Rozprawy doktorskie na temat „HDR brachytherapy”

One out of eight deaths throughout the world is due to cancer. Developing new treatments and improving existing treatments is hence of major importance. In this thesis we have studied how mathematical optimization can be used to improve an existing treatment method: high-dose-rate (HDR) brachytherapy. HDR brachytherapy is a radiation modality used to treat tumours of for example the cervix, prostate, breasts, and skin. In HDR brachytherapy catheters are implanted into or close to the tumour volume. A radioactive source is moved through the catheters, and by adjusting where the catheters are placed, called catheter positioning, and how the source is moved through the catheters, called the dwelling time pattern, the dose distribution can be controlled. By constructing an individualized catheter positioning and dwelling time pattern, called dose plan, based on each patient's anatomy, it is possible to improve the treatment result. Mathematical optimization has during the last decade been used to aid in creating individualized dose plans. The dominating optimization model for this purpose is a linear penalty model. This model only considers the dwelling time pattern within already implanted catheters, and minimizes a weighted deviation from dose intervals prescribed by a physician. In this thesis we show that the distribution of the basic variables in the linear penalty model implies that only dwelling time patterns that have certain characteristics can be optimal. These characteristics cause troublesome inhomogeneities in the plans, and although various measures for mitigating these are already available, it is of fundamental interest to understand their cause. We have also shown that the relationship between the objective function of the linear penalty model and the measures commonly used for evaluating the quality of the dose distribution is weak. This implies that even if the model is solved to optimality there is no guarantee that the generated plan is optimal with respect to clinically relevant objectives, or even near-optimal. We have therefore constructed a new model for optimizing the dwelling time pattern. This model approximates the quality measures by the concept conditional value-at-risk, and we show that the relationship between our new model and the quality measures is strong. Furthermore, the new model generates dwelling time patterns that yield high-quality dose distributions. Combining optimization of the dwelling time pattern with optimization of the catheter positioning yields a problem for which it is rarely possible to find a proven optimal solution within a reasonable time frame. We have therefore developed a variable neighbourhood search heuristic that outperforms a state-of-the-art optimization software (CPLEX). We have also developed a tailored branch-and-bound algorithm that is better at improving the dual bound than a general branch-and-bound algorithm. This is a step towards the development of a method that can find proven optimal solutions to the combined problem within a reasonable time frame.

This thesis describes experimental work performed (1998-2001) during the author's involvement with the Brachytherapy group at the Peter MacCallum Cancer Centre (PMCC), where he was employed by its Department of Physical Sciences and subsequent modeling and analytical studies. When PMCC added HDR brachytherapy to its radiation therapy practice, an existing operating suite was considered the ideal location for such procedures to be carried out. The integration of brachytherapy into the theatre environment was considered logical due to the relatively invasive nature of brachytherapy techniques and the availability of medical equipment. This thesis contains the detailed study of three key Research Questions involved in clinical aspects relating to quality assurance of an HDR brachytherapy practice. An investigative chapter is dedicated to the pursuit of each of the Research Questions. The first question asked… Is the novel approach to using modular shielding combined with time and distance constraints adequately optimized during HDR brachytherapy? In order to establish optimal clinical practices, this project evaluates the effectiveness of additional shielding added to the modular shielding system without modification of the previously determined time and distance constraints for PMCC staff, other patients, and member of the public. The DOSXYZnrc user code for the EGSnrc Monte Carlo radiation transport code has been used to model exposure pathways to strategic locations used for measurement in and around the operating theatre suite. Modeling allowed exposure pathways to various areas with the facility to be tested without the need to use real sources. The second Research Question asked… How well is dose anisotropy characterized in the near field range of the clinic's HDR 192Ir source? This study experimentally investigated the anisotropy of dose around a 192Ir HDR source in a water phantom using MOSFETs as relative dosimeters. In addition, modeling using the DOSRZnrc user code for the EGSnrc Monte Carlo radiation transport code was performed to provide a complete dose distribution consistent with the MOSFET measurements. Measurements performed for radial distances from 5 to 30 mm extend the range of measurements to 5 mm which has not been previously reported for this source construction. The third Research Question is aimed at the patient level. Is the dose delivered to in vivo dosimeters, located within critical anatomical structures near the prostate, within acceptable clinical tolerance for a large group of HDR prostate patients? An in vivo dosimetry technique employing TLDs to experimentally measure doses delivered to the urethra and rectum during HDR prostate brachytherapy was investigated. Urethral and rectal in vivo measurements for 56 patients have been performed in the initial fraction of four-fraction brachytherapy boost. In the absence of comparable in vivo data, the following local corrective action level was initially proposed: more than 50% of the prostatic urethra receiving a dose 10% beyond the urethral tolerance. The level for investigative action is considered from the analyses of dose differences between measured data and TPS calculation.

