This thesis is an investigation of diagnostic staging and palliative radiation therapy (RT) for appendicular osteosarcoma (OSA) in dogs. Osteosarcoma is a common, highly metastatic primary bone tumour of dogs. The purpose of the first study was to assess the utility of whole body computed tomography (CT) in evaluation of metastasis in dogs with primary appendicular OSA. The objectives were to determine the utility of whole body CT as a staging tool for dogs with appendicular OSA, compare the lesion detection rate of bone scintigraphy, long bone survey radiography and whole body CT in dogs with appendicular OSA and determine the prevalence of CT-detected lung metastasis in dogs with appendicular OSA that have normal thoracic radiographs. This was a prospective cross-sectional observational study involving fifteen dogs. Test modalities were assessed against a construct reference standard for detection of bone metastasis and thoracic radiographs negative for metastatic lesions were compared against thoracic CT. Bone scintigraphy identified 5 bone lesions in 4 dogs with 2 false positive and 2 false negative results. No lesions were identified on survey radiographs or CT during blinded assessment. CT was useful for further characterizing lesions identified by bone scintigraphy. Thoracic CT identified both definitive and equivocal lesions not visible radiographically. Four dogs had equivocal ground glass pulmonary lesions on CT; 3 of these lesions progressed to radiographically discrete nodules. Overall, bone scintigraphy was the only modality that identified metastatic bone lesions. Whole body CT did not appear to be useful as alternative to bone scintigraphy; however, it may have some utility as an adjunctive diagnostic modality. Thoracic CT identified pulmonary lesions that were not visible radiographically. Ground glass pulmonary lesions in dogs should be considered suspicious for metastasis and serially monitored. The purpose of the second study was to retrospectively assess factors affecting survival time in dogs undergoing palliative RT for appendicular OSA. Fifty dogs undergoing a palliative RT protocol for spontaneous primary appendicular bone tumours were included and divided into treatment groups based on treatments administered in addition to RT. Median survival times (MST) were longest for dogs receiving RT and chemotherapy (307 days; 95%CI= 279-831) and shortest in dogs receiving RT and pamidronate (69 days; 95%CI=47-112 days). The difference in MST between dogs who received pamidronate and those who did not in this population was statistically significant on univariate (p=0.039) and multivariate analysis (p=0.0015). The addition of chemotherapy into any protocol improved survival (p<0.001). Based on the findings in this study, chemotherapy should be recommended in addition to a palliative RT protocol to improve survival of dogs with primary appendicular bone tumours. When combined with RT +/- chemotherapy, pamidronate decreased MST. / Ontario Veterinary College Pet Trust Fund

The goal of radiotherapy is to operate within the therapeutic window - delivering doses of ionizing radiation to achieve locoregional tumour control, while minimizing normal tissue toxicity. A greater therapeutic ratio can be achieved by utilizing radiosensitizing agents designed to enhance the effects of radiation at the tumour. Gold nanoparticles (AuNP) represent a novel radiosensitizer with unique and attractive properties. AuNPs enhance local photon interactions, thereby converting photons into localized damaging electrons. Experimental reports of AuNP radiosensitization reveal this enhancement effect to be highly sensitive to irradiation source energy, cell line, and AuNP size, concentration and intracellular localization. This thesis explored the physics and some of the underlying mechanisms behind AuNP radiosensitization. A Monte Carlo simulation approach was developed to investigate the enhanced photoelectric absorption within AuNPs, and to characterize the escaping energy and range of the photoelectric products. Simulations revealed a 10^3 fold increase in the rate of photoelectric absorption using low-energy brachytherapy sources compared to megavolt sources. For low-energy sources, AuNPs released electrons with ranges of only a few microns in the surrounding tissue. For higher energy sources, longer ranged photoelectric products travelled orders of magnitude farther. A novel radiobiological model called the AuNP radiosensitization predictive (ARP) model was developed based on the unique nanoscale energy deposition pattern around AuNPs. The ARP model incorporated detailed Monte Carlo simulations with experimentally determined parameters to predict AuNP radiosensitization. This model compared well to in vitro experiments involving two cancer cell lines (PC-3 and SK-BR-3), two AuNP sizes (5 and 30 nm) and two source energies (100 and 300 kVp). The ARP model was then used to explore the effects of AuNP intracellular localization using 1.9 and 100 nm AuNPs, and 100 and 300 kVp source energies. The impact of AuNP localization was most significant for low-energy sources. At equal mass concentrations, AuNP size did not impact radiosensitization unless the AuNPs were localized in the nucleus. This novel predictive model of AuNP radiosensitization could help define the optimal use of AuNPs in potential clinical strategies by determining therapeutic AuNP concentrations, and recommending when active approaches to cellular accumulation are most beneficial.

