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1
Mairs, Robert J. "Targeted radiotherapy of cancer." Thesis, University of Glasgow, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248190.
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Radu, Calin. "Optimising Radiotherapy in Rectal Cancer Patients." Doctoral thesis, Uppsala universitet, Enheten för onkologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-172531.
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Rectal cancer is the eight most common cancer diagnosis in Sweden in both men and women, with almost 2000 new cases per year. Radiotherapy, which is an important treatment modality for rectal cancer, has evolved during the past decades. Diagnostic tools have also improved, allowing better staging and offering information used to make well-founded decisions in multidisciplinary team conferences. In a retrospective study (n=46) with locally advanced rectal cancer (LARC) patients, unfit for chemoradiotherapy, patients were treated with short-course radiotherapy. Delayed surgery was done when possible. Radical surgery was possible in 89% of the patients who underwent surgery (80%). Grade IV diarrhoea affected three elderly patients. Target radiation volume should be reduced in elderly or metastatic patients. In a prospective study (n=68) with LARC patients, magnetic resonance imaging (MRI) and 2-18F-fluoro-2-D-deoxyglucose (FDG) positron emission tomography (PET) were used to determine if FDG-PET could provide extra treatment information. Information from FDG-PET changed the stage of 10 patients. Delineation with FDG-PET generally resulted in smaller target volumes than MRI only. Seven of the most advanced LARC patients in the above cohort were used for a methodological study to determine if dose escalation to peripheral, non-resectable regions was feasible. Simultaneous integrated boost plans with photons and protons were evaluated. While toxicity was acceptable in five patients with both protons and photons, two patients with very large tumours had unacceptable risk for intestinal toxicity regardless of modality. In the interim analysis of the Stockholm III Trial (n=303, studying radiotherapy-fractionation and timing of surgery in relation to radiotherapy) compliance was acceptable and severe acute toxicity was infrequent, irrespective of fractionation. Short-course radiotherapy with immediate surgery tended to give more postoperative complications, but only if surgery was delayed more than 10 days after the start of radiotherapy. Quality-of-life in the Stockholm III Trial was studied before, during and shortly after treatment using the EORTC QLQ-C30 and CR38 questionnaires. Surgery accounted for more adverse effects than radiotherapy in all groups. Postoperatively, the poorest quality-of-life was seen in patients given short-course radiotherapy followed by immediate surgery. No postoperative differences were seen between the two groups with delayed surgery.
3
Martling, Anna. "Rectal cancer : staging, radiotherapy and surgery /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-461-5/.
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Langlands, Fiona Elizabeth. "Sensitivity to radiotherapy in breast cancer." Thesis, University of Leeds, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.582111.
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Radiotherapy (RT) is a component of treatment for breast cancer in more than 50% of cases. Patients are selected for RT on the basis of limited clinical and histopathological factors with no reference to the molecular phenotype of tumours. Breast cancer is a highly heterogeneous disease and some tumours are refractory to RT treatment. Selection of patients for RT using predictive markers may improve RT efficacy and cancer outcomes. The aims of the work described in this thesis were to identify and test potential predictive markers for RT in cancer treatment. I examined whether the classic histopathological breast cancer subtypes or the levels of expression of five molecular markers, 26S proteasome, GRP78, HJURP, IGFlR and PARPl, would provide predictive insights into response to RT in the context of both cultured breast cancer cell lines, and archival patient samples supported by clinical follow up. Clonogenic survival assays revealed that cell lines representative of luminal or basal breast cancers did not display subtype specific responses to RT. Similarly, expression levels of 26S proteasome, GRP78, HJURP, IGFlR and PARPl did. not correlate with specific responses to RT in cell lines. In breast cancer patients who underwent RT high expression of 26S proteasome was significantly associated with increased rates of local recurrence. High expression of HJURP was associated with reduced rates of local recurrence, as was high expression of PARPl. Importantly, these associations were not found in patients who were treated without RT, suggesting that these markers provide predictive in sights into RT response, rather than prognostic insights into the likelihood of local recurrence overall. Finally, high expression of 26S proteasome was also found to be associated with increased rates of local recurrence in bladder cancer patients, suggesting that this marker may have predictive value for RT in a range of cancer settings.
5
Taylor, Carolyn W. "Breast cancer radiotherapy and heart disease." Thesis, University of Oxford, 2008. http://ora.ox.ac.uk/objects/uuid:c9dda3ca-8cb3-4a38-938d-0b75b4f6471d.
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Introduction: Some past breast cancer radiotherapy regimens led to an increased risk of death from heart disease. Although heart dose from breast cancer radiotherapy has generally reduced over the past few decades, there may still be some cardiac risk. Estimation of future risk for women irradiated today requires both measurement of their cardiac dose and dose-response relationships, which depend on cardiac dosimetry of past regimens, in conjunction with long-term follow-up data. Methods: Virtual simulation and computed tomography 3-dimensional treatment planning on a representative patient were used to estimate mean heart and coronary artery doses for women irradiated since 1950 in 71 randomised trials in the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) overview. Patient-to-patient variability in cardiac dose was assessed. Heart and coronary artery doses were also calculated for breast cancer radiotherapy regimens used since the 1950s in Sweden. Cardiac doses from contemporary (year 2006) radiotherapy were assessed for 55 patients who received tangential breast cancer irradiation at a large UK radiotherapy centre. The maximum heart distance (i.e. the maximum distance between the anterior cardiac contour and the posterior tangential field edges) was measured for the left-sided patients, and its value as a predictor of cardiac doses assessed. Results: Mean heart dose for women irradiated in the EBCTCG trials varied from <1 to 18 Gray, and mean coronary artery dose from <1 to 57 Gray. Patient-to-patient variability was moderate. Mean heart dose for women irradiated in Sweden since the 1950s varied from <1 to 24 Gray, and mean coronary artery dose from <1 to 46 Gray. Heart dose from tangential irradiation has reduced over the past four decades. However, mean heart dose for left-sided patients irradiated in 2006 was 2 Gray and around half of them still received >20 Gray to parts of the heart and left anterior descending coronary artery. For these patients, maximum heart distance was a reliable predictor of cardiac doses. For the other patients, mean heart dose varied little and was usually less than 2 Gray. Conclusions: Cardiac doses from breast cancer radiotherapy can be estimated reliably and are now available for use in deriving dose-response relationships in the EBCTCG data and in a Scandinavian case-control study. Cardiac dose has reduced over the past four decades. Therefore the cardiac risk is also likely to have reduced. Nevertheless, for some patients, parts of the heart still receive >20 Gray in the year 2006.
6
吳曉靑 and Xiaoqing Wu. "Post-radiotherapy cervical metastasis in nasopharyngeal carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1999. http://hub.hku.hk/bib/B31222018.
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Cheng, Kun. "Deformable models for adaptive radiotherapy planning." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/22893.
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Radiotherapy is the most widely used treatment for cancer, with 4 out of 10 cancer patients receiving radiotherapy as part of their treatment. The delineation of gross tumour volume (GTV) is crucial in the treatment of radiotherapy. An automatic contouring system would be beneficial in radiotherapy planning in order to generate objective, accurate and reproducible GTV contours. Image guided radiotherapy (IGRT) acquires patient images just before treatment delivery to allow any necessary positional correction. Consequently, real-time contouring system provides an opportunity to adopt radiotherapy on the treatment day. In this thesis, freely deformable models (FDM) and shape constrained deformable models (SCDMs) were used to automatically delineate the GTV for brain cancer and prostate cancer. Level set method (LSM) is a typical FDM which was used to contour glioma on brain MRI. A series of low level image segmentation methodologies are cascaded to form a case-wise fully automatic initialisation pipeline for the level set function. Dice similarity coefficients (DSCs) were used to evaluate the contours. Results shown a good agreement between clinical contours and LSM contours, in 93% of cases the DSCs was found to be between 60% and 80%. The second significant contribution is a novel development to the active shape model (ASM), a profile feature was selected from pre-computed texture features by minimising the Mahalanobis distance (MD) to obtain the most distinct feature for each landmark, instead of conventional image intensity. A new group-wise registration scheme was applied to solve the correspondence definition within the training data. This ASM model was used to delineated prostate GTV on CT. DSCs for this case was found between 0.75 and 0.91 with the mean DSC 0.81. The last contribution is a fully automatic active appearance model (AAM) which captures image appearance near the GTV boundary. The image appearance of inner GTV was discarded to spare the potential disruption caused by brachytherapy seeds or gold markers. This model outperforms conventional AAM at the prostate base and apex region by involving surround organs. The overall mean DSC for this case is 0.85.