A protocol of establishing radiochromic film based reference dosimetry for high dose rate Ir-192 brachytherapy source was assessed and described. A comparison between calibration curves created in water and Solid Water are provided. Solid Water was shown to be a viable alternative to water in establishing calibration curve for Ir-192 radiation beam. A Monte Carlo correction factor was calculated to convert the dose to water into dose to Solid Water and the experimental methods that we performed agreed with the Monte Carlo results where the ratio (DSW/DW)Ir-192 was found to be 0.9808 ± 0.14% (1σ). EBT-2 GAFCHROMIC film model was also investigated for absorption properties and found to be a less sensitive than its predecessor (EBT-1) in terms of net change of absorbance, but that did not affect the dosimetric value that this film possesses. A dose error assessment method has been described for EBT-2 film model (and is applicable to other types as well) that can establish the time error constraints on the post-irradiation scanning time that will still provide an acceptable dose error for clinical applications if the protocol employing the shorter post-irradiation scanning time is implemented in the clinic. We show that for two post-irradiation scanning times of 30 minutes and 24 hours the 1% dose error can be granted if the scanning time window is less than ± 5 minutes and ± 2 hours, respectively. Performance of EBT-2 model was also evaluated in water and it was concluded that a suggested correction protocol is necessary for immersion times that exceed 2 hours. This correction was tested with the calibration curve created from water setup and found to be effective when compared to the dose-corrected calibration curve in Solid Water.
Un protocole d'établir film radiochromique dosimétrie de référence en fonction de débit de dose élevé source Ir-192 curiethérapie été évalués et décrits. Une comparaison entre les courbes d'étalonnage créé dans l'eau et Solid WaterTM sont fournis. Solid WaterTM s'est révélée être une alternative viable à l'eau dans l'établissement de la courbe d'étalonnage pour les Ir-192 faisceau de rayonnement. Un facteur de correction de Monte Carlo a été calculé pour convertir la dose à l'eau en dose à Solid WaterTM et les méthodes expérimentales que nous avons réalisé d'accord avec les résultats de Monte Carlo où le ratio (DSW/DW)Ir-192 a été trouvé à 0.9808 ± 0.14% (1σ). EBT-2 modèle GAFCHROMICTM film a également été étudiée pour les propriétés d'absorption et jugé être un moins sensible que son prédécesseur (EBT-1) en termes de variation nette de l'absorbance, mais cela n'a pas d'incidence sur la valeur dosimétrique que ce film possède. Une méthode d'évaluation des doses d'erreur a été décrit pour le modèle EBT-2 film (et est applicable à d'autres types ainsi) qui permet d'établir les contraintes de temps d'erreur sur le post-irradiation temps de balayage, qui va encore donner une erreur de dose acceptable pour des applications cliniques, si le protocole emploie le plus court post-irradiation de numérisation temps est mis en œuvre dans la clinique. Nous montrons que pour deux post-irradiation de numérisation fois de 30 minutes et 24 heures, la dose d'erreur de 1% peut être accordée si la fenêtre de temps de balayage est inférieure à ± 5 minutes et de ± 2 heures, respectivement. Performance de la EBT-2 modèle a également été évaluée dans l'eau et il a été conclu un protocole de correction proposé est nécessaire pour que les temps d'immersion supérieure à 2 heures. Cette correction a été testé avec la courbe de calibration créée à partir d'installation de l'eau et ont été jugés effic

In High Dose Rate (HDR) brachytherapy, treatment dose to patients is highly dependent on the accuracy of positioning and duration of the source. Source misplacement or wrong duration of treatment could potentially result in adverse clinical side effects to patients. In order to maintain successful treatment for patients, an independent Quality Assurance (QA) verification is crucial to measure the High Dose Rate (HDR) source positioning and dwell time periodically to ensure the prescribed dose is correct and safe for brachytherapy treatment. The current QA practice used to validate the accuracy of dwell time of the source is by using a stopwatch and measure the dwell position on the source position check ruler. Nevertheless, reaction time of human poses a major concern regarding the accuracy in these manual operating procedures. In this thesis, a new QA tool is proposed to acquire accurate information about time structure and source positioning in HDR brachytherapy. The tool consists of a consumer-grade webcam, a source position check ruler, a laptop computer and a custom-made combined camera-ruler mounting tool. The camera is used to capture the motion of the moving source in real time. Each frame contains positional and temporal information that are important to determine the difference between the measured and the actual HDR source position and time structure. Finally, a Graphical User Interface (GUI) application program is developed to receive the input from the camera for image processing. The measured results (time structure and positional information) are displayed on the computer screen as the output of the designed application. The tool was found to be able to reduce the time required significantly for the QA and minimize the impact of human errors. At the time of writing, the sensitivity of the system to luminous changes in the environment warrants further efforts to render the tool even more useful. Based on the experimental results, the accuracy of dwell time measured by the proposed system was ± 40 ms. The minimum detectable dwell time of the proposed system was 200 ms. The range of effective dwell position that could be measured by the system ranged from 1300 mm to 1500 mm (excluding 1300 mm and 1500 mm). The accuracy of dwell position measured by the proposed system was ± 1mm.
published_or_final_version
Diagnostic Radiology
Master
Master of Medical Sciences

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

During gynaecological high-dose rate (HDR) intracavitary brachytherapy (ICBT), invivo dosimetry is done to monitor the dose received by the bladder and rectum. This study was aimed at validating the need to do in-vivo dosimetry during ICBT. Thirty patients were recruited to participate in the study. Treatment setup data from the thirty patients was used to reproduce applicator and in-vivo diode treatment setups in a water phantom. Radiation doses administered to the patients were replicated in the water phantom to measure the doses at marked dose reference positions.