Aims: To describe use of post-operative radiation for endometrial cancer in Ontario. To identify system-related and patient-related factors affecting access to this treatment. Materials and Methods: We performed a retrospective population-based cohort study of patients with surgically resected endometrial cancer in the Canadian province of Ontario between 1992-2003. Patients with evidence of incurable cancer at diagnosis or previous cancer diagnosis were excluded. We used multiple logistic regression to assess patient and system factors affecting radiation use. We controlled for disease-related and treatment-related factors: histology, surgical staging, type of hysterectomy and peritoneal biopsy. We applied a mixed model to account for clustering of data by operating hospital. Results: 9,411 women comprised the study cohort. The median age was 63 years. 26.2% received adjuvant radiation. The proportion of patients receiving radiation varied between cancer centre catchment areas from 18.0% to 34.3% (median 26.3%). In multivariate analysis, older patients were more likely to receive radiation up to the age of 80 (p<.0001). Patients who lived further from regional cancer centres were less likely to receive radiation (p=.0210). Patients who had their surgery during longer prevailing wait times at regional cancer centres were less likely to receive radiation (p=.0441). There was a 2.7-fold variation in the odds of radiation use between cancer centre catchments (p<.0001). Management at a comprehensive gynecologic oncology centre was associated with use of radiation for patients who had surgical staging of lymph nodes. Year of diagnosis and neighborhood income quintile did not significantly affect the use of radiation. Conclusions: There is wide variation in use of radiation for endometrial cancer in Ontario. There is evidence that system factors unrelated to patient’s needs affect use of adjuvant radiation for endometrial cancer in Ontario. Age is a key patient-related factor affecting radiation use. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2009-08-07 22:02:37.308

Cobalt 60 (Co-60) radiation therapy is a simple and reliable method of treating cancer by irradiating treatment volumes within the patient with high energy gamma rays. Medical linear accelerators (linacs) began to replace Co-60 units during the 1960’s in more developed countries, but Co 60 has remained the main source of radiotherapy treatment in less developed countries around the world. As a result, technological advancements made in more developed countries to deliver more precise radiation treatment that improves patient outcome have not been clinically applied to Co-60 machines. The medical physics group at the Cancer Centre of Southeastern Ontario has shown that these same technological advancements can be applied to Co-60 machines which would increase the accessibility of these modern improvements in radiotherapy treatment. However, for these modern treatments to improve patient outcome they require more precise localization of the patient prior to therapy. In more developed countries, this is currently provided by comparing computed tomography (CT) used for treatment planning with images acquired on the linac immediately before treatment. In the past decade, cone-beam CT (CBCT) has been developed to provide 3D CT images of the patient immediately prior to treatment on a linac. This imaging modality would also be ideal for patient localization when conducting modern Co-60 treatments since it would only require the addition of an imaging panel to produce CBCT images using the Co-60 source. A prototype Co-60 CBCT imaging system was implemented and characterized. Image noise, contrast, spatial resolution, and artifacts were studied. Algorithms to reduce the image artifacts were implemented and found to improve perceived image quality. The imaging system was found to have a ~1.8 mm high-contrast spatial resolution and the ability to detect 3 cm low-contrast soft-tissue structures in water. Anthropomorphic phantoms were also imaged and the observed anatomy in Co-60 CBCT images was comparable to kilovoltage CT. These results are comparable to clinically relevant linac-based CBCT using high energy X rays of similar energies to Co-60 gamma rays. This suggests that Co-60 CBCT should be able to provide the necessary images to localize patients for modern Co-60 radiation treatments. / Thesis (Master, Physics, Engineering Physics and Astronomy) -- Queen's University, 2010-11-30 13:40:07.61

No description available.

