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1
Jain, Pooja. "Optimising Radiotherapy for Cancers affected by Respiratory Motion using Image Guided Radiotherapy." Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492923.
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Conformal and intensity modulated radiotherapy (IMRT) can reduce normal tissue toxicity and facilitate radiation dose escalation by creating steep dose gradients between irradiated volume and normal organs.
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PINZI, VALENTINA. "Immuno-Radiotherapy for brain glioma: sorting out the immunomodulatory effects of radiotherapy." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2023. https://hdl.handle.net/10281/402376.
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BACKGROUND. Glioblastoma (GBM) is a fast-growing and aggressive brain tumor. GBM is the most frequent malignant primary brain tumour and it can result in death in three-six months, if untreated. The current standard of care (SOC) therapy consists in maximal safe surgical resection followed by radiation therapy and adjuvant temozolomide (Stupp protocol), with a median overall survival (OS) of 8-10 months. However, more than half of GBM patients die within one year from the diagnosis, and only 5% survive more than 5 years despite aggressive therapies. Research has now shifted additional attention to methods of modulating the innate immune system for the treatment of GBM. Moreover, radiotherapy, that plays a key role in GBM treatment, has the potential to convert immunologically ‘cold’ tumors into ‘hot’ tumors by a combination of distinct mechanisms. Overall, literature data indicate that local radiation produces systemic, immune-mediated anti¬tumour and, potentially, antimetastatic effects. Additionally, the combination of local radiotherapy and immune-modulation can augment local tumour control and cause distant (abscopal) antitumour effects through increased tumour-antigen release and antigen-presenting cell (APC) cross-presentation, improved dendritic-cell (DC) function, and enhanced T cell priming.
In order to sort out the immunomodulatory effects of radiotherapy for brain glioma we conducted this project, also in association with immunetherapy. The radiological response has been evaluated as well.
METHODS. Radiotherapy treatment in combination with dendritic cell immunotherapy was evaluated. GL261-glioma bearing immune-competent mice were treated by means of RT (3 fractions, 1 fr/day) as exclusive and concomitant immunotherapy (dendritic cells).
Two clinical trials were studied as well. The population was GBM patients treated by means of standard therapy plus DC-vaccine therapy.
Response assessment of GBM after radio-chemotherapy and during immunotherapy by delayed contrast trams (treatment response assessment maps) was evaluated as well.
RESULTS. Survival, CD8+ T, NK cells were significantly and slightly significant different: control vs RT vs RT-IT. We found that activated microglia persists in both tumor and contralateral brain of irradiated mice. Moreover, RT promoted antitumoral M1 polarization and RT contributed to a massive recruitment of Th1 CD4+ T cells; RT and DC combination contributes to a robust infiltrate of CD8+ T cells.
CONCLUSION. Our results confirm that RT can modulate the TME creating a specific chemokine gradient involved in T cell homing. RT in combination with IT can induce an anti-tumour systemic long-lasting effector CD8+ T cell response as well as a local infiltration of NK cells and CD8+ T cells. The combinatorial approach seems to be a promising therapy for GBM patients. It might be evaluated trough other clinical trials in order to confirm the preliminary results.BACKGROUND. Glioblastoma (GBM) is a fast-growing and aggressive brain tumor. GBM is the most frequent malignant primary brain tumour and it can result in death in three-six months, if untreated. The current standard of care (SOC) therapy consists in maximal safe surgical resection followed by radiation therapy and adjuvant temozolomide (Stupp protocol), with a median overall survival (OS) of 8-10 months. However, more than half of GBM patients die within one year from the diagnosis, and only 5% survive more than 5 years despite aggressive therapies. Research has now shifted additional attention to methods of modulating the innate immune system for the treatment of GBM. Moreover, radiotherapy, that plays a key role in GBM treatment, has the potential to convert immunologically ‘cold’ tumors into ‘hot’ tumors by a combination of distinct mechanisms. Overall, literature data indicate that local radiation produces systemic, immune-mediated anti¬tumour and, potentially, antimetastatic effects. Additionally, the combination of local radiotherapy and immune-modulation can augment local tumour control and cause distant (abscopal) antitumour effects through increased tumour-antigen release and antigen-presenting cell (APC) cross-presentation, improved dendritic-cell (DC) function, and enhanced T cell priming. In order to sort out the immunomodulatory effects of radiotherapy for brain glioma we conducted this project, also in association with immunetherapy. The radiological response has been evaluated as well. METHODS. Radiotherapy treatment in combination with dendritic cell immunotherapy was evaluated. GL261-glioma bearing immune-competent mice were treated by means of RT (3 fractions, 1 fr/day) as exclusive and concomitant immunotherapy (dendritic cells). Two clinical trials were studied as well. The population was GBM patients treated by means of standard therapy plus DC-vaccine therapy. Response assessment of GBM after radio-chemotherapy and during immunotherapy by delayed contrast trams (treatment response assessment maps) was evaluated as well. RESULTS. Survival, CD8+ T, NK cells were significantly and slightly significant different: control vs RT vs RT-IT. We found that activated microglia persists in both tumor and contralateral brain of irradiated mice. Moreover, RT promoted antitumoral M1 polarization and RT contributed to a massive recruitment of Th1 CD4+ T cells; RT and DC combination contributes to a robust infiltrate of CD8+ T cells. CONCLUSION. Our results confirm that RT can modulate the TME creating a specific chemokine gradient involved in T cell homing. RT in combination with IT can induce an anti-tumour systemic long-lasting effector CD8+ T cell response as well as a local infiltration of NK cells and CD8+ T cells. The combinatorial approach seems to be a promising therapy for GBM patients. It might be evaluated trough other clinical trials in order to confirm the preliminary results.