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Taylor, Alexandra. "Intensity-modulated radiotherapy for cervical cancer : optimising target volume definition and radiotherapy delivery." Thesis, University of London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.510901.
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Murphy, Caroline Claire Scanlon. "A history of radiotherapy to 1950 : cancer and radiotherapy in Britain 1850-1950." Thesis, University of Manchester, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278710.
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Riekki, R. (Riitta). "Late dermal effects of breast cancer radiotherapy." Doctoral thesis, University of Oulu, 2006. http://urn.fi/urn:isbn:9514282760.
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Abstract
Radiotherapy is used in the treatment of breast cancer in order to reduce local recurrence rate. However, radiation is known to cause both acute and delayed side-effects on normal tissues. A common late complication of radiotherapy is fibrosis of skin and other organs. Fibrosis has been described as excessive accumulation of extracellular matrix components, especially collagens.
Collagens are a group of extracellular matrix proteins that provide connective tissues with tensile strength. Type I and III collagens are the major structural proteins in skin. Alterations in collagen synthesis occur in various pathological conditions, during ageing and in association with diverse medical therapies. Collagens are degraded by matrix metalloproteinase enzymes (MMPs). The activity of MMPs is restrained by their specific tissue inhibitors (TIMPs).
Elastic fibres constitute about 2–4% of skin dry weight. Despite their low quantity, elastic fibres are responsible for the resilient and elastic properties of skin. Dermal elastic fibres may be affected by intrinsic ageing, by extrinsic reasons such as photodamage and in several connective tissue diseases.
The effect of radiotherapy on human skin type I and III collagen synthesis was investigated in a group of women who had been treated for breast cancer surgically and with radiotherapy. The levels of MMP-9, MMP-2/TIMP-2 complex, TIMP-1 and TIMP-2 in irradiated skin were also analysed. The effect of radiotherapy on elastic fibres was analysed using skin samples. The physio-mechanical properties of radiotherapy-treated skin were studied using ultrasound and elastometer devices, and compared with those of non-treated skin.
In addition, skin samples were stained for haematoxylin-eosin, tenascin and mast cells. Factor VIII immunostaining was performed to visualize dermal blood vessels. Wound regeneration in irradiated skin was also studied using suction blister as a model.
The synthesis of type I and III collagens was markedly increased as a result of radiotherapy. An increased amount of cross-linked type I collagen was detected in irradiated skin, and collagen turnover was also increased in irradiated skin. No difference in the amount or structure of the elastic fibres could be found between radiotherapy-treated and non-treated skin. A slight increase of skin thickness and stiffness was found in irradiated skin compared to non-treated skin. Increased tenascin expression was found in irradiated skin. The number of dermal blood vessels visualized by FVIII immunostaining was slightly higher in irradiated than in control skin. The amount of mast cells positive for tryptase, Kit receptor and chymase was increased in the upper dermis of irradiated skin. No difference in epidermal regeneration was found between irradiated and non-treated skin.
The results of this study suggest that alteration of collagen metabolism contributes to dermal side effects of therapeutic irradiation.
11
Belderbos, Josepha Sophia Antonia. "Radiotherapy in lung cancer: a moving field." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2007. http://dare.uva.nl/document/45315.
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Burnet, Neil Gunn. "The relationship between cellular radiation sensitivity and normal tissue response to radiotherapy : prospects for individualising radiotherapy prescriptions." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357208.
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Ramroth, Johanna Rankin. "Radiotherapy dose-fractionations and outcomes in cancer patients." Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:8c5a99de-7d8c-4b19-9a91-e6cf4efa7bd2.
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Radiotherapy cures many cancers, but the optimum total doses and fractionations used to treat different cancer types remain uncertain. While conventional fractionation (≈2 Gy per fraction) is common in many countries, UK practice has been highly variable. This thesis compared different curative-intent radiotherapy dose-fractionations used in non-small cell lung and breast cancer. These two cancers together make up over a quarter of UK cancer incidence and mortality, and radiotherapy can increase cure rates of both cancers. Two studies were conducted: (A) A meta-analysis of randomised radiotherapy trials in non-small cell lung cancer and (B) A cohort study of non-small cell lung and breast cancer radiotherapy in the Thames Valley. For the meta-analysis, a systematic search was conducted. Eligible studies were randomised comparisons of two or more radiotherapy regimens. Median survival ratios were calculated for each comparison and pooled. 3,795 patients in 25 randomised comparisons of radiotherapy dose were studied. When radiotherapy was given alone, the higher dose within-trial resulted in increased survival (median survival ratio 1.13, 95% confidence interval 1.04-1.22). When radiotherapy was given with concurrent chemotherapy, the higher dose within-trial resulted in decreased survival (median survival ratio 0.83, 95% confidence interval 0.71-0.97). For the cohort study, multiple Public Health England data sources were combined to obtain information on radiotherapy, patient characteristics, and outcomes. Multivariable Cox regressions were conducted separately by cancer site. 324 non-small cell lung, 8,879 invasive breast, and 477 ductal carcinoma in situ patients were studied. In analyses of both non-small cell lung and invasive breast cancer, increasing radiotherapy dose was associated with improved survival in some treatment centres, while in other centres the opposite was true. These opposite trends by treatment centre were unlikely to be explained by chance, and they suggest that differences in patient selection were driving results. There were insufficient events among ductal carcinoma in situ patients to assess associations. Findings from the meta-analysis support consideration of further radiotherapy dose escalation trials, making use of modern methods to reduce toxicity. Findings from the cohort study suggest that it is not possible to use observational studies to examine causal effects of radiotherapy dose-fractionation. This thesis therefore shows the continued importance of conducting sufficiently large randomised trials to ascertain optimal dose-fractionation in radiotherapy.
14
Gozbasi, Halil Ozan. "Optimization approaches for planning external beam radiotherapy." Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/34726.
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External beam radiotherapy is delivered from outside the body aimed at cancer cells to damage their DNA making them unable to divide and reproduce. The beams travel through the body and may damage nearby healthy tissues unless carefully planned. Therefore, the goal of treatment plan optimization is to find the best system configuration to deliver sufficient dose to target structures while avoiding damage to healthy tissues. This thesis investigates optimization approaches for two external beam radiation therapy techniques: Intensity-Modulated Radiation Therapy (IMRT) and Volumetric-Modulated Arc Therapy (VMAT). We develop an automated treatment planning technology for IMRT which generates several high-quality treatment plans satisfying the provided requirements in a single invocation and without human guidance. Our approach is based on an existing linear programming-based fluence map optimization model that approximates dose-volume requirements using conditional value-at-risk (C-VaR) constraints. We show how the parameters of the C-VaR constraints can be used to control various metrics of treatment plan quality. A novel bi-criteria scoring based beam selection algorithm is developed which finds the best beam configuration at least ten times faster for real-life brain, prostate, and head and neck cases as compared to an exact mixed integer programming model. Patient anatomy changes due to breathing during the treatment of lung cancer need to be considered in treatment planning. To date, a single phase of the breathing cycle is typically selected for treatment and radiation is shut-off in other phases. We investigate optimization technology that finds optimal fluence maps for each phase of the breathing cycle by considering the overall dose delivered to a patient using image registration algorithms to track target structures and organs at risk. Because the optimization exploits the opportunities provided in each phase, better treatment plans are obtained. The improvements are shown on a real-life lung case. VMAT is a recent radiation treatment technology which has the potential to provide treatments in less time compared to other delivery techniques. This enhances patient comfort and allows for the treatment of more patients. We build a large-scale mixed-integer programming model for VMAT treatment plan optimization. The solution of this model is computationally prohibitive. Therefore, we develop an iterative MIP-based heuristic algorithm which solves the model multiple times on a reduced set of decision variables. We introduce valid inequalities that decrease solution times, and, more importantly, that identify higher quality integer solutions within specified time limits. Computational studies on a spinal tumor and a prostate tumor case produce clinically acceptable results.
