Uncertainties are inevitably part of the radiotherapy process. Uncertainty in the dose deposited in the tumour exists due to organ motion, patient positioning errors, fluctuations in machine output, delineation of regions of interest, the modality of imaging used, and treatment planning algorithm assumptions among others; there is uncertainty in the dose required to eradicate a tumour due to interpatient variations in patient-specific variables such as their sensitivity to radiation; and there is uncertainty in the dose-volume restraints that limit dose to normal tissue. This thesis involves three major streams of research including investigation of the actual dose delivered to target and normal tissue, the effect of dose uncertainty on radiobiological indices, and techniques to display the dose uncertainty in a treatment planning system. All of the analyses are performed with the dose distribution from a four-field box treatment using 6 MV photons. The treatment fields include uniform margins between the clinical target volume and planning target volume of 0.5 cm, 1.0 cm, and 1.5 cm. The major work is preceded by a thorough literature review on the size of setup and organ motion errors for various organs and setup techniques used in radiotherapy. A Monte Carlo (MC) code was written to simulate both the treatment planning and delivery phases of the radiotherapy treatment. Using MC, the mean and the variation in treatment dose are calculated for both an individual patient and across a population of patients. In particular, the possible discrepancy in tumour position located from a single CT scan and the magnitude of reduction in dose variation following multiple CT scans is investigated. A novel convolution kernel to include multiple pretreatment CT scans in the calculation of mean treatment dose is derived. Variations in dose deposited to prostate and rectal wall are assessed for each of the margins and for various magnitudes of systematic and random error, and penumbra gradients. The linear quadratic model is used to calculate prostate Tumour Control Probability (TCP) incorporating an actual (modelled) delivered prostate dose. The Kallman s-model is used to calculate the normal tissue complication probability (NTCP), incorporating actual (modelled) fraction dose in the deforming rectal wall. The impact of each treatment uncertainty on the variation in the radiobiological index is calculated for the margin sizes. / Thesis (Ph.D.)--Department of Physics and Mathematical Physics, 2002.

A special work evolution was performed at Los Alamos National Laboratory (LANL) with a particular 73As/74As source but the worker’s extremity dosimeter did not appear to provide appropriate dosimetric information for the tasks performed. This prompted a reconstruction of the dose to the worker’s hands. The computer code MCNP was chosen to model the tasks that the worker performed to evaluate the potential nonuniform hand dose distribution. A model was constructed similar to the worker’s hands to represent the performed handling tasks. The model included the thumb, index finger, middle finger, and the palm. The dose was calculated at the 7 mg cm-2 skin depth. To comply with the Code of Federal Regulations, 10 CFR 835, the 100 cm2 area that received the highest dose must be calculated. It could be determined if the dose received by the worker exceeded any regulatory limit. The computer code VARSKIN was also used to provide results to compare with those from MCNP where applicable. The results from the MCNP calculations showed that the dose to the worker’s hands did not exceed the regulatory limit of 0.5 Sv (50 rem). The equivalent nonuniform dose was 0.126 Sv (12.6 rem) to the right hand and 0.082 Sv (8.2 rem) to the left hand.

Made available in DSpace on 2014-06-12T23:16:56Z (GMT). No. of bitstreams: 2 arquivo9089_1.pdf: 1085916 bytes, checksum: 99db33e1bf6f9c3487f83df708df47c4 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2006 / Dentre os procedimentos especiais de fluoroscopia destacam-se a histerossalpingografia (HSG) e a dacriocistografia (DCG). A HSG é uma técnica radiodiagnostica capaz de detectar patologias uterinas e tubárias, e é fundamental para a investigação de infertilidade. A DCG trata-se do exame radiográfico do sistema lacrimal, sendo importante para mostrar o nível de obstrução, a presença de dilatação do saco lacrimal, bem como alterações em estruturas vizinhas. Neste trabalho, foi efetuado o estudo da dose de entrada na pele do paciente devido a estes dois procedimentos especiais de fluoroscopia, bem como a avaliação da dose na equipe médica que executa os exames. Para tanto, foram avaliados os procedimentos de 22 pacientes de HSG e 8 pacientes de DCG. Dosímetros de TLD-100 foram utilizados e fixados na pele dos pacientes em pontos anatômicos envolvidos em cada exame. No caso da HSG os resultados mostraram que a dose na entrada da pele variou de 0,5 mGy a 73,4 mGy, com um valor médio de 22,1 mGy. A dose no útero foi estimada em 5,5 mGy, e 6,6 mGy foi a dose média estimada para os ovários. As doses de entrada na pele dos pacientes submetidos a exames de DCG variaram de 2,1 mGy a 10,6 mGy, e a dose média entre os olhos foi de 6,1 mGy. Os resultados das doses ocupacionais mostraram que, na HSG, a dose média na mão direita do médico é de 4,3 mGy por exame. Este valor é devido ao fato que o médico introduz o meio de contraste manualmente durante as exposições com contraste na histerossalpingografia. Em relação a DCG, os valores de doses ocupacionais foram da ordem dos valores ambientais, evidenciando que, dentro dos limites permitidos, não há risco para os médicos neste procedimento

