Dissertations / Theses: 'Prostate – Cancer – Radiotherapy'

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Rios, Patiño Richard. "Statistical modeling of bladder motion and deformation in prostate cancer radiotherapy." Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1S116/document.

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Le cancer de la prostate est le cancer le plus fréquent chez les hommes dans la plupart des pays développés. C'est le cancer le plus fréquent chez les hommes en France (73.609 cas en 2014) et en Colombie (9564 cas en 2014). En outre, c'est la troisième cause de décès par cancer chez les hommes dans les deux pays (9,3 % en France et 7,1 % en Colombie en 2014). L'une des techniques de traitement est la radiothérapie externe, qui consiste à délivrer un rayonnement ionisant à une cible clinique, à savoir la prostate et les vésicules séminales. En raison des variations anatomiques au cours du traitement, qui consiste en environ 40 fractions de rayonnement délivrant une dose totale allant de 70 à 80Gy, des marges de sécurité sont définies autour de la cible tumorale lors de la planification du traitement. Ceci entraîne des portions d'organes sains voisins de la prostate - la vessie et le rectum - à être inclus dans le volume cible, pouvant conduire à des événements indésirables affectant les fonctions urinaires (hématurie et cystite, entre autres) ou rectale (saignement rectal, incontinence fécale, Etc.). La vessie présente les plus grandes variations de forme entre fractions de traitement, provoquées par des changements continus de volume. Ces variations de forme introduisent des incertitudes géométriques qui rendent difficile l'évaluation de la dose réellement délivrée à la vessie pendant le traitement. Ces incertitudes limitent la possibilité de modéliser une relation dose-volume pour la toxicité génito-urinaire tardive (GU). Le projet QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) a déclaré que la relation dose-réponse pour la toxicité gastro-intestinale tardive (GI) était loin d'être établie. Les variables dosimétriques obtenues à partir de la tomodensitométrie de planification peuvent être faiblement représentative de la dose effectivement administrée. En conséquence, il est crucial de quantifier les incertitudes produites par les variations inter-fraction de la vessie afin de déterminer les facteurs dosimétriques qui affectent les complications GU tardives. Le but de cette thèse était donc de caractériser et de prédire les incertitudes produites par les variations géométriques de la vessie entre les fractions de traitement, en utilisant uniquement la tomodensitométrie de planification comme information d'entrée. En pratique clinique, une seule tomodensitométrie est disponible au moment de la planification du traitement pour un patient typique, alors que des images supplémentaires peuvent être acquises en cours de traitement. Dans cette thèse une approche population a été utilisée pour obtenir suffisamment de données pour apprendre les directions les plus importantes du mouvement et de la déformation de la vessie en utilisant l'analyse en composante principales (ACP). Comme dans les travaux de référence, ces directions ont ensuite été utilisées pour développer des modèles basés population pour prédire et quantifier les incertitudes géométriques de la vessie. Cependant, nous avons utilisé une analyse longitudinale afin de caractériser correctement la variance du patient et les modes spécifiques du patient à partir de la population. Nous avons proposé d'utiliser un modèle à effets mixtes (ME) et une ACP hiérarchique pour séparer la variabilité intra et inter-patients afin de contrôler les effets de cohorte confondus. Finalement, nous avons présenté des modèles sur l'APC comme un outil pour quantifier des incertitudes de la dose produit par le mouvement et déformation de la vessie entre fractions
Prostate cancer is the most common cancer amongst the male population in most developed countries. It is the most common cancer amongst the male population in France (73.609 cases in 2014) and in Colombia (9564 cases in 2014). It is also the third most common cause of cancer deaths in males in both countries (9.3% and 7.1% in France and in Colombia in 2014, respectively). One of the standard treatment methods is external radiotherapy, which involves delivering ionizing radiation to a clinical target, namely the prostate and seminal vesicles. Due to the uncertain location of organs during treatment, which involves around forty (40) radiation fractions delivering a total dose ranging from 70 to 80Gy, safety margins are defined around the tumor target upon treatment planning. This leads to portions of healthy organs neighboring the prostate or organs at risk — the bladder and rectum — to be included in the target volume, potentially resulting in adverse events affecting patients’ urinary (hematuria and cystitis, among others) or rectal (rectal bleeding, fecal incontinence, etc.) functions. The bladder is notorious for presenting the largest inter-fraction shape variations during treatment, caused by continuous changes in volume. These variations in shape introduce geometric uncertainties that render assessment of the actual dose delivered to the bladder during treatment difficult, thereby leading to dose uncertainties that limit the possibility of modeling dose-volume response for late genitourinary (GU) toxicity. The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) project has stated that a similar dose-response to that of late gastrointestinal (GI) toxicity is far from being established. The dosimetric variables obtained from the planning CT prove to be very poor surrogates for the real delivered dose. As a result, it appears crucial to quantify uncertainties produced by inter-fraction bladder variations in order to determine dosimetric factors that affect late GU complications. The aim of this thesis was thus to characterize and predict uncertainties produced by geometric variations of the bladder between fractions, using solely the planning CT as input information. In clinical practice, a single CT scan is only available for a typical patient during the treatment planning while on-treatment CTs/CBCTs are seldom available. In this thesis, we thereby used a population approach to obtain enough data to learn the most important directions of bladder motion and deformation using principal components analysis (PCA). As in groundwork, these directions were then used to develop population-based models in order to predict and quantify geometrical uncertainties of the bladder. However, we use a longitudinal analysis in order to properly characterize both patient-specific variance and modes from the population. We proposed to use mixed-effects (ME) models and hierarchical PCA to separate intra and inter-patient variability to control confounding cohort effects. . Subsequently, we presented PCA models as a tool to quantify dose uncertainties produced by bladder motion and deformation between fractions

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Knight, Kellie Ann. "Daily Image Guided Radiation Therapy for Prostate Cancer: An assessment of treatment plan reproducibility." Thesis, The University of Sydney, 2006. http://hdl.handle.net/2123/1628.

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It is well documented that for prostate cancer patients undergoing radiation therapy there is a correlation between target volume displacement and changes in bladder and rectal volumes. However, these studies have used a methodology that has captured only a subset of all treatment positions. This research used daily Computer Tomography (CT) imaging to comprehensively assess organ volumes, organ motion and their effect on dose, something that has never been performed previously, thus adding considerably to the understanding of the topic. Daily CT images were obtained using a Siemens Primus Linear Accelerator equipped with an in-room Somatom CT unit in the accelerator suite, marketed as ‘Primatom’, to accurately position the patient prior to treatment delivery. The internal structures of interest were contoured on the planning workstation by the investigator. The daily volume and location of the organs were derived from the computer to assess and analyse internal organ motion. The planned dose distribution was then imported onto the treatment CT datasets and used to compare the planned dose to i) the actual isocentre, where the isocentre was actually placed for that fraction, ii) the uncorrected isocentre, by un-doing any on-line corrections performed by the treatment staff prior to treatment delivery, and iii) the future isocentre, by placing the isocentre relative to internal organ motion on a daily basis. The results of this study did not confirm a statistically significant decrease in rectum volumes over time (hypothesis 1), however large fluctuations in bladder volume were confirmed (hypothesis 2). Internal organ motion for the rectum and bladder was demonstrated to be related to organ filling. Ideal planning volumes for these organs have been reported to minimise systematic and random uncertainty in the treatment volumes. An observed decrease in prostate volume over time, a systematic uncertainty in the location of the prostate at the time of the planning CT scan and a significant relationship between prostate centre of volume and rectum and bladder volumes has resulted in a recommendation that patients should be re-scanned during treatment to ensure appropriate clinical target volume coverage. A significant relationship between rectal and bladder volumes and the dose delivered to these organs was found (hypothesis 3). The dose delivered to the planning target volume was not related to the rectal or bladder volumes, although it was related to the motion of these organs. Despite these results only minimal effects on the dose delivered to any of the three isocentres occurred, indicating that the planned dose was accurately delivered using the methodology presented here (hypothesis 4). However the results do indicate that the patient preparation instructions need to be improved if margins are to be reduced in the future. It is unrealistic to assume that Image Guided Radiation Therapy will ever become routine practice due to infrastructure costs and time limitations. This research will inform radiation therapy centres of the variables associated with prostate cancer treatment on a daily basis, something that has never before been realistically achievable. As a result centres will be able to devise protocols to improve treatment outcomes.

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3

Knight, Kellie Ann. "Daily Image Guided Radiation Therapy for Prostate Cancer: An assessment of treatment plan reproducibility." University of Sydney, 2006. http://hdl.handle.net/2123/1628.

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Doctor of Health Science
It is well documented that for prostate cancer patients undergoing radiation therapy there is a correlation between target volume displacement and changes in bladder and rectal volumes. However, these studies have used a methodology that has captured only a subset of all treatment positions. This research used daily Computer Tomography (CT) imaging to comprehensively assess organ volumes, organ motion and their effect on dose, something that has never been performed previously, thus adding considerably to the understanding of the topic. Daily CT images were obtained using a Siemens Primus Linear Accelerator equipped with an in-room Somatom CT unit in the accelerator suite, marketed as ‘Primatom’, to accurately position the patient prior to treatment delivery. The internal structures of interest were contoured on the planning workstation by the investigator. The daily volume and location of the organs were derived from the computer to assess and analyse internal organ motion. The planned dose distribution was then imported onto the treatment CT datasets and used to compare the planned dose to i) the actual isocentre, where the isocentre was actually placed for that fraction, ii) the uncorrected isocentre, by un-doing any on-line corrections performed by the treatment staff prior to treatment delivery, and iii) the future isocentre, by placing the isocentre relative to internal organ motion on a daily basis. The results of this study did not confirm a statistically significant decrease in rectum volumes over time (hypothesis 1), however large fluctuations in bladder volume were confirmed (hypothesis 2). Internal organ motion for the rectum and bladder was demonstrated to be related to organ filling. Ideal planning volumes for these organs have been reported to minimise systematic and random uncertainty in the treatment volumes. An observed decrease in prostate volume over time, a systematic uncertainty in the location of the prostate at the time of the planning CT scan and a significant relationship between prostate centre of volume and rectum and bladder volumes has resulted in a recommendation that patients should be re-scanned during treatment to ensure appropriate clinical target volume coverage. A significant relationship between rectal and bladder volumes and the dose delivered to these organs was found (hypothesis 3). The dose delivered to the planning target volume was not related to the rectal or bladder volumes, although it was related to the motion of these organs. Despite these results only minimal effects on the dose delivered to any of the three isocentres occurred, indicating that the planned dose was accurately delivered using the methodology presented here (hypothesis 4). However the results do indicate that the patient preparation instructions need to be improved if margins are to be reduced in the future. It is unrealistic to assume that Image Guided Radiation Therapy will ever become routine practice due to infrastructure costs and time limitations. This research will inform radiation therapy centres of the variables associated with prostate cancer treatment on a daily basis, something that has never before been realistically achievable. As a result centres will be able to devise protocols to improve treatment outcomes.

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4

Cheng, Kun. "Deformable models for adaptive radiotherapy planning." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/22893.

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Radiotherapy is the most widely used treatment for cancer, with 4 out of 10 cancer patients receiving radiotherapy as part of their treatment. The delineation of gross tumour volume (GTV) is crucial in the treatment of radiotherapy. An automatic contouring system would be beneficial in radiotherapy planning in order to generate objective, accurate and reproducible GTV contours. Image guided radiotherapy (IGRT) acquires patient images just before treatment delivery to allow any necessary positional correction. Consequently, real-time contouring system provides an opportunity to adopt radiotherapy on the treatment day. In this thesis, freely deformable models (FDM) and shape constrained deformable models (SCDMs) were used to automatically delineate the GTV for brain cancer and prostate cancer. Level set method (LSM) is a typical FDM which was used to contour glioma on brain MRI. A series of low level image segmentation methodologies are cascaded to form a case-wise fully automatic initialisation pipeline for the level set function. Dice similarity coefficients (DSCs) were used to evaluate the contours. Results shown a good agreement between clinical contours and LSM contours, in 93% of cases the DSCs was found to be between 60% and 80%. The second significant contribution is a novel development to the active shape model (ASM), a profile feature was selected from pre-computed texture features by minimising the Mahalanobis distance (MD) to obtain the most distinct feature for each landmark, instead of conventional image intensity. A new group-wise registration scheme was applied to solve the correspondence definition within the training data. This ASM model was used to delineated prostate GTV on CT. DSCs for this case was found between 0.75 and 0.91 with the mean DSC 0.81. The last contribution is a fully automatic active appearance model (AAM) which captures image appearance near the GTV boundary. The image appearance of inner GTV was discarded to spare the potential disruption caused by brachytherapy seeds or gold markers. This model outperforms conventional AAM at the prostate base and apex region by involving surround organs. The overall mean DSC for this case is 0.85.

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Ospina, Arango Juan David. "Predictive models for side effects following radiotherapy for prostate cancer." Thesis, Rennes 1, 2014. http://www.theses.fr/2014REN1S046/document.

