Medicine and Health Sciences Commons^™

Assessment Of Post-Treatment Imaging Changes Following Radiotherapy Using Magnetic Susceptibility Techniques, Jean-Guy Belliveau

Electronic Thesis and Dissertation Repository

Radiation therapy (RT) is a common treatment for brain neoplasms and is used alone or in combination with other therapies. The use of RT has been found to be successful in controlling tumors and extending the overall survival of patients; however, there are many unanswered questions regarding radiotherapy effects in the normal brain surrounding or infiltrated by tumor. Changes to the vascular and parenchyma have been documented, and more recently inflammatory mechanisms have been postulated to play a role in radiation injury. Traditional imaging techniques used within the clinic (CT and MRI) are often lacking in their ability to differentiate …

Optimizing Respiratory Gated Intensity Modulated Radiation Therapy Planning And Delivery Of Early-Stage Non-Small Cell Lung Cancer, Ilma Xhaferllari

Electronic Thesis and Dissertation Repository

Stereotactic ablative body radiotherapy (SABR) is the standard of care for inoperable early-stage non-small cell lung cancer (NSCLC) patients. However, thoracic tumours are susceptible to respiratory motion and, if unaccounted for, can potentially lead to dosimetric uncertainties. Respiratory gating is one method that limits treatment delivery to portions of the respiratory cycle, but when combined with intensity-modulated radiotherapy (IMRT), requires rigorous verification. The goal of this thesis is to optimize respiratory gated IMRT treatment planning and develop image-guided strategies to verify the dose delivery for future early-stage NSCLC patients.

Retrospective treatment plans were generated for various IMRT delivery techniques, including …

Non-Invasive Imaging For The Assessment Of Cardiac Dose And Function Following Focused External Beam Irradiation, Omar El-Sherif

Electronic Thesis and Dissertation Repository

Technological advances in imaging and radiotherapy have led to significant improvement in the survival rate of breast cancer patients. However, a larger proportion of patients are now exhibiting the less understood, latent effects of incidental cardiac irradiation that occurs during left-sided breast radiotherapy. Here, we examine the utility of four-dimensional computed tomography (4D-CT) for the accurate assessment of cardiac dose; and a hybrid positron emission tomography (PET) magnetic resonance imaging (MRI) system to longitudinally study radiation-induced cardiac effects in a canine model.

Using 4D-CT and deformable dose accumulation, we assessed the variation caused by breathing motion in the estimated dose …

Oncolytic Virus Therapy For The Treatment Of Metastatic Ovarian Cancer, Jessica Tong

Electronic Thesis and Dissertation Repository

The management of patients with epithelial ovarian cancer (EOC) faces two major challenges which standard treatments fail to effectively address: 1) Diffuse metastasis as a consequence of late stage diagnosis and 2) intra-tumoral heterogeneity, which fuels tumor evolution and drives the acquisition of chemotherapeutic resistance. In this thesis, we tested new therapeutic strategies using a 3-dimensional in vitro spheroid culture model that mimics key steps of epithelial ovarian cancer metastasis; and another model that mimics both temporal and cellular heterogeneity by establishing multiple cell lines from a single patient over the course of disease progression. Using these models, we investigated …

Phase Ii Clinical Trial Of Concurrent Neoadjuvant Chemotherapy With Radiotherapy In Locally Advanced Breast Cancer, Muriel Brackstone

Electronic Thesis and Dissertation Repository

Locally advanced breast cancer (LABC) represents 15% of all non-metastatic breast cancers, with an overall poor prognosis, despite current guidelines that recommend neoadjuvant chemotherapy followed by surgery and adjuvant radiation. Therefore, a novel treatment paradigm using concurrent neoadjuvant chemoradiotherapy was proposed. A clinical trial was designed, where 32 LABC patients were treated with q3 weekly 5-fluorouracil, epirubicin and cyclophosphamide for three cycles, followed by weekly docetaxel for 9 weeks with concurrent regional radiation (45+5.4Gy) for the first 6 weeks. Patients subsequently underwent modified radical mastectomies. Pathological complete responses (pCR) and 3 year overall survival rates were compared to a matched …

Interpretation Of Mutations, Expression, Copy Number In Somatic Breast Cancer: Implications For Metastasis And Chemotherapy, Stephanie Dorman

