published_or_final_version / Clinical Oncology / Doctoral / Doctor of Philosophy

Lung cancer is the leading cause of cancer-related deaths worldwide. Radiotherapy is one of the main treatment modalities of lung cancer. However, the achievable accuracy of radiotherapy treatment is limited for lung-based tumors due to respiratory motion. Four-dimensional radiotherapy explicitly accounts for anatomic motion by characterizing the motion, creating a treatment plan that accounts for this motion, and delivering this plan to the moving anatomy. This thesis focuses on the current problems and solutions throughout the course of four-dimensional radiotherapy. For characterization of respiratory-induced motion, patient tumor motion data were analyzed. It is shown that tumor motion can be significant during radiotherapy treatment, and its extent, direction, and linearity vary considerably between patients, between treatment fractions, and between respiratory cycles. After this, approaches to four-dimensional intensity-modulated radiation therapy treatment planning were developed and investigated. Among the techniques to manage respiratory motion, tumor tracking using a dynamic multileaf collimator delivery technique was chosen as a promising method. A formalism to solve a general four-dimensional intensity-modulated radiation therapy treatment-planning problem was developed. Specific solutions to this problem accounting for tumor motion initially in one dimension and extending this to three dimensions were developed and investigated using four-dimensional computed tomography planning scans of lung cancer patients. For four-dimensional radiotherapy treatment delivery, accuracy of two-dimensional projection imaging methods was investigated. Geometric uncertainty due to the limitation of two-dimensional imaging in monitoring three-dimensional tumor motion during treatment delivery was quantified. This geometric uncertainty can be used to estimate proper margins when a single two-dimensional projection imager is used for four-dimensional treatment delivery. Lastly, tumor-tracking delivery using a moving average algorithm was investigated as an alternative delivery technique that reduces mechanical motion constraints of a multileaf collimator. Moving average tracking provides an approximate solution that can be immediately implemented for delivery of four-dimensional intensity-modulated radiation therapy treatment. The clinical implementation of four-dimensional guidance, intensity-modulated radiation therapy treatment planning, and dynamic multileaf collimator tracking delivery may have a positive impact on the treatment of lung cancer.

by Mei Chun Cheung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 34-41). / Abstract and questionare in English and Chinese. / ABSTRACT --- p.ii / ACKNOWLEDGEMENTS --- p.iii / TABLE OF CONTENTS --- p.iv / LIST OF TABLES --- p.v / Chapter CHAPTER I - --- INTRODUCTION --- p.1 / Chapter CHAPTER II - --- METHOD --- p.7 / Chapter CHAPTER III - --- RESULTS --- p.17 / Chapter CHAPTER IV - --- DISCUSSION --- p.29 / REFERENCES --- p.34 / APPENDIX --- p.42