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La radiothérapie externe (EBRT en anglais pour External Beam Radiotherapy) est l'un des traitements référence du cancer de prostate. Les objectifs de la radiothérapie sont, premièrement, de délivrer une haute dose de radiations dans la cible tumorale (prostate et vésicules séminales) afin d'assurer un contrôle local de la maladie et, deuxièmement, d'épargner les organes à risque voisins (principalement le rectum et la vessie) afin de limiter les effets secondaires. Des modèles de probabilité de complication des tissus sains (NTCP en anglais pour Normal Tissue Complication Probability) sont nécessaires pour estimer sur les risques de présenter des effets secondaires au traitement. Dans le contexte de la radiothérapie externe, les objectifs de cette thèse étaient d'identifier des paramètres prédictifs de complications rectales et vésicales secondaires au traitement; de développer de nouveaux modèles NTCP permettant l'intégration de paramètres dosimétriques et de paramètres propres aux patients; de comparer les capacités prédictives de ces nouveaux modèles à celles des modèles classiques et de développer de nouvelles méthodologies d'identification de motifs de dose corrélés à l'apparition de complications. Une importante base de données de patients traités par radiothérapie conformationnelle, construite à partir de plusieurs études cliniques prospectives françaises, a été utilisée pour ces travaux. Dans un premier temps, la fréquence des symptômes gastro-Intestinaux et génito-Urinaires a été décrite par une estimation non paramétrique de Kaplan-Meier. Des prédicteurs de complications gastro-Intestinales et génito-Urinaires ont été identifiés via une autre approche classique : la régression logistique. Les modèles de régression logistique ont ensuite été utilisés dans la construction de nomogrammes, outils graphiques permettant aux cliniciens d'évaluer rapidement le risque de complication associé à un traitement et d'informer les patients. Nous avons proposé l'utilisation de la méthode d'apprentissage de machine des forêts aléatoires (RF en anglais pour Random Forests) pour estimer le risque de complications. Les performances de ce modèle incluant des paramètres cliniques et patients, surpassent celles des modèle NTCP de Lyman-Kutcher-Burman (LKB) et de la régression logistique. Enfin, la dose 3D a été étudiée. Une méthode de décomposition en valeurs populationnelles (PVD en anglais pour Population Value Decomposition) en 2D a été généralisée au cas tensoriel et appliquée à l'analyse d'image 3D. L'application de cette méthode à une analyse de population a été menée afin d'extraire un motif de dose corrélée à l'apparition de complication après EBRT. Nous avons également développé un modèle non paramétrique d'effets mixtes spatio-Temporels pour l'analyse de population d'images tridimensionnelles afin d'identifier une région anatomique dans laquelle la dose pourrait être corrélée à l'apparition d'effets secondaires
External beam radiotherapy (EBRT) is one of the cornerstones of prostate cancer treatment. The objectives of radiotherapy are, firstly, to deliver a high dose of radiation to the tumor (prostate and seminal vesicles) in order to achieve a maximal local control and, secondly, to spare the neighboring organs (mainly the rectum and the bladder) to avoid normal tissue complications. Normal tissue complication probability (NTCP) models are then needed to assess the feasibility of the treatment and inform the patient about the risk of side effects, to derive dose-Volume constraints and to compare different treatments. In the context of EBRT, the objectives of this thesis were to find predictors of bladder and rectal complications following treatment; to develop new NTCP models that allow for the integration of both dosimetric and patient parameters; to compare the predictive capabilities of these new models to the classic NTCP models and to develop new methodologies to identify dose patterns correlated to normal complications following EBRT for prostate cancer treatment. A large cohort of patient treated by conformal EBRT for prostate caner under several prospective French clinical trials was used for the study. In a first step, the incidence of the main genitourinary and gastrointestinal symptoms have been described. With another classical approach, namely logistic regression, some predictors of genitourinary and gastrointestinal complications were identified. The logistic regression models were then graphically represented to obtain nomograms, a graphical tool that enables clinicians to rapidly assess the complication risks associated with a treatment and to inform patients. This information can be used by patients and clinicians to select a treatment among several options (e.g. EBRT or radical prostatectomy). In a second step, we proposed the use of random forest, a machine-Learning technique, to predict the risk of complications following EBRT for prostate cancer. The superiority of the random forest NTCP, assessed by the area under the curve (AUC) of the receiving operative characteristic (ROC) curve, was established. In a third step, the 3D dose distribution was studied. A 2D population value decomposition (PVD) technique was extended to a tensorial framework to be applied on 3D volume image analysis. Using this tensorial PVD, a population analysis was carried out to find a pattern of dose possibly correlated to a normal tissue complication following EBRT. Also in the context of 3D image population analysis, a spatio-Temporal nonparametric mixed-Effects model was developed. This model was applied to find an anatomical region where the dose could be correlated to a normal tissue complication following EBRT

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Foo, Kerwyn Yi Min. "Methodological uncertainties in radiotherapy dose-effect analysis." Thesis, University of Sydney, 2020. https://hdl.handle.net/2123/24421.

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Cancer and normal tissues in patient populations exhibit variability in biological response to the same dose of radiation. Sources of this variability include: • Inherent biological factors of patient, tumour or tissue • Metrics to measure, classify or declare biological outcomes • Volumetric (prescription of target or avoidance regions) • Dosimetric and delivery Dosimetric and delivery variation is easily measured and has relatively little impact on variation of outcome in modelling studies. Volumetric variation contributes greatly to uncertainty, dependent on human judgement by oncologists. However, analysis methodology is generally overlooked as a source of variation in reported dose-effect results and is the subject of investigation in this thesis. Dosimetric and clinical data from clinical trials and prospective cohort studies have been used to illustrate the contribution of analysis methodology to variation in dose-effect relationships using evidence from prostate cancer radiation therapy. The primary data source is the Trans-Tasman Radiation Oncology Group clinical trial 03.04 “RADAR”, which investigated dose escalation in external beam radiotherapy for prostate cancer. Systematic review of the medical physics literature shows that prostate cancer radiotherapy toxicity reporting does not fully account for fractionation, which biases and causes unreported variation in dose-effect results. The toxicity-dose-volume-effect relationship is shown to depend on the anatomical subsite delineated and the type/grade of toxicity outcome chosen. Multivariate regression of multiple dose factors is not reliable due to multicollinearity of these factors. Heterogeneity in method of analysis is an important and overlooked component of variability in reported results of dose effect relationships in radiotherapy studies. Harmonisation of analysis or correction for this heterogeneity will reduce uncertainties to allow better modelling of biological effects in the molecular oncology era.

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Rimmer, Yvonne Louise. "The Implementation and Optimisation of Image-Guided Radiotherapy in Prostate Cancer." Thesis, University of East Anglia, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.521025.

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Khoo, Vincent. "A study of conformal radiotherapy methods for brain and prostate cancer." Thesis, Institute of Cancer Research (University Of London), 2000. http://publications.icr.ac.uk/9718/.

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State-of-the-art radiotherapy involves a technology chain that includes 3D tumour imaging, 3D treatment planning, treatment delivery using conformal or intensity modulated techniques, and treatment verification. This thesis evaluates some of the recent imaging and planning developments to assess their role in optimisation of the technology chain for brain and prostate cancer. I focused on two major links in this technology chain. The 'imaging' link compared the use of MRI and CT in localising target volumes. An image registration protocol was developed to combine CT and MRI images in the brain. For the localisation of skull base meningiomas, MRI was found to provide contrasting information to CT. A composite target volume derived from both CT and MR information provided the most appropriate volume. For prostate radiotherapy, four MRI sequences were compared to CT. All MRI sequences provided improved localisation of relevant radiotherapy volumes-of-interest especially for the prostatic apex and rectum. The 'treatment planning' link investigated the impact of intra-fraction prostate motion for prostate planning margins, the creation of planning margins, the optimisation of beam orientations for prostate radiotherapy, and the utility of IMRT methods for brain tumours. Cine MR demonstrated a significant relationship between moderate rectal distension and increased rectal activity resulting in prostate motion. Mean prostate motion was < 5mm and lasted < 5% of a7 minute period indicating that the current 10mm prostate planning margin was adequate. The use of a 3D margin-growing method allowed the planning target margin to be accurately realised in all spatial orientations and avoided problems associated with 2D margin growing methods. A variety of co-planar arrangements using 3-, 4-, and 6-fields were evaluated for conformal prostate radiotherapy. Standard prostate plans could be optimised by proper consideration of beam orientations. A 3-field plan with gantry angles of 0", 90', 270' Provided the best rectal sparing for both prostate alone and prostate plus seminal vesicles volumes. Using this 3-field plan, dose escalation may be achieved with a smaller increase in predicted late rectal complications than with other 3-, 4-, or 6-field plans. An IMRT tomotherapy method was compared with conformal radiotherapy for convex shaped brain tumours to assess its potential for improved dose conformation. This IMRT method provided slightly improved PTV coverage but also higher OARs doses. However, these OARs doses remained within acceptable clinical limits. This IMRT tomotherapy method did not provide significant planning improvement compared to current conformal radiotherapy technique.

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Murray, Louise Janet. "Optimising treatment outcomes using Stereotactic Body Radiotherapy (SBRT) for prostate cancer." Thesis, University of Leeds, 2014. http://etheses.whiterose.ac.uk/8666/.

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Aims: to optimise linear accelerator-based prostate stereotactic ablative radiotherapy (SABR) through planning studies, tumour control probability (TCP) and normal tissue complication probability (NTCP) calculations and radiation-induced second primary cancer (RISPC) risk assessment. Methods: A planning study was performed to develop a class solution for prostate SABR. A second planning study delivered boosts to dominant intra-prostatic lesions (DILs) and TCP and NTCP were calculated. A third planning study compared prostate SABR planning using flattened and flattening filter free (FFF) beams. A systematic review examined RISPC risk following prostate radiotherapy. A final study estimated RISPC risks following prostate SABR in comparison to other contemporary radiation techniques. Results: Prostate SABR was optimal using a single anterior arc which resulted in highly conformal plans, lower rectal doses and improved delivery times and monitor unit requirements for most patients. Boosting DILs resulted in small TCP increases, but the benefit was offset by increases in NTCP. SABR to the whole prostate without DIL boosting resulted in high TCP and low NTCP. Plans using flattened and FFF beams were dosimetrically similar but FFF resulted in reduced delivery times. Clinical evidence, largely based on older radiation techniques, suggests that prostate radiotherapy increases RISPC risk. Clinical evidence concerning risk following modern techniques is too immature to draw firm conclusions. The final study demonstrated that SABR techniques resulted in lower estimated RISPC risks in all organs compared to conventionally fractionated techniques, while FFF techniques reduced RISPC risks in out-of-field organs. Conclusions: Linear accelerator-based prostate SABR delivered with a single partial arc is optimal and high levels of TCP and low levels of NTCP are predicted from whole prostate SABR. FFF allows faster treatment delivery. Second malignancy risk is lower using SABR, particularly with FFF, compared to conventionally fractionated techniques. Phase III trials are required to investigate prostate SABR in practice.

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Wirth, Manfred P., and Michael Fröhner. "Adjuvant Hormonal Treatment for Prostate Cancer: The Bicalutamide Early Prostate Cancer Program." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133551.

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Adjuvant hormonal therapy has been demonstrated to be able to delay disease progression in nonmetastatic prostate cancer. To date, however, a favorable impact on survival has only been demonstrated in lymph-node-positive disease and in external-beam radiotherapy series with locally advanced and probably mainly micrometastatic tumors. The Bicalutamide Early Prostate Cancer Program is the largest study under way to define the role of adjuvant treatment in early prostate cancer and identify subgroups of patients likely to benefit from immediate hormonal therapy. At the time of the most recently published analysis, the risk of objective clinical progression was significantly reduced in the bicalutamide arm (hazards ratio 0.58, 95% confidence interval 0.51–0.66, p < 0.0001). However, further maturation of data is needed to see whether this difference will lead to a survival advantage
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

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Wirth, Manfred P., and Michael Fröhner. "Adjuvant Hormonal Treatment for Prostate Cancer: The Bicalutamide Early Prostate Cancer Program." Karger, 2003. https://tud.qucosa.de/id/qucosa%3A27515.

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Adjuvant hormonal therapy has been demonstrated to be able to delay disease progression in nonmetastatic prostate cancer. To date, however, a favorable impact on survival has only been demonstrated in lymph-node-positive disease and in external-beam radiotherapy series with locally advanced and probably mainly micrometastatic tumors. The Bicalutamide Early Prostate Cancer Program is the largest study under way to define the role of adjuvant treatment in early prostate cancer and identify subgroups of patients likely to benefit from immediate hormonal therapy. At the time of the most recently published analysis, the risk of objective clinical progression was significantly reduced in the bicalutamide arm (hazards ratio 0.58, 95% confidence interval 0.51–0.66, p < 0.0001). However, further maturation of data is needed to see whether this difference will lead to a survival advantage.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

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Bellera, Carine A. "Hierarchical changepoint modeling of post-radiotherapy prostate-specific antigen (PSA) series in men with prostate cancer." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=100321.

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Prostate-specific antigens (PSA) help monitor the post-therapy course of prostate cancer. If radiotherapy is successful, levels reach a nadir, and remain low or possibly rise very slowly. A sustained steep increase indicates biochemical failure.
Serial PSA measurements are rarely perfectly monotonic. The American Society for Therapeutic Radiology and Oncology (ASTRO) consensus panel defines biochemical failure as three consecutive PSA increases. I examined the sensitivity and specificity of the ASTRO criterion using simulations of realistic, sophisticated data sets, that accurately reflect the systematic and random variations observed in PSA series.
In a preliminary analysis, I estimated the underlying PSA trajectories in a cohort of 470 men treated with radiotherapy for localized prostate cancer. I exploited the flexibility of Bayesian hierarchical regression models to describe the individual PSA series, each with its own changepoint, and non-constant variance.
The estimates provided by the hierarchical model allowed me to simulate a large set of true PSA series. From these, I generated observed PSA series: each underlying PSA value was distorted by adding a realistic amount of 'noise'. To evaluate the performance of rules for biochemical failure, including the ASTRO criterion, I then compared the generated observed PSA series to the underlying true PSA series. My results suggest that another rule might outperform ASTRO. This simulation-based approach can be applied to evaluate other rules that purport to rapidly and accurately detect up (down) turns in noisy series, such as in other medical data, and in data series used to monitor economic trends.
Finally, I present a practical charting paper for physicians to record post-treatment PSA values of individual patients. The plotted serial values provide rapid and accurate estimates of the PSA doubling time, without any difficult computations.

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Montgomery, Dean. "Improving radiotherapy using image analysis and machine learning." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/23554.