Cette étude porte sur le développement d’un outil de contrôle qualité basé sur l’expérience, dérivé du concept de frontière stochastique en économie et s’appuyant sur des connaissances géométriques spécifiques au patient pour améliorer la qualité des traitements de curiethérapie à haut débit de dose pour le cancer de la prostate. Cent plans cliniques de curiethérapie à haut débit de dose de la prostate ont été utilisés dans cette étude, dans laquelle l’échographie transrectale était la seule modalité d’imagerie. Une fraction unique de 15 Gy a était prescrite à tous ces patients. Un algorithme de recuit simulé de planification inverse a été appliqué pour réaliser tous les plans et Oncentra Prostate a été employé comme système d’imagerie et de planification du traitement en temps réel. Les recommandations relatives aux paramètres de dose de la société américaine de curiethérapie pour la cible et les organes à risque ont été suivies. Les relations entre les paramètres géométriques et les paramètres dosimétriques d’intérêt sont examinées. Les paramètres géométriques sont liés aux dimensions anatomiques des patients et ceux associés aux cathéters. Pour déterminer les paramètres géométriques dominants dans un modèle de frontière stochastique donné, les relations monotones entre les paramètres géométriqueset les paramètres dosimétriques d’intérêt sont mesurées avec une approche non paramétrique, à savoir le coefficient de corrélation de Spearman. Ensuite, une recherche de force brute est effectuée pour un modèle donné dans lequel différents modèles, incluant toutes les combinaisons possibles des paramètres géométriques dominantes, sont optimisés. L’optimisation est accomplie en utilisant une méthode de vraisemblance maximale implémentée dans le progiciel de calcul statistique R, avec son algorithme de recuit simulée généralisée. Le test du rapport de vraisemblance et sa valeur-p correspondante sont utilisés pour comparer la signification statistique de l’ajout de nouveaux paramètres géométriques aux modèles. Un modèle de production pour la cible et un modèle de coût pour chacun des organes à risque sont développés pour le traitement par curiethérapie à haut débit de dose guidé par l’échographie transrectale. De plus, pour valider si chacun des modèles développés est universel, nous l’appliquons à une autre catégorie de traitement de la curiethérapie à haut débit de dose, dans laquelle la tomodensitométrie était utilisée comme modalité d’imagerie plutôt que de l’échographie transrectale. Ainsi, une nouvelle cohorte de cent plans cliniques curiethérapie à haut débit de dose guidés par la tomodensitométrie est prise en compte. Un modèle de frontière stochastique de production pour la cible et trois modèles de coût pour les organes à risque basés sur la tomodensitométrie sont développés. Enfin, les modèles intégrés de la tomodensitométrie et de l’échographie transrectale sont comparés.
This thesis focuses on developing an experience-based quality control (QC) tool, derived from the concept of stochastic frontier (SF) analysis in economics and based on patient-specific geometric knowledge to improve the quality of the high-dose-rate brachytherapy (HDR-BT) treatment for prostate cancer. One hundred clinical HDR prostate BT plans, using the transrectal ultrasound (TRUS) asthe only imaging modality, all treated with a single fraction of 15 Gy, and made using Inverse PlanningSimulated Annealing (IPSA) algorithm, are studied. Also, Oncentra Prostate system is employed as the real-time 3D prostate imaging and treatment planning system. American Brachytherapy Society dose parameter recommendations for target and organs at risk (OARs) were followed. Relationships between all the different geometric parameters (GPs) and the four dosimetric parameters (DPs) V100 of the prostate, V75 of the bladder and rectum, and D10 of the urethra were examined. Geometricinformation of the patients and catheters are considered as different GPs. To find the dominant GPs in a given SF model, monotonic relationships between the GPs and DPs of interest are measured using a nonparametric approach: the Spearman correlation coefficient. Then, to determine the optimal SF model for each of the target production SF, and the OARs cost SF models, brute-force searches are performed. Different SF models including all the possible combinations of the dominant GPs in the SF model under study are optimized. Optimization is done using a maximum likelihood method implemented in the statistical computing package R, along with its Generalized Simulated Annealing algorithm. The likelihood ratio test and its corresponding p-value are used to compare the statistical significance of adding new GPs to SF models. A production SF (PSF) model for the target, and a costSF (CSF) model for each of the bladder, rectum, and urethra are developed for TRUS-guided HDR-BTtreatment. The difference between the dose value of a plan obtained by IPSA and the one predicted by an SF model is explored. Additionally, to verify if each of the models developed for the TRUS-guided category of the HDR-BT treatment for prostate is universal, we apply it on another category of HDR-BT treatment, in which computed tomography (CT) was used as the imaging modality. So, a different cohort of one hundred clinical CT-guided HDR-BT plans is taken into consideration. A target production SF and three OARs cost SF models are developed for the CT-based plans. Subsequently, the built-in SF models for the TRUS-based and CT-based plans are compared.