Ng Kenway. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 169-189). / Abstracts in English and Chinese ; questionnaire also in Chinese. / ABSTRACT --- p.I / 摘要 --- p.IV / ACKNOWLEDGEMENT --- p.V / TABLE OF CONTENTS --- p.VII / ABBREVIATION --- p.XI / LIST OF TABLES --- p.XIII / LIST OF FIGURES --- p.XIV / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter CHAPTER 2 --- LITERATURE REVIEW --- p.4 / Chapter 2.1 --- SIDE EFFECTS OF RADIATION THERAPY IN HEAD & NECK CACNER PATIENTS --- p.6 / Chapter 2.2 --- NUTRITIONAL ALTERATIONS IN CANCER PATIENTS --- p.9 / Chapter 2.3 --- FACTORS INFLUENCING ALTERATION IN CALORIE INTAKE IN CANCER PATIENTS --- p.12 / Chapter 2.3.1 --- Evidence for impaired calorie intake in cancer patients --- p.12 / Chapter 2.3.2 --- Anorexia --- p.13 / Chapter 2.3.2.1 --- Mucositis of upper food passage --- p.13 / Chapter 2.3.2.2 --- "Change in saliva and taste, food aversions" --- p.14 / Chapter 2.3.2.3 --- Psychological and emotional factors --- p.14 / Chapter 2.3.2.4 --- Cytokines --- p.15 / Chapter 2.4 --- FACTORS INFLUENCING ENERGY EXPENDITURE IN CANCER PATIETNS --- p.17 / Chapter 2.4.1 --- Introduction --- p.17 / Chapter 2.4.2 --- Components of total energy expenditure --- p.22 / Chapter 2.4.2.1 --- Measurement of Basal metabolic rate --- p.22 / Chapter 2.4.2.2 --- Energy cost of physical activity --- p.25 / Chapter 2.4.2.3 --- Thermic effect of food (TEF) --- p.26 / Chapter 2.5 --- METHODS FOR NUTRITIONAL ASSESSMENT --- p.27 / Chapter 2.5.1 --- Body weight and body composition --- p.27 / Chapter 2.5.2 --- Dietary intake --- p.30 / Chapter 2.6 --- METHODS FOR ENERGY EXPENDITURE MEASUREMENT --- p.35 / Chapter 2.7 --- CYTOKINES AND LEPTIN CHANGES IN CANCER PATIENTS --- p.40 / Chapter 2.7.1 --- Cytokines --- p.40 / Chapter 2.7.1.1 --- Tumor necrosis factor --- p.40 / Chapter 2.7.1.2 --- Interleukin 1 and interleukin 6 --- p.44 / Chapter 2.7.2 --- Leptin --- p.45 / Chapter 2.8 --- THE IMPACT OF MALNUTRITION ON CANCER SURVIVAL --- p.49 / Chapter CHAPTER 3 --- OBJECTIVES OF STUDY --- p.53 / Chapter CHAPTER 4 --- METHODS --- p.55 / Chapter 4.1 --- RETROSPECTIVE STUDY --- p.56 / Chapter 4.1.1 --- Patients --- p.56 / Chapter 4.1.2 --- Cancer staging --- p.56 / Chapter 4.1.3 --- Cancer treatment --- p.57 / Chapter 4.1.4 --- Outcome endpoints --- p.57 / Chapter 4.1.5 --- Determinants --- p.58 / Chapter 4.1.6 --- Statistical analysis --- p.58 / Chapter 4.2 --- PROSPECTIVE STUDY --- p.59 / Chapter 4.2.1 --- "Patients, oncological treatment, and assessment time points" --- p.59 / Chapter 4.2.2 --- Assessment of nutritional intake by food record --- p.60 / Chapter 4.2.3 --- Assessment of radiotherapy-induced symptoms --- p.61 / Chapter 4.2.4 --- Assessment of Basal metabolic rate --- p.62 / Chapter 4.2.5 --- Assessment of total energy expenditure and energy balance --- p.63 / Chapter 4.2.6 --- Assessment of body composition --- p.65 / Chapter 4.2.7 --- Measurement of cytokines --- p.68 / Chapter 4.2.7.1 --- Serum TNF-α --- p.69 / Chapter 4.2.7.2 --- Serum Human Leptin --- p.72 / Chapter CHAPTER 5 --- RESULTS --- p.80 / Chapter 5.1 --- RETROSPECTIVE STUDY --- p.81 / Chapter 5.1.1 --- The 5-year profile of bodyweight change during and after the end of radiotherapy --- p.81 / Chapter 5.1.2 --- Analysis on relation between weight loss and survival --- p.82 / Chapter 5.1.2.1 --- Patient and cancer stage --- p.82 / Chapter 5.1.2.2 --- Percentage of patients with weight loss