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Nilsson, Greger. "Cardiovascular Side Effects of Radiotherapy in Breast Cancer." Doctoral thesis, Uppsala universitet, Enheten för onkologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-179811.
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The aim of the thesis was to study cardiovascular side effects of radiotherapy (RT) in breast cancer (BC). In a study base of 25,171 women with BC diagnosed 1970-2000, we found a statistically significant 12% increase of stroke, compared to the stroke incidence in the background population. A case-control study of 282 cases with BC followed by a stroke and 1:1 matched controls with BC but not stroke was performed. In women irradiated to internal mammary chain (IMC) and supraclavicular lymph nodes (SCL) vs. a pooled group of women not irradiated or irradiated to targets other than IMC and SCL, a statistically significant increase of stroke with an odds ratio of 1.8 was observed. There were no associations between BC laterality, targets of RT, and hemisphere location of stroke. The radiation targets IMC and SCL, showed a statistically significant trend for an increased risk of stroke with daily fraction dose. A study of 199 patients with BC, examined by coronary angiography, detected a four- to seven-fold increase of high grade coronary artery stenosis in mid and distal left anterior descending artery (LAD), including distal diagonal branch, when comparing women with irradiated left-sided BC to those with right-sided. An increase of clinically significant coronary artery stenosis was found in pre-specified hotspot areas for radiation among women irradiated to the left breast/chest wall or to the IMC. Thus, the coronary arteries should be regarded as organs at risk in RT of BC. In a study of 15 BC patients treated with 3D conformal RT, a marked difference in dose distribution in mid and distal LAD between left- and right-sided BC was demonstrated. Irradiated right-sided BC mainly received low doses of scattered and transmitted radiation to the coronary arteries. On the contrary, tangential RT to the left breast without regional lymph node irradiation yielded coronary artery max doses of approximately 50 Gray to distal LAD, probably not safe concerning late radiation vascular effects. To conclude, we found cardiovascular side effects in women irradiated for BC, resulting in stroke and coronary artery disease, and showed an association between the targets for RT and the anatomical location of these vascular events.
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Pollack, Johan. "Preoperative staging and radiotherapy in rectal cancer surgery /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-742-1/.
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Henson, Katherine Elizabeth. "Heart disease and lung cancer risks after radiotherapy." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:119bdbd9-00a7-484d-96f0-6b1e59dab696.
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Radiotherapy has been shown to increase the subsequent risk of heart disease among survivors of breast cancer, but little is known about factors, other than the dose of radiation delivered to the heart, which determine the magnitude of the risk. In addition, survivors of teenage and young adult cancer are internationally acknowledged as an understudied population, and limited information is available on their late health risks. This thesis sought to utilise the largest observational datasets available to date for these populations: the Collaborative Group on Observational Studies of Breast Cancer Survivors and the Teenage and Young Adult Cancer Survivor Study. These were used to firstly characterise the radiation-related risks of heart disease and lung cancer, and secondly to provide an overview of the long-term risk of heart disease for the entire spectrum of cancers diagnosed in teenagers and young adults aged 15 to 39. Initially, a methodology study and systematic review demonstrated that selection effects and other biases can be very problematic during analyses of observational cohorts, particularly when using a radiotherapy comparison. However, in the case of heart disease and lung cancer, one can take advantage of the breast being a paired organ and use a laterality comparison, particularly when laterality played little effect in treatment selection. This comparison was used throughout the analyses of breast cancer patients. This thesis demonstrated that adjuvant radiotherapy for breast cancer significantly increased the risk of heart disease among women with left-sided breast cancer and those patients with ipsilateral lung cancer. Interestingly, younger women were at the highest risk of heart disease, and a progressive proportional decrease in risk with increasing age at diagnosis was found, which has not been shown before. It also suggested that radiotherapy and chemotherapy combined may further increase the risk of heart disease among breast cancer patients. Survivors of teenage and young adult cancer, particularly Hodgkin lymphoma, were at a significantly raised cardiac mortality risk compared to the matched general population. The findings of this thesis provide evidence to support continued follow-up for cancer patients, as survivors were found to be at a substantial risk into the second or third decade after treatment. It has permitted the detection of groups of individuals at particularly increased risks, for example younger patients and survivors of Hodgkin lymphoma diagnosed in teenagers and young adults, for whom closer monitoring for late effects or measures to reduce the risk, such as adaptations to treatment, may be appropriate. Finally, evidence was also presented to support the development of clinical follow-up guidelines specifically for survivors of teenage and young adult cancer.
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Beasley, William. "Optimising adaptive radiotherapy for head and neck cancer." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/optimising-adaptive-radiotherapy-for-head-and-neck-cancer(96e831b0-751a-454d-8a6d-4dd490b6a88f).html.
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Anatomic changes occur throughout head and neck radiotherapy, and a new treatment plan is often required to mitigate the resulting changes in delivered dose to key structures. This process is known as adaptive radiotherapy (ART), and can be labour-intensive. The aim of this thesis is to optimise ART, addressing some of the technical and clinical challenges facing its routine clinical implementation. Optimising the frequency and timing of adaptive replanning is important, and it has been shown here that intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) are equally robust to weight loss during head and neck radiotherapy. Plan adaptation strategies that have previously been developed for IMRT are therefore applicable to VMAT.Contour propagation is an important component of ART, and it is essential to ensure that propagated contours are accurate. A method for assessing the suitability of a metric for measuring automatic segmentation accuracy has been developed and applied to the head and neck. For the parotids and larynx, metrics based on surface agreement were better than the commonly used Dice similarity coefficient. By establishing a consensus on which metrics should be used to assess segmentation accuracy, comparison of different algorithms is more objective and should lead to more accurate automatic segmentation. A novel method of assessing contour propagation accuracy on a patient-specific basis has also been developed. This was demonstrated on a cohort of head and neck patients and shows potential as a tool for identifying propagated contours that are subject to a high degree of uncertainty. This is a novel tool that will increase the efficiency of automatic segmentation and, therefore, ART.Optimum ART requires consideration of different radiotherapy-related toxicities, and image-based data mining is a powerful technique for spatially localising dose-response relationships. Correction for multiple comparisons through permutation testing is essential, but has so far only been applied to categorical data. A novel method has been developed for performing permutation testing and image-based data mining with a continuously variable clinical endpoint. Application to trismus for head and neck radiotherapy identified a region with a dose-response relationship in the ipsilateral masseter. Sparing this structure during radiotherapy should reduce the severity of radiation-induced trismus. ART mitigates the dosimetric effects of anatomic changes, and this thesis has addressed technical and clinical challenges that have so far limited its clinical implementation. Detailed knowledge of dose-response relationships will enable selection of patients for ART based on potential clinical benefit, and accurate contour propagation will make ART more efficient, facilitating its routine implementation.
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Parker, Michelle. "Mitochondrial dynamics in the radiation response of cancer cells." Doctoral thesis, University of Cape Town, 2017. http://hdl.handle.net/11427/26948.
