacije na mokraćnoj bešici.
High–dose rate brachytherapy (HDR–BT) is an effective therapy modality for patients with localized prostate cancer (CaP) of all risks. In contrast to an external beam radiotherapy and low–dose rate brachytherapy (LDR–BT), in these patients, the interstitial HDR–BT, the total radiation dose and fractionation is not unambiguously defined. Between 2009–2018 35 patients with localized CaP (6 (17.1%) low–risk patients, 21 (60%) patients medium–risk and 8 (22.9%) high–risk) were treated with HDR–BT, as the only treatment (monotherapy) in the General Hospital Medical System Belgrade. The group of patients with medium–risk and high–risk were merged into a single group (group with a higher–risk). Technique implementation of HDR–BT was similar as in the LDR–BT. Application of needles, segmentation, delineation, and planning of HDR–BT was performed with transrectal ultrasound (TRUS) and izocentrically mounted radioscopic C–arm. Irradiation was done on the Microselectron–HDR brachytherapy unit with a sealed radioactive source 192Ir (370 GBq). The dose (TD), in the range of 30–57 Gy was given fractionated in independent fractions (3–4) with a pause of 2–3 weeks between fractions. TD was individualized according to the risk, the conditions of organs at risk (OAR) and quality of the application (coverage index CI100%), as well as, the ability to protect OAR. Treatment result was evaluated by the achieved biochemical control (BFS – biochemical–free–survival) according to ASTRO and/or Phoenix criteria, as well as an overall survival in the period of 5 years (2–9 years) after the completion of the treatment. In the low–risk group, BFS has been achieved in all patients and overall survival rate is 100%. In the group of patients with higher risk BFS was achieved in 95.8% of treated patients, and 5–year survival rate was 96.4%. BFS in this study was proved to be statistically significantly better than showed by other authors. On the basis of the risk, the level of PSA, TD and CI100%, modeling was performed using the MANN (multilayer artificial neural network). The determined optimal dose TD for localized CaP of low risk is 40.7 Gy for CI100% = 1.0. At higher risk TD = 50.9 Gy for CI100% = 1.6. TD was given in 4 independent fractions with the interval of 2–3 weeks between each fraction. These HDR–BT parameters (TD, CI100%, and the fractionation scheme) with the individualization and control during each application would provide an acceptable level of late complications grade G1–G3 to the urethra (in less than 17% of treated patients), with minimum complications on the rectum (predominantly grade G1–G2) and insignificant complications rate on the urinary bladder.

Les faisceaux de photons produits par les accélérateurs d'électrons linéaires médicaux sont plats, grâce à un cône égalisateur. Les technologies ont évolué et la présence d'un cône n'est plus indispensable. On parle alors de faisceaux FFF (flattening filter free). Les faisceaux FFF présentent des débits de dose plus élevés, des profils de dose hétérogènes, des spectres énergétiques différents et une diminution de la dose hors-champ. Cette thèse a eu pour but d'étudier les caractéristiques des faisceaux FFF, ainsi que l'impact de leur utilisation thérapeutique. Plusieurs thématiques ont été. Des expériences d'irradiation in vitro ont tout d'abord permis de s'assurer que les débits de dose FFF n'ont pas d'impact radiobiologique sur la réponse des cellules irradiées. Une large revue de la littérature a permis de corroborer ces résultats. Afin de maitriser les caractéristiques physiques des faisceaux FFF, des mesures ont été faites avec différents détecteurs. Les effets du spectre et du débit de dose sur la calibration en dose ont aussi été étudiés. Les faisceaux FFF ont été modélisés dans deux TPS. Les modèles ont été comparés entre les deux types de faisceaux et entre les deux TPS. La mise en place des traitements stéréotaxiques a aussi été l'occasion d'appréhender la dosimétrie des petits faisceaux. Nous avons étudié des cas VMAT de cancer de la prostate et des cas de stéréotaxies 3D de tumeurs pulmonaires. La comparaison donne un avantage aux faisceaux FFF. La maitrise de la physique et de la biologie des haut débits a permis de débuter les traitements FFF à l'IPC. Des études comparatives nous permettent aujourd'hui d'adapter leur utilisation au cas par cas
In medical linear electron accelerators, photon beams profiles are homogenised using flattening filters. Technologies have evolved and the presence of this filter is no longer necessary. Flattening filter free (FFF) beams exhibit higher dose rates, heterogeneous dose profiles, modified energy spectra and lower out-of-field dose. This PhD aimed at studying the characteristics of unflattened beams, as well as their impact in clinical utilization. Several subjects were thoroughly investigated: radiobiology, dosimetry, quality controls, modelling and treatment planning. In vitro experiments ensured that the high dose-rate of FFF beams had not a radiobiological impact. A wide review of the literature was conducted to corroborate these results. In order to understand thoroughly the characteristics of FFF beams, measurements were conducted using several detectors. The effect of the spectra and dose rates of unflattened beams on dose calibration were also studied. FFF beams were modeled in two TPSs. The methods, results and model parameters have been compared between the available beam qualities as well as between both TPSs. Furthermore, the implementation of stereotactic treatments technique was the occasion to investigate small beam dosimetry. Prostate cancer cases treated with VMAT and pulmonary tumors treated with stereotactic 3D beams were also studied. The comparison of dose distributions and treatment metrics give advantage to FFF beams. Mastering physical and biological aspects of flattening filter free beams allowed the IPC to start FFF treatments. Comparative studies have since resulted in a deeper understanding on the pertinent use of these beams

In the absence of a fusion neutron source, research on the structural integrity of materials in the fusion environment relies on current fission data and simulation methods. Through investigation of the Fe-Cr system, this detailed study explores the challenges and limitations in the use of currently available radiation sources for fusion materials research. An investigation of ion-irradiated Fe12%Cr using nanoindentation with a cube corner, Berkovich and spherical tip, and micro-cantilever testing with two different geometries, highlighted that the measurement of irradiation hardening was largely dependent on the type of test used. Selected methods were used for the comparison of Fe6%Cr irradiated by ions and neutrons to a dose of 1.7dpa at a temperature of 288°C. Micro-cantilever tests of the Fe6%Cr alloy with beam depths of 400 to 7000nm, identified that size effects may significantly obscure irradiation hardening and that these effects are dependent on radiation conditions. Irradiation hardening in the neutron-irradiated alloy was approximately double that of the ion-irradiated alloy and exhibited increased work hardening. Similar differences in hardening were observed in an Fe5%Cr alloy after ion-irradiation to a dose of 0.6dpa at 400°C and doses rates of 6 x 10^-4dpa/s and 3 x 10^-5dpa/s. Identified by APT, it was shown that increased irradiation hardening was likely to be caused by the enhanced segregation of Cr observed in the alloy irradiated with the lower dose rate. These observations have significant implications for future fusion materials research in terms of the simulation of fusion relevant radiation conditions and micro-mechanical testing.