Radiation therapy is continuously increasing in complexity due to technological innovation in delivery techniques, necessitating thorough dosimetric verification. Comparing accurately predicted portal dose images to measured images obtained during patient treatment can determine if a particular treatment was delivered correctly. The goal of this thesis was to create a method to predict portal dose images that was versatile and accurate enough to use in a clinical setting. All measured images in this work were obtained with an amorphous silicon electronic portal imaging device (a-Si EPID), but the technique is applicable to any planar imager. A detailed, physics-motivated fluence model was developed to characterize fluence exiting the linear accelerator head. The model was further refined using results from Monte Carlo simulations and schematics of the linear accelerator. The fluence incident on the EPID was converted to a portal dose image through a superposition of Monte Carlo-generated, monoenergetic dose kernels specific to the a-Si EPID. Predictions of clinical IMRT fields with no patient present agreed with measured portal dose images within 3% and 3 mm. The dose kernels were applied ignoring the geometrically divergent nature of incident fluence on the EPID. A computational investigation into this parallel dose kernel assumption determined its validity under clinically relevant situations. Introducing a patient or phantom into the beam required the portal image prediction algorithm to account for patient scatter and attenuation. Primary fluence was calculated by attenuating raylines cast through the patient CT dataset, while scatter fluence was determined through the superposition of pre-calculated scatter fluence kernels. Total dose in the EPID was calculated by convolving the total predicted incident fluence with the EPID-specific dose kernels. The algorithm was tested on water slabs with square fields, agreeing with measurement within 3% and 3 mm. The method was then applied to five prostate and six head-and-neck IMRT treatment courses (~1900 clinical images). Deviations between the predicted and measured images were quantified. The portal dose image prediction model developed in this thesis work has been shown to be accurate, and it was demonstrated to be able to verify patients’ delivered radiation treatments.

<p>To date, image localization of mobile tumors prior to radiation delivery has primarily been confined to 2D and 3D technologies, such as fluoroscopy and 3D cone-beam CT (3D-CBCT). Due to the limited information from these images, larger volumes of healthy tissue are often irradiated in order to ensure the radiation field encompasses the entirety of the target motion. Since the overarching goal of radiation therapy is to deliver maximum dose to cancerous cells and simultaneously minimize the radiation delivered to healthy surrounding tissues, it would be ideal to use 4D imaging to obtain time-resolved volume images of the tumor motion during respiration. </p><p>4D-CBCT imaging has been previously investigated, but has not yet seen large clinical translation due to the obstacles of long acquisition time and large image radiation dose. Furthermore, 4D-CBCT currently requires the use of external surrogates to correlate the patient's respiration with the image acquisition process. This correlation has been under question by a multitude of studies demonstrating the uncertainties that exist between the surrogate and the actual motion of the internal anatomy. Errors in the correlation process may result in image artifacts, which could potentially lead to reconstructions with inaccurate target volumes, thereby defeating the purpose of even using 4D-CBCT. </p><p>It is therefore the aim of this dissertation to initially highlight an additional limitation of using 3D-CBCT for imaging respiratory motion and thereby reiterate the need for 4D-CBCT imaging in the treatment room, develop a simple and efficient technique to achieve markerless, self-sorted 4D-CBCT and finally to comprehensively evaluate its robustness across a variety of potential clinical scenarios with a digital human phantom. </p><p>People often spend a longer period of time exhaling as compared with inhaling, and some do so in an extremely disproportionate manner. To demonstrate the disadvantage of using 3D-CBCT in such instances, a dynamic thorax phantom was imaged with a large variety of simulated and patient-derived respiratory traces of ratios of time spent in the inspiration phase versus time spent in the expiration phase (I/E ratio). Canny edge detection and contrast measures were employed to compare the internal target volumes (ITVs) generated per profile. The results revealed that an I/E ratio of less than one can lead to potential underestimation of the ITV with the severity increasing as the inspiration becomes more disproportionate to the expiration. This occurs because of the loss of contrast in the inspiration phase, due to the fewer number of projections acquired there. The measured contrast reduction was as high as 94% for small targets (0.5 cm) moving large amplitudes (2.0 cm) and still as much as 22.3% for large targets (3.0 cm) moving small amplitudes (0.5 cm). This is alarming because the degraded visibility of the target in the inspiration phase may inaccurately impact the alignment of the planning ITV with that of the FB-CBCT and thereby affect the accuracy of the localization and consequent radiation delivery. These potential errors can be avoided with the use of 4D-CBCT instead, to form the composite volume and serve as the verification ITV for alignment.</p><p>In order to delineate accurate target volumes from 4D-CBCT phase images, it is crucial that the projections be properly associated with the patient's respiration. Thus, in order to improve previously developed 4D-CBCT techniques, the basics of Fourier Transform (FT) theory were utilized to extract the respiratory signal directly from the acquired projection data. Markerless, self-sorted 4D-CBCT reconstruction was achieved by developing methods based on the phase and magnitude information of the Fourier Transform. Their performance was subsequently compared to the gold standard of visual identification of peak-inspiration projections. Slow-gantry acquired projections of two sets of physical phantom data with sinusoidal respiratory cycles of 3 and 6 seconds as well as three patients were used as initial evaluation of the feasibility of the Fourier technique. Quantitative criteria consisted of average difference in respiratory phase (ADRP) and percentage of projections assigned within 10% respiratory phase of the gold standard (PP10). For all five projection datasets, the results supported feasibility of both FT-Phase and FT-Magnitude methods with ADRP values less than 5.3% and PP10 values of 87.3% and above. </p><p>Because the technique proved to be promising in the initial feasibility study, a more comprehensive evaluation was necessary in order to assess the robustness of the technique across a larger set of possibilities that may be encountered in the clinic. A 4D digital XCAT phantom was used to generate an array of respiratory and anatomical variables that affect the performance of the technique. The respiratory variables studied included: inspiration to expiration ratio, respiratory cycle length, diaphragmatic motion amplitude, AP chest wall expansion amplitude, breathing irregularities such as baseline shift and inconsistent peak-inspiration amplitude, as well as six breathing profiles derived from cine-MRI images of three healthy volunteers and three lung cancer patients. The anatomical variables studied included: male and female patient size (physical dimension and adipose content), body-mass-index (BMI) category, tumor location, and percentage of the lung in the field-of-view (FOV) of the projection data. CBCT projections of each XCAT phantom were then generated. Additional external imaging factors such as image noise and detector wobble were added to select cases with different percentages of lung in the projection FOV to investigate any effects on the robustness. FT-Phase and FT-Magnitude were each applied and quantitatively compared to the gold standard. Both methods proved to be robust across the studied scenarios with ADRP<10% and PP10>90%, when incorporating minor modifications to region-of-interest (ROI) selection and/or low-frequency location to certain cases of diaphragm amplitude and lung percentage in the FOV of the projection (for which a method may have previously struggled). Nevertheless, in the instance where one method initially faltered, the other method prevailed and successfully identified peak-inspiration projections. This is promising because it suggests that the two methods provide complementary information to each other. To ensure appropriate clinical adaptation of markerless, self-sorted 4D-CBCT, perhaps an optimal integration of the two methods can be developed.</p> / Dissertation