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Mitochondria are involved in the regulation of key cellular processes that determine the response of cells to damage. Mitochondrial fission and fusion are associated with cell cycle regulation, apoptosis, cellular bioenergetics and redox status, which contribute to cellular homeostasis and damage response. The study aimed to describe and correlate cancer cell mitochondrial features and inherent radiosensitivity, and to determine the effect of modulation of mitochondrial dynamics on radiation response using a fission inhibitor, Mdivi-1. Methods: Mitochondrial status in a number of cancer cell lines was characterised by assessment of mitochondrial morphology, respiration and membrane potential using MitoTracker® Red staining, respirometry and JC-1 ratiometric staining, respectively. Correlations with radiation sensitivity were performed. Radiation- and Mdivi-1-induced changes in mitochondrial morphology were also examined. Responses to various schedules of radiation and Mdivi-1 treatment were assessed using clonogenic survival. Microscopy was used to quantify apoptosis, micronuclei and mitotic features, while cell cycle dynamics were analysed using flow cytometry. Results: Notably, modulation of mitochondrial fission using Mdivi-1 significantly increased radiation response in A549 cancer cells. Mdivi-1 reduced fragmentation, increased membrane potential and induced cytotoxicity, cytogenetic damage, apoptosis and G2/M cell cycle arrest. However, with the exception of survival, sub-additive responses were consistently observed when Mdivi-1 was combined with radiation. Sub-lethal damage repair was unaffected by Mdivi-1. Characterisation of cancer cell lines revealed inherent diversity in radiation response and mitochondrial morphology, membrane potential and respiration, and several correlations were identified. Discussion and conclusions: Inhibition of mitochondrial fission was shown for the first time to enhance radiosensitivity in cancer cells, and to induce cytotoxicity. Mitochondrial modulators may therefore have therapeutic application. However, the sub-additive responses observed with Mdivi-1-radiation interactions suggest that optimisation of treatment scheduling may be important. The Mdivi-1-induced mitotic arrest may, in part, be responsible for the observed radiosensitisation, as cells accumulate in a radiosensitive cell cycle phase. In addition, the finding that Mdivi-1 treatment induced micronuclei suggested that the radiosensitisation may result from the interaction of cytogenetic damage induced by each agent. Overall, mitochondrial dynamics appears to significantly influence radiation response.
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Cheng, Chi-yuen Harry, and 鄭致遠. "Image-guided adaptive radiotherapy for nasopharyngeal carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47164116.
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Nasopharyngeal carcinoma (NPC) is an endemic malignant disease in
Southern China. Intensity-modulated radiotherapy (IMRT) has been employed as a standard treatment for NPC because it delivers highly conformal dose
distribution to target volumes and spares organs at risk (OARs). The success of radiotherapy depends on the accurate delivery of the planned doses throughout the treatment. This can be achieved with the help of advanced image-guided adaptive radiotherapy (IGART) such as kilovoltage (kV) cone beam computed tomography (CBCT) which can reduce the geometric setup uncertainty, monitor the intra-course anatomic and dosimetric changes and adjust the treatment plan.
The aim of this thesis is to study the role of repeat imaging for NPC and the radiation dose from CBCT to patients. The objectives of this thesis are to evaluate the volumetric and dosimetric changes during a course of IMRT for loco-regionally advanced NPC patients with the contribution of repeat computed tomography (CT) and magnetic resonance imaging (MRI) scans; to quantify the absorbed dose, effective dose and the estimation of the additional risk of inducing fatal cancers from CBCT for NPC patients undergoing IMRT; and to compare the image quality of different head protocols.
Nineteen loco-regionally advanced NPC patients treated with IMRT were recruited prospectively. Repeat CT and MRI were acquired at 30 and 50 Gy
intervals. Recontouring of target volumes and OARs was based on the fused CT-MRI images. Hybrid plans with recontouring were generated. The volumetric and dosimetric changes were assessed by comparing the hybrid plans with the original plan. There was volume reduction of target volumes and parotid glands over the course of IMRT. Relative to the original plan, the hybrid plans demonstrated significantly higher dose to the target volumes with greater dose inhomogeneity, higher maximum doses to the spinal cord and brainstem, and higher medium doses to the parotid glands.
The image quality and dosimetry on the Varian CBCT system between software Versions 1.4.13 (“new” protocol) and 1.4.11 (“old” protocol) were studied. A calibrated Farmer-type ionization chamber and a standard cylindrical Perspex CT dosimetry head phantom were used to measure the weighted CBCT dose index (CBCTDIw) of the Varian CBCT system. The absorbed dose of different organs was measured in a female anthropomorphic phantom with thermoluminescent dosimeters (TLD) and the total effective dose was estimated according to ICRP Publication 103. The dosimetry and image quality were studied for head-and-neck region and comparison was made between the new and old protocols. The values of the CBCTDIw, absorbed dose, effective dose of the new head protocol were much lower than the old head protocol in each imaging group. The additional fatal cancer risk from daily CBCT might be up to 1.6%. In conclusion, replanning with repeat imaging at 30 Gy is essential to keep a satisfactory dose to the target volumes and avoid overdosing the OARs for NPC patients. The new Varian CBCT provides volumetric information for image guidance with acceptable image quality and lower radiation dose. This CBCT gives a better standard for NPC patient daily setup verification.<br>published_or_final_version<br>Clinical Oncology<br>Doctoral<br>Doctor of Philosophy
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Wu, Xiaoqing. "Post-radiotherapy cervical metastasis in nasopharyngeal carcinoma /." Hong Kong : University of Hong Kong, 1999. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20843252.
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Greer, Peter Brian. "A dual assembly multileaf collimator for radiotherapy." Title page, table of contents and abstract only, 2000. http://web4.library.adelaide.edu.au/theses/09PH/09phg81659.pdf.
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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.
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韋霖 and William I. Wei. "Surgery for post-radiotherapy cervical metastasis in nasopharyngeal carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1991. http://hub.hku.hk/bib/B31979543.
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Montgomery, Dean. "Improving radiotherapy using image analysis and machine learning." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/23554.
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With ever increasing advancements in imaging, there is an increasing abundance of images being acquired in the clinical environment. However, this increase in information can be a burden as well as a blessing as it may require significant amounts of time to interpret the information contained in these images. Computer assisted evaluation is one way in which better use could be made of these images. This thesis presents the combination of texture analysis of images acquired during the treatment of cancer with machine learning in order to improve radiotherapy. The first application is to the prediction of radiation induced pneumonitis. In 13- 37% of cases, lung cancer patients treated with radiotherapy develop radiation induced lung disease, such as radiation induced pneumonitis. Three dimensional texture analysis, combined with patient-specific clinical parameters, were used to compute unique features. On radiotherapy planning CT data of 57 patients, (14 symptomatic, 43 asymptomatic), a Support Vector Machine (SVM) obtained an area under the receiver operator curve (AUROC) of 0.873 with sensitivity, specificity and accuracy of 92%, 72% and 87% respectively. Furthermore, it was demonstrated that a Decision Tree classifier was capable of a similar level of performance using sub-regions of the lung volume. The second application is related to prostate cancer identification. T2 MRI scans are used in the diagnosis of prostate cancer and in the identification of the primary cancer within the prostate gland. The manual identification of the cancer relies on the assessment of multiple scans and the integration of clinical information by a clinician. This requires considerable experience and time. As MRI becomes more integrated within the radiotherapy work flow and as adaptive radiotherapy (where the treatment plan is modified based on multi-modality image information acquired during or between RT fractions) develops it is timely to develop automatic segmentation techniques for reliably identifying cancerous regions. In this work a number of texture features were coupled with a supervised learning model for the automatic segmentation of the main cancerous focus in the prostate - the focal lesion. A mean AUROC of 0.713 was demonstrated with 10-fold stratified cross validation strategy on an aggregate data set. On a leave one case out basis a mean AUROC of 0.60 was achieved which resulted in a mean DICE coefficient of 0.710. These results showed that is was possible to delineate the focal lesion in the majority (11) of the 14 cases used in the study.
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Pande, Maneesha. "Development of targeted / site - specific drug - delivery systems for cancer." Thesis, IIT Delhi, 2019. http://eprint.iitd.ac.in:80//handle/2074/8110.
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Bosmans, Geert. "CT-PET imaging of lung cancer patients for radiotherapy." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Universiteit Maastricht [host], 2007. http://arno.unimaas.nl/show.cgi?fid=9450.
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Muirhead, Rebecca. "The optimization of image guided radiotherapy in lung cancer." Thesis, University of Glasgow, 2011. http://theses.gla.ac.uk/2711/.