Cette étude porte sur le développement d’un outil de contrôle qualité basé sur l’expérience, dérivé du concept de frontière stochastique en économie et s’appuyant sur des connaissances géométriques spécifiques au patient pour améliorer la qualité des traitements de curiethérapie à haut débit de dose pour le cancer de la prostate. Cent plans cliniques de curiethérapie à haut débit de dose de la prostate ont été utilisés dans cette étude, dans laquelle l’échographie transrectale était la seule modalité d’imagerie. Une fraction unique de 15 Gy a était prescrite à tous ces patients. Un algorithme de recuit simulé de planification inverse a été appliqué pour réaliser tous les plans et Oncentra Prostate a été employé comme système d’imagerie et de planification du traitement en temps réel. Les recommandations relatives aux paramètres de dose de la société américaine de curiethérapie pour la cible et les organes à risque ont été suivies. Les relations entre les paramètres géométriques et les paramètres dosimétriques d’intérêt sont examinées. Les paramètres géométriques sont liés aux dimensions anatomiques des patients et ceux associés aux cathéters. Pour déterminer les paramètres géométriques dominants dans un modèle de frontière stochastique donné, les relations monotones entre les paramètres géométriqueset les paramètres dosimétriques d’intérêt sont mesurées avec une approche non paramétrique, à savoir le coefficient de corrélation de Spearman. Ensuite, une recherche de force brute est effectuée pour un modèle donné dans lequel différents modèles, incluant toutes les combinaisons possibles des paramètres géométriques dominantes, sont optimisés. L’optimisation est accomplie en utilisant une méthode de vraisemblance maximale implémentée dans le progiciel de calcul statistique R, avec son algorithme de recuit simulée généralisée. Le test du rapport de vraisemblance et sa valeur-p correspondante sont utilisés pour comparer la signification statistique de l’ajout de nouveaux paramètres géométriques aux modèles. Un modèle de production pour la cible et un modèle de coût pour chacun des organes à risque sont développés pour le traitement par curiethérapie à haut débit de dose guidé par l’échographie transrectale. De plus, pour valider si chacun des modèles développés est universel, nous l’appliquons à une autre catégorie de traitement de la curiethérapie à haut débit de dose, dans laquelle la tomodensitométrie était utilisée comme modalité d’imagerie plutôt que de l’échographie transrectale. Ainsi, une nouvelle cohorte de cent plans cliniques curiethérapie à haut débit de dose guidés par la tomodensitométrie est prise en compte. Un modèle de frontière stochastique de production pour la cible et trois modèles de coût pour les organes à risque basés sur la tomodensitométrie sont développés. Enfin, les modèles intégrés de la tomodensitométrie et de l’échographie transrectale sont comparés.
Cette étude porte sur le développement d’un outil de contrôle qualité basé sur l’expérience, dérivé du concept de frontière stochastique en économie et s’appuyant sur des connaissances géométriques spécifiques au patient pour améliorer la qualité des traitements de curiethérapie à haut débit de dose pour le cancer de la prostate. Cent plans cliniques de curiethérapie à haut débit de dose de la prostate ont été utilisés dans cette étude, dans laquelle l’échographie transrectale était la seule modalité d’imagerie. Une fraction unique de 15 Gy a était prescrite à tous ces patients. Un algorithme de recuit simulé de planification inverse a été appliqué pour réaliser tous les plans et Oncentra Prostate a été employé comme système d’imagerie et de planification du traitement en temps réel. Les recommandations relatives aux paramètres de dose de la société américaine de curiethérapie pour la cible et les organes à risque ont été suivies. Les relations entre les paramètres géométriques et les paramètres dosimétriques d’intérêt sont examinées. Les paramètres géométriques sont liés aux dimensions anatomiques des patients et ceux associés aux cathéters. Pour déterminer les paramètres géométriques dominants dans un modèle de frontière stochastique donné, les relations monotones entre les paramètres géométriqueset les paramètres dosimétriques d’intérêt sont mesurées avec une approche non paramétrique, à savoir le coefficient de corrélation de Spearman. Ensuite, une recherche de force brute est effectuée pour un modèle donné dans lequel différents modèles, incluant toutes les combinaisons possibles des paramètres géométriques dominantes, sont optimisés. L’optimisation est accomplie en utilisant une méthode de vraisemblance maximale implémentée dans le progiciel de calcul statistique R, avec son algorithme de recuit simulée généralisée. Le test du rapport de vraisemblance et sa valeur-p correspondante sont utilisés pour comparer la signification statistique de l’ajout de nouveaux paramètres géométriques aux modèles. Un modèle de production pour la cible et un modèle de coût pour chacun des organes à risque sont développés pour le traitement par curiethérapie à haut débit de dose guidé par l’échographie transrectale. De plus, pour valider si chacun des modèles développés est universel, nous l’appliquons à une autre catégorie de traitement de la curiethérapie à haut débit de dose, dans laquelle la tomodensitométrie était utilisée comme modalité d’imagerie plutôt que de l’échographie transrectale. Ainsi, une nouvelle cohorte de cent plans cliniques curiethérapie à haut débit de dose guidés par la tomodensitométrie est prise en compte. Un modèle de frontière stochastique de production pour la cible et trois modèles de coût pour les organes à risque basés sur la tomodensitométrie sont développés. Enfin, les modèles intégrés de la tomodensitométrie et de l’échographie transrectale sont comparés.
