There is a growing global need for proper access to radiation therapy. This need exists predominantly in low- and middle-income countries but exists in some high-income countries as well. The solution to this problem is complex and requires changes in government policy, education and technology. The objective of the work contained in this dissertation is the development of a novel external beam radiation therapy system capable of treating a variety of cancers. The intent of this system is to provide a cost-effective radiation therapy system, which can primarily be utilized in low- and middle-income countries. This new system uses kilovoltage rather than megavoltage x-rays and is therefore much more cost-effective. The ultimate purpose of this kilovoltage radiation therapy system is to improve access to radiation therapy worldwide by supplementing current radiation therapy technology. As a first step, the kilovoltage x-ray arc therapy or KVAT system was modeled using the EGSnrc BEAMnrc and DOSXYZnrc Monte Carlo software tools. For this initial study 200 kV arc-therapy was simulated on cylindrical water phantoms of two sizes, each of which contained a variety of planning target volume (PTV) sizes and locations. Additionally, prone and supine partial breast irradiation treatment plans were generated using KVAT. The objective of this work was to determine whether or not skin-sparing could be achieved using the KVAT system while also delivering a clinically relevant dose rate to the PTV. The results of the study indicated that skin-sparing is indeed achievable and that the quality of KVAT treatment plans improves for full 360-degree arcs and smaller PTV sizes. The second step of this project involved the Monte Carlo simulation of KVAT treatment plans for breast, lung and prostate cancer. Spherical PTVs of 3-cm diameter were used for the breast and lung treatment plans while a 4-cm diameter PTV was used for prostate. Additionally, inverse optimization was utilized to make full use of the non-conformal irradiation geometry of KVAT. As a means of comparison, megavoltage treatment plans that could be delivered by a clinical linear accelerator were generated for each patient as well. In order to evaluate the safety of KVAT treatment plans, dose constraints were taken from published Radiation Therapy Oncology Group (RTOG) reports. The results of this study indicated that the 200 kV breast and 225 kV lung KVAT treatment plans were within dose constraints and could be delivered in a reasonable length of time. The 225 kV prostate treatment plan, while technically within dose constraints, delivered a large dose to non-critical healthy tissues due to the limited number of beam angles that did not pass through boney anatomy. It was concluded that plans such as prostate with large volumes of bone present might not be feasible for KVAT treatment. The third step aimed to expand upon previous work and simulated more realistic KVAT treatment plans by using PTV volumes contoured by radiation oncologists. Additionally, this study used a completely redesigned KVAT geometry, which employed a stationary reflection anode and a new collimator design. The design modeled in this study was based upon the specifications of the prototype system under construction by PrecisionRT, a commercial partner. Three stereotactic ablative radiotherapy (SABR) lung patients were selected that had received treatment at the Vancouver Island Cancer Centre. In order to fully cover the PTVs of each patient, spherical sub-volumes were placed within the clinically contoured PTV of each patient. Dose constraints for at-risk organs were taken from an RTOG report on stereotactic body radiation therapy and were used to inversely optimize the 200 kV KVAT treatment plans. The calculated KVAT plans were compared with the clinical 6 MV SABR plans delivered to each patient. The results of this study indicated that KVAT lung plans were within dose constraints for all three patients with the exception of the ribs in the second patient who had a tumor directly adjacent to the rib cage. The fourth and last step of this project was the experimental validation of a simple, proof-of-principle KVAT system. Simple geometric methods were used to design a collimator consisting of two slabs of brass separated by ~6 cm, each with 5 apertures, which would create an array of 5 converging beamlets. The collimator was used with a tabletop x-ray tube system. A rectangular solid water phantom and cylindrical TIVAR 1000 phantom were placed on a rotation stage and irradiated using 360-degree arcs. EBT3 gafchromic film was placed in each phantom to measure two-dimensional dose distributions. Film dose distributions were analyzed and compared to Monte Carlo generated dose distributions. Both the rectangular solid water phantom and cylindrical TIVAR phantom showed skin-sparing effects in their dose distributions. The highest degree of skin-sparing was achieved in the larger, 20 cm diameter cylindrical phantom. Furthermore, the measured film data and calculated metrics of the rectangular phantom were within 10% of the MC calculated values for two out of three films. The discrepancy in the third film can be explained by errors in the experimental setup. In conclusion, the work contained in this dissertation has established the feasibility of a cost-effective kilovoltage arc-therapy system designed to treat deep-seated lesions by means of Monte Carlo simulations and experimental dosimetry. The studies performed so far suggest that KVAT is most suitable for smaller lesions in patient anatomy that does not involve large amounts of boney anatomy. Perhaps most importantly, an experimental study has demonstrated the skin-sparing ability of a simple KVAT prototype. / Graduate / 2020-07-10