at end of radiotherapy --- p.82 / Chapter 5.1.2.3 --- Cancer treatment outcome --- p.82 / Chapter 5.1.2.4 --- Univariate analysis --- p.82 / Chapter 5.1.2.5 --- Multivariate analysis --- p.83 / Chapter 5.2 --- PROSPECTIVE STUDY --- p.84 / Chapter 5.2.1 --- The profile of nutritional measurements during radiotherapy --- p.84 / Chapter 5.2.1.1 --- Bodyweight and body composition before and during RT --- p.84 / Chapter 5.2.1.2 --- Calorie intake before and during RT --- p.85 / Chapter 5.2.1.3 --- Energy expenditure before and during RT --- p.86 / Chapter 5.2.1.4 --- Energy balance before and during RT --- p.88 / Chapter 5.2.2 --- The profile of nutritional measurements during the 6-month period after radiotherapy --- p.88 / Chapter 5.2.2.1 --- Body weight and body composition during the 6 months after radiotherpay --- p.88 / Chapter 5.2.2.2 --- Calorie intake during the 6 months after radiotherapy --- p.90 / Chapter 5.2.2.3 --- Energy expenditure during the 6 months after radiotherapy --- p.91 / Chapter 5.2.2.4 --- Energy balance during the 6 months after radiotherapy --- p.92 / Chapter 5.2.3 --- Radiotherapy-induced Symptoms --- p.92 / Chapter 5.2.3.1 --- Profile of symptoms after RT --- p.92 / Chapter 5.2.3.2 --- Detailed profile of symptoms during RT --- p.95 / Chapter 5.2.4 --- The profile of cytokines during and after completion of RT --- p.95 / Chapter 5.2.4.1 --- SerumTNF-α --- p.96 / Chapter 5.2.5.2 --- Serum leptin --- p.96 / Chapter CHAPTER 6 --- DISCUSSION --- p.144 / Chapter 6.1 --- RETROSPECTIVE STUDY --- p.145 / Chapter 6.2 --- PROSPECTIVE STUDY --- p.147 / Chapter 6.2.1 --- The magnitude of the problem --- p.147 / Chapter 6.2.2 --- The potential determinants of weight loss --- p.147 / Chapter 6.2 3 --- Is weight loss due to the cancer or due to its treatment? --- p.148 / Chapter 6.2.4 --- "Is the weight loss influenced by pre-treatment factors, i. e. anthropometrical data?" --- p.148 / Chapter 6.2.5 --- "Is the pattern weight loss compatible with the model of calorie-protein malnutrition, similar to a starvation state?" --- p.149 / Chapter 6.2.6 --- Is the weight loss due to increased energy expenditure? --- p.150 / Chapter 6.2.7 --- Is the weight loss due to reduced calorie intake? --- p.151 / Chapter 6.2.8 --- Is weight loss during radiotherapy due to negative energy balance? --- p.151 / Chapter 6.2.9 --- What causes reduced calorie intake: Are radiotherapy-induced symptoms contributive? --- p.152 / Chapter 6.2.10 --- What are the observations on and implications of cytokine changes? --- p.155 / Chapter 6.2.11 --- What determines the recovery of body weight during 6 months after end of radiotherapy? --- p.158 / Chapter 6.2.12 --- Is the weight loss in the post RT recovery period due to negative energy balance? --- p.159 / Chapter 6.2.13 --- What are the implications on nutritional intervention? --- p.159 / Chapter 6.2.14 --- Limitations and future studies --- p.164 / Chapter CHAPTER 7 --- CONCLUSIONS --- p.166 / REFERENCES --- p.169 / APPENDIX 1 CONSENT FORM I (IN ENGLISH) --- p.190 / APPENDIX 2 CONSENT FORM I (IN CHINESE) --- p.193 / APPENDIX 3 CONSENT FORM II (IN ENGLISH) --- p.196 / APPENDIX 4 CONSENT FORM II (IN CHINESE) --- p.199 / APPENDIX 5 3-DAY DIET RECORD --- p.202 / APPENDIX 6 24-HOUR DIETARY RECALL --- p.206 / APPENDIX 7 SUBJECTIVE NUTRITIONAL ASSESSMENT --- p.208 / APPENDIX 8 PHYSICAL ACTIVITY QUESTIONNAIRE --- p.210 / APPENDIX 9 BONE SCAN REPORT --- p.215