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The hypothesis of this work was whether IGRT could be safely implemented for clinical use in a busy oncology centre. I aimed to study a number of questions that remain unresolved in the current literature regarding safe and optimised implementation of IGRT techniques. The first study undertaken was the calculation of a local set up margin using two widely recognised margin recipes. This involved the assessment and analysis of multiple images belonging to 100 patients. This allowed progression onto the next project which was assessment of the optimal safe method of delineation of 4DCT. The most efficient method was compared to gold standard. At this point a different aspect of the radiation process was assessed, namely verification. A feasibility study of a simple, efficient form of imaging for use in review of a particular error was performed. This also involved the use of a novel tool which required independent assessment. This progressed into a further study of a larger number of patients using this tool and the images assessed previously to verify a novel form of radiation delivery. Lastly a planning study was performed to quantify the clinical benefit of another delivery system. This involved the delineation and planning of a large number of radical lung patients with standard radiation treatment and the novel radiation treatment and an assessment of the potential clinical benefits. The work presented in this thesis has answered some specific questions in IGRT in lung cancer, and contributed both locally and in the wider lung cancer community to increasing the use of IGRT in lung cancer.
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Eminowicz, G. K. D. "Standardisation and optimisation of radical radiotherapy for cervical cancer." Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1513290/.
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Cervical cancer is a significant worldwide health burden despite primary and secondary prevention measures in developed countries. Survival rates for locally advanced cervical cancers treated with radical chemoradiation (FIGO stage IB2 to IVA) ranges from 10 to 85% at 5 years. A significant proportion of patients relapse within the pelvis and therefore the quality and accuracy of radiotherapy delivery is paramount. This thesis aims to review the extent of potential uncertainties within cervical cancer radiotherapy with the aim of developing and assessing methods to optimise and standardise those uncertainties. To date, the INTERLACE trial radiotherapy quality assurance (RTQA) programme has been completed by over half of United Kingdom (UK) centres treating cervical cancer. Using these RTQA test cases, I analysed one of largest known uncertainties in radiotherapy planning; target volume delineation. Having quantified the variation in comparison to a gold standard I investigated the dosimetric impact of the observed variation. I also produced a step-by-step pictorial delineation atlas, having reviewed all available published guidance, and assessed its impact on delineation variation. Daily variation in pelvic organ position is the second uncertainty investigated within this thesis. By retrospectively reviewing computed tomography (CT) imaging during chemoradiation for cervical cancer I analysed the variation of bladder and bowel filling and its relationship with target volume position and coverage. The movements that I measured allowed me to calculate margins necessary to maintain acceptable coverage. However, by understanding the variation observed I propose methods of standardisation that can be applied in UK clinical practice without the need to increase margin size. I also estimated the dosimetric impact of this variation and the subsequent potential dosimetric gain of the standardisation methods.
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Evert, Jasmine. "Molecular studies of radiotherapy and chemotherapy in colorectal cancer." Doctoral thesis, Örebro universitet, Institutionen för hälsovetenskap och medicin, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-43635.
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Coles, Charlotte E. "Development of three-dimensional radiotherapy techniques in breast cancer." Thesis, University of Leicester, 2005. http://hdl.handle.net/2381/29491.
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Radiotherapy following conservation surgery decreases local relapse and death from breast cancer. Currently, the challenge is to minimise the morbidity caused by this treatment without losing efficacy. Despite many advances in radiation techniques in other sites of the body, the majority of breast cancer patients are still planned and treated using 2-dimensional simple radiotherapy techniques. In addition, breast irradiation currently consumes 30% of the UK's radiotherapy workload. Therefore, any change to more complex treatment should be of proven benefit. The primary objective of this research is to develop and evaluate novel radiotherapy techniques to decrease irradiation of normal structures and improve localisation of the tumour bed. I have developed a forward-planned intensity modulated (IMRT) breast radiotherapy technique, which has shown improved dosimetry results compared to standard breast radiotherapy. Subsequently, I have developed and implemented a phase III randomised controlled breast IMRT trial. This National Cancer Research Network adopted trial will answer an important question regarding the clinical benefit of breast IMRT. It will provide DNA samples linked with high quality clinical outcome data, for a national translational radiogenomics study investigating variation in normal tissue toxicity. Thus, patients with significant late normal tissue side effects despite good dose homogeneity will provide the best model for finding differences due to underlying genetics. I evaluated a novel technique using high definition free-hand 3-dimensional (3D) ultrasound in a phantom study, and the results suggested that this is an accurate and reproducible method for tumour bed localisation. I then compared recognised methods of tumour bed localisation with the 3D ultrasound method in a clinical study. The 3D ultrasound technique appeared to accurately represent the shape and spatial position of the tumour cavity. This tumour bed localisation research facilitated protocol development of a proposed national breast radiotherapy trial investigating IMRT and partial breast irradiation.
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朱慧玲 and Wai-ling Chu. "A clinical guideline to minimise radiation-induced dermatitis in womenwith breast cancer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40720718.
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Baustert, Isabelle Catherine. "Quantitative MR imaging in planning and assessing novel cancer treatments." Thesis, Institute of Cancer Research (University Of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248446.
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Foo, Kerwyn Yi Min. "Methodological uncertainties in radiotherapy dose-effect analysis." Thesis, University of Sydney, 2020. https://hdl.handle.net/2123/24421.
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Cancer and normal tissues in patient populations exhibit variability in biological response to the same dose of radiation. Sources of this variability include:
• Inherent biological factors of patient, tumour or tissue
• Metrics to measure, classify or declare biological outcomes
• Volumetric (prescription of target or avoidance regions)
• Dosimetric and delivery
Dosimetric and delivery variation is easily measured and has relatively little impact on variation of outcome in modelling studies. Volumetric variation contributes greatly to uncertainty, dependent on human judgement by oncologists. However, analysis methodology is generally overlooked as a source of variation in reported dose-effect results and is the subject of investigation in this thesis.
Dosimetric and clinical data from clinical trials and prospective cohort studies have been used to illustrate the contribution of analysis methodology to variation in dose-effect relationships using evidence from prostate cancer radiation therapy. The primary data source is the Trans-Tasman Radiation Oncology Group clinical trial 03.04 “RADAR”, which investigated dose escalation in external beam radiotherapy for prostate cancer.
Systematic review of the medical physics literature shows that prostate cancer radiotherapy toxicity reporting does not fully account for fractionation, which biases and causes unreported variation in dose-effect results.
The toxicity-dose-volume-effect relationship is shown to depend on the anatomical subsite delineated and the type/grade of toxicity outcome chosen. Multivariate regression of multiple dose factors is not reliable due to multicollinearity of these factors.
Heterogeneity in method of analysis is an important and overlooked component of variability in reported results of dose effect relationships in radiotherapy studies. Harmonisation of analysis or correction for this heterogeneity will reduce uncertainties to allow better modelling of biological effects in the molecular oncology era.
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Tung, Pui-lam, and 董沛霖. "Randomized study on therapeutic gain by changing the chemo-radiotherapy from concurrent-adjuvant to induction-concurrentsequence, and the radiotherapy from conventional to acceleratedfractionation for advanced nasopharyngeal carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43958497.
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Smit, Kathleen Ann. "In vitro prediction of inherent cellular radiosensitivity." Thesis, Cape Peninsula University of Technology, 2005. http://hdl.handle.net/20.500.11838/1492.
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Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2005<br>The principal objective in irradiating tumours is to permanently inhibit their
reproductive ability. More than half of all malignancies are primarily treated
with radiation but tumours of different histologies differ greatly in response to
radiotherapy as well as individual patients displaying great variability in
response to treatment. The need for reliable assays predicting tumour and
normal tissue response to radiation is therefore a prime objective of clinical
oncology. The requirement of such a test would be that it would relate to
clinical outcome Le. the possibility of recurrence of disease or of tumour
control as well as indicating whether the treatment should be administered
more aggressively or not. These are important factors that, if known, could be
used as part of the treatment planning in radiotherapy and selection of best
therapy modality.
The colony forming c1onogenic assay has been shown to be a reliable
reflection of a cells ability to maintain reproductive integrity after radiation
exposure. In this study it has successfully been used to demonstrate the
surviving fraction of cells but has the limitation of cells needing to process the
ability to form colonies. Cells from primary tumours do not readily form
colonies and may display poor anchorage making this assessment of
radiosensitivity in the clinic less desirable. These data are presented together
with unpublished data obtained using the micronucleus assay. Micronuclei
frequency (MNF) varies in different cell types with test doses and provides a
means to rank the cell in terms of response to radiation. In normal cells a
linear inverse correlation exits between MNF and cell survival. However, MNF
does not rank malignant cells according to their intrinsic survival to radiation
displaying a weak correlation between MNF and cell survival.