The purpose of this work is to evaluate quasi-3D arrays for use with intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) and to determine their clinical relevance. This is achieved using a Delta4 from Scandidos and ArcCheck from Sun Nuclear and the associated software. While certain aspects of these devices and software have been previously evaluated, the main goal of this work is to evaluate the new aspects, such as reconstructing dose on a patient CT set, and extending the capabilities. This includes the capability to reconstruct the dose based on a helical delivery as well as studying the dose to a moving target using measurement-guided motion simulations. It was found that Sun Nuclear's ArcCheck/3DVH system exhibited excellent agreement for dose reconstruction for IMRT/VMAT using a traditional C-arm linear accelerator and stringent 2%/2mm comparison constraints. It also is a powerful tool for measurement-guided dose estimates for moving targets, allowing for many simulations to be performed based on one measurement and the target motion data. For dose reconstruction for a helical delivery, the agreement was not as good for the stringent comparison but was reasonable for the clinically acceptable 3%/3mm comparison. Scandidos' Delta4 shows good agreement with stringent 2%/2mm constraints for its dose reconstruction on the phantom. However, the dose reconstruction on the patient CT set was poor and needs more work. Overall, it was found that quasi-3D arrays are powerful tools for dose reconstruction and treatment plan comparisons. The ability to reconstruct the dose allows for a dose resolution comparable to the treatment plan, which negates the previous issues with inadequate sampling and resolution issues found when just comparing the diodes. The ability to quickly and accurately compare many plans and target motions with minimum setup makes the quasi-3D array an attractive tool for both commissioning and patient specific quality assurance.

Bibliography: leaves 241-250. A multileaf collimator for radiation therapy has been designed that splits each leaf bank into two vertically displaced assemblies or levels with each level consisting of alternate leaves and leaf spaces. The radiation profiles transmitted for image formation through the collimator design were investigated to examine their dependence on the collimator design features.

The primary goal of this thesis is to improve the precision and efficiency of radiation therapy treatment. This goal is achieved by developing and implementing a direct aperture optimization (DAO) platform where the multileaf collimator (MLC) is rotated between each aperture. The approach is referred to as rotating aperture optimization (RAO). A series of tests is performed to evaluate how a final optimized plan depends on MLC parameters. Imposing constraints on the leaf sequence results in increased efficiency and a simplification of the treatment plan without compromising the quality of the dose distribution. It is also shown that an arrangement of equispaced collimator angles takes full advantage of the flexibility associated with collimator rotation. A study including ten recurring nasopharynx cancer patients is used to evaluate the capabilities of RAO compared to other optimization techniques. It is shown that RAO plans require significantly less linac radiation output (monitor units or MU) while maintaining equivalent dose distribution quality compared to plans generated with the conventional fluence based approach. Furthermore with an improved collimator rotation speed, the RAO plans should be executable in the same or less time than plans generated with the fluence-based approach. For the second part of the study it is shown that plans generated with RAO are as good as or better than plans generated with standard fixed collimator DAO. Film and ion chamber measurements indicate that RAO plans can be delivered more accurately than DAO plans. Additional applications of DAO were investigated through collaboration with two PhD students. First, Monte Carlo was used to generate pencil beam dose distributions for DAO inverse treatment planning (MC-DAO). The MC-DAO technique correctly models traditionally difficult treatment geometries such as small fields and tissue inhomogeneities. The MC-DAO also takes advantage of the improved MU efficiency associated with the DAO technique. Secondly DAO is proposed for adaptive radiation therapy. The results show that plan re-adaptation can be performed more quickly than complete plan regeneration thereby minimizing the time the patient has to spend in the treatment room and reducing the potential for geometric errors in treatment delivery.