Electronic Thesis and Dissertation Repository

Breast cancer (BC) patient management has been transformed over the last two decades due to the development and application of genome-wide technologies. The vast amounts of data generated by these assays, however, create new challenges for accurate and comprehensive analysis and interpretation. This thesis describes novel methods for fluorescence in-situ hybridization (FISH), array comparative genomic hybridization (aCGH), and next generation DNA- and RNA-sequencing, to improve upon current approaches used for these technologies. An ab initio algorithm was implemented to identify genomic intervals of single copy and highly divergent repetitive sequences that were applied to FISH and aCGH probe design. FISH …

Development Of A Small Animal Conformal Irradiator With Dual Energy X-Ray Computed Tomography Imaging For Kilovoltage Dosimetry, Michael D. Jensen

Electronic Thesis and Dissertation Repository

External beam radiotherapy has become technically sophisticated with image guided radiation therapy (IGRT) and intensity modulated radiation therapy (IMRT). These technologies allow for precise delivery of radiation to geometric targets in cancer patients. However, many questions remain on how to best define targets based on biological information, such as functional imaging, and how to combine radiation with other cancer therapies. To help answer these questions, small animal preclinical studies are needed to generate data to inform clinical trials. However, the precise radiation delivery capabilities of IGRT and IMRT have not been available in the preclinical labs. To enable translational experiments …

Design Of Novel Sensors And Instruments For Minimally Invasive Lung Tumour Localization Via Palpation, Anish Srinivasan Naidu

Electronic Thesis and Dissertation Repository

Minimally Invasive Thoracoscopic Surgery (MITS) has become the treatment of choice for lung cancer. However, MITS prevents the surgeons from using manual palpation, thereby often making it challenging to reliably locate the tumours for resection. This thesis presents the design, analysis and validation of novel tactile sensors, a novel miniature force sensor, a robotic instrument, and a wireless hand-held instrument to address this limitation. The low-cost, disposable tactile sensors have been shown to easily detect a 5 mm tumour located 10 mm deep in soft tissue. The force sensor can measure six degrees of freedom forces and torques with temperature …

Kiss1r Signaling Promotes Breast Cancer Drug Resistance, Alexandra J. Blake

Electronic Thesis and Dissertation Repository

Kisspeptins signal via the G-protein coupled receptor, KISS1R, and act as metastasis suppressors in numerous cancers. In estrogen receptor (ERα)-negative breast cancer cells, however, KISS1R signaling promotes cell invasion by activating the epidermal growth factor receptor (EGFR). Unfortunately, clinical success of anti-EGFR therapeutics has been limited, as patients often develop drug resistance. Recently, another receptor tyrosine kinase, AXL, has been shown to promote breast cancer drug resistance. We hypothesize that KISS1R promotes EGFR expression and induces breast cancer drug resistance. We demonstrated that KISS1R increases EGFR transcription, by increasing SP-1 binding to the EGFR promoter, as demonstrated by chromatin immunoprecipitation …

Investigating The Role Of Hydrogen Sulfide In The Survival, Growth And Angiogenic Potential Of Clear Cell Renal Cell Carcinoma Cell Lines And Xenografts, Eric Sonke

Electronic Thesis and Dissertation Repository

Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H₂S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H₂S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism, and angiogenesis. Using H₂S-specific probes, it was found that H₂S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H₂S-producing enzymes could reduce the proliferation, metabolism …

Exploiting High-Throughput Cell Line Drug Screening Studies To Identify Candidate Therapeutic Agents In Head And Neck Cancer, Anthony C Nichols, Morgan Black, John Yoo, Nicole Pinto, Andrew Fernandes, Benjamin Haibe-Kains, Paul C Boutros, John W Barrett

Oncology Publications

BACKGROUND: There is an urgent need for better therapeutics in head and neck squamous cell cancer (HNSCC) to improve survival and decrease treatment morbidity. Recent advances in high-throughput drug screening techniques and next-generation sequencing have identified new therapeutic targets in other cancer types, but an HNSCC-specific study has not yet been carried out. We have exploited data from two large-scale cell line projects to clearly describe the mutational and copy number status of HNSCC cell lines and identify candidate drugs with elevated efficacy in HNSCC.

METHODS: The genetic landscape of 42 HNSCC cell lines including mutational and copy number data …

Overall Survival And Biochemical Failure-Free Survival Comparison Of Brachytherapy Treatment Options Versus External Beam Radiation Therapy For Both Low And Intermediate-Risk Prostate Cancer: A Propensity-Score Matched Analysis, Graham D. Smith

Electronic Thesis and Dissertation Repository

Purpose: This study compares overall survival (OS) and biochemical failure-free survival (bFFS) in low- and intermediate-risk prostate cancer patients that received brachytherapy [low-dose-rate brachytherapy (LDR-BT) or high-dose-rate brachytherapy with external beam radiation therapy (HDR-BT+EBRT)] versus external beam radiation therapy (EBRT) alone.