Yes / Objectives; To evaluate radiation doses for all low-dose CT scans performed during the first year of a lung screening trial. Methods; For all lung screening scans that were performed using a CT protocol that delivered image quality meeting the RSNA QIBA criteria, , radiation dose metrics, participant height, weight, gender and age were recorded. Values of CTDIvol and DLP were evaluated as a function of weight in order to assess the performance of the scan protocol across the participant cohort. Calculated effective doses were used to establish the additional lifetime attributable cancer risks arising from trial scans. Results; Median values of CTDIvol, DLP and effective dose (IQR) from the 3521 scans were 1.1mGy (0.70), 42.4mGycm (24.9) and 1.15mSv (0.67), whilst for 60-80kg participants the values were 1.0mGy (0.30), 35.8mGycm (11.4) and 0.97mSv (0.31). A statistically significant correlation between CTDIvol and weight was identified for males (r=0.9123, p<0.001) and females (r=0.9052, p<0.001), however the effect of gender on CTDIvol was not statistically significant (p=0.2328) despite notable differences existing at the extremes of the weight range. The additional lifetime attributable cancer risks from a single scan were in the range 0.001-0.006%. Conclusions; Low radiation doses can be achieved across a typical lung screening cohort using scan protocols that have been shown to deliver high levels of image quality. The observed dose levels may be considered as typical values for lung screening scans on similar types of scanner for an equivalent participant cohort. Advances in Knowledge; Presentation of typical radiation dose levels for CT lung screening examinations in a large UK trial. Effective radiation doses can be of the order of 1mSv for standard sized participants. Lifetime attributable cancer risks resulting from a single LDCT scan did not exceed 0.006%. / The Yorkshire Lung Screening Trial is funded by Yorkshire Cancer Research (award reference L403).

No description available.

First-in-man (FIM) Phase I clinical trials are part of the critical path in the development of a new compound entity (NCE). Since FIM clinical trials are the first time that an NCE is dosed in human subjects, the designs used in these trials are unique and geared toward patient safety. We develop a method for obtaining the desired response using an adaptive non-linear approach. This method is applicable for studies in which MTD, NOEL,NOAEL, PK, PD effects or other such endpoints are evaluated to determine the desired dose. The method has application whenever a measurable PD marker is an indicator of potential efficacy and could be particularly useful for dose finding studies. The advantages in the adaptive non-linear methodology is that the actual range of dose response and lowest non-effective dose levels are more quickly and accurately determined using fewer subjects than typically needed for a conventional early phase clinical trial. Using the nonlinear logistic model, we demonstrate, with simulations, that the DOSEFIND approach has better asymptotic relative efficiency than a fixed-dose approach. Further, we demonstrate that, on average, this method is consistent in reproducing .the target dose, that it has very little bias. This is an indicator of reproducibility of the method, showing that the long-run average error is quite small. Additionally, DOSEFIND is more cost effective because the sample size needed to obtain the desired target dose is much smaller than that needed in the fixed dose approach.

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.