The rising desire for individualized medical physics models has sparked a transition from the use of tangible phantoms toward the employment of computational software for medical physics applications. One such computational software for radiation transport modeling is the Monte Carlo N-Particle (MCNP) radiation transport code. However, no comprehensive document has been written to introduce the use of the MCNP code for simulating medical physics applications. This document, a primer, addresses this need by leading the medical physics user through the basic use of MCNP and its particular application to the medical physics field. This primer is designed to teach by example, with the aim that each example will illustrate a practical use of particular features in MCNP that are useful in medical physics applications. These examples along with the instructions for reproducing them are the results of this thesis research. These results include simulations of: dose from Tc-99m diagnostic therapy, calculation of Medical Internal Radiation Dose (MIRD) specific absorbed fraction (SAF) values using the ORNL MIRD phantom, x-ray phototherapy effectiveness, prostate brachytherapy lifetime dose calculations, and a radiograph of the head using the Zubal head phantom. Also included are a set of appendices that include useful reference data, code syntax, and a database of input decks including the examples in the primer. The sections in conjunction with the appendices should provide a foundation of knowledge regarding the MCNP commands and their uses as well as enable users to utilize the MCNP manual effectively for situations not specifically addressed by the primer.

Enhanced resistance to radiation could be caused by both chronic hypoxia and acute hypoxic which has been reported in prostate cancer in various studies. Therefore currently used dose prescriptions (70Gy in 35 fractions) for external beam radiation therapy (EBRT) of prostate cancer has been suggested insufficient to provide optimum clinical outcome. In this study, we propose a Biologically Guided Radiation Therapy approach to boost dose in hypoxic prostate tumor regions while sparing the urethra. A previously proposed hypoxia model was modified for prostate cancer and incorporated into treatment plan optimization. The concept of equivalent uniform dose (EUD) was used in the optimization and evaluation of results. CT data from 25 prostate cancer patients who recently received EBRT at the British Columbia Cancer Agency (BCCA) and hypothetical hypoxic regions manually drawn on these CT scans were selected for this study. The results show that our methods could boost dose in target volume to substantially higher levels. EUD of planning target volume increased to more than 80Gy, despite accounting for effects of hypoxia. This increase was achieved with only minor changes in dose in normal tissues, typically less than 5Gy. Notably, urethra sparing was excellent with a EUD around 64Gy. Robustness of the proposed approach is verified against various hypoxic settings. EUD comparison between RT plans in biological guided and conventional approaches using the same RT technique (Volumetric Modulated Arc Therapy) also suggests that biologically guided radiation therapy (BGRT) approach is more suitable for dose painting purposes with the advantage of delivering sufficient dose to hypoxia region in different scenarios and sparing normal tissue better. Furthermore, we also investigated the impact of inter-fraction patient set-up error and intra-fraction organ motion on the high dose gradients achieved with this proposed dose painting method and explored the feasibility of adapting geometrical uncertainties (represented as systematic error and random error) into treatment planning. Image error obtained from EPID images are used to derive systematic uncertainty and random uncertainty. During the geometrical uncertainty adapted optimization, dose matrix in PTV is shifted based on systematic error and convolved with a Gaussian kernel which is pre-calculated using random error. CT sets and organ contours from five patients who enrolled in the previous dose painting i study are selected. For each of them, seven plans are generated using cumulated uncertainty data which was collected after every five fractions. We also present the outcome in terms of equivalent uniform dose (EUD). For four of the patients, EUD history of all seven plans suggests using the proposed optimization method with uncertainty data from the first five fractions, it is possible to achieve the same target coverage of static treatment plans (difference in EUD less than 1Gy). Meanwhile, the elimination of PTV margin also leads to a significant dose reduction (more than 15Gy) in rectum.