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With ever increasing advancements in imaging, there is an increasing abundance of images being acquired in the clinical environment. However, this increase in information can be a burden as well as a blessing as it may require significant amounts of time to interpret the information contained in these images. Computer assisted evaluation is one way in which better use could be made of these images. This thesis presents the combination of texture analysis of images acquired during the treatment of cancer with machine learning in order to improve radiotherapy. The first application is to the prediction of radiation induced pneumonitis. In 13- 37% of cases, lung cancer patients treated with radiotherapy develop radiation induced lung disease, such as radiation induced pneumonitis. Three dimensional texture analysis, combined with patient-specific clinical parameters, were used to compute unique features. On radiotherapy planning CT data of 57 patients, (14 symptomatic, 43 asymptomatic), a Support Vector Machine (SVM) obtained an area under the receiver operator curve (AUROC) of 0.873 with sensitivity, specificity and accuracy of 92%, 72% and 87% respectively. Furthermore, it was demonstrated that a Decision Tree classifier was capable of a similar level of performance using sub-regions of the lung volume. The second application is related to prostate cancer identification. T2 MRI scans are used in the diagnosis of prostate cancer and in the identification of the primary cancer within the prostate gland. The manual identification of the cancer relies on the assessment of multiple scans and the integration of clinical information by a clinician. This requires considerable experience and time. As MRI becomes more integrated within the radiotherapy work flow and as adaptive radiotherapy (where the treatment plan is modified based on multi-modality image information acquired during or between RT fractions) develops it is timely to develop automatic segmentation techniques for reliably identifying cancerous regions. In this work a number of texture features were coupled with a supervised learning model for the automatic segmentation of the main cancerous focus in the prostate - the focal lesion. A mean AUROC of 0.713 was demonstrated with 10-fold stratified cross validation strategy on an aggregate data set. On a leave one case out basis a mean AUROC of 0.60 was achieved which resulted in a mean DICE coefficient of 0.710. These results showed that is was possible to delineate the focal lesion in the majority (11) of the 14 cases used in the study.

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Pettersson, Anna. "Diet and Gastrointestinal Symptoms in Patients with Prostate Cancer Treated with Radiotherapy." Doctoral thesis, Uppsala universitet, Enheten för onkologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-215410.

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Objective The main objective of this thesis was to explore the effects of diet on gastrointestinal symptoms in prostate cancer patients treated with local curative radiotherapy, by evaluating dietary intake prior to treatment (Study I), the psychometric properties of a new questionnaire on patient-reported gastrointestinal side effects (Study II), and the effect of a dietary intervention on acute and long-term gastrointestinal symptoms up to 2 years after radiotherapy completion (Study III-IV). Methods A total of 130 men with localized prostate cancer referred to dose-escalated radiotherapy (ED2 87-102 Gy, α/β=3 Gy) were recruited to a dietary intervention trial. Patients were randomized to receive either standard care plus the dietary intervention of a fibre- and lactose-restricted diet (intervention group, IG; n=64) or standard care alone (standard care group, SCG; n=66). Data on gastrointestinal symptoms and dietary intake were collected pre-treatment and at seven time points during a follow-up period of 26 months. Results Prior to treatment, grain products and milk products were major sources of energy. Unbalanced fatty acid intake and low intake of selenium were observed (Study I). Validation of the Gastrointestinal Side Effects Questionnaire (GISEQ) revealed satisfactory internal consistency, moderate concurrent validity and adequate responsiveness (Study II). There were no significant effects of the intervention on acute or long-term gastrointestinal symptoms, but a tendency towards lower prevalence and severity of bloating and diarrhoea in the IG compared to the SCG during radiotherapy. Gastrointestinal symptoms were predominantly mild, and the frequency of clinically relevant symptoms was merely a few percent. Dietary adherence in the IG was initially good, but tended to decline beyond 12 months post-radiotherapy (Study III-IV). Conclusions A fibre- and lactose-restricted diet was not superior to the habitual diet in reducing gastrointestinal symptoms in patients undergoing high-dose, small-volume radiotherapy for localized prostate cancer. The GISEQ enables assessment of patient-perceived change in symptoms, but further work is needed to strengthen its psychometric qualities. It is suggested that continued research in this area target patient categories referred to irradiation of larger pelvic volumes with a higher risk of gastrointestinal symptoms, and that dietary interventions incorporate established strategies to enhance adherence and effectiveness.

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Fargeas, Aureline. "Classification, feature extraction and prediction of side effects in prostate cancer radiotherapy." Thesis, Rennes 1, 2016. http://www.theses.fr/2016REN1S022/document.

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Le cancer de la prostate est l'un des cancers les plus fréquents chez l'homme. L'un des traitements standard est la radiothérapie externe, qui consiste à délivrer un rayonnement d'ionisation à une cible clinique, en l'occurrence la prostate et les vésicules séminales. Les objectifs de la radiothérapie externe sont la délivrance d'une dose d'irradiation maximale à la tumeur tout en épargnant les organes voisins (principalement le rectum et la vessie) pour éviter des complications suite au traitement. Comprendre les relations dose/toxicité est une question centrale pour améliorer la fiabilité du traitement à l'étape de planification inverse. Des modèles prédictifs de toxicité pour le calcul des probabilités de complications des tissus sains (normal tissue complication probability, NTCP) ont été développés afin de prédire les événements de toxicité en utilisant des données dosimétriques. Les principales informations considérées sont les histogrammes dose-volume (HDV), qui fournissent une représentation globale de la distribution de dose en fonction de la dose délivrée par rapport au pourcentage du volume d'organe. Cependant, les modèles actuels présentent certaines limitations car ils ne sont pas totalement optimisés; la plupart d'entre eux ne prennent pas en compte les informations non-dosimétrique (les caractéristiques spécifiques aux patients, à la tumeur et au traitement). De plus, ils ne fournissent aucune compréhension des relations locales entre la dose et l'effet (dose-espace/effet relations) car ils n'exploitent pas l'information riche des distributions de planification de dose 3D. Dans un contexte de prédiction de l'apparition de saignement rectaux suite au traitement du cancer de la prostate par radiothérapie externe, les objectifs de cette thèse sont : i) d'extraire des informations pertinentes à partir de l'HDV et des variables non-dosimétriques, afin d'améliorer les modèles NTCP existants et ii) d'analyser les corrélations spatiales entre la dose locale et les effets secondaires permettant une caractérisation de la distribution de dose 3D à l'échelle de l'organe. Ainsi, les stratégies visant à exploiter les informations provenant de la planification (distributions de dose 3D et HDV) ont été proposées. Tout d'abord, en utilisant l'analyse en composantes indépendantes, un nouveau modèle prédictif de l'apparition de saignements rectaux, combinant d'une manière originale l'information dosimétrique et non-dosimétrique, a été proposé. Deuxièmement, nous avons mis au point de nouvelles approches visant à prendre conjointement profit des distributions de dose de planification 3D permettant de déceler la corrélation subtile entre la dose locale et les effets secondaires pour classer et/ou prédire les patients à risque de souffrir d'un saignement rectal, et d'identifier les régions qui peuvent être à l'origine de cet événement indésirable. Plus précisément, nous avons proposé trois méthodes stochastiques basées sur analyse en composantes principales, l'analyse en composantes indépendantes et la factorisation discriminante en matrices non-négatives, et une méthode déterministe basée sur la décomposition polyadique canonique de tableaux d'ordre 4 contenant la dose planifiée. Les résultats obtenus montrent que nos nouvelles approches présentent de meilleures performances générales que les méthodes prédictives de la littérature
Prostate cancer is among the most common types of cancer worldwide. One of the standard treatments is external radiotherapy, which involves delivering ionizing radiation to a clinical target, in this instance the prostate and seminal vesicles. The goal of radiotherapy is to achieve a maximal local control while sparing neighboring organs (mainly the rectum and the bladder) to avoid normal tissue complications. Understanding the dose/toxicity relationships is a central question for improving treatment reliability at the inverse planning step. Normal tissue complication probability (NTCP) toxicity prediction models have been developed in order to predict toxicity events using dosimetric data. The main considered information are dose-volume histograms (DVH), which provide an overall representation of dose distribution based on the dose delivered per percentage of organ volume. Nevertheless, current dose-based models display limitations as they are not fully optimized; most of them do not include additional non-dosimetric information (patient, tumor and treatment characteristics). Furthermore, they do not provide any understanding of local relationships between dose and effect (dose-space/effect relationship) as they do not exploit the rich information from the 3D planning dose distributions. In the context of rectal bleeding prediction after prostate cancer external beam radiotherapy, the objectives of this thesis are: i) to extract relevant information from DVH and non-dosimetric variables, in order to improve existing NTCP models and ii) to analyze the spatial correlations between local dose and side effects allowing a characterization of 3D dose distribution at a sub-organ level. Thus, strategies aimed at exploiting the information from the radiotherapy planning (DVH and 3D planned dose distributions) were proposed. Firstly, based on independent component analysis, a new model for rectal bleeding prediction by combining dosimetric and non-dosimetric information in an original manner was proposed. Secondly, we have developed new approaches aimed at jointly taking advantage of the 3D planning dose distributions that may unravel the subtle correlation between local dose and side effects to classify and/or predict patients at risk of suffering from rectal bleeding, and identify regions which may be at the origin of this adverse event. More precisely, we proposed three stochastic methods based on principal component analysis, independent component analysis and discriminant nonnegative matrix factorization, and one deterministic method based on canonical polyadic decomposition of fourth order array containing planned dose. The obtained results show that our new approaches exhibit in general better performances than state-of-the-art predictive methods

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De, Armas Ricardo Eduardo. "Impact of intrafractional prostate motion on the accuracy and efficiency of prostate cancer treatment on CyberKnife radiotherapy." Thesis, Massachusetts Institute of Technology, 2015. http://hdl.handle.net/1721.1/98920.

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Thesis: S.B., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2015.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 39-41).
One of the most common treatments for men with localized prostate cancer is radiation therapy, which involves delivering small doses of radiation to the prostate for an extended period of time. Stereotactic-body radiation therapy (SBRT) is a form of radiotherapy that delivers increased dosage to the prostate with more precision. The results are shorter treatment times, increased effectiveness, and less toxicity to surrounding tissue. However, the prostate has been found to move around during treatment (intrafraction) and between treatments (interfraction). With greater precision, there is a greater risk of missing the target while the prostate is moving. This study assesses the impact of intrafractional prostate motion on the accuracy and efficiency of SBRT on CyberKnife. Prostate tracking log files were acquired from 6 patients with prostate cancer, which comprises18 SBRT fractions and 1,892 X-ray image registrations. Each image contains real-time prostate motion in 6D. The data were compared against clinically used margins to identify periods of large prostate motion during treatment. Results indicate significant periods of prostate motion, with the greatest movement occurring in anterior-posterior translation (6.2% outside margin) and pitch rotation (4.3% outside margin). The percentage of prostate motion beyond margins varied among patients, with an average of 12.8% outside clinical margins and 36.0% outside hypothetically reduced margins. The treatment time for each fraction was also recorded to quantify the efficiency of CyberKnife delivery. Because of motion-related delays, optimal setup of 5-15 minutes was seen in only 50% of the fractions, and optimal beam delivery times of 30-40 minutes in 44% of fractions. Thus, results suggest that treatment accuracy and efficiency were negatively affected by the occurrence of large prostate motion. Techniques that immobilize the prostate during treatment may be considered to reduce intrafractional prostate motion and ensure greater accuracy and efficiency of prostate cancer SBRT.
by Ricardo Eduardo De Armas.
S.B.

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Neal, Anthony James. "Optimisation of radiotherapy treatment planning for tumours of the breast, prostate and brain." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306922.

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Nagy, Ábel. "The synthesis and analysis of a bombesin analogue for radiotherapy of prostate cancer." Thesis, KTH, Skolan för kemi, bioteknologi och hälsa (CBH), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-261352.

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Targeted radionuclide therapy is becoming a widely used cancer treatment strategy. By radiolabeling receptor-specific peptides, cancer cells overexpressing the receptor can be selectively targeted, and the cytotoxic radionuclide can be delivered to the target cell or tissue for therapeutic or diagnostic purposes. Bombesin analogues have been previously developed and utilized to target the gastrin-releasing peptide receptor (GRPR), a receptor commonly overexpressed in prostate cancer cells. The RM26 analogue derived from the native bombesin is an antagonistic ligand of GRPR and a possible candidate for targeted radiotherapy. Prolonging the half-life of the molecule is an important aspect of developing a new protein therapeutic. Using albumin binding domain (ABD) for this purpose is an emerging strategy in recent years. ABD is able to bind to serum albumin and thus remains in the blood circulation for a long period of time. It is also a scaffold for protein engineering efforts and by coupling receptor-specific ligands to ABD, the target-specific binding along with extended in vivo halflife can be achieved. In this project, an RM26 analogue with a PEG linker and ABD with a DOTA chelator for future radiolabeling were synthesized with solid phase peptide synthesis (SPPS), conjugated, purified by RP-HPLC and analyzed by mass spectrometry. The binding properties of the conjugate were evaluated by SPR-based biosensory studies, and further experiments are planned for the testing the product and its potential application in radionuclide therapy.
Riktad radioterapi är en allt vanligare metod för behandling av cancer. Genom att radioinmärka receptor-specifika peptider kan dessa selektivt levereras till tumörceller som uttrycker receptorn. Radioterapi kan användas för diagnostik eller terapi, beroende på kopplad radionuklid. Bombesinanaloger har utvecklats och använts för att selektivt binda gastrinfrisättande peptidreceptor (gastrin-releasing peptide receptor, GRPR), en receptor som ofta är överuttryckt i prostatacancer. Bombesinanalogen RM26, som har sitt ursprung från nativt bombesin, är en antagonist till GRPR och kan möjligen användas för riktad radioterapi av prostatacancer. Vid utvecklingen av nya proteinläkemedel är halveringstiden i serum en viktig aspekt. En nyligen utvecklad strategi för att förlänga halveringstiden i serum är fusion av det tumörspecifika proteinet till en albumin-bindande domän (ABD). ABD binder till albumin, ochsåledes kan fusionsproteinet bevaras i blodcirkulationen under en längre tid. I detta projekt, har både RM26 med en PEG-linker, och ABD med en DOTA kelator syntetiserats med fastfaspeptidsyntes (solid phase peptide synthesis, SPPS). RM26-PEG och DOTA-ABD har därefter konjugerats, renats med RP-HPLC och analyserats med massspektrometri. Bindning till albumin har utvärderats med ytplasmonresonans (surface plasmon resonance, SPR). Vidare studier planeras för att utvärdera peptid-proteinkonjugatet och dess potential för riktad radioterapi.