This thesis focuses on developing an experience-based quality control (QC) tool, derived from the concept of stochastic frontier (SF) analysis in economics and based on patient-specific geometric knowledge to improve the quality of the high-dose-rate brachytherapy (HDR-BT) treatment for prostate cancer. One hundred clinical HDR prostate BT plans, using the transrectal ultrasound (TRUS) asthe only imaging modality, all treated with a single fraction of 15 Gy, and made using Inverse PlanningSimulated Annealing (IPSA) algorithm, are studied. Also, Oncentra Prostate system is employed as the real-time 3D prostate imaging and treatment planning system. American Brachytherapy Society dose parameter recommendations for target and organs at risk (OARs) were followed. Relationships between all the different geometric parameters (GPs) and the four dosimetric parameters (DPs) V100 of the prostate, V75 of the bladder and rectum, and D10 of the urethra were examined. Geometricinformation of the patients and catheters are considered as different GPs. To find the dominant GPs in a given SF model, monotonic relationships between the GPs and DPs of interest are measured using a nonparametric approach: the Spearman correlation coefficient. Then, to determine the optimal SF model for each of the target production SF, and the OARs cost SF models, brute-force searches are performed. Different SF models including all the possible combinations of the dominant GPs in the SF model under study are optimized. Optimization is done using a maximum likelihood method implemented in the statistical computing package R, along with its Generalized Simulated Annealing algorithm. The likelihood ratio test and its corresponding p-value are used to compare the statistical significance of adding new GPs to SF models. A production SF (PSF) model for the target, and a costSF (CSF) model for each of the bladder, rectum, and urethra are developed for TRUS-guided HDR-BTtreatment. The difference between the dose value of a plan obtained by IPSA and the one predicted by an SF model is explored. Additionally, to verify if each of the models developed for the TRUS-guided category of the HDR-BT treatment for prostate is universal, we apply it on another category of HDR-BT treatment, in which computed tomography (CT) was used as the imaging modality. So, a different cohort of one hundred clinical CT-guided HDR-BT plans is taken into consideration. A target production SF and three OARs cost SF models are developed for the CT-based plans. Subsequently, the built-in SF models for the TRUS-based and CT-based plans are compared.
This thesis focuses on developing an experience-based quality control (QC) tool, derived from the concept of stochastic frontier (SF) analysis in economics and based on patient-specific geometric knowledge to improve the quality of the high-dose-rate brachytherapy (HDR-BT) treatment for prostate cancer. One hundred clinical HDR prostate BT plans, using the transrectal ultrasound (TRUS) asthe only imaging modality, all treated with a single fraction of 15 Gy, and made using Inverse PlanningSimulated Annealing (IPSA) algorithm, are studied. Also, Oncentra Prostate system is employed as the real-time 3D prostate imaging and treatment planning system. American Brachytherapy Society dose parameter recommendations for target and organs at risk (OARs) were followed. Relationships between all the different geometric parameters (GPs) and the four dosimetric parameters (DPs) V100 of the prostate, V75 of the bladder and rectum, and D10 of the urethra were examined. Geometricinformation of the patients and catheters are considered as different GPs. To find the dominant GPs in a given SF model, monotonic relationships between the GPs and DPs of interest are measured using a nonparametric approach: the Spearman correlation coefficient. Then, to determine the optimal SF model for each of the target production SF, and the OARs cost SF models, brute-force searches are performed. Different SF models including all the possible combinations of the dominant GPs in the SF model under study are optimized. Optimization is done using a maximum likelihood method implemented in the statistical computing package R, along with its Generalized Simulated Annealing algorithm. The likelihood ratio test and its corresponding p-value are used to compare the statistical significance of adding new GPs to SF models. A production SF (PSF) model for the target, and a costSF (CSF) model for each of the bladder, rectum, and urethra are developed for TRUS-guided HDR-BTtreatment. The difference between the dose value of a plan obtained by IPSA and the one predicted by an SF model is explored. Additionally, to verify if each of the models developed for the TRUS-guided category of the HDR-BT treatment for prostate is universal, we apply it on another category of HDR-BT treatment, in which computed tomography (CT) was used as the imaging modality. So, a different cohort of one hundred clinical CT-guided HDR-BT plans is taken into consideration. A target production SF and three OARs cost SF models are developed for the CT-based plans. Subsequently, the built-in SF models for the TRUS-based and CT-based plans are compared.