This thesis details an investigation of the suitability of commercially-available single crystal and polycrystalline diamond films made via chemical vapor deposition (CVD) that were not studied previously for use in radiotherapy dosimetry. Novel sandwich-type detectors were designed and constructed to investigate the dosimetric response of diamond films under clinical conditions. Relatively inexpensive diamond films were obtained from three manufacturers: Diamonex, Diamond Materials GmbH and Element Six. Spectrophotometry, Raman spectroscopy and bulk conductivity studies were used to characterize these films and correlate crystalline quality with detector performance. Novel detectors were designed and constructed to investigate detectors under clinical conditions, including Perspex encapsulations and PCBs to minimize fluence perturbations. The dosimetric response of these diamond detectors was examined using a 6 MV beam from a Varian Clinac 600C linear accelerator. Diamond detectors were evaluated by measuring a number of response characteristics. Polycrystalline CVD diamond films from Diamonex (100, 200, 400-μm thicknesses) were considered unsuitable for dosimetric applications due to their lack of stability, low sensitivity, high leakage currents, high priming dose and dependence on dose rate. High-quality polycrystalline diamond films from Diamond Materials (100, 200, 400-μm thicknesses) displayed characteristics that varied with film thickness. A 100-μm film featured slow response dynamics and high priming doses. Thicker films featured suitable dosimetric characteristics, e.g. negligible leakage currents, low priming doses, fast response dynamics and good sensitivity with small sensitive volumes. Element Six single crystal CVD diamond films (500-μm thicknesses) with small sensitive volumes (0.39 mm³) exhibited suitable characteristics for dosimetry. These films showed negligible leakage currents (< 1.25 pA), low priming doses (1–10 Gy), quick response dynamics, high sensitivity (47–230 nC Gy⁻¹) and were weakly dependent on dose rate and directional dependence (±1%). A relatively inexpensive single crystal CVD diamond film from Element Six that exhibited high sensitivity (230 nC Gy⁻¹ at 0.5 V μm⁻¹), amongst other favourable characteristics, was selected for further analyses. An appropriate operating voltage was determined before further clinically relevant measurements could be conducted. This included how changes in an applied electric field affected detector response, and determined whether an optimal operating voltage could be realized within the parameters of conventional instrumentation used in radiation therapy. The results of this study indicated a preference towards using 62.5 V (at ~0.13 V μm⁻¹) out of a range of 30.8–248.0 V for temporal response as required for modulated beams due to its minimal rise time (2 s) and fall time (2 s) yet sufficient sensitivity (37 nC Gy⁻¹) and weak dependence on polarity (±1.5%). Investigations were then performed on the same diamond detector to evaluate its performance under more clinically relevant conditions. Repeatability experiments revealed a temporary loss in sensitivity due to charge detrapping effects following irradiation, which was modelled to make corrections that improved short-term precision. It was shown that this detector could statistically distinguish between dose values separated by a single Monitor Unit, which corresponded to 0.77 cGy. Dose rate dependence was observed when using low, fixed doses in contrast to using stabilized currents and higher doses. Depth dose measurements using this detector compared well with ion chambers and diode dosimeters. Comparisons of initial measurements with values in the literature indicate encouraging results for fields sizes < 4 x 4 cm², but further measurements and comparisons with Monte Carlo calculations are required. Using this detector to make off-axis measurements in the edge-on orientation reduced perturbation of the beam due to its sandwich configuration and thin 150 nm Ag contacts. This diamond detector was found to be suitable for routine dosimetry with conventional radiotherapy instrumentation with a materials cost of < NZ$200.