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Fridriksson, Jon Örn. "Adverse effects of curative treatment of prostate cancer." Doctoral thesis, Umeå universitet, Urologi och andrologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-128709.

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Background Screening for prostate cancer is debated, there is conflicting data on the net benefit of screening. Men who consider screening need to be informed on the pros and cons. Rehospitalization after surgery can be used as an indicator of general quality of care. For radical prostatectomy, little is known on the readmission rate after surgery. Men diagnosed with low- and intermediate-risk prostate cancer have low prostate-cancer specific mortality. However, adverse effects after curative treatment can be severe and decrease quality of life. Curative treatments for prostate cancer differ mainly in the pattern of adverse effects but detailed analysis of long-term adverse effects is lacking. The aim of this thesis was to assess the perioperative quality of radical prostatectomy and the risk of adverse effects after curative treatment for prostate cancer. Material and Methods In this thesis, data from the National Prostate Cancer Register (NPCR) and other nationwide Swedish registers were used. By use of the Swedish personal identity number, NPCR was cross-linked to other registers creating Prostate Cancer data Base Sweden (PCBaSe), a large dataset for research. Results The proportion of men who had received information on the pros and cons of screening for prostate cancer with PSA testing was low (14%) indicating that the majority of men who were screened did not make an informed decision. The risk of rehospitalization within 90 days after radical prostatectomy was approximately 10% and similar after retropubic and robot-assisted radical prostatectomy. Compared to controls, there was an increased risk of adverse effects after both radiotherapy and radical prostatectomy up to twelve years after treatment and the overall risk was quite similar after retropubic and robot-assisted radical prostatectomy. Conclusion Improved information to men on the pros and cons of PSA screening is warranted. The risk of adverse effects was elevated up to 12 years after curative treatment for prostate cancer. The pattern of adverse effects was different after radiotherapy and radical prostatectomy but quite similar after retropubic and robot-assisted radical prostatectomy.

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Hewson, Emily. "Enabling Real-Time Adaptive Radiotherapy for Multiple Targets." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/27841.

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Treating cancer safely and effectively using radiotherapy requires accurate targeting of the tumour. However, internal motion of the tumour due to physiological activity compromises the accuracy of radiotherapy treatment. Managing motion during radiotherapy is further complicated for patients with advanced cancer or oligometastases, where multiple targets can undergo large, independent motion. Prior to this thesis no solution existed to adapt to the motion of independent targets in real time. The aim of this thesis was to develop the first real-time multi-target tracking method. The first two studies in this thesis investigate the use of Kilovoltage Intrafraction Monitoring (KIM) for image guidance (Chapter 4), and multileaf collimator (MLC) tracking as a real-time adaptation method (Chapter 5) for single-target prostate cancer treatments in a clinical trial. KIM was found to be accurate for prostate motion monitoring and MLC tracking was found to be dosimetrically accurate. A multi-target MLC tracking algorithm was then developed and tested for simulated locally advanced prostate cancer treatments, described in Chapter 6. Multi-target MLC tracking was found to irradiate the two targets with a higher accuracy compared to previously implemented methods. Multi-target MLC tracking was then experimentally implemented in Chapter 7, demonstrating that the radiation beam could be adapted to multiple targets simultaneously using a clinical treatment system. Finally in Chapter 8 a multi-target MLC tracking method that adapts to dosimetric errors in real time was developed and evaluated. This method reduced errors compared to the fluence-based approach to allow for multi-target tracking with improved target coverage. Through this thesis, a novel real-time multi-target tracking system was developed, advancing the current state of radiotherapy by providing a world-first, accessible method that will improve the accuracy of treatments for patients with multiple cancer targets.

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Wirth, Manfred P., and Michael Fröhner. "Perspectives in Adjuvant Treatment of Prostate Cancer." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133839.

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Stewart, Grant Duncan. "Novel survival factors and approaches to the treatment of hypoxic prostate cancer." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/4390.

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Tumour hypoxia has been demonstrated to cause development of an aggressive tumour phenotype and is associated with increased patient mortality and poorer response to treatments such as chemotherapy and radiotherapy. Previous studies have established that hypoxia exists within a nidus of prostate cancer. Based on the importance of the tumour microenvironment, especially hypoxia, in prostate cancer, the major aims of this thesis were to establish: (a) the role of a novel putative survival factor, dermcidin, in prostate cancer survival under hypoxia/oxidative stress; and (b) the effect of nitric oxide-donating non-steroidal anti-inflammatory drugs (NO-NSAIDS), a new class of drugs, on the killing of prostate cancer cells subjected to hypoxia. A wide-range of confirmatory, cellular and molecular biology techniques were employed in this thesis. The PC-3 hormone-insensitive prostate cancer cell line was used for the majority of studies as this cell line represents hormone-independent prostate cancer, treatment of which is currently palliative. Cell incubation at 0.2% oxygen for 48 hours was established as suitable conditions to stimulate the development of the hypoxia response. Upregulation of nuclear hypoxia-inducible factor-1α protein was the main marker used to assess the hypoxia response. Dermcidin messenger RNA production was found to occur in a range of prostate cancer cell lines; was upregulated in cell lines by both hypoxic and oxidative stress; and found to act as a proliferation, survival and pro-invasion factor under hypoxia and oxidative stress in immortalised prostate cancer cell lines. Furthermore, the portion of the dermcidin molecule responsible for the survival advantage was localised to the proteolysis-inducing factor core peptide subunit. However, subsequent analysis of primary cancer samples from prostate cancer patients revealed that dermcidin was not expressed in these tumours, although dermcidin mRNA was identified in analysis of other primary tumours. As such, the role of dermcidin in prostate cancer was not evaluated further in this thesis. Investigation of NO-sulindac (a NO-NSAID drug) in hypoxic PC-3 cells showed that these agents were significantly more pro-necrotic, pro-apoptotic and anti-invasive than traditional, unnitrated sulindac. NO-sulindac was found to downregulate the hypoxia response mounted by PC-3 cells under hypoxia via the Akt signalling pathway. Finally, analysis of the role of NO-sulindac in radiosensitising hypoxic PC-3 cells showed that NO-sulindac caused significant radiosensitisation under normoxia, but particularly in hypoxic conditions. As such, NO-NSAIDs show great promise as neoadjuvant, concurrent and adjuvant treatments for patients with hypoxic prostate cancer. The findings of this thesis illustrate several potential novel strategies for treatment of hormone-independent prostate cancer.

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Fullerton, Natasha Eileen. "Gene therapy and targeted radiotherapy applied to bladder and prostate cancer : examination of radiation-induced bystander effects in targeted radiotherapy." Thesis, University of Glasgow, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.438687.

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Gershkevitsh, Eduard. "Dose to bone marrow and leukaemia risk in external beam radiotherapy of prostate cancer /." Online version, 2005. http://dspace.utlib.ee/dspace/bitstream/10062/1271/5/gerskevitsh.pdf.

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Chen, Yong. "Daily three-dimensional ultrasound imaging for Monte Carlo based adaptive radiotherapy of prostate cancer." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66928.

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This thesis retrospectively analyzes prostate's daily motion provided by three-dimensional US localization and investigates its dosimetric impacts based on XVMC calculation which takes into account patient geometry, heterogeneity and prostate motion correction. The retrospective analysis on 32 prostate patients shows that the mean  SD displacements of prostate in the AP, SI, and RL directions are -3.3  7.9 mm, -1.1  6.4 mm, -0.2 5.6 mm, respectively. The largest rotation occurs about lateral axis with mean  SD of -0.9  4.6, ranging between -6.7 and 8.0 from a preliminary study including three patients. To assess the dosimetric impacts of prostate motion, five motion scenarios including with and without prostate translation and correction, with translation and rotation but no correction or only having translation correction are simulated. Analysis based on dose-volume histograms and isodose curves shows that prostate motion (translation and rotation) will deteriorate the dose delivered to patient target and OARs. With translation correction method, the degraded patient dose could be recovered nearly completely. For the scenarios with both translation and rotation, translation correction method could dramatically improve the degraded patient dose, but could not completely eliminate the dosimetric impact of prostate motion. Besides, the dosimetric impact of metal prosthesis in three patients has been analysed as well. Up to 5% discrepancies in their D90%, D95%, V90%, and D95% for PTV have been observed.
Le mouvement de la prostate est un problème critique dans le traitement conforme du cancer de la prostate, le plus commun cancer parmi les hommes au Canada. La radiothérapie guidée par l'image (IGRT) utilisant les images ultrasons (US) quotidiennes est une technique largement utilisée pour régler ce problème. Une nouvelle technique de localisation ultrasons en trois dimensions, basée sur une méthode de vérification intra modalités, a été testée à l'Hôpital General de Montreal en 2005. L'objectif principal de cette thèse a été de mieux quantifier l'amplitude du mouvement de la prostate à travers une analyse rétrospective de 32 patients et d'évaluer son impacte dans la dosimétrie des traitements de la prostate avec et sans localisation US. L'analyse rétrospective a montré que la moyenne  écart-type des mouvements de la prostate dans les directions AP, SI et DG est de -3.3  7.9 mm, -1.1  6.4 mm et -0.2  5.6 mm, respectivement. La plus grande rotation survient autour de l'axe latérale, avec une moyenne  écart-type de -0.9  4.6, s'échelonnant entre -6.7 et 8.0. Pour estimer l'impacte dosimétrique du mouvement rigide de la prostate, la dose a été calculée en utilisant la méthode XVMC, qui prend en considération la géométrie du patient, les hétérogénéités et les corrections pour le mouvement. Une déviation moyenne de la D95% de jusqu'à -11.9% a été observe pour le PTV, -5.1% pour le CTV et -4.2% pour le GTV. Le V95% du PTV a été réduit par un facteur de -22.2% lorsque la translation quotidienne de la prostate était présente mais aucune correction n'a été appliquée. La dégradation de la dose à la cible a pu être corrige presque complètement en appliquant une correction du mouvement de translation, cependant lorsque la rotation a été prise en compte, le recouvrement de la dose a été moins adéquat. L'effet des prothèses m

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Ariyaratne, Hemal. "Dosimetric investigation of image-guided radiotherapy for prostate cancer using cone-beam computed tomography." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10046186/.

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Objectives: 1. To survey the current practice of image-guided radiotherapy (IGRT) for prostate cancer in the United Kingdom. 2. To validate a practical dose calculation strategy on cone-beam computed tomography (CBCT) 3. To assess the effect of CBCT verification imaging frequency on actual dose delivered to target volume and organs at risk during a course of image-guided radiotherapy for prostate cancer. 4. To compare the dosimetric effects of reduction of CTV-PTV margin with daily imaging. / Material and Methods: 59 radiotherapy centres in the United Kingdom were included in an online survey of IGRT practice. The survey covered details of verification strategy during prostate radiotherapy, with specific questions on imaging frequency. A validation study of the CBCT dose calculation strategy was evaluated on 37 fractions using Bland-Altman plots. The study technique was compared to the density-override technique. A pilot comparison of CTV coverage with bone matching to soft tissue matching was performed. For the principal dosimetric analysis, 844 cone-beam CT (CBCT) images from 20 patients undergoing radical prostate radiotherapy were included. Patients received a dose of 74 Gy in 37 fractions using 7-field intensity-modulated radiotherapy. Target volume and organs at risk were contoured manually on each CBCT image. A daily online CBCT verification schedule was compared with a protocol of day 1-3 followed by weekly imaging. 3 mm, 5 mm, and 7 mm CTV-PTV margins were compared for daily imaging. / Results: CBCT is the principal verification imaging modality in the UK for prostate cancer, used by 66% of centres. There is no consensus on optimal imaging schedule, with 2 main strategies used. These are the daily online schedule and the day 1-3 followed by weekly schedule. Use of CBCT contours on planning CT showed good agreement with the density-override technique, provided multifield IMRT was used. There were clear drops in target coverage if a bone match strategy was used in comparison to soft tissue matching. 90% of patients had improved target coverage with daily online in comparison to weekly online soft tissue match. A median of 37 fractions achieved CTV coverage with daily imaging compared with 34 fractions with a weekly online protocol. 80% of patients had a reduction in rectal dose with the daily protocol. Margin reduction to 5 mm with adequate target coverage was feasible with daily imaging. / Conclusions: Daily online CBCT verification improves CTV coverage and reduces rectal dose during IGRT for prostate cancer. Daily CBCT imaging allows reduction of CTV-PTV margin for radiotherapy.

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Wang, Man-Tzu. "Identification and characterization of stem-like cancer cells in prostate tumor recurrence after radiotherapy /." Available to subscribers only, 2008. http://proquest.umi.com/pqdweb?did=1594476861&sid=12&Fmt=2&clientId=1509&RQT=309&VName=PQD.

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Thesis (M.S.)--Southern Illinois University Carbondale, 2008.
"Department of Molecular Biology, Microbiology and Biochemistry." Includes bibliographical references (p. 48-51). Also available online.

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Wirth, Manfred P., and Michael Fröhner. "Perspectives in Adjuvant Treatment of Prostate Cancer." Karger, 2002. https://tud.qucosa.de/id/qucosa%3A27540.

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Ng, Jin. "Kilovoltage intrafraction monitoring (KIM): a novel real-time targeting system for cancer radiotherapy." Thesis, The University of Sydney, 2014. http://hdl.handle.net/2123/12298.