Materials/Methods: Patient data was obtained from the ProCaRS database, which contains 7974 prostate cancer patients treated at four Canadian institutions. Propensity score (PS) matching was used to generate matched cohorts with balanced baseline prognostic factors.

Results/Conclusions: Final PS matches included two 1:1 intermediate-risk patient matches, LDR-BT vs. EBRT (total n = 254) and HDR-BT+EBRT vs. EBRT (total n=388), and …

Mri Relaxation Rates: A Quantitative Approach To Track Tumour Cells Expressing Maga, Anindita Sengupta

Electronic Thesis and Dissertation Repository

Using magnetic resonance imaging, relaxation rate measurements were

performed in cancer cells overexpressing a magnetotactic bacterial gene, MagA.

Measurements of magnetic resonance relaxation rates in this expression

system is important for optimizing cell detection and specificity, for developing

quantification methods, and for refinement of gene-based iron contrast using

magnetosome associated genes. We measured the total transverse

relaxation rate (R2^*), its irreversible and reversible components (R2 and R2^′,

respectively) and the longitudinal relaxation rate (R1) in MDA-MB-435 tumor cells.

Clonal lines overexpressing MagA were cultured in the presence and absence of

iron supplementation, and mounted in a …

Multiparametric Imaging And Mr Image Texture Analysis In Brain Tumors, Harish A. Sharma

Electronic Thesis and Dissertation Repository

Discrimination of tumor from radiation injured (RI) tissues and differentiation of tumor types using noninvasive imaging is essential for guiding surgical and radiotherapy treatments are some of the challenges that clinicians face in the course of treatment of brain tumors. The first objective in this thesis was to develop a method to discriminate between glioblastoma tumor recurrences and radiation injury using multiparametric characterization of the tissue incorporating conventional magnetic resonance imaging signal intensities and diffusion tensor imaging parameters. Our results show significant correlations in the RI that was missing in the tumor regions. These correlations may aid in differentiating between …

Has The Use Of Computers In Radiation Therapy Improved The Accuracy In Radiation Dose Delivery?, Jacob Van Dyk, Jerry J. Battista Dr.

Oncology Publications

Purpose: It is well recognized that computer technology has had a major impact on the practice of radiation oncology. This paper addresses the question as to how these computer advances have specifically impacted the accuracy of radiation dose delivery to the patient. Methods: A review was undertaken of all the key steps in the radiation treatment process ranging from machine calibration to patient treatment verification and irradiation. Using a semi-quantitative scale, each stage in the process was analysed from the point of view of gains in treatment accuracy. Results: Our critical review indicated that computerization related to digital medical imaging …

Measuring The Sixth Vital Sign: A Descriptive Analysis Of Distress In Individuals With Head And Neck Cancer And Their Caregivers, Catherine C. Bornbaum

Electronic Thesis and Dissertation Repository

Introduction: Distress has become so problematic in oncology that it has been recognized as the “sixth vital sign” implying that distress monitoring should occur as routinely as the monitoring of one’s temperature or blood pressure. The research reported herein investigated the impact of head and neck cancer on levels of distress, commonly reported problems, and perceptions of quality of life in individuals with head and neck cancer and their caregivers.

Method: Two distinct studies were conducted; the first explored the patient experience of distress and quality of life while the second assessed the caregiver experience of these same constructs. A …

The Impact Of Lateral Electron Disequilibrium On Stereotactic Body Radiation Therapy Of Lung Cancer, Brandon Disher

Electronic Thesis and Dissertation Repository

Stereotactic Body Radiation Therapy (SBRT) is an effective treatment option for patients with inoperable early-stage lung cancer. SBRT uses online image-guidance technology [e.g. cone-beam CT (CBCT)] to focus small-fields of high energy x-rays onto a tumour to deliver ablative levels of radiation dose (e.g. 54 Gy) in a few treatment fractions (e.g. 3). For the combination of these treatment parameters and a low density lung, lateral electron disequilibrium (LED) can potentially occur, reducing lung and tumour doses. The goal of this thesis was to determine the impact of LED on stereotactic body radiation therapy for lung cancer.

The effect of …

Body Talk I: Habituation To Bodily Changes After Breast Surgery In Women, Jenny Slatman

Future Directions in Feminist Phenomenology

No abstract provided.