Dose assessments produced using the computer code MCNP are important to simulate events that are difficult to recreate experimentally. An emergency scenario involving whole-body skin contamination is one example of such an event. For these scenarios, an anthropomorphic phantom of a 10-year-old male with uniform skin contamination was created and combined with MCNP for dose calculations. Activity on the skin was modeled with gamma-ray sources at energies of 50 keV, 100 keV, 250 keV, 500 keV, 750 keV, 1 MeV, 1.25 MeV, 1.5 MeV, and 2 MeV. The radionuclides 60Co, 137Cs, and 131I were also modeled. The effective dose to the body and major organs was calculated for each scenario. Exposure rate contour lines were also produced around the body. The activity required to result in a dose equal to the legal limit of 0.1 mSv for minors was calculated for each scenario. The highest activity required to produce this limit was from the 50 keV gamma-ray source. This activity was increased by an arbitrary value, approximately tenfold the current value, to represent an emergency scenario. This new activity concentration of 1 mCi per 100 cm2 was used to produce doses for each of the scenarios. The lowest effective dose for the body was 0.82 mSv, produced from the 50 keV source. The highest effective dose was 19.59 mSv, produced from the 2 MeV source. The exposure rates nearest the body were approximately 1.25 R/h, decreasing to100 mR/h approximately 60 cm from the body. The data points were found to be dependent on the energy of the gamma ray. These data can also be improved by deriving solutions previously assumed in this scenario. For example, the skin may be broken down into multiple regions to allow for independent calculations for regional contamination. The activity on the skin can also be derived from air concentration models, allowing for the use of other models to be used in conjunction with this research.

The objective of this project was to develop a simple MCNPX model of the human eye to approximate dose delivered from proton therapy. The calculated dose included that due to proton interactions and secondary interactions, which included multiple coulombic energy scattering, elastic and inelastic scattering, and non-elastic nuclear reactions (i.e., the production of secondary particles). After benchmarking MCNPX with a known proton simulation, the proton therapy beam used at Laboratori Nazionali del Sud-INFN was modeled for simulation. A virtual water phantom was used and energy tallies were found to correspond with the direct measurements from the therapy beam in Italy. A simple eye model was constructed and combined with the proton beam to measure dose distributions. Two treatment simulations were considered. The first simulation was a typical treatment scenario-where dose was maximized to a tumor volume and minimized elsewhere. The second case was a worst case scenario to simulate a patient gazing directly into the treatment beam during therapy. Dose distributions for the typical treatment yielded what was expected, but the worst case scenario showed the bulk of dose deposited in the cornea and lens region. The study concluded that MCNPX is a capable platform for patient planning but laborious for programming multiple simulation configurations.

Naturally occurring radioactive material (NORM) exists in connate waters and, under the right conditions during oil drilling, can plate out on the interior surfaces of oil and gas industry equipment. Once deposited, this material is commonly referred to as ??scale.?? This thesis is concerned with the presence of 226Ra in scale deposited on the inner surfaces of oil drilling pipes and the internal dose consequences of inhalation of that scale once released. In the process of normal operation, barium sulfate scale with a radium component adheres to the inside of downhole tubulars in oil fields. When crude flow is diminished below acceptable operational requirements, the pipe is sent to a descaling operation to be cleaned, most likely by a method known as rattling. The rattling process generates dust. This research investigated the chemical composition of that aerosol and measured the solubility of pipe scale from three oilfield formations. Using standard in-vitro dissolution experimental equipment and methods, pipe scale is introduced into simulated lung fluid over a two-week period. These samples are analyzed using quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS), known for very low detection limits. Analysis reveals virtually no 226Ra present in the lung fluid exposed to pipe scale. Sample measurements were compared against background measurements using Student??s t test, which revealed that nearly all the samples were statistically insignificant in comparison to the lung fluid blanks. This statistical test proves within a 95% confidence interval that there is no 226Ra present in the lung fluid samples. These results indicate that inhaled NORM pipe scale should be classified as Class S and serve to further confirm the extreme insolubility of petroleum pipe scale. For dose calculations, the S classification means that the lung is the main organ of concern. Radium-226 from petroleum pipe scale does not solubilize in the interstitial lung fluid, and does not, therefore, enter the bloodstream via respiratory pathways. Since there is no removal by dissolution, the 500 day biological half-life implied by the S classification is based solely on the mechanical transport of 226Ra out of the lungs by phagocytosis or the mucociliary escalator.