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In cancer radiotherapy, there is a need for a highly accurate, widely applicable, cost effective real-time tumour localization modality with a low barrier to clinical implementation. This thesis documents the bench-to-bedside translation of Kilovoltage Intrafraction Monitoring (KIM), a novel real-time localization modality. This thesis consists of three main studies, each with specific aims which, when combined, culminate in the clinical implementation of real-time KIM. The first study aimed to implement KIM clinically but in a retrospective manner. This was to ascertain if KIM could determine intrafraction prostate motion in a clinical setting. The second study aimed to calculate the additional imaging dose delivered by KIM to determine if KIM uses a safe quantity of imaging dose. The third study aimed to develop a Quality Assurance framework for real-time KIM to ensure that it can be delivered safely and effectively in a clinical setting. KIM was successfully implemented for the first time in a 10 patient prostate cancer clinical trial. KIM could only determine prostate motion retrospectively, i.e. not in real-time. This meant that real-time adaptation could not be made. However, this study proved that KIM could determine intrafraction prostate motion accurately in a clinical setting. KIM delivers additional kV imaging dose. This dose was quantified. We found that the additional dose delivered was within clinically acceptable limits for patients. This study proved that KIM could be used on patients with no additional risk from dose. Significant efforts were made to enable real-time capability for KIM. A Quality Assurance framework was adapted and developed to assess real-time KIM. This study proved that KIM could be implemented safely and effectively in a clinical setting. These three studies enabled the first clinical implementation of real-time KIM. The first patient was treated on 16 September 2014. At the time of writing, three patients are undergoing treatment.

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Norkus, Darius. "Neišplitusio priešinės liaukos vėžio hipofrakcionuoto išorinio spindulinio gydymo saugumo ir efektyvumo tyrimas." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2010. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2009~D_20100204_103040-19767.

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Darbo tikslas. Atsitiktinės atrankos perspektyviniame klinkiniame tyrime nustatyti ir palyginti lokalaus priešinės liaukos vėžio įprastai frakcionuoto (CFRT) ir hipofrakcionuoto (HFRT) išorinio trimačio konforminio spindulinio gydymo sukeliamas ūmines spindulines reakcijas, gydymo efektyvumą, bei lėtines spindulines reakcijas. Tyrimo medžiaga ir metodai. CFRT taikyta 44 pacientams, švitinta prostata ir sėklinių pūslelių pagrindas 37 frakcijos po 2,0 Gy iki suminės 74 Gy dozės. HFRT taikyta 47 pacientams, toks pat taikinys švitintas 13 frakcijų po 3,0 Gy ir 4 frakcijos po 4,5 Gy iki suminės 57 Gy dozės. Pacientai stebėti mažiausiai 2 metus. Rezultatai. Ūminių 2 laipsnio šlapimo pūslės spindulinių reakcijų buvo statistiškai reikšmingai mažiau HFRT pacientų grupėje. Visų tiesiosios žarnos ūminių spindulinių reakcijų trukmė buvo mažesnė HFRT grupėje . Lėtinių šlapimo pūslės ir tiesiosios žarnos spindulinių reakcijų dažnumas pacientų grupėse nesiskyrė. Biocheminio atsako į gydymą dydis ir greitis pacientų grupėse per 2 metų stebėjimo laiką nesiskyrė. Išvados. Taikytas hipofrakcionuotas išorinis lokalaus prostatos vėžio spindulinis gydymas yra saugus, tačiau atokiam šio gydymo metodo efektyvumui nustatyti reikalingas ilgesnis pacientų stebėjimo laikas.
The aim of the study. To investigate and compare toxicity and efficacy of conventionally fractionated (CFRT) vs. hypofractionated (HFRT) three dimensional conformal external beam radiotherapy for localized prostate carcinoma within prospective randomized study. Matherial and Methods. Forty-four patients in the CFRT treatment arm were irradiated with 74 Gy in 37 fractions (2 Gy per fraction), and 47 in the HFRT arm were treated with 57 Gy, given in 13 fractions of 3 Gy plus 4 fractions of 4.5 Gy. The clinical target volume includes the prostate and a base of seminal vesicles. A minimum follow-up was 2 years. Results. The only grade 2 genitourinary acute toxicity proportion was significantly lower in the HFRT arm. The median duration of overall gastrointestinal acute toxicity was significantly shorter with HFRT. There were no statistically significant differences in the late toxicity rates, biochemical tumor response rates and time to the response between study arms during 2 year follow-up. Conclusions. The investigated hypofractionated 3DCRT for localized prostate carcinoma found to be safe, but extended follow-up is needed to justify the efficacy of our fractionation schedule in the long term.

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FELISI, MARCO MARIA JACOPO. "Clinical implementation of MRI-only radiotherapy treatment workflow for prostate cancer with a standard linac." Doctoral thesis, Università degli Studi di Milano, 2020. http://hdl.handle.net/2434/855304.

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BACKGROUND AND AIM The purpose of this work is the clinical implementation of radiotherapy treatment workflow for prostate cancer based only on MRI images (MRI-only) with a standard linac, using the technological tools available in a big general hospital. In the recent years the growing interest in using solely MRI images, due to the excellent soft tissue contrast that makes it unique, both for identification and precise delineation of target volumes and organs at risk (OAR), emerged strongly. Especially in those regions characterized by soft tissues, as the pelvis site, the method has several benefits, including improvement of inter-observer robustness in target delineation, a reduction in contoured structures which potentially leads to smaller irradiated volumes and a major efficiency of the workflow by both reducing the time and costs of patients imaging and removing residual registration error compared to a CT/MR workflow. However, there are several challenges in the implementation and application of MRI-only workflow; the most important one is the Electron Densities (ED) estimation. In fact, unlike CT images, where the voxels intensities are directly linked to the physical properties of the tissues ED, required by the Treatment Planning System (TPS) for dose calculation, MRI signals do not depend on ED but correlate with tissue proton density and thus cannot be directly used. Therefore, it is mandatory to convert MRI data to ED maps to allow the dose distribution even in this case. These generated maps are known as synthetic CT (sCT). Several aspects of the implementation have been examined in this thesis in order to validate the overall workflow. MATERIAL AND METHODS Imaging acquisition was performed using a 3D T1 VIBE Dixon gradient echo sequence that is a good compromise between image quality and acquisition time; it takes 2 minutes and 30 seconds and provides 4 contrasts (Water, Fat, In-phase and Out-of-phase) useful for the visualization of target and different OARs. The acquisition on the MR scanner was possible thanks to the use of a home-made table-top, commercial MR safe markers and properly controlled internal laser system; furthermore, the geometric distortions in obtained images were evaluated. A hybrid method was adopted to generate sCT from MRI; it consists in a combination of bulk ED and multi atlas-based approach. For this purpose, the MR images of 20 volunteers and patients undergoing diagnostic acquisitions were collected, manually contoured in bones and main OARs, and then inserted, after verification by a radiation oncologist, as reference in the database of ADMIRE software (research version 1.13.5, Elekta AB, Stockholm, Sweden), utilized for automatic contouring process. The software approximates the anatomy contours by comparing several individual atlases, applying elements of maximum likelihood forms to a new patient image-set, and creates a structure set to fit the actual patient’s anatomy. Therefore, sCTs were finally generated in the TPS by assigning to each structure bulk ED values, calculated averaging over 20 patients who previously underwent prostate radiotherapy. Once the sCT was generated, different evaluations were made using quantitative methods such as dose-volume histogram (DVH) and 2D local gamma analysis, in order to test the dose differences between the sCT and the gold standard CT, both in terms of homogeneous EDs assignment and contours delineated on the MR images. At first, 20 VMAT prostate treatment plans, calculated on standard CT images with 10 MV X-rays, were recalculated using the same field, segments and monitor unit (MU) arrangements on the sCT, where only fixed EDs were assigned instead of the heterogenous ones. Afterwards, the combination between the assignment of an average ED and the different contours in the two imaging modalities was evaluated for 7 patients undergoing both CT and MR acquisitions. The optimized plans, calculated on the CT images, were first copied using the same field, segment and MU arrangements and recalculated on the sCTs, obtained by MRI, and thus were optimized again keeping the same plan constraints as CT-based ones. Finally, the feasibility of patient positioning in the linac room using CBCT-MR matching was verified. For 9 selected images of different fractions and patients, the shifts obtained through CT-CBCT registration were compared to the those resulting from the evaluations of three radiation oncologists, who blindly and manually matched the CBCT images with those from MRI. RESULTS AND DISCUSSIONS The MR sequence used for this work was optimized in order to achieve adequate image quality in a reasonable time, reducing the artifacts and minimizing the patient discomfort. Furthermore, the internal laser system of the MRI scanner, used patient positioning, was checked. It was verified that the laser cross, projected from a single point inside the scanner, was centered in the isocenter and not tilted. The mean tilt angle was 0.3°± 0.2° (range 0.2° to 0.4°) in all positions tested, corresponding to difference approximately of 1±0.4 mm at 15-20 cm from the isocenter. In addition, the geometric distortions, evaluated in the absence of the patient less than 2 mm, are minimized by the active shimming system of the scanner. The auto-contouring delineation process performed by ADMIRE (research version 1.13.5, Elekta AB, Stockholm, Sweden) was executed in an average time of approximatively 20 minutes and considered satisfactory by radiation oncologists; further 5 to 10 minutes were needed to better define some contours and to identify the target. Regarding the evaluation made on the same CT images, where only the EDs were changed, the mean deviation of PTV and OARs DVH parameters were approximately 0.5%, except for the rectum were the percentage difference reached higher values (Dmean of 1% and V40 of 2.4%) due to different filling. In addition, further evaluations performed by 2D local γ-analysis resulted in average passing rate from 98.5% to 99.4% in the three views, using an acceptance criterion of 2%-2mm. On the sCT obtained by MR images, despite the mean percentage differences in PTV coverage were limited, below the 1% in the first case and around 0.5% in the second one, the differences for OARs were considerably higher; mean percentage differences for bladder and femoral heads were approximatively -25% and -2% in both the described steps, while Dmean of rectum ranged from +11.5% to +4% and V40 passed from +26% to +8%. Anyhow, this issue is not relevant in the implementation of the workflow, as only MRI acquisitions will be made for planning purposes. Rather, this behaviour is representative of the differences in filling of different OARs, such as rectum and bladder, between two consecutive fractions of the treatment. Moreover, however, the PTV and OARs compliance with the constraints, used in our center, was evaluated for the re-optimized plans: for 7 patients and 8 different parameters, only 1 time over 56 a constraint exceeded the limits. Finally, as far as the matching between CBCT-MR for patient positioning before each treatment fraction, the averaged differences in displacements respect to standard CT-based method, resulted 2.8±1.7 mm, 3.8±1.6 mm and 0.1±1.4 mm for transverse, longitudinal and vertical directions respectively, despite the physiological differences of the rectum and bladder between the two imaging modalities. CONCLUSIONS This study demonstrates that MRI-only workflow for prostate patients seems to be feasible using the clinical optimized method, providing a better contrast in the structures of clinical interest. Therefore, the future goal is to gradually move towards the use of MRI-only in the clinical routine. Meanwhile, the proposed method will be used for special cases, such as patient with metal hip prosthesis.

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Haworth, Annette. "Post implant dosimetric analysis for prostate brachytherapy." University of Western Australia. School of Surgery and Pathology, 2005. http://theses.library.uwa.edu.au/adt-WU2005.0107.

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Nassef, Mohamed. "Monitoring de dose pour la radiothérapie du cancer de la prostate." Thesis, Rennes 1, 2016. http://www.theses.fr/2016REN1S033/document.

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Cette thèse porte sur la prise en compte des variations anatomiques, notamment les déformations d’organes à risque (rectum, vessie), pouvant survenir lors du traitement de radiothérapie conformationnelle par modulation d’intensité du cancer de la prostate. Ces variations peuvent entrainer d’importants écarts dosimétriques par rapport au plan de traitement initialement optimisé, et augmenter le risque de complications. Grâce à l’évolution des dispositifs d’imagerie et des méthodes de traitement d’images, des approches permettant de cumuler la dose au cours du traitement ont été récemment proposées mais restent mal évaluées et leur intégration dans un schéma de radiothérapie adaptative suscite de nombreuses questions. Ainsi, la première partie de ce travail a consisté à évaluer, à l’aide d’un fantôme numérique, une méthode de suivi de dose développée récemment au LTSI. Les résultats obtenus ont montré que les incertitudes dosimétriques liées à l’algorithme de cumul de dose sont limitées par rapport aux dérives dosimétriques observées chez les patients. La seconde partie de ce travail a consisté à proposer une stratégie de radiothérapie adaptative reposant sur le suivi de dose et à évaluer son bénéfice dosimétrique sur trois patients pour lesquels des dérives avaient été observées. Le principe de cette méthode est de détecter les dérives dosimétriques entre la dose planifiée et la dose réellement délivrée et, si besoin, de les compenser grâce à une ou plusieurs replanifications. Les résultats obtenus ont montré que cette approche permet une réduction de la dérive aux organes à risque, tout en augmentant la dose au volume cible en comparaison à un traitement standard par IGRT, avec un nombre limité de replanifications (une ou deux) permettant d’envisager une implémentation clinique
This thesis concerns the compensation of the anatomical variations, mainly the organs at risk (rectum, bladder) deformations, which occur during intensity modulated radiotherapy of the prostate cancer. These variations can lead to significant dose drift compared to the initially planned dose, increasing the risk of toxicity. Thanks to the evolution of imaging devices and of image processing methods, dose accumulation processes, allowing to estimate the cumulated dose during the treatment, have been recently proposed. Nevertheless those strategies suffer of a lack of evaluation and their integration into an adaptive radiotherapy raises many questions. Thus, in the first part of this work, a dose accumulation method recently developed at the LTSI was evaluated using a numerical phantom. The results obtained showed that the dosimetric uncertainties related to the cumulated dose process remain low compared to the dose drifts observed for patients. The second part of this work aimed to develop a dose guided adaptive radiotherapy process and to evaluate its dosimetrical benefit using three patients showing a dose drift. The principle of this method is to detect a potential drift between the planned and actually delivered doses and, if necessary, to compensate them thanks to one or more replanning(s). The results have shown that this approach has reduced the dose drift to the organs at risk, while increasing the dose to the prostate compared to standard IGRT treatment, with a limited number of replannings (one or two), enabling to consider a clinical implementation

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Mylona, Eugenia. "From global to local spatial models for improving prediction of urinary toxicity following prostate cancer radiotherapy." Thesis, Rennes 1, 2019. http://www.theses.fr/2019REN1S109.