36
Land, Imke. "The delivery limitations of adaptive radiotherapy systems." Thesis, University of Warwick, 2009. http://wrap.warwick.ac.uk/2276/.
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Organ motion - whether due to respiration, cardiac motion or digestive processes - is one of the major problems in external beam radiotherapy as it limits the achievable precision in dose delivery. Adaptive radiotherapy (ART) is a novel approach for a more precise dose delivery where measured patient-specific variations are used to change the delivery pattern throughout the treatment course. The aim of the work described in this thesis has been to contribute to the progress of ART by developing dynamic phantoms for the simulation of target motion, evaluating adaptive treatment strategies, and providing tools for the assessment of optimal patient-specific treatment parameters. A dynamic, anthropomorphic and tissue equivalent thorax phantom has been developed and assessed. The phantom provides accurate, three-dimensional regular or irregular motion of both a tumour within the lungs and the chest wall independently. It has been designed to investigate the effect of organ motion on the dose delivered to a moving target, to evaluate the potential benefit of adaptive treatment strategies and to assess ART delivery systems. The potential of the phantom has been evaluated through experiments on a respiratory-gated CT system and during tests on a real-time motion tracking system. In addition, the principles used for the thoracic phantom have been used to design dynamic phantoms for the prostate and bladder. An adaptive off-line correction strategy accounting for inter-fractional prostate motion has been evaluated using radiobiological modelling. This work revealed that it is important to consider the normal tissue complication probability of the rectum and the direction of anterior-posterior prostate motion when determining the optimal timing for re-optimisation of the treatment plan. Specifically, relying on calculations of the tumour control probability alone provides misleading results. In general off-line correction based on only a few observations in the early treatment course is shown to improve the probability of uncomplicated tumour control. Target coverage for respiratory-gated radiotherapy has been modelled with simulated and real breathing traces. The results have demonstrated that maximum benefit is achieved with amplitude gating at end of exhalation. The analysis showed that treatment parameters should be adjusted prior to each fraction. As part of this work a model that assists on deciding the most appropriate gating parameters on an individual patient basis has been developed. Finally, a treatment strategy decision support tool has been developed and applied to respiratory data obtained from patients. The tool not only identifies whether tumour mobility justifies implementing an adaptive treatment technique but where it does the tool supports selecting the optimal ART technique to be used together with the appropriate treatment parameters that will provide the greatest benefit to an individual lung cancer patient.
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Aylott, Ilona Natalia. "Investigating the innate immune response to cancer radiotherapy in zebrafish." Thesis, University of Bristol, 2017. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715834.
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Gyenes, Gábor. "Cardiac side-effects of adjuvant radiotherapy for early breast cancer /." [Budapest] ; Stockholm, 1997. http://diss.kib.ki.se/1997/963-9106-04-6.
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Bhide, Shreeang Arvind. "Optimization of intensity modulated radiotherapy in head and neck cancer." Thesis, Institute of Cancer Research (University Of London), 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.511161.
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Lei, Mary Wei-Ching. "Image guided intensity modulated radiotherapy in head and neck cancer." Thesis, University of Surrey, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.600034.
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Image Guided Intensity Modulated Radiotherapy (IG-IMRT) incorporates novel imaging strategies into IMRT planning and delivery. FDG-PET/CT imaging may be used to identify potentially radioresistant tumour cell populations in head and neck cancer (HNC). Dose-painting with IMRT is a novel technique which provides an opportunity to widen the therapeutic window by dose escalation to radioresistant subvolumes. The purpose of this thesis was to evaluate the feasibility of th is technique, to provide methodology for identification of the FDG-avid region and to inform on a reasonable dose level to use in a future phase I clinical study investigating dose-painting to the FDG-avid target volume. This technique requires confidence in the quality of geometric and dosimetric accuracy of delivery and this issue was investigated in this thesis. Pre-clinical work included a comparison of five different FDG segmentation techniques. One of these techniques was used to identify the FOG-avid biological volume selected to receive dose-painting with IMRT in a planning study. Four dose levels were tested. Radiobiological modelling was used to determine an optimal dose level as the basis for a future clinical study and to determine the impact of using different FDG segmentation techniques. A clinical study was performed in patients with HNC to compare in -room volumetric imaging - cone beam computed tomography (CBCT) - with planar kilovoltage (kV) electronic portal imaging (EPI) for aspects of image guidance and to inform on appropriate planning margins. Pre-clinical work suggested that dose-painting with IMRT to the FOG-avid subvolume would be associated with increases in estimated tumour control probability (TCP) and with acceptable increases in normal tissue complication probability (NTCP). Verification using CBCT provided accurate data to guide treatment delivery and appropriate planning margins. The findings reported in this thesis provide valuable information that will inform the design of future clinical studies.
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Leslie, Martin David. "Salivary gland function after radiotherapy for head and neck cancer." Thesis, University College London (University of London), 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341706.
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Ospina, Arango Juan David. "Predictive models for side effects following radiotherapy for prostate cancer." Thesis, Rennes 1, 2014. http://www.theses.fr/2014REN1S046/document.
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La radiothérapie externe (EBRT en anglais pour External Beam Radiotherapy) est l'un des traitements référence du cancer de prostate. Les objectifs de la radiothérapie sont, premièrement, de délivrer une haute dose de radiations dans la cible tumorale (prostate et vésicules séminales) afin d'assurer un contrôle local de la maladie et, deuxièmement, d'épargner les organes à risque voisins (principalement le rectum et la vessie) afin de limiter les effets secondaires. Des modèles de probabilité de complication des tissus sains (NTCP en anglais pour Normal Tissue Complication Probability) sont nécessaires pour estimer sur les risques de présenter des effets secondaires au traitement. Dans le contexte de la radiothérapie externe, les objectifs de cette thèse étaient d'identifier des paramètres prédictifs de complications rectales et vésicales secondaires au traitement; de développer de nouveaux modèles NTCP permettant l'intégration de paramètres dosimétriques et de paramètres propres aux patients; de comparer les capacités prédictives de ces nouveaux modèles à celles des modèles classiques et de développer de nouvelles méthodologies d'identification de motifs de dose corrélés à l'apparition de complications. Une importante base de données de patients traités par radiothérapie conformationnelle, construite à partir de plusieurs études cliniques prospectives françaises, a été utilisée pour ces travaux. Dans un premier temps, la fréquence des symptômes gastro-Intestinaux et génito-Urinaires a été décrite par une estimation non paramétrique de Kaplan-Meier. Des prédicteurs de complications gastro-Intestinales et génito-Urinaires ont été identifiés via une autre approche classique : la régression logistique. Les modèles de régression logistique ont ensuite été utilisés dans la construction de nomogrammes, outils graphiques permettant aux cliniciens d'évaluer rapidement le risque de complication associé à un traitement et d'informer les patients. Nous avons proposé l'utilisation de la méthode d'apprentissage de machine des forêts aléatoires (RF en anglais pour Random Forests) pour estimer le risque de complications. Les performances de ce modèle incluant des paramètres cliniques et patients, surpassent celles des modèle NTCP de Lyman-Kutcher-Burman (LKB) et de la régression logistique. Enfin, la dose 3D a été étudiée. Une méthode de décomposition en valeurs populationnelles (PVD en anglais pour Population Value Decomposition) en 2D a été généralisée au cas tensoriel et appliquée à l'analyse d'image 3D. L'application de cette méthode à une analyse de population a été menée afin d'extraire un motif de dose corrélée à l'apparition de complication après EBRT. Nous avons également développé un modèle non paramétrique d'effets mixtes spatio-Temporels pour l'analyse de population d'images tridimensionnelles afin d'identifier une région anatomique dans laquelle la dose pourrait être corrélée à l'apparition d'effets secondaires<br>External beam radiotherapy (EBRT) is one of the cornerstones of prostate cancer treatment. The objectives of radiotherapy are, firstly, to deliver a high dose of radiation to the tumor (prostate and seminal vesicles) in order to achieve a maximal local control and, secondly, to spare the neighboring organs (mainly the rectum and the bladder) to avoid normal tissue complications. Normal tissue complication probability (NTCP) models are then needed to assess the feasibility of the treatment and inform the patient about the risk of side effects, to derive dose-Volume constraints and to compare different treatments. In the context of EBRT, the objectives of this thesis were to find predictors of bladder and rectal complications following treatment; to develop new NTCP models that allow for the integration of both dosimetric and patient parameters; to compare the predictive capabilities of these new models to the classic NTCP models and to develop new methodologies to identify dose patterns correlated to normal complications following EBRT for prostate cancer treatment. A large cohort of patient treated by conformal EBRT for prostate caner under several prospective French clinical trials was used for the study. In a first step, the incidence of the main genitourinary and gastrointestinal symptoms have been described. With another classical approach, namely logistic regression, some predictors of genitourinary and gastrointestinal complications were identified. The logistic regression models were then graphically represented to obtain nomograms, a graphical tool that enables clinicians to rapidly assess the complication risks associated with a treatment and to inform patients. This information can be used by patients and clinicians to select a treatment among several options (e.g. EBRT or radical prostatectomy). In a second step, we proposed the use of random forest, a machine-Learning technique, to predict the risk of complications following EBRT for prostate cancer. The superiority of the random forest NTCP, assessed by the area under the curve (AUC) of the receiving operative characteristic (ROC) curve, was established. In a third step, the 3D dose distribution was studied. A 2D population value decomposition (PVD) technique was extended to a tensorial framework to be applied on 3D volume image analysis. Using this tensorial PVD, a population analysis was carried out to find a pattern of dose possibly correlated to a normal tissue complication following EBRT. Also in the context of 3D image population analysis, a spatio-Temporal nonparametric mixed-Effects model was developed. This model was applied to find an anatomical region where the dose could be correlated to a normal tissue complication following EBRT
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Angenete, Eva. "Remodelling of extracellular matrix in rectal cancer and preoperative radiotherapy /." Göteborg : Institute of Clinical Sciences at Sahlgrenska Academy, University of Gothenburg, 2009. http://hdl.handle.net/2077/19389.