An approach to quantitatively determine patient surface contours as part of an augmented reality (AR) system for patient position and posture correction was developed. Quantitative evaluation of the accuracy of patient positioning and posture correction requires the knowledge of coordinates of the patient contour. The system developed uses the surface contours from the planning CT data as the reference surface coordinates. The corresponding reference point cloud is displayed on screen to enable AR assisted patient positioning. A 3D computer vision system using structured light then captures the current 3D surface of the patient. The offset between the acquired surface and the reference surface, representing the desired patient position, is the alignment error. Two codification strategies, spatial encoding, and temporal encoding, were examined. Spatial encoding methods require a single static pattern to work, thus enabling dynamic scenes to be captured. Temporal encoding methods require a set of patterns to be successively projected onto the object, the encoding for each pixel is only complete when the entire series of patterns has been projected. The system was tested on a camera tracking object. The structured light reconstruction was accurate to within ±1 mm, ±1.5 mm, and ±4 mm in x, y, and z-directions (camera optical axis) respectively. The method was integrated into a simplified AR system and a visualization scheme based on z-direction offset was developed. A demonstration of how the final AR-3D vision hybrid system can be used in a clinical situation was given using an anatomical teaching phantom. The system and visualisation worked well and demonstrated the proof of principal of the approach. It was found that the achieved accuracy was not yet sufficient for clinical use. Further work on improving the projector calibration accuracy is required. Both the camera registration process and 3D computer vision using structured light have been shown to be capable of sub-millimeter accuracy on their own. If that level of accuracy can be reproduced in this system, the concept presented can potentially be used in Oncology departments as a cost-effective patient setup guidance system for external beam radiotherapy, used in addition to current laser/portal imaging/cone beam CT based setup procedures.

Radiation therapy is continuously increasing in complexity due to technological innovation in delivery techniques, necessitating thorough dosimetric verification. Comparing accurately predicted portal dose images to measured images obtained during patient treatment can determine if a particular treatment was delivered correctly. The goal of this thesis was to create a method to predict portal dose images that was versatile and accurate enough to use in a clinical setting. All measured images in this work were obtained with an amorphous silicon electronic portal imaging device (a-Si EPID), but the technique is applicable to any planar imager. A detailed, physics-motivated fluence model was developed to characterize fluence exiting the linear accelerator head. The model was further refined using results from Monte Carlo simulations and schematics of the linear accelerator. The fluence incident on the EPID was converted to a portal dose image through a superposition of Monte Carlo-generated, monoenergetic dose kernels specific to the a-Si EPID. Predictions of clinical IMRT fields with no patient present agreed with measured portal dose images within 3% and 3 mm. The dose kernels were applied ignoring the geometrically divergent nature of incident fluence on the EPID. A computational investigation into this parallel dose kernel assumption determined its validity under clinically relevant situations. Introducing a patient or phantom into the beam required the portal image prediction algorithm to account for patient scatter and attenuation. Primary fluence was calculated by attenuating raylines cast through the patient CT dataset, while scatter fluence was determined through the superposition of pre-calculated scatter fluence kernels. Total dose in the EPID was calculated by convolving the total predicted incident fluence with the EPID-specific dose kernels. The algorithm was tested on water slabs with square fields, agreeing with measurement within 3% and 3 mm. The method was then applied to five prostate and six head-and-neck IMRT treatment courses (~1900 clinical images). Deviations between the predicted and measured images were quantified. The portal dose image prediction model developed in this thesis work has been shown to be accurate, and it was demonstrated to be able to verify patients’ delivered radiation treatments.