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.

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.

The thesis aims to improve treatment dose accuracy in brachytherapy using a high dose rate (HDR) Ir-192 stepping source and in external beam therapy using intensity modulated radiation therapy (IMRT). For HDR brachytherapy, this has been achieved by investigating dose errors in the near field and the transit dose of the HDR brachytherapy stepping source. For IMRT, this study investigates the volume effect of detectors in the dosimetry of small fields, and the clinical implementation and dosimetric verification of a 6MV photon beam for IMRT. For the study of dose errors in the near field of an HDR brachytherapy stepping source, the dose rate at point P at 0.25 cm in water from the transverse bisector of a straight catheter was calculated with Monte Carlo code MCNP 4.A. The Monte Carlo (MC) results were used to compare with the results calculated with the Nucletron Brachytherapy Planning System (BPS) formalism. Using the MC calculated radial dose function and anisotropy function with the BPS formalism, 1% dose calculation accuracy can be achieved even in the near field with negligible extra demand on computation time. A video method was used to analyse the entrance, exit and the inter-dwell transit speed of the HDR stepping source for different path lengths and step sizes ranging from 2.5 mm to 995 mm. The transit speeds were found to be ranging from 54 to 467 mm/s. The results also show that the manufacturer has attempted to compensate for the effects of inter-dwell transit dose by reducing the actual dwell time of the source. A well-type chamber was used to determine the transit doses. Most of the measured dose differences between stationary and stationary plus inter-dwell source movement were within 2%. The small-field dosimetry study investigates the effect of detector size in the dosimetry of small fields and steep dose gradients with a particular emphasis on IMRT measurements. Due to the finite size of the detector, local discrepancies of more than 10 % are found between calculated cross profiles of intensity modulated beams and intensity modulated profiles measured with film. A method to correct for the spatial response of finite sized detectors and to obtain the

Background and purpose: Historically HDR brachytherapy treatment planning systems ignore the transit dose in the computation of patient dose. However, the total radiation dose delivered during each treatment cycle is equal to the sum of the static dose and the transit dose and every HDR application therefore results in two radiation doses. Consequently, the absorbed dose to the target volume is more than the prescribed dose as computed during treatment planning. The aim of this study was to determine the magnitude of the transit dose component of two 192Ir HDR brachytherapy units and assess its dosimetric significance. Materials and Methods: Ionization chamber dosimetry systems (well-type and Farmertype ionization chambers) were used to measure the charge generated during the transit of the 192Ir source from a GammaMed and a Nucletron MicroSelectron HDR afterloader using single catheters of lengths 120 cm. Different source configurations were used for the measurements of integrated charge. Two analysis techniques were used for transit time determination: the multiple exposure technique and the graphical solution of zero exposure. The transit time was measured for the total transit of the radioactive source into (entry) and out of (exit) the catheters. Results: A maximum source transit time of 1.7 s was measured. The transit dose depends on the source activity, source configuration, number of treatment fractions, prescription dose and the type of remote afterloader used. It does not depend on the measurement technique, measurement distance or the analysis technique used for transit time determination. Conclusion: A finite transit time increases the radiation dose beyond that due to the programmed source dwell time alone. The significance of the transit dose would increase with a decrease in source dwell time or a higher activity source.

Submitted in fulfillment of the requirements of the degree of the Master of Technology : Radiography, Durban University of Technology, 2014.
Research Aims The purpose of this study is to compare 2D HDR Brachytherapy planning and 3D HDR Brachytherapy planning in terms of dose distribution in order to accurately determine bladder and rectal doses. Further research questions were explored to determine whether relationships existed between Computer Tomography volumes and bladder and rectum dose. Methodology The 30 female patients that volunteered for the study were conveniently selected. Their age and ethnic group did not contribute to their selection. All participants were prepared for cervical HDR Brachytherapy. The Brachytherapy templates were computer generated and treatments were given based on the templates. They then had a Computer Tomography (CT) scan (3D data set) of the pelvis. The computer generated templates for 2D Brachytherapy planning were applied to the CT data set i.e. 2DBP. The plans were optimised to take into consideration the dose to the bladder and the rectum i.e. 3DBP. The 2DBP and the 3DBP were then evaluated in order to determine which method of planning yielded more acceptable dose distributions to the bladder and rectum. Results Significant differences in dose distribution were noted on comparison of 2DBP and 3DBP. A significant relationship was noted in respect of bladder mean dose and rectum mean dose. 3DBP proved to be more efficient in yielding lower mean dose to the bladder and the rectum. Whilst a significant relationship was noted in respect of bladder maximum dose, an insignificant relationship was noted for rectum maximum dose. Therefore, the efficiency of 3DBP to yield lower bladder maximum dose was established but its efficiency to yield lower rectum maximum dose is questionable. This has implications for the management of patients’ with cervical cancer who require cervical Brachytherapy. Recommendations It is imperative that imaging modalities be used for the accurate planning of cervical Brachytherapy. This study recommends that CT be used for HDR Brachytherapy planning by proving its greater efficiency compared to template planning.