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Wey, Mark Tao Teong. "DNA repair in bladder cancer predisposition and radiotherapy treatment response." Thesis, University of Leeds, 2012. http://etheses.whiterose.ac.uk/8087/.
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The genetic contribution to bladder cancer risk remains undetermined, while the role of radiotherapy versus surgery in muscle-invasive bladder cancer (MIBC) treatment is hotly debated with the need for predictive biomarkers of treatment response. DNA repair pathways are involved in repairing DNA damage from carcinogens thus preventing carcinogenesis, but also form one of the 5 R’s of radiobiology for determining cancer response to radiotherapy. The aims of this project were: 1) To study the contribution of germline DNA repair gene variants, specifically rare variants (RV) and 3’-untranslated region (3’UTR) single nucleotide polymorphisms (SNP), on bladder cancer risk. 2) To investigate the predictive value of germline DNA repair gene variants and tumour DNA repair protein expression on radiotherapy outcomes in MIBC. RVs can only be identified by sequencing so a developmental multiplexed next-generation sequencing (NGS) project was undertaken, identifying two approaches, with the choice of method based on balancing costs and labour versus accuracy and data needed. Using these methods, candidate RVs were identified in the DNA repair genes, MUTYH and XPC, with XPC RVs being associated with an increased bladder cancer risk (P=0.008) independent of previously identified GWAS SNPs. Putatively functional DNA repair gene 3’UTR SNPs, PARP1 rs8679 and RAD51 rs7180135, were found to increase bladder cancer risk (P=0.05) and predict improved survival following radiotherapy (P=0.01) respectively. Multiplexed NGS of MRE11A identified rs1805363 to be predictive of survival following radiotherapy (P=0.001) but not surgery (P=0.89), and to affect MRE11A isoform expression. Tumour DNA repair protein expression of CtIP, MUTYH and XPC were not found to predict survival following radiotherapy. This study demonstrated the contribution of DNA repair gene variants in bladder cancer risk and predicting radiotherapy response. These findings could contribute to the goal of personalised medicine for targeted primary prevention, early diagnosis and treatment individualisation.
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Rios, Patiño Richard. "Statistical modeling of bladder motion and deformation in prostate cancer radiotherapy." Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1S116/document.
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Le cancer de la prostate est le cancer le plus fréquent chez les hommes dans la plupart des pays développés. C'est le cancer le plus fréquent chez les hommes en France (73.609 cas en 2014) et en Colombie (9564 cas en 2014). En outre, c'est la troisième cause de décès par cancer chez les hommes dans les deux pays (9,3 % en France et 7,1 % en Colombie en 2014). L'une des techniques de traitement est la radiothérapie externe, qui consiste à délivrer un rayonnement ionisant à une cible clinique, à savoir la prostate et les vésicules séminales. En raison des variations anatomiques au cours du traitement, qui consiste en environ 40 fractions de rayonnement délivrant une dose totale allant de 70 à 80Gy, des marges de sécurité sont définies autour de la cible tumorale lors de la planification du traitement. Ceci entraîne des portions d'organes sains voisins de la prostate - la vessie et le rectum - à être inclus dans le volume cible, pouvant conduire à des événements indésirables affectant les fonctions urinaires (hématurie et cystite, entre autres) ou rectale (saignement rectal, incontinence fécale, Etc.). La vessie présente les plus grandes variations de forme entre fractions de traitement, provoquées par des changements continus de volume. Ces variations de forme introduisent des incertitudes géométriques qui rendent difficile l'évaluation de la dose réellement délivrée à la vessie pendant le traitement. Ces incertitudes limitent la possibilité de modéliser une relation dose-volume pour la toxicité génito-urinaire tardive (GU). Le projet QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) a déclaré que la relation dose-réponse pour la toxicité gastro-intestinale tardive (GI) était loin d'être établie. Les variables dosimétriques obtenues à partir de la tomodensitométrie de planification peuvent être faiblement représentative de la dose effectivement administrée. En conséquence, il est crucial de quantifier les incertitudes produites par les variations inter-fraction de la vessie afin de déterminer les facteurs dosimétriques qui affectent les complications GU tardives. Le but de cette thèse était donc de caractériser et de prédire les incertitudes produites par les variations géométriques de la vessie entre les fractions de traitement, en utilisant uniquement la tomodensitométrie de planification comme information d'entrée. En pratique clinique, une seule tomodensitométrie est disponible au moment de la planification du traitement pour un patient typique, alors que des images supplémentaires peuvent être acquises en cours de traitement. Dans cette thèse une approche population a été utilisée pour obtenir suffisamment de données pour apprendre les directions les plus importantes du mouvement et de la déformation de la vessie en utilisant l'analyse en composante principales (ACP). Comme dans les travaux de référence, ces directions ont ensuite été utilisées pour développer des modèles basés population pour prédire et quantifier les incertitudes géométriques de la vessie. Cependant, nous avons utilisé une analyse longitudinale afin de caractériser correctement la variance du patient et les modes spécifiques du patient à partir de la population. Nous avons proposé d'utiliser un modèle à effets mixtes (ME) et une ACP hiérarchique pour séparer la variabilité intra et inter-patients afin de contrôler les effets de cohorte confondus. Finalement, nous avons présenté des modèles sur l'APC comme un outil pour quantifier des incertitudes de la dose produit par le mouvement et déformation de la vessie entre fractions<br>Prostate cancer is the most common cancer amongst the male population in most developed countries. It is the most common cancer amongst the male population in France (73.609 cases in 2014) and in Colombia (9564 cases in 2014). It is also the third most common cause of cancer deaths in males in both countries (9.3% and 7.1% in France and in Colombia in 2014, respectively). One of the standard treatment methods is external radiotherapy, which involves delivering ionizing radiation to a clinical target, namely the prostate and seminal vesicles. Due to the uncertain location of organs during treatment, which involves around forty (40) radiation fractions delivering a total dose ranging from 70 to 80Gy, safety margins are defined around the tumor target upon treatment planning. This leads to portions of healthy organs neighboring the prostate or organs at risk — the bladder and rectum — to be included in the target volume, potentially resulting in adverse events affecting patients’ urinary (hematuria and cystitis, among others) or rectal (rectal bleeding, fecal incontinence, etc.) functions. The bladder is notorious for presenting the largest inter-fraction shape variations during treatment, caused by continuous changes in volume. These variations in shape introduce geometric uncertainties that render assessment of the actual dose delivered to the bladder during treatment difficult, thereby leading to dose uncertainties that limit the possibility of modeling dose-volume response for late genitourinary (GU) toxicity. The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) project has stated that a similar dose-response to that of late gastrointestinal (GI) toxicity is far from being established. The dosimetric variables obtained from the planning CT prove to be very poor surrogates for the real delivered dose. As a result, it appears crucial to quantify uncertainties produced by inter-fraction bladder variations in order to determine dosimetric factors that affect late GU complications. The aim of this thesis was thus to characterize and predict uncertainties produced by geometric variations of the bladder between fractions, using solely the planning CT as input information. In clinical practice, a single CT scan is only available for a typical patient during the treatment planning while on-treatment CTs/CBCTs are seldom available. In this thesis, we thereby used a population approach to obtain enough data to learn the most important directions of bladder motion and deformation using principal components analysis (PCA). As in groundwork, these directions were then used to develop population-based models in order to predict and quantify geometrical uncertainties of the bladder. However, we use a longitudinal analysis in order to properly characterize both patient-specific variance and modes from the population. We proposed to use mixed-effects (ME) models and hierarchical PCA to separate intra and inter-patient variability to control confounding cohort effects. . Subsequently, we presented PCA models as a tool to quantify dose uncertainties produced by bladder motion and deformation between fractions
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Costa, Ferreira Brigida da. "Biological optimization of angle of incidence and intensity modulation in breast and cervix cancer radiation therapy /." Stockholm : Division of medical radiation physics, Karolinska Institutet and Stockholm University, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-313.