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La radiothérapie externe est un traitement locorégional du cancer. L’objectif de la radiothérapie impose un compromis entre la délivrance d’une dose maximale dans la tumeur afin d’augmenter le contrôle local et la curabilité, et d’une dose minimale aux organes sains afin de limiter la toxicité. Les symptômes urinaires peuvent être liés à l’irradiation de régions spécifiques de la vessie ou de l'urètre. Dans ce cas, la dose reçue par l'ensemble de la vessie peut ne pas suffire à expliquer la toxicité urinaire. Dans le contexte du traitement du cancer de la prostate par radiothérapie, ce travail de thèse vise à analyser les corrélations spatiales entre la dose et les effets secondaires, cette problématique étant abordée dans un cadre d'analyse de population. Pour évaluer la contribution de l'urètre à la toxicité urinaire, nous proposons une méthode de segmentation basée sur plusieurs atlas pour identifier avec précision cette structure sur les images CT. Nous utilisons ensuite deux méthodes pour analyser la distribution de dose spatiale. L'une basée sur la construction de cartes 2D dose-surface (DSM) couplée à des comparaisons pixel par pixel et l'autre basée sur des cartes 3D dose-volume (DVM) combinées à des comparaisons par voxel. Les sous-régions identifiées ont été validées dans des populations externes, ouvrant la perspective d'une planification de traitement spécifique du patient. Nous étudions également le potentiel d'une amélioration complémentaire de la prédiction en exploitant de méthodes d'apprentissage automatique
External beam radiotherapy (EBRT) is a clinical standard for treating prostate cancer. The objective of EBRT is to deliver a high radiation dose to the tumor to maximize the probability of local control while sparing the neighboring organs (mainly the rectum and the bladder) in order to minimize the risk of complications. Developing reliable predictive models of genitourinary (GU) toxicity is of paramount importance to prevent radiation-induced side-effects, and improve treatment reliability. Urinary symptoms may be linked to the irradiation of specific regions of the bladder or the urethra, in which case the dose received by the entire bladder may not be sufficient to explain GU toxicity. Going beyond the global, whole-organ-based models towards more local, sub-organ approaches, this thesis aims to improve our understanding of radiation-induced urinary side-effects and ameliorate the prediction of urinary toxicity following prostate cancer radiotherapy. With the objective to assess the contribution of urethra damage to urinary toxicity, we propose a multi-atlas-based segmentation method to accurately identify this structure on CT images. The second objective is to identify specific symptom-related subregions in the bladder and the urethra predictive of different urinary symptoms. For this purpose, we propose two methodologies for analyzing the spatial dose distribution; one based on the construction of 2D dose-surface maps (DSM) coupled with pixel wise comparisons and another based on 3D dosevolume maps (DVMs) combined with voxel-wise comparisons. Identified subregions are validated in external populations, opening the perspective for patient specific treatment planning. We also implement and compare different machine learning strategies and data augmentation techniques, paving the way to further improve urinary toxicity prediction. We open the perspective of patient-specific treatment planning with reduced risk of complications

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Lindskog, Maria. "Clinical Investigations of Image Guided Radiation Therapy for Prostate Cancer with an On-Board Imager." Thesis, Stockholm University, Medical Radiation Physics (together with KI), 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-8320.

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The daily uncertainty concerning tumor localization is one of the major problems during the course of radiation therapy. Image guided-radiation therapy (IGRT) can be used to improve the localization and adjustment of the planning target volume. The aim of this work was to evaluate both the IGRT technique used for prostate cancer patients at the department of the Karolinska University Hospital and an alternative on-line adaptive radiation therapy (ART) method with an On-Board Imager (OBI).

In the first part of the thesis 2D and 3D image registration with an OBI were compared. Ten prostate cancer patients were involved in the analyses. Two different statistical tests were used to determine significant systematic deviations between the two methods. The second part concerns daily dose verifications and dose plan reoptimization of one intensity modulated radiation therapy (IMRT) prostate cancer patient treated with IGRT. The study was based on cone-beam computed tomography (CBCT) images acquired at 6 different treatment fractions. The risk of developing late rectal and bladder toxicity was quantified using normal tissue complication probability (NTCP) calculations. Additional measurements on an Alderson phantom were performed to verify the accuracy of using the CBCT images for dose calculations.

A statistically significant difference between the 2D-2D and the 3D-3D match applications could be observed in lateral and longitudinal direction. However, the effect differed among the patients. The phantom measurements showed small dose deviations between the CT and CBCT image, with a mean dose increase to the prostate and seminal vesicles (SV) of 2.5 %. The daily dose to the prostate and SV of the IMRT patient showed to be satisfactory. The daily dose to the rectum did not exceed the prescribed rectal dose except at one treatment fraction and the highest risk of developing late rectal toxicity was about 10.4 %. Large daily bladder dose variations were observed and at two treatment fractions the bladder dose restrictions were exceeded. With a reoptimization process of the dose plan, the dose to the bladder could be reduced while conserving the dose to the target.

This work shows that for these specific patient cases appropriate doses to the prostate and SV can be delivered with IGRT. However, introducing a suitable ART method could lead to a reduction of inter-fractional rectal and bladder dose variations.

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Ovtcharov, Slav. "Impact of TMPRSS2-ERG fusion gene on prostate cancer cell response to chemotherapy, radiotherapy and androgen deprivation therapy." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:f30bf48d-fff5-49e7-8258-107a500c8752.

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Many aspects of the mechanisms by which prostate cancer (PCa) progresses from being a confined tumour to advanced metastatic and castration-resistant disease remain unclear. The aim of this study is to evaluate in vitro the potential role of the fusion gene TMPRSS2-ERG in the response of PCa cells to ionising radiation (IR) and androgen deprivation therapy (ADT). This research focused on assessing the presence of the TMPRSS2-ERG transcript across various PCa cell lines and identifying any correlation between the TMPRSS2-ERG transcript and other genes, particularly genes related to DNA damage repair pathways. Several genes involved in cell metabolism and development were found to correlate with TMPRSS2-ERG but not genes involved in DNA repair. In accordance with previous reports, this research confirmed a proliferative advantage for cells expressing ERG. However this project also tested the role of ERG-status in response to chemotherapy, radiation and ADT. The data showed that VCaP and DuCaP cells exposed to low-dose radiation demonstrated decreased viability irrespective of their ERG-status. Similarly ADT decreased the viability of VCaP cells and seemed to neutralise the proliferative advantage of TMPRSS2-ERG positive cells. Stimulation with dihydrotestosterone caused increased radioresistance of TMPRSS2-ERG positive cells. Treatment with taxanes showed stronger effect on cells with lower ERG expression. This work suggests that the proliferative advantage conferred by ERG overexpression in in vitro models can be neutralised by castration and IR.

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Guimarães, Flávio da Silva. "Análise da implementação do protocolo de tratamento da neoplasia localizada da próstata com radioterapia 3D-CRT ou IMRT utilizando esquema de hipofracionamento moderado (70Gy em 28 frações)." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17159/tde-04012017-162138/.

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A partir de um melhor entendimento sobre a radiossensibilidade do câncer de próstata, com a redefinição de parâmetros radiobiológicos, atualmente os esquemas hipofracionados de próstata tornaram-se um dos principais desafios da radioterapia moderna. Associado a este conhecimento, o emprego de técnicas precisas de radioterapia possibilitaram a entrega de maiores doses por fração, com manutenção da toxicidade e melhor controle de qualidade dos planos de tratamento. Pretendemos avaliar a implementação da radioterapia tridimensional computadorizada (3D-CRT) ou intensidade modulada do feixe (IMRT) utilizando o regime de hipofracionamento moderado (70 Gy em 28 frações) em pacientes com neoplasia localizada da próstata na rotina do departamento de radioterapia do Hospital das Clínicas da FMRP-USP. Avaliação da viabilidade técnica e do impacto financeiro na utilização da radioterapia hipofracionada na instituição.
Evaluate the implementation of computerized three-dimensional radiation therapy (3D-CRT) or intensity modulated beam (IMRT) using moderate hypofractionation schedule (70 Gy in 28 fractions) in patients with localized prostate cancer (no metastasis lymph node or distant metastasis) in routine of department of radiotherapy of the Hospital of FMRP-USP. Assessment of technical feasibility and financial impact on the use of hypofractionated radiotherapy in the institution.

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Heikkilä, V. P. (Vesa-Pekka). "New techniques and methods for decreasing healthy tissue dose in prostate cancer radiotherapy, with special reference to rectal doses." Doctoral thesis, Oulun yliopisto, 2016. http://urn.fi/urn:isbn:9789526212081.

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Abstract Prostate cancer is the most common cancer among men in Western industrialized countries. Approximately 60% of prostate cancer patients receive radiotherapy at some phase of the disease, a treatment based on the use of ionizing radiation to kill or control malignant cells. Unfortunately, adjoining healthy tissues are also affected by exposure to ionization, potentially leading to the emergence of adverse side effects, even several years later. The main radiation treatment modalities are external radiotherapy and low dose rate (LDR) or high dose rate (HDR) brachytherapy. Different techniques and methods are used to decrease the dose to healthy tissues, thus limiting the possibility of adverse effects. In this thesis a novel technique and associated equipment were developed whereby brachytherapy can be performed by inserting all needles simultaneously. This reduces the implantation time, thus minimizing the impairing effect on seed positioning accuracy resulting from prostate swelling. A phantom model was also constructed for testing and training purposes. DuraSeal® was investigated as a spacer material between the prostate and rectum, and its effect on rectal dose was evaluated during brachytherapy and external radiotherapy. DuraSeal® is resorbed over one to six months, thus altering rectal doses compared with the original dose plan. In brachytherapy, the resorption effect on rectal doses was calculated along with an evaluation of the potential of using different isotopes. In external radiotherapy, the resorption effect on rectal dose-volume histograms (DVHs) was calculated and the need for adaptive planning considered. DuraSeal®, as a spacer gel, clearly has favorable effects on rectal and anterior rectal wall DVHs in brachytherapy and external radiotherapy, and has the potential to decrease adverse effects. It is especially beneficial in hypofractionated treatments and external radiotherapy and brachytherapy combination treatment. In LDR brachytherapy using permanent seeds, dose planning is recommended prior to gel injection to prevent excessive rectal tolerance doses in situations where gel is rapidly resorbed. In external radiotherapy, the use of adaptive planning with a spacer gel improves rectal DVH, but is not necessary according to this thesis
Tiivistelmä Eturauhasen syöpä on läntisten teollistuneiden maiden miesten yleisin syöpä. Arviolta 60 % eturauhassyöpäpotilaista saa sairauden jossain vaiheessa sädehoitoa. Sädehoito perustuu syöpäsolujen kontrolloimiseen ja tuhoamiseen ionisoivalla säteilyllä. Valitettavasti ionisoiva säteily vaikuttaa myös ympäröivään tervekudokseen aiheuttaen mahdollisia haittavaikutuksia jopa vuosien päästä. Sädehoidon kolme päätyyppiä ovat ulkoinen sädehoito sekä matala- ja korkea-annosnopeuksinen tykösädehoito (brakyterapia). Tervekudosannosten pienentämiseksi ja siten myös mahdollisten haittavaikutusten vähentämiseksi käytetään eri menetelmiä ja tekniikoita. Tässä väitöskirjassa kehitettiin uusi menetelmä ja laitteisto, joiden avulla voidaan brakyterapiassa asettaa kaikki neulat samanaikaisesti eturauhaseen. Menetelmä nopeuttaa implantointivaihetta, jolloin eturauhasen turpoaminen ei ehdi vaikuttaa jyvien asettelutarkkuutta heikentävästi. Samassa yhteydessä rakennettiin myös fantomi laadunvalvontaa ja harjoittelua varten. Työssä tutkittiin ja arvioitiin myös DuraSeal® geelin käyttöä välikemateriaalina eturauhasen ja peräsuolen välissä sekä geelin vaikutusta peräsuoliannoksiin. DuraSeal® resorboituu kuuden kuukauden aikana muuttaen alkuperäisen annossuunnitelman mukaista peräsuoliannosta. Brakyterapiassa tutkittiin ja laskettiin resorption vaikutusta sekä arvioitiin eri isotooppien käyttöä. Ulkoisessa sädehoidossa laskettiin resorption vaikutusta peräsuolen tilavuushistogrammeihin ja tutkittiin mahdollisen adaptiivisen suunnittelun käyttöä. DuraSeal® geelin käyttö välikemateriaalina pienentää selkeästi peräsuoliannoksia ja siten myös mahdollisesti tervekudosten haittavaikutuksia sekä ulkoisessa sädehoidossa että brakyterapiassa. Geelin käyttö on erityisen hyödyllistä hypofraktiohoidoissa sekä ulkoisen sädehoidon ja brakyterapian kombinoidussa käytössä. Matala-annosnopeuksisessa brakyterapiassa (jyvähoidoissa) annossuunnitelma suositellaan tehtäväksi ennen geelin ruiskutusta, jotta peräsuolen toleranssiannoksia ei ylitettäisi vaikka geeli resorboituisikin nopeasti. Ulkoisessa sädehoidossa adaptiivinen suunnittelu välikegeelin kanssa tuo lisäarvoa pienentämällä edelleen peräsuoliannoksia, mutta ei ole välttämätöntä

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Al-Derwish, Omer. "Viral HSV1-TK gene, radiolabeled FIAU, and ganciclovir : combined gene targeted radiotherapy and suicide gene therapy for prostate cancer." Thesis, University of Glasgow, 2008. http://theses.gla.ac.uk/220/.