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Radiações em Diagnóstico e Terapia)Universidade de Lisboa, Faculdade de Ciências, 2016
Na Europa, o cancro da próstata é um dos tumores malignos mais comum nos homens. A idade média no diagnóstico é de 65 anos, raramente sendo este tumor diagnosticado antes dos 50 anos. Em Portugal, segundo a Direção Geral de Saúde, a taxa de incidência de cancro da próstata ´e aproximadamente 82 casos por 100 000 habitantes. Na Holanda, 11 158 novos casos de cancro da próstata são diagnosticados por ano. A radioterapia tem vindo a ocupar um lugar de elevada importância no que diz respeito a tratamento de foro oncológico. Novas técnicas de radioterapia com intuito curativo do cancro da próstata têm surgido ao longo dos anos. No entanto, nos últimos anos, a braquiterapia de alta taxa (HDR) tem vindo a ocupar um lugar importante no tratamento de tumores malignos na próstata. Inicialmente, esta terapia foi combinada com a radioterapia externa convencional, funcionando como reforço de radiação na próstata, vulgarmente conhecido pelo termo inglês “boost”. Este tratamento combinado ´e administrado em pacientes de intermédio-alto risco de cancro de próstata. Ao longo dos anos, HDR braquiterapia tem vindo a ser bastante utilizada como terapia única em pacientes de baixo risco, evitando deste modo procedimento mais radicais como a prostatectomia radical. A braquiterapia de alta taxa é caracterizada por uma distribuição de dose bem conformada na próstata e por ter “dose fall-off.” acentuado. Assim, esta técnica salvaguarda os órgãos de risco (bexiga e reto) de uma forma mais eficaz do que outras técnicas de radioterapia, tais como a radioterapia de intensidade modelada (IMRT) ou radioterapia conformada tridimensional (3D RT). No ErasmusMC – Cancer Institute (Roterdão, Holanda) este tratamento é executado em 4 sessões de 9.5Gy (38Gy) cada, separadas de um intervalo mínimo de 6 horas. O doente é internado por 2 dias, e tem alta médica no final do segundo dia. O procedimento clinico da implementação das agulhas é guiada por ultrassons e é indolor, uma vez que o paciente está sob o efeito de anestesia epidural. Antes de cada sessão de tratamento, uma imagem de raios-x lateral é adquirida por forma a verificar possíveis desvios das agulhas na direção caudal. Os desvios superiores 3 mm são corrigidos de modo a evitar o risco de subdosagem na próstata e/ou sobredosagem nos órgãos de risco. A braquiterapia da alta taxa como terapia única é conhecida por ter uma incidência de toxicidades agudas nos tecidos reduzida e por ter um controlo bioquímico bastante elevado. Contudo, existem alguns efeitos secundários após o tratamento, tais como a retenção urinária aguda (AUR) e o sangramento retal (RB). Estes efeitos secundários, embora transitórios, provocam um acréscimo de ansiedade e desconforto no paciente afetando as suas rotinas diárias sendo importante investigar as possíveis causas. Nesta tese, o principal objetivo é investigar quais são os fatores associados a estes dois efeitos secundários de forma a minimizá-los e a melhorar a qualidade de vida dos pacientes após o tratamento. Para cada um dos efeitos secundários, ferramentas estatísticas apropriadas, tais como Mann-Whitney teste, Chi-Square teste e Regressão Logística uni-variável e multivariável, foram usadas para comparar parâmetros dosimétricos (dosevolume histograms - DVH) e clínicos (idade, IPSS - International Prostate Symptom Score, volume da próstata, etc.) entre o grupo de casos (14 AUR e 15 RB) e o grupo de pacientes considerado como controlo (28 no-AUR e 30 no-RB). Dos vários parâmetros clínicos e dosimétricos em estudo, apenas o fluxo urinário medido antes do tratamento (Baseline urinary .ow - Qmax) inferior 10 ml/s e 25% do volume da bexiga recebendo doses (Bexiga D25) superiores a 30-40% da dose prescrita foram os principais fatores associados a um elevado risco de desenvolvimento de retenção urinária aguda com a necessidade de argália após o tratamento. Este resultado foi confirmado quando se analisaram estas variáveis novamente, na base de dados completa dos pacientes tratados com HDR braquiterapia (210 pacientes). Outro parâmetro, uretra membranosa D0.5cc ˍ˃ 55% da dose prescrita, mostrou-se estar estatisticamente associado a um aumento do risco de desenvolvimento de retenção urinária aguda após o tratamento. No entanto, este resultado necessita de ser confirmado em estudos futuros. Para além disso, por forma a confirmar os valores limite de dose para os quais o risco de desenvolvimento de AUR é elevado, foram utilizadas as curvas ROC (Receiver Operating Characteristic Curve). Este método provou que Qmax < 10 ml/s e bexiga D25 ˍ˃ 30-40% estimam bem o risco associado ao desenvolvimento de retençãoo urinária aguda com uma área abaixo da curva ROC superior a 0.7. No que diz respeito ao segundo efeito secundário, RB, os resultados são inconclusivos, quer em termos de parâmetros dosimétricos quer em termos de variáveis clínicas. Embora alguns parâmetros dosimétricos se tenham mostrado estar estatisticamente relacionados com o desenvolvimento de sangramento retal, estes não têm significado clinico relevante. PTV volume ˍ˃ 55 cc e Hipertensão mostraram-se estar estatisticamente associados ao risco de RB mas essa relação não é fidedigna, uma vez que PTV volume ˍ˃ 55 cc não se mostrou estar estatisticamente associado ao RB na base de dados de 210 pacientes e não existem dados que indiquem que os pacientes hipertensos estão a ser corretamente medicados e/ou que seguem o tratamento prescrito. Em suma, este estudo é o primeiro estudo retrospetivo sobre HDR braquiterapia como terapia única com resultados bastante promissores. Os resultados sugerem que se deve limitar a dose entregue a 25% do volume da bexiga, a 30%-40% da dose prescrita, e que Qmax deve ser incluído na lista de critérios de seleção de pacientes para o tratamento. Este projeto, sugere ainda que se deve ter em conta a dose recebida em 0.5cc de volume da uretra membranosa, mas este resultado está sujeito a futuras investigações.
Prostate cancer is the most common cancer in Europe for males. In Portugal, it is estimated that prostate cancer has an incidence of 82 cases per 100 000 inhabitants. In the Netherlands, 11 158 new cases of prostate cancer are diagnosed each year. For the past years, High-Dose Rate Brachytherapy (HDR BT) as monotherapy has been playing an important role in treatment of prostate cancer. .is type of radiotherapy has excellent results because of its highly conformal dose distribution within the prostate with a rapid dose fall-o. outside, sparing the organs at risk. Even so, side effects, such as acute urinary retention (AUR) and rectal bleeding (RB), occur a.er treatment. In this thesis, predictive factors for AUR and RB were investigated in order to find and/or improve new treatment constraints to avoid and/or minimize the occurrence of these side effects, consequently, improving patient’s quality of life a.er treatment. In two investigations, dose-volume histograms (DVH) and clinical parameters were compared, between cases (14 AUR and 15 RB) and controls (28 no-AUR and 30 no-RB). In both projects, appropriate statistical tools, such as Chi-Square test, Mann-Whitney test and Univariate and Multivariate Logistic Regression, were used. In AUR project, baseline urinary .ow (Qmax) < 10 ml/s and 25% of bladder volume receiving doses (bladder D25) ˍ˃30-40% of prescribed dose were the most important risk factors for AUR. .ese two parameters were afterwards confirmed as risk factors for AUR in a large dataset of 210 patients and also through the Receiver Operating Characteristic Curve (ROC). Another dosimetric parameter, urethra membranous D0.5cc ˍ˃˃ 55% of PD, was statistically associated with the increased risk of AUR. However, this result needs to be confirmed in future studies. In RB project, either in terms of DVH or clinical parameters, the results were inconclusive. Some DVH parameters of cranial rectum were statistically correlated with RB but without clinical relevance. PTV volume ˍ˃ 55 cc and Hypertension were statistically significant but they did not show a clear relationship with RB. In summary, this first HDR BT retrospective study suggests that bladder D25 and Qmax could be considered during selection and treatment patients to minimize AUR.