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Fokas, Emmanouil. "Targeting the PI3K/mTOR and ATK/Chk1 pathways to improve radiation efficacy for cancer therapy." Thesis, University of Oxford, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.572788.
Pełny tekst źródłaStreszczenie:
The purpose of the present thesis was to better understand the effect of targeting key biological mechanisms in order to improve radiotherapy response. Two important and distinct pathways were targeted using novel agents: (1) the phosphoinoside-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway; (2) the ataxia telangiectasia-mutated-Rad3-related (ATR)/Chkl pathway. The role of the PI3K1mTOR signalling pathway in tumour radiosensitivity and tumour microerivlronment (TME) was examined using three, recently-developed signalling inhibitors obtained from Novartis Pharma: NVP-BEZ235 (dual PI3K1mTOR inhibitor), NVP-BGT226 (dual PI3K1mTOR inhibitor) and NVP-BKM120 (single PI3K inhibitor). The radiosensitising potential of NVP-BEZ235 and NVP-BGT226 was demonstrated in tumour and endothelial cells. Additionally, a thorough research into the effects ofNVP-BKM120 and NVP-BEZ235 on TME showed that oncogenic signalling inhibitors can improve vascular morphology and increase tumour oxygenation and perfusion in tumour xenograft models, resulting in improved radiation response. Furthermore, a highly potent and selective A TR inhibitor, VE-822, that was obtained from Vertex Pharmaceuticals (Europe) Ltd, was tested in pancreatic ductal adenocarcinoma (PDAC) cells and tumour xenograft models. A TR inhibition by VE-822 resulted in sensitisation of tumour cells but not normal cells to radiation and gemcitabine. Similarly, VE-822 strongly enhanced radiation- and chemoradiation-induced tumour growth delay in tumour xenograft models. Importantly, VE-822 did not potentiate radiation-induced gastrointestinal tract epithelial damage. To summarize, the impact of targeting two distinct pathways in combination with radiation and chemoradiation was explored. Inhibition of the PI3K1mTOR and ATRlChkl signalling pathways increases response of tumours to radiotherapy they and might be promising targeting strategies for cancer treatment. Our findings have considerable translational implications and future clinical trials should aim to validate these observations.
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Wu, Wing-cheung Vincent, and 胡永祥. "Dose analysis of 2-dimensional and 3-dimensional radiotherapy techniques in the treatment of nasopharyngeal carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1997. http://hub.hku.hk/bib/B31220149.
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胡寶文 and Po-man Wu. "The application of the tumor control probability model of nasopharyngeal carcinoma in three dimensional conformal treatment planevaluation." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31241232.
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Chiu, Siu-hau, and 招兆厚. "A search for optimal radiation therapy technique for lung tumours stereotactic body radiation therapy (SBRT) : dosimetric comparison of 3D conformal radiotherapy, static gantry intensity modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) with flattening filter (FF) or flattening filter-free (FFF) beams." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196549.
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Materials/Methods:
Ten patients who underwent thoracic SBRT with primary stage I (T1/2N0) lung cancer or oligometastatic lung lesion, with PTV diameter ≤ 5cm were selected and were immobilized with Easyfoam or Vac-Lock. Planned/treated with inspiratory breath-hold (25 seconds, 70 to 80% of vital capacity) assisted with Active Breathing Control (ABC). Four treatment plans: non-coplanar 3DCRT, coplanar static gantry IMRT, coplanar VMAT (FF) and VMAT (FFF) were generated. Field arrangements, either static fields or partial arcs (duration=20 sec) were used to avoid direct beam entry to contralateral lung. All plans were compared in terms of dosimetric performance included dose to PTV or organs at risk (OAR), high/low dose spillage, integral dose (body and lungs), dose delivery efficiency (MU/Gy) and estimated beam-on time (BOT) with reference to the RTOG 0813 protocol.
Results:
All plans complied with RTOG 0813 protocol. VMAT (FF/ FFF) techniques improved target coverage and dose conformity, with the highest conformity number (CN > 0.91), compared to IMRT (0.88) and 3DCRT (0.85). The control of high dose spillage (NT>105% and CI) for IMRT (3.04% and 1.08) and VMAT (FF/ FFF) (1.08/ 1.06% and 1.03/ 1.04) techniques were comparable (p > 0.05) and significantly better than 3DCRT (4.22% and 1.11, p < 0.005) technique. In addition, VMAT (FF/ FFF) techniques performed the best in controlling low dose spillage (D2cm and R50%) compared with IMRT (reduction: 4.7%, p=0.036 and >5.9%, p = 0.009) and 3DCRT (reduction: > 16.3%, p < 0.001 and > 10%, p = 0.002). Benefits of rapid and isotropic dose fall-off were shown from superior tissue sparing (reduction ranges from 3.2% up to 67%) of ipsilateral brachial plexus, skin (0-5mm), great vessels and ribs. Also lung V10, V12.5, esophagus and heart tend to receive lower dose with VMAT technique. The relatively lower integral dose to whole body (> 3Gy∙L reduction, p < 0.013) and ipsilateral lung (0.65Gy∙L reduction, p = 0.025) compared with 3DCRT, were associated with lower risk of radiation induced cancers. The MU/Gy and BOT were substantial lower for VMAT (FF) (22.4% and 32.4%) compared with IMRT. Apart from higher (7%) maximum skin dose, dosimetric performance for VMAT (FFF) was comparable with VMAT (FF), with advantages of further reduction of MU/Gy (1.8% lesser), partial arc numbers (from 12-14 arcs down to 8 arcs) and BOT (35% shortened), owing to the increased dose output with flattening filter removal.
Conclusions:
VMAT (FF and FFF) plans maintained IMRT equivalent plan qualities, simultaneously enhanced the delivery efficiency with shortened BOT. VMAT (FFF) further reduced the required arcs number and BOT, significantly minimized the intra-fraction motions and more tolerable to patient with long SBRT treatment duration.<br>published_or_final_version<br>Medicine<br>Master<br>Master of Medical Sciences