The primary goal of this thesis is to improve the precision and efficiency of radiation therapy treatment. This goal is achieved by developing and implementing a direct aperture optimization (DAO) platform where the multileaf collimator (MLC) is rotated between each aperture. The approach is referred to as rotating aperture optimization (RAO). A series of tests is performed to evaluate how a final optimized plan depends on MLC parameters. Imposing constraints on the leaf sequence results in increased efficiency and a simplification of the treatment plan without compromising the quality of the dose distribution. It is also shown that an arrangement of equispaced collimator angles takes full advantage of the flexibility associated with collimator rotation. A study including ten recurring nasopharynx cancer patients is used to evaluate the capabilities of RAO compared to other optimization techniques. It is shown that RAO plans require significantly less linac radiation output (monitor units or MU) while maintaining equivalent dose distribution quality compared to plans generated with the conventional fluence based approach. Furthermore with an improved collimator rotation speed, the RAO plans should be executable in the same or less time than plans generated with the fluence-based approach. For the second part of the study it is shown that plans generated with RAO are as good as or better than plans generated with standard fixed collimator DAO. Film and ion chamber measurements indicate that RAO plans can be delivered more accurately than DAO plans. Additional applications of DAO were investigated through collaboration with two PhD students. First, Monte Carlo was used to generate pencil beam dose distributions for DAO inverse treatment planning (MC-DAO). The MC-DAO technique correctly models traditionally difficult treatment geometries such as small fields and tissue inhomogeneities. The MC-DAO also takes advantage of the improved MU efficiency associated with the DAO technique. Secondly DAO is proposed for adaptive radiation therapy. The results show that plan re-adaptation can be performed more quickly than complete plan regeneration thereby minimizing the time the patient has to spend in the treatment room and reducing the potential for geometric errors in treatment delivery.

Cancer is a global problem, and many people in low-income countries do not have access to the treatment options, such as radiation therapy, that are available in wealthy countries. Where radiation therapy is available, it is often delivered using older Co-60 equipment that has not been updated to modern standards. Previous research has indicated that an updated Co-60 radiation therapy machine could deliver treatments that are equivalent to those performed with modern linear accelerators. Among the key features of these modern treatments is a tightly conformal dose distribution-- the radiation dose is shaped in three dimensions to closely match the tumour, with minimal irradiation of surrounding normal tissues. Very accurate alignment of the patient in the beam is therefore necessary to avoid missing the tumour, so all modern radiotherapy machines include imaging systems to verify the patient's position before treatment. Imaging with the treatment beam is relatively cost-effective, as it avoids the need for a second radiation source and the associated control systems. The dose rate from a Co-60 therapy source, though, is more than an order of magnitude too high to use for computed tomography (CT) imaging of a patient. Digital tomosynthesis (DT), a limited-arc imaging method that can be thought of as a hybrid of CT and conventional radiography, allows some of the three-dimensional selectivity of CT but with shorter imaging times and a five- to fifteen-fold reduction in dose. In the present work, a prototype Co-60 DT imaging system was developed and characterized. A class of clinically useful Co-60 DT protocols has been identified, based on the filtered backprojection algorithm originally designed for CT, with images acquired over a relatively small arc. Parts of the reconstruction algorithm must be modified for the DT case, and a way to reduce the beam intensity will be necessary to reduce the imaging dose to acceptable levels. Some additional study is required to determine whether improvements made to the DT imaging protocol translate to improvements in the accuracy of the image guidance process, but it is clear that Co-60 DT is feasible and will probably be practical for clinical use. / Thesis (Master, Physics, Engineering Physics and Astronomy) -- Queen's University, 2012-01-30 12:56:56.075