Targeted Sirna Delivery Methods For Rnai-Based Therapies, Di Chen

Electronic Thesis and Dissertation Repository

RNAi has great potential in future therapeutics as it has the ability to regulating many disease-related genes. However, many barriers prevent practical applications. To overcome the barriers, the specific targeting, efficient delivery system, the validated gene and the potent siRNA sequence are all vital important. The studies throughout this thesis have been focued on examining the validation of three RNAi therapies for two different disease models: allergic contact dermatitis and melanoma. For allergic contact dermatitis, I developed and tested a novel topical delivery system for siRNAs targeting TNFα (siTNFα) and MyD88 siRNA (siMyD88). While siRNAs applied without the transdermal enhancer …

The Impact Of The Neuropeptide Y System On The Progression Of Breast Cancer, Philip J. Medeiros

Electronic Thesis and Dissertation Repository

Chronic stress is associated with elevated levels of sympathetic neurotransmitter release and immunosuppression. A growing body of evidence suggests that stress-related factors may contribute to the initiation, development and progression of breast cancer. Neuropeptide Y (NPY) has recently been determined as such a factor, however few investigations have addressed the functional effects of NPY on breast cells and tumors. Thus, the overall objective of this thesis was to elucidate the mechanisms by which NPY may contribute to the disease. Using the 4T1 murine breast cancer model, we began by first characterizing NPY receptor expression in cancer cells and tumors. Y1R, …

Targeted Intracellular Therapeutic Delivery Using Liposomes Formulated With Multifunctional Fast Proteins, Rae L. Nesbitt

Electronic Thesis and Dissertation Repository

Prostate cancer is the most common malignancy in North American men and there is no treatment currently available which offers a clear survival advantage to patients with prostate cancer. We studied liposomes formulated with the fusion-associated small transmembrane (FAST) protein, p14. In this study, we hypothesized that therapeutics delivered in molecular targeted fusogenic liposomes will increase intracellular delivery and specificity for prostate cancer. We demonstrated that liposomes formulated with p14-bombesin significantly increased the delivery of fluorescein isothiocyanate (FITC) into human prostate cancer (PC-3) cells compared to either standard liposomes or non-targeted fusogenic liposomes. Delivery of FITC to benign prostate hyperplasia …

Medical Physics Staffing For Radiation Oncology: A Decade Of Experience In Ontario, Canada., Jerry J. Battista Dr., Brenda G Clark, Michael S Patterson, Luc Beaulieu, Michael B Sharpe, L John Schreiner, Miller S Macpherson, Jacob Van Dyk

Oncology Publications

The January 2010 articles in The New York Times generated intense focus on patient safety in radiation treatment, with physics staffing identified frequently as a critical factor for consistent quality assurance. The purpose of this work is to review our experience with medical physics staffing, and to propose a transparent and flexible staffing algorithm for general use. Guided by documented times required per routine procedure, we have developed a robust algorithm to estimate physics staffing needs according to center-specific workload for medical physicists and associated support staff, in a manner we believe is adaptable to an evolving radiotherapy practice. We …

Strategies For Reducing The Impact Of Tumour Motion During Helical Tomotherapy, Bryan Kim

Electronic Thesis and Dissertation Repository

Tumour motion presents a significant limitation for effective radiotherapy of lung cancer, and more specifically for helical tomotherapy. The simultaneous and continuous movements of tomotherapy subsystems (gantry, couch, and binary multi-leaf collimator) can lead to inaccurate dose delivery, when combined with tumour motion. In this thesis, we have investigated the impact of tumour motion and strategies to reduce the resulting dose discrepancies for helical tomotherapy, through computer simulations and film measurements performed in a dynamic body phantom. Three distinctively different types of dose discrepancies have been isolated: dose rounding, dose rippling, and the intensity-modulated radiation therapy (IMRT) asynchronization effect. Each …

Metastatic Disease: Interactions Between Tumor Cells And Host Environment During Cancer Cell Spread, Jennifer M. Maclean

Electronic Thesis and Dissertation Repository

Tumor and metastasis formation are not cell autonomous phenomena, but rather an evolution of disease within and responding to the host environment. Metastatic spread from a primary tumor occurs as a result of a complex interplay between tumor cells and the host, wherein tumor cells must escape the primary tumor, enter the host vasculature, travel to and arrest in a distant tissue and survive and grow in that new organ. It is known that cells that progress through these stages must both escape and exploit host systems, yet the mechanisms used are not fully understood. Therefore, the goal of this …