Cheung Mei-chun. / "January 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 66-94). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

O controle de qualidade do feixe é fundamental para garantir os requisitos mínimos de operação aos serviços de radioterapia, visto que a avaliação de parâmetros como simetria, planura, penumbra, fatores filtro e bandeja além de outros parâmetros dosimétricos é imprescindível para garantir constância aos tratamentos radioterápicos minimizando erros na entrega da dose. A avaliação destes parâmetros em radioterapia normalmente é realizada através de câmaras de ionização, filmes radiográficos ou detectores semicondutores sendo eles diodos e MOSFETs. Nos últimos anos o crescimento da utilização da dosimetria opticamente estimulada (OSL) na dosimetria individual externa em diversos países da Europa, USA e America latina como México e Peru proporcionou a aplicação de detectores OSL também na dosimetria em radioterapia visando à avaliação de parâmetros de feixe. A técnica de OSL une características técnicas encontradas em filmes e TLD, acrescidas de novas propriedades não possíveis nas tecnologias utilizadas anteriormente, por exemplo: possibilidade de re-leitura do dosímetro, integração de dose com avaliação de doses intermediárias entre exposições no mesmo dosímetro e simplicidade no processo de leitura. Recentemente a Landauer Inc lançou no mercado americano fitas dosimétricas de OSL para a análise do perfil de dose em Tomografia Computadorizada (TC). Neste trabalho foi avaliada a utilização deste detector OSL em forma de fita, na determinação de parâmetros de qualidade em radioterapia tais como simetria e planura, fatores filtro e bandeja, porcentagem e dose profunda (PDP) e penumbra. Os resultados obtidos permitem concluir que o detector estudado se apresenta eficaz na determinação dos parâmetros de qualidade, porém a metodologia de análise de dados bem como o setup utilizado na irradiação inicial devem ser reformulados buscando obter resultados mais precisos de forma a validar a utilização deste método na rotina de trabalho em radioterapia. / Beam´s quality control is fundamental to ensure minimum operation requirements to radiotherapy services, since parameters evaluation, such as symmetry, planura, shade, filter factors and tray, amongst other ones, is necessary to guarantee stability to radiotherapy treatments, which minimize errors at dose delivery. The evaluation of those parameters in radiotherapy is normally executed through ionization compartments, radiographic films or semiconductor detectors, specifically diode and MOSFETs. Through the last years, the utilization of optically stimulated dosimetry at external individual dosimetry increased in several Europe countries, USA and Latin America countries, such as Mexico and Peru, which made it possible to apply OSL detectors at dosimetry to radiotherapy as well, in order to evaluate clusters parameters of quality. The OSL technique incorporate technical characteristics, found in films and TLD, to new proprieties, which were not available at preceding technologies, such as: possibility of dosimetry rereading, dose integration with intermediary doses evaluation between exposure at the same dosimeter and simplicity at the reading process. Recently, Launder Inc launched in the American market OSL dosimetric ribbons to dose profile analysis in computed tomography (TC). In this paper, it was analyzed this OSL tape shaped detector utilization, in order to determine parameters of quality in radiotherapy, such as symmetry and beam flatness, filter factors and tray, depth dose percentage and dose and shade. The results allowed to conclude that the studied detector is effective to determine parameters of quality. However, analysis methodology, as well as the used setup at initial irradiation, must be reformulated in order to get more accurate results, which it will allow to validate this method utilization at daily work routine in radiotherapy.

This research demonstrates that a 3D printed bolus can be customized for electron radiation therapy. Both extruder and powder based printers were used, along with, paraffin wax, super stuff, and H20. The plan dose coverage and conformity for the planning target volume (PTV), was such that the distal side of the PTV was covered by the 90% isodose line. The structure is read, and converted into an STL file. The file is sent to a slicer to print. The object was filled with parafin wax, superstuff or water and sealed. Materials Hounsfield units were analyzed, along with the structure stability. This method is evaluated by scanning the 3D printed bolus. The dose conformity is improved compared to that with no bolus. By generating a patient specific 3D printed bolus there is an in improvement in conformity of the prescription isodose surface while sparing immediately adjacent normal tissues. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2017. / FAU Electronic Theses and Dissertations Collection

The purpose of this study is to verify and validate the dose at various points of interest in accelerated partial breast irradiation (APBI) treated with the Strut Adjusted Volume Implant (SAVI) applicator using Thermoluminescent Dosimeters (TLDs). A set of CT images were selected from a patient’s data who had received APBI using the SAVI applicator. The images were used to make 3D models. TLDs were calibrated for Brachytherapy. Various points of interest were marked out and slots were carved in the 3D models to fit the TLDs. CT scans were taken of the 3D models with expanded SAVI applicator inserted. A plan was made following B-39 protocol. The TLDs were read and the absorbed doses were calculated and compared to the delivered doses. The results of this study show that the overall average reading of the TLDs is within expected value. The TPS shows overestimated dose calculations for brachytherapy. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2017. / FAU Electronic Theses and Dissertations Collection

