Masters Research - Masters of Philosophy / INTRODUCTION: Level III dosimetric intercomparison studies test the entire radiotherapy patient treatment chain from diagnostic imaging to treatment delivery and verification imaging at multiple radiotherapy centres. The anthropomorphic phantom employed in an intercomparison needs to meet specific criteria including portability, tissue equivalence and accommodation of radiation detectors to ensure clinical relevance and dosimetric accuracy. The proposition that a purpose-built phantom can encompass all the attributes necessary for precise Level III dosimetric intercomparisons for prostate cancer is the premise of this body of work. METHODS: Organ outlines were generated from a human computed tomography image set and incorporated into the phantom design to replicate human anatomy as closely as possible. Twenty-five points of interest were located throughout the dataset to identify where point-dose values could be measured with thermoluminescence dosimeters. The centre of the prostate was identified as the location for measurement with a small-volume ionization chamber. The materials used in this phantom were tested against water to determine relative attenuation, density and Hounsfield Units. Three materials were chosen to mimic bone, organs, and a backfill material and the phantom was manufactured using modern prototyping techniques into five separate coronal slices. Time lines and resource requirements for the phantom design and manufacture were recorded. The ability of the phantom to mimic the entire treatment chain was tested at the Calvary Mater Newcastle Hospital. RESULTS: The phantom CT images indicated the densities and organ geometries were comparable to the original patient. The phantom proved simple to load for dosimetry and rapid to assemble. Measurements indicated the reproducibility to be in the order of 1% for the ionization chamber measurement and within 3% for thermoluminescence dosimeters. Due to heat release during manufacture, small airgaps were present throughout the phantom producing artifacts on lateral images. The overall cost for production of the prototype phantom was comparable to other commercial anthropomorphic phantoms ($AU45,000). The phantom was shown to be suitable for use as a “patient” to mimic the entire treatment chain for typical external beam radiotherapy for prostate and rectal cancer. Outlining of relevant structures by a radiation oncologist was uncomplicated and the computerised treatment plan compared well with the dose measured using ionisation chambers and thermoluminescence dosimeters. DISCUSSION & CONCLUSIONS: The phantom constructed for the present study incorporates all characteristics necessary for accurate Level III intercomparison studies and will be an effective tool for an intercomparison of pelvic treatments in Australasia. These results may benefit analysis of outcomes for prostate cancer treatments, especially in the clinical trial environment. It will be of significant interest in the future to use the phantom to assess advanced radiotherapy delivery techniques such as Intensity Modulated Radiation Therapy (IMRT).

Abstract In New Zealand there are currently no regular external audits to verify the full treatment chain in radiotherapy. This thesis reports on a project to devise such an audit procedure suitable to assess the accuracy of the delivery of prescribed radiotherapy doses to patients over the full treatment process. The National Radiation Laboratory (NRL), regulatory authority, will use the method developed to conduct biennial audits of all radiotherapy centres. A commercial chest phantom with a MOSFET dosimetry system was provided for this project. The MOSFETs were commissioned and their characteristics determined, namely reproducibility, energy dependence and angular dependence. The MOSFETs were also tested in a clinical environment with the phantom. Measurements were carried out to test the MOSFET capabilities in both lung and soft tissue in the phantom. Two plans were devised for the audit process, a straightforward one with two parallel opposed beams and a more complex one involving lung tissue and wedges. These plans were designed to test the entire treatment planning and delivery process. It was found that each MOSFET detector needed to be individually calibrated. Reproducibility was found to have an average standard deviation of 2% on standard sensitivity and 1.2% on high sensitivity. The angular dependence of the detectors showed that when the MOSFET was rotated by 90 degrees to the beam axis a drop in response of 3% was observed with 6 MV. The energy dependence factor was constant within uncertainty for all MOSFETs. Overall, the MOSFET and phantom dosimetry system was determined to be suitable for the audit. The measurements with phantom showed that doses in high dose regions could be determined accurately. The greatest variation from the Treatment Planning system dose to the measured dose was 6%. The trial runs of the audit in two New Zealand radiotherapy centres showed that the procedure created is able to find discrepancies within the desired 5%, recommended by the ICRU, in the prescribed dose to the phantom.

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. / Science, Faculty of / Physics and Astronomy, Department of / Graduate

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. / Science, Faculty of / Physics and Astronomy, Department of / Graduate

No description available.