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The strategy of suicide gene therapy in cancer is based on the idea of enabling tumour cells, by gene transfer, to convert a non-toxic pro-drug into a toxic product. Previous work has shown that the combination of herpes simplex virus type 1 thymidine kinase gene (HSV1-tk) transfer with the pro-drug ganciclovir (GCV) to be a promising suicide gene therapy in cancer. Unlike several other gene therapy systems, early-phase clinical trials of this strategy have shown encouraging results. Therefore, methods to improve its therapeutic efficacy are urgently sought. The thymidine analogue 5-iodo-2’-fluoro-2’-deoxy-1-ß-D-arabino-furonosyluracil (FIAU) is an alternative substrate of the HSV1-TK enzyme. The iodine atom of FIAU can be substituted with radioactive iodine, for example; [123I]-iodine, and thereby utilised for the delivery of ionising radiation into tumour cells expressing the viral tk gene. The aim of this study was primarily to investigate the therapeutic potential of combining HSV1-tk gene transfer and [123I]FIAU for the targeted radiation cytotherapy of prostate cancer cells alone or in combination with GCV. The HSV1-tk gene was cloned into the plasmid vector pcDNA3.1. This plasmid, driven by the ubiquitous promoter of CMV, was then used to transfect the prostate cancer cell line DU145 and the glioma cell line UVW. A viral TK positive, commercially available cell line derived from osteosarcoma (143B-TK) along with its TK-negative clone were also used for comparison. The viral tk gene transfection efficiency was assessed by three independent methods. Firstly, the uptake of [123I]FIAU normalised to the uptake of tritiated thymidine ([methyl-3H]TdR); secondly, GCV sensitivity, assessed by the MTT assay; and thirdly, by the detection of HSV1-tk gene by RT-PCR. The highest specific activity of [123I]FIAU was obtained by the use of a no-carrier added method of synthesis. The cytotoxicity of [123I]FIAU was assessed by clonogenic assay after incubating monolayers of parental and TK-positive clones of the cell lines with a range of doses of [123I]FIAU for the periods of 4 h, 8 h and a period equal to their doubling times. The effect of this treatment on cell cycle progression was assessed by FACS analysis after staining the cellular DNA with propodium iodide. Combination therapy using GCV and [123I]FIAU for the treatment of TK-positive clones of the prostate cancer cell line DU-145 and the osteosarcoma cell line 143B was assessed by the method of median effect analysis and combination index. Monolayers were treated with a constant ratio of various doses of [123I]FIAU for 4h or GCV for 72h. The combination therapy followed three different timing schedules of GCV-before-[123I]FIAU, [123I]FIAU-before-GCV, or simultaneous therapy. The expression of HSV1-tk gene by the three cell lines was confirmed by the three methods described above. For instance, the TK positive clone of the cell line DU145 exhibited 4.25 ± 0.15 times higher [123I]FIAU/ [methyl-3H]TdR uptake ratio and 43 times higher sensitivity to GCV compared with the parental cell line. The three cell lines demonstrated sensitivity to radiolabelled FIAU, which was significantly enhanced by HSV1-tk gene expression. This sensitivity was time-, dose-, and proliferation-dependent. Maximum cell kill was achieved when the monolayers were exposed to [123I]FIAU for a period equavelant to the cellular doubling time. For example, the sensitivity enhancement factor by tk gene expression of the cell line DU145 increased from 5.2 to 7.6 when the treatment period was prolonged from 4 h to 26 h (doubling time of DU145). Following the treatment with [123I]FIAU for a period equal to the doubling time, cells were arrested at G2/M phase of the cell cycle. For instance, 49% of DU145-TK cells treated with 1 MBq/ml for 26 h were at G2/M phase compared with 21.9% of the untreated cells. In contrast, incubation of DU145-TK or 143B-TK cell lines with lethal doses of [123I]FIAU for 4 h and GCV for 72 h had no significant effect on cell cycle progression. Comparison of the effectiveness of [123I]FIAU in the monolayer and spheroid cultures indicated that clonogenic cell kill resulting from Auger electron bombardment was restricted to targeted rather than bystander cells. The combination therapy of [123I]FIAU and GCV of the cell line DU145-TK resulted in antagonistic effect throughout the examined dose range of the schedules of FIAU-before-GCV and simultaneous therapy and the low toxicity concentration range (lower surviving fractions) of the GCV-before-FIAU schedule. The high toxicity concentration range of the latter schedule has shown evidence of additive effect. For the osteosarcoma cell line 143B-TK, synergistic effect was observed at the high toxicity concentration range of the three combination schedules and antagonism at the low toxicity concentration range of the combinations. We concluded from this in vitro study that the combination of HSV1-tk gene transfer and the delivery of radiolabelled FIAU is a promising strategy for targeted radiation cytotherapy of prostate cancer. This proliferation-dependent therapy has caused significant cell cycle arrest that warrants further investigation. Furthermore, the combination of GCV and radiolabelled FIAU for the treatment of tumour cells expressing the gene of viral TK resulted in a dose- and schedule-dependent synergism. We believe that these encouraging results should be substantiated by in vivo experiments in the near future.

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40

Helal, Azza Mahmoud. "The effect of patient anatomy on optimised intensity modulated radiotherapy dose distributions for head and neck and prostate cancer." Thesis, University of Nottingham, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.438639.

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41

Landmark, Fredrika. "Production and Evaluation of a Bombesin Analogue Conjugated to the Albumin-Binding Domain and DOTA for Prostate Cancer Radiotherapy." Thesis, KTH, Proteinvetenskap, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-302214.

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Prostate cancer is one of the most common types of cancer worldwide and claims hundreds of thousands of lives annually. Currently the most common treatment for prostate cancer is external beam radiotherapy, however, this treatment comes with serious side effects since it lacks selectivity for the cancer cells. Therefore, less harmful treatments are needed and sought for, such as targeted treatments that are intended to only affect cancer cells and thereby reduce the side effects. Targeted treatments require a target that differentiates the cancer cells from healthy cells. A promising target candidate that has gained attention in recent years is gastrin releasing peptide receptor (GRPR), a protein commonly overexpressed in prostate cancer cells. Furthermore, a targeting molecule intended to bind to the target is also required. For this purpose, the bombesin analogue RM26, a high affinity GRPR binder, shows promise. Previous studies have led to the development of RM26-conjugates for the purpose of targeted prostate cancer radiotherapy. In these conjugates RM26 has been linked to a DOTA-chelator for radiolabeling, and an albumin binding domain (ABD) to prolong the conjugate’s half-life in vivo by binding to human serum albumin (HSA). The idea is that the RM26-conjugate will bind to both HSA in the blood and to GRPR on the prostate cancer cells and eliminate the cancer cells with the radiation from the radionuclide attached to the DOTA-chelator. Although these earlier studied conjugates have been very promising some improvements of certain aspects need to be achieved, mainly to improve the biodistribution with retained GRPR binding affinity. Therefor the purpose of this project was to produce three new versions of previous RM26- conjugates and evaluate if they are suitable for further prostate cancer therapy studies. The three RM26-conjugates were developed with primarily recombinant expression in E. coli cells and solid phase peptide synthesis (SPPS). The characterization phase in this project was carried out with mainly five different methods: matrix-assisted laser desorption ionization time- of-flight mass spectrometry (MALDI-TOF-MS), electrospray ionization- mass spectrometry (ESI-MS), circular dichroism (CD), surface plasmon resonance (SPR) and flow cytometry. The results showed that all three new RM26-conjugates were possible to produce and yielded final products corresponding to the expected molecular weights. Furthermore, the results indicate that all three RM26-conjuagtes are stable and maintain their structural properties under in vivo- temperatures and that they have high binding affinity for HSA. Further studies need to be conducted before drawing any certain conclusions regarding GRPR binding affinity.
Prostatacancer är en av de mest vanligt förekommande cancertyperna världen över och skördar hundratusentals liv årligen. I nuläget är extern strålbehandling det vanligaste terapialternativet mot prostatacancer, men denna behandling kommer med allvarliga biverkningar på grund av att den saknar selektivitet för cancerceller. Därför finns ett stort behov av mindre skadliga behandlingsformer, såsom riktade behandlingar som endast är avsedda att påverka cancerceller och därigenom minska biverkningarna. Riktade behandlingar kräver ett mål som skiljer cancercellerna från friska celler. En lovande målkandidat som har uppmärksammats de senaste åren är gastrinfrisättande peptidreceptor (GRPR), ett protein som vanligtvis överuttrycks i prostatacancerceller. I tillägg så krävs också en målsökande molekyl avsedd att binda till målet. För detta ändamål visar bombesinanalogen RM26, en GRPR-bindare med hög affinitet, sig vara lovande. Tidigare studier har utvecklat RM26-konjugat för målinriktad strålbehandling av prostatacancer. Dessa konjugat består av en RM26-peptid bunden till en DOTA-kelator för radioinmärkning och en albuminbindande domän (ABD) för att förlänga konjugatens halveringstid in vivo genom att binda till humant serumalbumin (HSA). Syftet med RM26- konjugaten är att de ska binda till både HSA i blodet och GRPR på prostatacancercellerna, och därmed eliminera cancercellerna med strålning från den radioinmärkta DOTA-kelatorn. Även om de tidigare RM26-konjugaten har varit mycket lovande krävs det att vissa förbättringar av några aspekter uppnås, främst affiniteten för GRPR. Syftet med detta projekt var därför att producera tre nya versioner av tidigare RM26-konjugat och utvärdera ifall de uppvisar tillfredsställande egenskaper. De tre RM26-konjugaten utvecklades primärt rekombinant i E. coli-celler och fastfas- peptidsyntes (SPPS). Karaktäriseringsfasen i detta projekt genomfördes med huvudsakligen fem olika metoder: MALDI-TOF-MS, elektrosprejjonisering-masspektrometri (ESI-MS), cirkulär dikroism (CD), ytplasmonresonans (SPR) och flödescytometri. Resultaten visade att alla tre nya RM26-konjugat var möjliga att producera och gav slutprodukter motsvarande de förväntade molekylvikterna. Vidare indikerar resultaten att alla tre RM26-konjugat är stabila och bibehåller sina strukturella egenskaper under in vivo-temperaturer och att de har hög affinitet för HSA. Ytterligare studier bör utföras innan säkrare slutsatser kan dras angående GRPR-bindningsaffinitet.

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Dréan, Gaël. "Mise en correspondance inter-individus pour la prédiction de la toxicité en radiothérapie du cancer de la prostate." Thesis, Rennes 1, 2014. http://www.theses.fr/2014REN1S041/document.

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Ces travaux de thèse s’inscrivent dans le contexte de la prédiction de la toxicité en radiothérapie du cancer de la prostate. Dans l'objectif d'analyser les corrélations spatiales entre la dose et les effets secondaires cette problématique est abordée dans un cadre d'analyse de population. La mise en correspondance inter-individus de l'anatomie et de la distribution de dose planifiée soulève des difficultés liées aux fortes variabilités anatomiques et au faible contraste des images CT considérées. Nous avons envisagé différentes stratégies de recalage non-rigide exploitant les informations relatives aux structures anatomiques, aux combinaisons intensité-structure, ou aux relations inter-structures. Les méthodes proposées s'appuient notamment sur l’utilisation de descripteurs structurels des organes tels que les cartes de distances euclidiennes ou du champ scalaire solution de l’équation de Laplace. Ces méthodes ont permis d'améliorer significativement la précision de la mise en correspondance, tant au niveau anatomique que dosimétrique. Les plus performantes ont été utilisées pour analyser une population de 118 individus. Les comparaisons statistiques des distributions de dose entre les patients souffrant ou non de saignements rectaux ont permis d’identifier une sous-région du rectum où la dose semble corrélée à la toxicité. La sous-région rectale identifiée apparaît potentiellement impliquée et hautement prédictive du risque de saignement. L'approche proposée permet d’améliorer les performances des modèles mathématiques de prédiction de la toxicité
This thesis deals with the issue of predicting the toxicity within the context of prostate cancer radiotherapy. With the aim of analyzing the spatial correlations between dose and side effects, this problem is addressed in a population analysis framework. Inter-individual matching of both the anatomy and planned dose distribution raises difficulties related to high anatomical variability and low contrast in the CT images. We considered different strategies for non-rigid registration involving the use of information on anatomical structures, intensity-structure combinations, or inter-structures relations. The proposed methods are primarily based on the use of structural descriptors of organs such as Euclidean distance maps or scalar field solution of the Laplace equation. These methods allowed us to significantly improve the accuracy of the matching, at both the dosimetric and the anatomical level. The most accurate matching strategy has been used for analyzing a population of. Statistical comparisons of dose distributions between patients with or without rectal bleeding have been used to identify a rectal sub-region likely correlated with toxicity. The identified rectal sub-region appears potentially involved in side effects and highly predictive of the risk of bleeding. The proposed approach makes it possible to improve the performance of mathematical models for predicting the toxicity

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43

Fransson, Per. "Quality of life and side effects in patients with localized prostate cancer : evaluation with self-assessment questionnaires." Doctoral thesis, Umeå universitet, Onkologi, 2000. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-66906.