Cancer is a global problem, and many people in low-income countries do not have access to the treatment options, such as radiation therapy, that are available in wealthy countries. Where radiation therapy is available, it is often delivered using older Co-60 equipment that has not been updated to modern standards. Previous research has indicated that an updated Co-60 radiation therapy machine could deliver treatments that are equivalent to those performed with modern linear accelerators. Among the key features of these modern treatments is a tightly conformal dose distribution-- the radiation dose is shaped in three dimensions to closely match the tumour, with minimal irradiation of surrounding normal tissues. Very accurate alignment of the patient in the beam is therefore necessary to avoid missing the tumour, so all modern radiotherapy machines include imaging systems to verify the patient's position before treatment. Imaging with the treatment beam is relatively cost-effective, as it avoids the need for a second radiation source and the associated control systems. The dose rate from a Co-60 therapy source, though, is more than an order of magnitude too high to use for computed tomography (CT) imaging of a patient. Digital tomosynthesis (DT), a limited-arc imaging method that can be thought of as a hybrid of CT and conventional radiography, allows some of the three-dimensional selectivity of CT but with shorter imaging times and a five- to fifteen-fold reduction in dose. In the present work, a prototype Co-60 DT imaging system was developed and characterized. A class of clinically useful Co-60 DT protocols has been identified, based on the filtered backprojection algorithm originally designed for CT, with images acquired over a relatively small arc. Parts of the reconstruction algorithm must be modified for the DT case, and a way to reduce the beam intensity will be necessary to reduce the imaging dose to acceptable levels. Some additional study is required to determine whether improvements made to the DT imaging protocol translate to improvements in the accuracy of the image guidance process, but it is clear that Co-60 DT is feasible and will probably be practical for clinical use. / Thesis (Master, Physics, Engineering Physics and Astronomy) -- Queen's University, 2012-01-30 12:56:56.075

Enhanced resistance to radiation could be caused by both chronic hypoxia and acute hypoxic which has been reported in prostate cancer in various studies. Therefore currently used dose prescriptions (70Gy in 35 fractions) for external beam radiation therapy (EBRT) of prostate cancer has been suggested insufficient to provide optimum clinical outcome. In this study, we propose a Biologically Guided Radiation Therapy approach to boost dose in hypoxic prostate tumor regions while sparing the urethra. A previously proposed hypoxia model was modified for prostate cancer and incorporated into treatment plan optimization. The concept of equivalent uniform dose (EUD) was used in the optimization and evaluation of results. CT data from 25 prostate cancer patients who recently received EBRT at the British Columbia Cancer Agency (BCCA) and hypothetical hypoxic regions manually drawn on these CT scans were selected for this study. The results show that our methods could boost dose in target volume to substantially higher levels. EUD of planning target volume increased to more than 80Gy, despite accounting for effects of hypoxia. This increase was achieved with only minor changes in dose in normal tissues, typically less than 5Gy. Notably, urethra sparing was excellent with a EUD around 64Gy. Robustness of the proposed approach is verified against various hypoxic settings. EUD comparison between RT plans in biological guided and conventional approaches using the same RT technique (Volumetric Modulated Arc Therapy) also suggests that biologically guided radiation therapy (BGRT) approach is more suitable for dose painting purposes with the advantage of delivering sufficient dose to hypoxia region in different scenarios and sparing normal tissue better. Furthermore, we also investigated the impact of inter-fraction patient set-up error and intra-fraction organ motion on the high dose gradients achieved with this proposed dose painting method and explored the feasibility of adapting geometrical uncertainties (represented as systematic error and random error) into treatment planning. Image error obtained from EPID images are used to derive systematic uncertainty and random uncertainty. During the geometrical uncertainty adapted optimization, dose matrix in PTV is shifted based on systematic error and convolved with a Gaussian kernel which is pre-calculated using random error. CT sets and organ contours from five patients who enrolled in the previous dose painting i study are selected. For each of them, seven plans are generated using cumulated uncertainty data which was collected after every five fractions. We also present the outcome in terms of equivalent uniform dose (EUD). For four of the patients, EUD history of all seven plans suggests using the proposed optimization method with uncertainty data from the first five fractions, it is possible to achieve the same target coverage of static treatment plans (difference in EUD less than 1Gy). Meanwhile, the elimination of PTV margin also leads to a significant dose reduction (more than 15Gy) in rectum.