Τhe purpose of this study is to investigate and analyze the influence of the possible errors eventually occurring in a 3D-US based HDR Brachytherapy of prostate cancer on the quality of dose delivery. The influence of modulation restriction tool on the plan quality and sensitivity is also investigated. Materials: Twelve clinical implants for HDR Brachytherapy of prostate cancer have been selected out of the clinical routine. The range of the prostate volumes was 26-101 cm3. Due to the fact that the implanted needles are fixed on the template, the most probable error should be a systematic shift of the implanted catheters on the cranial-caudal direction caused by the movement of the patient relative to the template. The planning was done using HIPO which is implemented in the real time intraoperative planning system Oncentra Prostate (OcP). HIPO offers a unique modulation restriction option that limits the free modulation of dwell times. Firstly the reference plans, where no catheter shift has been simulated, the clinical with MR >0 and the theoretical with MR=0, for all 12 implants have been compared. Then for each of the 12 clinical implants, 10 systematic shifts of the implanted catheters in the range of [-5, +5] mm in step of 1mm were simulated. The influence of this systematic shift on DVH-, COIN, EI and radiobiological parameters of PTV and OARs is calculated and recorded. The analysis of the observed changes has been done firstly by addressing the quality of the implant. For this purpose the range of shift was estimated that the resulted 3D dose distributions keep fulfilling the clinical dosimetric protocol. Secondly, the focus was placed to the stability of the dose distribution. Here the range for the shift has been estimated which enables that the dosimetric, conformity and radiobiological parameters of the implant remain within ±5% or ±10% of the originally planned values. Results: The use of modulation restriction (MR>0) results in plans with more conformal dose distribution (COIN, EI) but slightly lower D90 and V100 , gEUD, EUD2,v and EUD2,s values. The quality analysis demonstrate that for the DVH based parameters values of prostate a maximal shift of ±1.0 mm can be tolerated, although in case of using the modulation restriction the sensitivity from the influence of the systematic shift is greater. Similar were the results for the DVH parameters for urethra, rectum and bladder. For the stability analysis in order to keep the dosimetric parameters within ±5% of the originally planned value for the prostate and OARs, a maximum shift of around ±0.5 mm can be tolerated and for the ±10% criterion this is -1.0/+0.5 mm. The same behavior applies for the radiobiological parameters. The analysis based on COIN considering only the target and also the OARs have shown a maximum shift range of ±1.5 mm. For the EI analysis this range is ±0.0 mm. For ±10% criterion this is ±2.5 mm and ±0.5 mm respectively. Conclusion: Our study has demonstrated that high modulated, high conformal Brachytherapy dose distributions for prostate HDR implants are sensitive to systematic catheter shift. The consequence of shift changes is not clear. We can generally speak about a required geometrical stability of the implant as high as ±1.0mm. Modulation restriction without improving this reduces significantly the total dwell time keeping the plan quality and increasing conformity (COIN, EI).
Ο σκοπός αυτής της μελέτης είναι να ερευνήσουμε και να αναλύσουμε την επιρροή που μπορεί να έχουν τα πιθανά λάθη που συμβαίνουν στην Υψηλού Ρυθμού Δόσης (HDR) Βραχυθεραπεία του καρκίνου του προστάτη, η οποία βασίζεται σε τρισδιάστατες εικόνες (3D) υπερήχου, στη ποιότητα εναπόθεσης δόσης. Επίσης διερευνάται η επίδραση του Modulation Restriction (MR) στην ποιότητα και ευαισθησία του πλάνου θεραπείας. Υλικά και Μέθοδοι: Επιλέχθηκαν 12 κλινικά εμφυτεύματα για την HDR Βραχυθεραπεία του καρκίνου του προστάτη από την κλινική ρουτίνα μας. Το εύρος του όγκου του προστάτη είναι 26-101 cm3. Επειδή οι βελόνες που εμφυτεύθηκαν στον προστάτη είναι σταθεροποιημένες πάνω στο template, το πιο πιθανό λάθος που μπορεί να συμβεί είναι η συστηματική μετατόπιση των εμφυτευμένων καθετήρων σε cranial – caudal (κρανιακή – ουραία ) διεύθυνση η οποία έχει προκληθεί από την κίνηση του ασθενούς σε σχέση με το template. Το πλάνο θεραπείας έγινε χρησιμοποιώντας την επιλογή HIPO του προγράμματος real time intraoperative planning system Oncentra Prostate (OcP). Το HIPO προσφέρει την δυνατότητα επιλογής του Modulation Restriction (MR) το οποίο περιορίζει την ελεύθερη διαμόρφωση των χρόνων παραμονής της πηγής στους καθετήρες. Στα αρχικά μας πλάνα θεραπείας (reference plans) δεν έχει γίνει προσομοίωση μετακίνησης του καθετήρα. Συγκρίνουμε τα κλινικά μας πλάνα (MR>0) και τα θεωρητικά μας (MR=0) και για τα 12 εμφυτεύματα. Στην συνέχεια για κάθε ένα από τα 12 εμφυτεύματα γίνεται η προσομοίωση 10 συστηματικών μετακινήσεων των εμφυτευμένων καθετήρων με εύρος [-5,+5]mm και με βήμα 1mm. Υπολογίζεται και καταγράφεται η επίδραση της συστηματικής μετακίνησης στα ιστογράμματα δόσης - όγκου (DVH), δείκτη συμμορφίας (conformity index- COIN), External Index (EI) και στις ραδιοβιολογικές παραμέτρους για τον όγκο στόχου (PTV) και των ευαίσθητων σε κίνδυνο οργάνων (OARs). Αρχικά η ανάλυση των παρατηρούμενων αλλαγών έχει γίνει σύμφωνα με την ποιότητα του εμφυτεύματος (quality analysis). Για αυτό τον λόγο το εύρος της μετακίνησης έχει υπολογιστεί έτσι ώστε τα αποτελέσματα από τις 3D κατανομές δόσεις να πληρούν το κλινικό δοσιμετρικό μας πρωτόκολλο. Στην συνέχεια εστιάσαμε στην σταθερότητα της κατανομής της δόσης (stability analysis). Σε αυτή την περίπτωση το εύρος μετακίνησης των καθετήρων έχει υπολογιστεί έτσι ώστε οι τιμές των DVH, COIN και ραδιοβιολογικών παραμέτρων των εμφυτευμάτων να παραμένουν μέσα στο ±5% ή στο ±10% των αρχικών πλάνων (reference). Αποτελέσματα: Χρησιμοποιώντας την επιλογή του Modulation Restriction (MR>0) προκύπτουν πλάνα με πιο ομοιόμορφη κατανομή της δόσης (COIN, EI) αλλά με ελαφρώς μικρότερες τιμές των D90, V100, gEUD, EUD2,v και EUD2,s. H “quality analysis” έδειξε ότι για τις δοσιμετρικές παραμέτρους του προστάτη η μέγιστη μετατόπιση που μπορούμε να έχουμε είναι ±1mm. Χρησιμοποιώντας την επιλογή του MR η μετατόπιση αυτή γίνεται ακόμα πιο ευαίσθητη. Παρόμοια ήταν τα αποτελέσματα μας για τις δοσιμετρικές παραμέτρους των OARs (ουρήθρα, κύστη και ορθό). Σύμφωνα με την “stability analysis” η μέγιστη μετατόπιση που μας επιτρέπεται έτσι ώστε να διατηρήσουμε τις τιμές των δοσιμετρικών παραμέτρων του προστάτη και των OARs μέσα στο ±5% της τιμής του αρχικού μας πλάνου είναι ±0.5mm ενώ για το ±10% το όριο αυτό είναι -1.0/+0.5 mm. Την ίδια συμπεριφορά παρατηρούμε και για τις ραδιοβιολογικές παραμέτρους. Η ανάλυση που βασίζεται στο COIN, συμπεριλαμβάνοντας αρχικά μόνο τον στόχο μας και στην συνέχεια και τα OARs έδειξε ότι η μέγιστη μετακίνηση μας έχει εύρος ±1.5mm . Για την ανάλυση που βασίζεται στο EI αυτό το εύρος είναι ±0.0 mm . Για το ±10% τα όρια είναι ±2.5mm και 0.5mm αντίστοιχα. Συμπεράσματα: Η μελέτη μας έδειξε ότι οι υψηλά διαμορφωμένες και οι υψηλά ομοιόμορφες κατανομές δόσης των εμφυτευμάτων της HDR βραχυθεραπείας του προστάτη είναι ευαίσθητες στις συστηματικές μετακινήσεις των καθετήρων. Οι συνέπειες από τις αλλαγές αυτών των μετακινήσεων δεν είναι ξεκάθαρες. Μπορούμε γενικά να μιλήσουμε για μια απαιτούμενη γεωμετρική σταθερότητα του εμφυτεύματος τόσο υψηλή όσο ±1.0mm. Η δυνατότητα επιλογής του MR χωρίς να βελτιώνει αυτό, μειώνει σημαντικά τον ολικό χρόνο παραμονής της πηγής στους καθετήρες διατηρώντας την ποιότητα του πλάνου θεραπείας και αυξάνοντας την ομοιομορφία στην κατανομή της δόσης (COIN, EI).

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