From Isolated Tumour Cells To Overt Lymph Node Metastases: Biological And Imaging Studies On The Development Of Experimental Lymph Node Metastases, Michael M. Lizardo

Electronic Thesis and Dissertation Repository

Metastatic colonization and establishment of overt lymph node (LN) tumours indicates poor prognosis for cancer patients. However, the basic biology that influences the development of LN metastasis is poorly understood due to the lack of basic animal models. The following work provides a new lymph node experimental metastasis assay (LEMA) that permits the assessment of tumour cell fate after they arrest in draining LNs. In using this new model, we discovered that only 8% of the tumour cells that arrive in the LN are successful in forming overt tumours. This work also explored the use of imaging approaches to monitor …

Optimal Slice Thickness For Cone-Beam Ct With On-Board Imager., Kyt Seet, A Barghi, Slav Yartsev, Jacob Van Dyk

Oncology Publications

PURPOSE: To find the optimal slice thickness (Δτ) setting for patient registration with kilovoltage cone-beam CT (kVCBCT) on the Varian On Board Imager (OBI) system by investigating the relationship of slice thickness to automatic registration accuracy and contrast-to-noise ratio.

MATERIALS AND METHOD: Automatic registration was performed on kVCBCT studies of the head and pelvis of a RANDO anthropomorphic phantom. Images were reconstructed with 1.0 ≤ Δτ (mm) ≤ 5.0 at 1.0 mm increments. The phantoms were offset by a known amount, and the suggested shifts were compared to the known shifts by calculating the residual error. A uniform cylindrical phantom …

Schedule For Ct Image Guidance In Treating Prostate Cancer With Helical Tomotherapy., G Beldjoudi, S Yartsev, G Bauman, Jerry J. Battista Dr., Jacob Van Dyk

Oncology Publications

The aim of this study was to determine the effect of reducing the number of image guidance sessions and patient-specific target margins on the dose distribution in the treatment of prostate cancer with helical tomotherapy. 20 patients with prostate cancer who were treated with helical tomotherapy using daily megavoltage CT (MVCT) imaging before treatment served as the study population. The average geometric shifts applied for set-up corrections, as a result of co-registration of MVCT and planning kilovoltage CT studies over an increasing number of image guidance sessions, were determined. Simulation of the consequences of various imaging scenarios on the dose …

A Review Of Autoimmune Diseases Associated With Cancer, Patricia Tai, Edward Yu, Kurian Joseph, Thomas Miale

Oncology Publications

The focus of this review is on the relationships between autoimmune diseases and cancer from two closely related perspectives: 1.Those autoimmune diseases which are often associated with malignancies. 2.Those prevalent cancers which may increase the risks of developing autoimmune disorders. The review concludes with a brief discussion of some selected innovative approaches to cancer immunotherapy.

The Effects Of Field-Of-View And Patient Size On Ct Numbers From Cone-Beam Computed Tomography., Katrina Y T Seet, Arvand Barghi, Slav Yartsev, Jacob Van Dyk

Oncology Publications

Cone-beam computed tomography (CBCT) is used for patient alignment before treatment and is ideal for use in adaptive radiotherapy to account for tumor shrinkage, organ deformation and weight loss. However, CBCT images are prone to artifacts such as streaking and cupping effects, reducing image quality and CT number accuracy. Our goal was to determine the optimum combination of cone-beam imaging options to increase the accuracy of image CT numbers. Several phantoms with and without inserts of known relative electron densities were imaged using the Varian on-board imaging system. It was found that CT numbers are most influenced by the selection …

What Factors Predict Outcome At Relapse After Previous Esophagectomy And Adjuvant Therapy In High-Risk Esophageal Cancer?, Edward Yu, Patricia Tai, Richard Malthaner, Larry Stitt, George Rodrigues, Rashid Dar, Brian Yaremko, Jawaid Younus, Michael Sanatani, Mark Vincent, Brian Dingle, Dalilah Fortin, Richard Inculet

Oncology Presentations

Management of patients who have disease relapse after completion of surgery and adjuvant chemo-radiation (CRT) is controversial.

Some oncologists would advocate intensive therapeutic intervention due to promising experience on treatment for recurrence disease while others would recommend palliative support due to the concerns for poor patient outcome post disease recurrence.

In Addition, it is not clear if patient outcome is improved post adjuvant CRT when patients at risk have resection margin involvement and if time interval to recurrence can affect patient survival post relapse.

The present study was conducted to determine what factors will affect patient outcome at relapse after …