<p>One of the most used irradiation techniques in modern radiation therapy is step-and-shoot IMRT. The accuracy of this technique when delivering complex dose distributions strongly depends on the size of the subfields. The aims of this study is to determine the minimum size of subfields that can be used efficiently in Step-and-Shoot IMRT, to investigate the validation process for beam delivery and treatment planning dose calculations, and to find recommendations for practical clinical implementations.</p><p>Two different detectors, a CC04 ion chamber and a SFD stereotactic diode, have been used for measuring head scatter factors in air (Sc), total output factors (Scp) and dose profiles in water for a wide range of field sizes. The measurements were compared to calculations done with a pre-release version of the Nucletron MasterPlanTM v 3.1 treatment planning system that employs a novel, high resolution fluence modelling for both its pencil beam and collapsed cone dose calculation algorithms. Collimator settings were explicitly checked using FWHM film measurements with a build-up sheet of tungsten placed close to the treatment head to reduce the influence from lateral electron transport and geometrical penumbra. An analysis of the influence and sensitivity of Scp for small fields with respect to the linear accelerator source size and shape was also made.</p><p>The measurements with the ionization chamber and the stereotactic diode showed good agreements with each other and with the treatment planning system calculations for field sizes larger than 2×2 cm2. For small field sizes, measurements with different detectors yielded different results. Calculations showed agreements with measurements with the smallest detector, provided careful field size calibration and commissioning of calculation parameters. Uncertainties in collimator settings and source characteristics were shown to yield large uncertainties in Scp for fields smaller than 2×2 cm2.</p><p>The treatment planning system was found to properly handle small subfields but results were very sensitive to uncertainties in source size, as well as calibration and reproducibility of the collimator settings. Therefore if subfields smaller than 2×2 cm2 are to be used in IMRT extra care should be taken to determine the source characteristics and to calibrate the collimators. The volume of the detectors used for validation of such small fields and the loss of charged particle equilibrium conditions also have to be taken into consideration.</p>

One of the most used irradiation techniques in modern radiation therapy is step-and-shoot IMRT. The accuracy of this technique when delivering complex dose distributions strongly depends on the size of the subfields. The aims of this study is to determine the minimum size of subfields that can be used efficiently in Step-and-Shoot IMRT, to investigate the validation process for beam delivery and treatment planning dose calculations, and to find recommendations for practical clinical implementations. Two different detectors, a CC04 ion chamber and a SFD stereotactic diode, have been used for measuring head scatter factors in air (Sc), total output factors (Scp) and dose profiles in water for a wide range of field sizes. The measurements were compared to calculations done with a pre-release version of the Nucletron MasterPlanTM v 3.1 treatment planning system that employs a novel, high resolution fluence modelling for both its pencil beam and collapsed cone dose calculation algorithms. Collimator settings were explicitly checked using FWHM film measurements with a build-up sheet of tungsten placed close to the treatment head to reduce the influence from lateral electron transport and geometrical penumbra. An analysis of the influence and sensitivity of Scp for small fields with respect to the linear accelerator source size and shape was also made. The measurements with the ionization chamber and the stereotactic diode showed good agreements with each other and with the treatment planning system calculations for field sizes larger than 2×2 cm2. For small field sizes, measurements with different detectors yielded different results. Calculations showed agreements with measurements with the smallest detector, provided careful field size calibration and commissioning of calculation parameters. Uncertainties in collimator settings and source characteristics were shown to yield large uncertainties in Scp for fields smaller than 2×2 cm2. The treatment planning system was found to properly handle small subfields but results were very sensitive to uncertainties in source size, as well as calibration and reproducibility of the collimator settings. Therefore if subfields smaller than 2×2 cm2 are to be used in IMRT extra care should be taken to determine the source characteristics and to calibrate the collimators. The volume of the detectors used for validation of such small fields and the loss of charged particle equilibrium conditions also have to be taken into consideration.