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Localized prostate cancer (LPC) is predominantly a tumor among older men, and few patients will get symptoms from the disease. All methods to treat LPC with a curative intent have different types and degrees of side effects. It is therefore very important to evaluate the side effects thoroughly to make sure that treatment complications will not decrease the quality of life more than the disease would have done. In search for new and better treatments, complications has to be registered and evaluated in relation to quality of life (QOL) for the patients. Few validated self-assessment questionnaires for evaluation of external radiotherapy (EBRT) induced side effects has yet been developed. The present project focus on the development of the PC-specific questionnaire, QUFW94, and evaluation of symptoms in patients treated with EBRT and un-treated (watchful waiting) patients with a LPC. In the newly developed LPC-specific questionnaire a reliability and responsiveness test was performed. Both the inter-rater test and the test-retest show high correlation coefficients (ICC), above 0.60 for all scales. The internal reliability exceeded the lower acceptable limit (Cronbach a >0.70). The questionnaire was proven to be valid for the evaluations of EBRT side effects in LPC patients. Late side effects were evaluated 4 years after treatment in 181 LPC patients, treated with conventional large field EBRT, and compared with 141 age-matched PC disease free men. The most prominent urinary side effects were urgency and leakage which were doubled in the patient group. A ten fold increase was seen in comparison to controls at the most prominent intestinal problems, blood, mucus and leakage. The results support the use 3-D conformai therapy to decrease irradiation dose to the rectum and the bladder and thereby decreased side effects. A prospective additional evaluation 8 years after EBRT did not show any changes in urinary problems between 4 and 8-yr follow-up in the patients or the controls. EBRT of LPC is also accompanied by disturbances in sexual function. These problems were therefore evaluated, 4 years after EBRT, in relation to the function in PC free men. Patients treated with EBRT indicated higher levels of sexual dysfunction than age-matched controls. No erection was reported from 12% of the control subjects, 56% of the patients who had only received radiotherapy (RT) and 87% of the RT+castration (RT+A) patients. The extended evaluation 8 years after EBRT show similar sexual function in all groups. QOL and late side effects/symptoms were evaluated in the first and only randomized trial between RT and deferred treatment (DT) and compared to age-matched controls. QOL was evaluated with the general QOL formula, EORTC's QLQ-C30 (+3), and LPC specific side effects with QUFW94 in 108 randomized patients with LPC 3 years after diagnosis. Social functioning was the only QOL scale where a significant difference was found between the two patient groups and in comparison with the control group. Multivariate regression analysis showed that hematuria, incontinence, mucus, and planning of the daily activities due to intestinal problems caused this decrease in QOL in the RT group. In conclusion, the LPC specific QUFW94 questionnaire was proven to be valid for evaluation of side effects and showed increased intestinal problems in the patients treated with conventional large field EBRT in comparison to untreated LPC patients. No difference in urinary and intestinal late side effects or sexual function was seen between a 4 year vs. 8 year follow-up.
digitalisering@umu

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44

Folkvaljon, Yasin. "Prognostic value of the ISUP 2015 Gleason grade groupings." Thesis, Uppsala universitet, Statistiska institutionen, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-256158.

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Background: New prognostic grade groupings were recently proposed for prostate cancer. They are based on Gleason grading of either biopsy or prostatectomy specimen. Former Gleason 6 corresponds to group 1, Gleason 7=3+4 corresponds to group 2, Gleason 7=4+3 corresponds to group 3, Gleason 8 corresponds to group 4, and Gleason 9-10 correspond to group 5. Objective: To assess the prognostic value of Gleason grade groups in men with prostate cancer from a nationwide population‑based cohort. Design, Setting and Participants: From the National Prostate Cancer Register of Sweden, we identified 5,880 men diagnosed with prostate cancer from 2005 to 2007, including 4,325 who had radical prostatectomy and 1,555 treated by radiotherapy. Outcome Measurements and Statistical Analysis: Kaplan-Meier survival analysis was used to calculate the cumulative 4-year biochemical recurrence-free survival. Cox proportional hazards regression models were used to examine the relationship between prognostic Gleason grade groups and biochemical recurrence after radical prostatectomy and radiotherapy. The 4-year biochemical progression-free survival was compared for groups based on biopsy and prostatectomy Gleason grade groups. Results and Limitations: Among men undergoing surgery, the 4‑year biochemical progression-free survival was 89%, 82%, 74%, 77%, and 49% for prognostic Gleason grade groups 1-5 on biopsy. The corresponding 4-year biochemical progression-free survival based on prostatectomy prognostic Gleason grade groups was 92%, 85%, 73%, 63%, and 51% for prognostic Gleason grade groups 1-5. For men undergoing radiotherapy, biopsy prognostic Gleason grade groups 1-5 had 4-year biochemical progression-free survival of 95%, 91%, 85%, 78%, and 70%. After adjusting for preoperative serum prostate specific antigen and clinical stage, biopsy prognostic Gleason grade groups were significant independent predictors of biochemical progression after radical prostatectomy and radiotherapy. There was no central review of pathology. Conclusions: These results confirm the prognostic value of the newly proposed prognostic Gleason grade groups in men undergoing radical prostatectomy and radiotherapy in a population-based setting.

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Biazotto, Bruna 1986. "Avaliação da correção de heterogeneidade em planejamentos 3D e IMRT de tratamentos radioterápicos de neoplasia de próstata." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/258963.

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Orientadores: Eduardo Tavares Costa, Paulo José Cecílio
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação
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Resumo: A experiência clínica em tratamentos radioterápicos de neoplasia de próstata baseia-se no cálculo de doses em meios homogêneos. Entretanto, o feixe de radiação atravessa tecidos de densidades eletrônicas diferentes como os ossos, que alteram a distribuição de dose. Com o advento da tomografia computadorizada e de algoritmos mais avançados que modelam o feixe de radiação, as heterogeneidades entre os tecidos podem ser incorporadas nos planejamentos de tratamentos radioterápicos. Todavia, não há consenso se as alterações na dose por correções de heterogeneidade são significativas. Por tais razões, pretendeu-se no presente trabalho avaliar a necessidade das correções de heterogeneidade em planejamentos de tratamentos radioterápicos de câncer de próstata. Para isso, analisaram-se as médias das diferenças percentuais nas doses em volume alvo e órgãos de risco obtidas em cálculos com e sem correções de heterogeneidade utilizando imagens tomográficas reais de pacientes que trataram dessa neoplasia. Essa avaliação foi realizada para dois métodos de tratamentos diferentes. O primeiro é o conformacional tridimensional (25 casos), algoritmos de cálculo Convolution, Superposition e Fast Superposition do sistema de planejamento XiO/Elekta, feixes de 6 e 10 MV e 4 campos em box. O segundo por intensidade modulada (14 casos), algoritmo de cálculo Pencil Beam Convolution do sistema de planejamento Eclipse/Varian com dois métodos de correção Batho Modificado e Razão Tecido-Ar Equivalente, feixe de 6 MV e geometria de 5 campos oblíquos. As diferenças percentuais médias resultantes nos volumes estudados foram menores que a incerteza aceita atualmente no cálculo de dose de 3% para as duas modalidades de tratamento. Apesar disso, a variabilidade na anatomia dos pacientes, geometria de campos e energia dos feixes apontam para a necessidade de tais correções e a utilização de métodos ainda mais exatos para a diminuição dessa incerteza no futuro
Abstract: Clinical experience in radiotherapy treatments for prostate cancer is based on the calculation of doses in homogeneous media. However, the radiation beam traverses different electron densities in tissues such as bone, altering the dose distribution. With the advent of computed tomography and more advanced algorithms that model the radiation beam, the heterogeneity between tissues can be incorporated in the planning of radiotherapy treatments. However, there is no consensus whether changes in dose for inhomogeneity corrections are significant. For these reasons, this study intended to evaluate the need for inhomogeneity corrections in treatment planning for radiotherapy of prostate cancer. We have analyzed the average percentage differences in doses in the target volume and organs at risk obtained by calculations with and without heterogeneity corrections using actual CT images of patients treated for this cancer. This evaluation was performed for two different methods of treatments. The first is the three-dimensional conformational (25 cases), calculation algorithms Convolution, Superposition and Fast Superposition from the computerized planning system XiO/Elekta, beams of 6 and 10 MV and 4 fields in box. The second by intensity modulated (14 cases), calculation algorithm Pencil Beam Convolution from the computerized planning system Eclipse/Varian with two correction methods Modified Batho and Equivalent Tissue-Air Ratio, 6 MV beam and geometry of 5 oblique fields. The resulting average percentage differences in volumes studied were smaller than the currently accepted uncertainty in the dose calculation of 3% for both treatment modalities. Nevertheless, variability in anatomy of patients, geometry and field energy beams brings the need for these corrections and the use of more accurate methods to reduce this uncertainty in the future
Mestrado
Engenharia Biomedica
Mestra em Engenharia Elétrica

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46

Ikeda, Itaru. "Assessment of interfractional prostate motion in patients immobilized in the prone position using a thermoplastic shell." Kyoto University, 2014. http://hdl.handle.net/2433/188682.

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47

Wirth, Manfred, and Michael Fröhner. "A Review of Studies of Hormonal Adjuvant Therapy in Prostate Cancer." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-134738.

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There is increasing interest in the use of adjuvant hormonal therapies, which are given after the resection or destruction of all gross disease, in early-stage prostate cancer, as a significant proportion of patients experience progression and/or die from the disease despite undergoing therapy with curative intent. Several retrospective studies suggest that adjuvant hormonal therapy may improve long-term outcome after radical surgery in men with positive lymph nodes, although this approach has yet to be studied in a prospective setting. No studies of adjuvant therapy for patients with extracapsular extension at surgery have been completed, but in an interim analysis of an open controlled trial, adjuvant flutamide significantly improved progression-free survival at 4 years. Three prospective studies in the radiotherapy setting have shown that adjuvant luteinizing hormone-releasing hormone (LH-RH) agonist therapy significantly improves progression-free and/or overall survival. Future studies need to define patient subgroups who will benefit most from adjuvant therapy. The side effects of the different therapeutic options also need to be compared. It is hoped that many of the outstanding questions concerning adjuvant hormonal therapy will be answered by the ongoing Bicalutamide Early Prostate Cancer Programme
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

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48

Dahrouge, Simone. "Prediction of recurrence in prostate cancer following radiotherapy: Value of biomarkers microvessel density, MIB-1, P-53, BCL2, and Bax." Thesis, University of Ottawa (Canada), 2003. http://hdl.handle.net/10393/26367.

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Background. Standard traditional parameters relied on for estimating the risk of disease recurrence after curative radiotherapy in prostate cancer are stage, Gleason score and PSA. Objectives. To elucidate the prognostic role of biomarkers: P-53, MIB-1, MVD, Bax and BCL2 in prostate cancer. Method. Cox proportional hazard model was used to estimate the risk of disease progression associated with these biomarkers and develop models based on traditional parameters only or incorporating biomarkers. Models were compared for their predictive potential using Akaike information criteria and concordance index. Results. Statistically significant associations were found between all biomarkers and risk of progression. MVD, Bax and Bax/BCL2 were independent predictors of outcome. Models incorporating biomarkers were superior to the traditional one in identifying patients at risk of local progression. Conclusions. Biomarkers may be useful in forecasting the risk of local recurrence following radiotherapy in prostate cancer patients. The results require validation in a separate cohort.

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Hornby, Colin, and n/a. "Tumour Control and Normal Tissue Complication Probabilities: Can they be correlated with the measured clinical outcomes of prostate cancer radiotherapy?" RMIT University. Medical Sciences, 2006. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20080702.123739.

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The chief aim in developing radiation treatment plans is to maximise tumour cell kill while minimising the killing of normal cells. The acceptance by a radiation oncologist of a radiation therapy treatment plan devised by the radiation therapist, at present is largely based on the oncologists' previous clinical experience with reference to established patterns of treatment and their clinical interpretation of the dose volume histogram. Some versions of radiotherapy planning computer software now incorporate a function that permits biologically based predictions about the probability of tumour control (TCP) and/or normal tissue complications (NTCP). The biological models used for these probabilities are founded upon statistical and mathematical principles as well as radiobiology concepts. TCP and NTCP potentially offer the capability of being able to better optimise treatments for an individual patient's tumour and normal anatomy. There have been few attempts in the past to correlate NTCPs to actual treatment complications, and the reported complications have generally not shown any significant correlation. Thus determining whether either or both NTCPs and TCPs could be correlated with the observed clinical outcomes of prostate radiotherapy is the central topic of this thesis. In this research, TCPs and NTCPs were prospectively calculated for prostate cancer patients receiving radiation therapy, and subsequently assessed against the clinical results of the delivered treatments. This research was conducted using two different types of NTCP models, which were correlated against observed treatment-induced complications in the rectum and bladder. The two NTCP models were also compared to determine their relative efficacy in predicting the recorded toxicities. As part of this research the refinement of some of the published bladder parameters required for NTCP calculations was undertaken to provide a better fit between predicted and observed complication rates for the bladder wall which was used in this research. TCPs were also calculated for each patient using the best available estimate of the radiosensitivity of the prostate gland from recent research. The TCP/NTCP data was analysed to determine if any correlations existed between the calculated probabilities and the observed clinical data. The results of the analyses showed that a correlation between the NTCP and a limited number of toxicities did occur. Additionally the NTCP predictions were compared to existing parameters and methods for radiotherapy plan evaluation - most notably DVHs. It is shown that NTCPs can provide superior discriminatory power when utilised for prospective plan evaluation. While the TCP could not be correlated with clinical outcomes due to insufficient follow-up data, it is shown that there was a correlation between the TCP and the treatment technique used.

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Wirth, Manfred, and Michael Fröhner. "A Review of Studies of Hormonal Adjuvant Therapy in Prostate Cancer." Karger, 1999. https://tud.qucosa.de/id/qucosa%3A27593.

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There is increasing interest in the use of adjuvant hormonal therapies, which are given after the resection or destruction of all gross disease, in early-stage prostate cancer, as a significant proportion of patients experience progression and/or die from the disease despite undergoing therapy with curative intent. Several retrospective studies suggest that adjuvant hormonal therapy may improve long-term outcome after radical surgery in men with positive lymph nodes, although this approach has yet to be studied in a prospective setting. No studies of adjuvant therapy for patients with extracapsular extension at surgery have been completed, but in an interim analysis of an open controlled trial, adjuvant flutamide significantly improved progression-free survival at 4 years. Three prospective studies in the radiotherapy setting have shown that adjuvant luteinizing hormone-releasing hormone (LH-RH) agonist therapy significantly improves progression-free and/or overall survival. Future studies need to define patient subgroups who will benefit most from adjuvant therapy. The side effects of the different therapeutic options also need to be compared. It is hoped that many of the outstanding questions concerning adjuvant hormonal therapy will be answered by the ongoing Bicalutamide Early Prostate Cancer Programme.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

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Dissertations / Theses on the topic 'Prostate – Cancer – Radiotherapy'

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