Purpose/Objectives: Intensity Modulated Radiation Therapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) provide advantages in delivery of radiation allowing conformality of delivered dose to the planning target and reducing dose to organs at risk (OAR), however, at the potential cost of low dose spread. Due to the central location of the esophagus and GE junction, dose to lungs, heart, spinal cord, liver, and kidneys must be considered. Low dose spread is of particular concern with respect to healthy lung tissue. This study comprehensively compares volumetric dose statistics of the standard three-dimensional conformal radiation therapy (3D-CRT) compared with VMAT and IMRT for distal esophageal cancer treatment. Materials/Methods: Forty patients who underwent pre-operative radiation therapy for esophageal cancer between 2012-2014 were retrieved from our database. Pinnacle planning software was used to create 3D-CRT, VMAT and IMRT radiation plans for all patients. Forty-five (45) Gy was prescribed for each patient with D95% > 42.75Gy for the planning target volume (PTV). All plans were optimized to maintain PTV coverage while reducing dose to OAR with specific emphasis on lung and heart dose. Volumetric dose statistics were obtained, and Wilcoxon signed rank test was used to compare 3D-CRT vs IMRT and VMAT for Conformity Index, Integral Dose, Monitor Units, lung (V5Gy, V20Gy, mean, max), heart (V30Gy, mean, max), spinal cord max, bilateral kidneys (V20Gy, mean) and liver mean dose. Comparison was also made for IMRT vs VMAT. Results: For both IMRT and VMAT compared with 3D-CRT, statistically significant pairwise differences were noted for Conformity Index (-28.51%, -30.70%, P<.001), Integral Dose (-14.0%, -14.8%, P<.001), Monitor Units (107.2%, 80.4%, P<.001), lung (V20Gy: -49.7%,-57.4%, mean: -20.3%,-24.9%, P <.001), heart (V30Gy : -10.1%,-14.3%, mean -10.4%,-13.4%, P <.001), spinal cord (max 13.3%,9.5%, P <.001) and liver (mean -29.9%,-24.3%, P <.001). No significant differences were noted for VMAT and IMRT compared with 3D-CRT for lung (V5Gy, max dose), heart (max dose) and bilateral kidneys (mean). VMAT did offer statistically significant improvement in Conformity Index, Monitor Units, lung V20Gy and mean dose as well as heart V30Gy and mean dose compared to IMRT. Conclusion: VMAT and IMRT offer excellent sparing of key organs (lung, heart) with respect to volumetric constraints. Max point doses as well as lung V5Gy, which can be an indication of low dose spread for esophageal treatment, were not conclusively different. While 3D-CRT offers acceptable treatment, VMAT should be the standard modality of radiation treatment where facilities exist. / Thesis / Master of Science (MSc)

Intensity Modulated Radiation Therapy (IMRT) is a well-known type of external beam radiation therapy. The advancement in technology has had an inevitable influence in radiation oncology as well that has led to a newer and faster dose delivery technique called Volumetric Modulated Arc Therapy (VMAT). Since the presence of the VMAT modality in clinics in the late 2000, there have been many studies in order to compare the results of the VMAT modality with the current popular modality IMRT for various tumor sites in the body such as brain, prostate, head and neck, cervix and anal carcinoma. This is the first study to compare VMAT with IMRT for breast cancer. The results show that the RapidArc technique in Eclipse version 11 does not improve all aspects of the treatment plans for the breast cases automatically and easily, but it needs to be manipulated by extra techniques to create acceptable plans thus further research is needed. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 6 uppsatser.

Gold nanoparticles can serve as an ideal radiosensitizer for radiation therapy due to the high-atomic-number nature of gold and the increased tumor specificity in nanoparticle form. The degree of radiosensitization is highly dependent on both the local gold nanoparticle concentration in the tumor and the radiation source type. Previous Monte Carlo simulations have demonstrated that the gamma-ray energy spectrum of Ytterbium-169 is a strong candidate for a high dose rate brachytherapy implementation of gold nanoparticle-aided radiation therapy. Therefore, the current study focuses on the design of a high dose rate Ytterbium-169 source that would maximize dose enhancement during gold nanoparticle-aided radiation therapy; while meeting the practical constraints for the production of a clinically relevant brachytherapy source. Different encapsulation materials are studied in order to determine its effect on the dosimetric characteristics of the source. Specifically, the photon spectra, secondary electron spectra, and dose enhancement characteristics are calculated via Monte Carlo simulations to elucidate the effects on potential radiosensitization during gold nanoparticle-aided radiation therapy. Furthermore, this project involves a study into the modification of external x-ray beams from a Philips RT-250 orthovoltage x-ray machine in an attempt to match the dosimetric characteristics of the Ytterbium-169 brachytherapy source. This investigation will enable the production of an external beam that can serve as a good surrogate of an actual brachytherapy source and facilitate the pre-clinical investigation of gold nanoparticle-aided radiation therapy with Ytterbium-169.

Introduction: Cancer-related fatigue is often described by patients as a lack of energy, mental or physical tiredness, diminished endurance, and prolonged recovery after activity. Etiologic mechanisms underlying CRF are not well understood. Methods: A literature review was conducted to examine studies that had investigated the association of mitochondrial dysfunction with fatigue. The major conclusion from this review was that alterations in energy metabolism may contribute to fatigue. Therefore, the dissertation study focused on laboratory techniques for measuring mitochondrial oxidative phosphorylation enzymes (complexes I-V) and a mitochondrial-specific oxidative stress marker (superoxide dismutase 2 [SOD2]). The primary aim of the dissertation research was to describe levels of biomarkers of mitochondrial function, fatigue, and health-related quality of life (HRQOL) before and at the completion of external beam radiation therapy (EBRT) in men with nonmetastatic prostate cancer (NM-PC). To achieve this aim a secondary analysis of a descriptive, longitudinal study was conducted (#10-NR-0128). Results: A total of n = 22 men with NM-PC were included in this study. There were significant increases in fatigue and a significant decrease HRQOL from baseline to the completion of EBRT. However, there was no significant change in the biomarkers of mitochondrial function from baseline to EBRT completion. Given the exploratory nature of the study, it was decided to further investigate the patient sample to understand the relationship of fatigue and mitochondrial function in a well-characterized fatigue phenotype. There was preliminary evidence to support the possibility of distinct patterns of mitochondrial enzyme levels between those with a high intensification of fatigue and those with a low intensification of fatigue during EBRT; however, these differences were not statistically significant. Discussion: To our knowledge, this is the first study to describe the relationship between mitochondrial enzymes and fatigue before and during EBRT in men with NM-PC. The most important preliminary finding from this study is the possibility that mitochondrial enzymes might be related to fatigue intensification during EBRT. Future studies will be critical to determine if these preliminary findings are replicable, and if so, whether there are potential therapeutic targets in individuals at highest risk for fatigue intensification during EBRT.