3
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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Millin, Anthony. "Verification of stereotactic radiotherapy." Thesis, Cardiff University, 2011. http://orca.cf.ac.uk/12287/.
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Investigations have been made into the use of a computer based simulation technique (Monte Carlo (MC)) to ionising radiation transport in order to verify the doses delivered during linear accelerator based stereotactic radiotherapy and radiosurgery. Due to the complex nature of the micro multi-leaf collimators (μMLC) used in this these treatments, a bespoke model of the μMLC was developed and combined with standard component modules to represent the remainder of the linear accelerator. Following validation of the above models, investigations were made into the dosimetry of small fields, defined by the μMLC and measured with a variety of detectors. Comparisons of relative output, profiles and depth doses were made against MC simulations, and a series of correction factors determined, to account for detector geometry and the non water equivalence of materials used in semiconductor detectors. An assessment was then made to determine the smallest fields that can be measured with each detector with confidence. Systems were then developed to independently simulate stereotactic treatments and compare doses simulated with those calculated by the treatment planning system (TPS); excellent agreement between TPS calculations and MC simulations was observed. The application of MC methods to determine the most appropriate treatment tactics and calculation algorithms for stereotactic body radiotherapy in the lung was then investigated with recommendations made on the most appropriate calculation algorithms and beam arrangements for the technique. The doses calculated using the type-b or collapsed cone algorithm agreed most closely with the MC simulation. There was little difference observed between plans using more than four beams in the treatment delivery. Treatment techniques using only three beams or less achieved poorer coverage of the tumour with dose, producing lower doses at the periphery of the tumour near the interface with the surrounding lung tissue, compared to using a greater number of beams. Finally, methods of transit dosimetry using Electronic Portal Imaging Devices were investigated for use in cranial stereotactic radiotherapy. Three methods were investigated based on a full MC simulation of the radiation transport through the patient and on to the imager, prediction of the dose based on a TPS calculation and an approximation of the radiological path length of the central axis of the beams to derive an expected dose at the imager plane. The MC method produced the best agreement at the expense of a longer time to acquire the comparison doses compared to the TPS calculation method. The equivalent path length method showed good agreement (within 3.5%) between delivered and predicted doses but at a single point.
5
Edwards, Craig Richard. "In-vivo radiotherapy dosimetry." Thesis, Keele University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269237.
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Helo, Y. "Cerenkov emission in radiotherapy." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1469478/.
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A new potential quality assurance (QA) method is explored for clinical electron beams and clinical proton beams based on imaging and measuring Cerenkov light. A simulation was performed of the deposited energy and of Cerenkov production in water using Geant4. Monte Carlo simulation was used to predict the measured light distribution around the water phantom, to reproduce Cerenkov images and to find the relation between deposited energy and Cerenkov production. The camera was modelled as a pinhole camera in Geant4, to attempt to reproduce Cerenkov images. The potential of using a standard commercial camera to image Cerenkov light generated from electrons in water for fast QA measurement of a clinical electron beam was explored and compared to ionization chamber measurements. The new method was found to be linear with dose and independent of dose rate (to within 3%). The uncorrected practical range measured using Cerenkov images was found to overestimate the actual value by 3 mm in the worst case. The field size measurements underestimated the field sizes at the edges by 5% without applying any correction factor. Still, the measured field size could be used to monitor relative changes in the beam profile. Finally, the beam-direction profile measurements were independent of the field size within 2%. We found that imaging Cerenkov emission from a breast phantom during electron irradiation could be a suitable tool to monitor the dose and the dose rate consistency with high precision and short-term repeatability better than 3% except when measuring very low doses. Cerenkov light measurements were linear with dose and independent of dose rate. The maximum light intensity occurred at an angle of 45.0°. We were unable to identify the regions of the phantom with higher scattering and absorption properties, designed to mimic diseased tissues using images of Cerenkov emission of an optical breast phantom. We found that the Cerenkov light emissions in proton therapy can be divided into two distinct mechanisms: a fast component due to prompt gamma interactions (99.13%) and neutron interactions (0.87%), and a slow component due to radioactive decay. The simulated depth distribution of the Cerenkov emission shows a strong relation with the depth distribution of the induced radioactive isotopes, which emit positrons. The fast component was found to be linear with dose and independent of dose rate, while the slow component increases non- linearly with dose and is highly dependent on dose rate. Imaging Cerenkov light during electron radiotherapy or proton therapy could be used as a very quick routine QA tool.
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Allahverdi, Mahmoud. "Accuracy in radiotherapy dosimetry." Thesis, University of Edinburgh, 1998. http://hdl.handle.net/1842/21135.
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The project involves an experimental analysis of achievable accuracy in the different steps of radiotherapy, including investigations of the basic dosimetry chain, considering the individual steps concerned in dosimeter and treatment beam calibration and some aspects of treatment planning and dose delivery. The results are investigated from these various areas and are analysed in terms of overall achievable accuracy and its relationship to clinical requirements and to quality assurance programmes. It is concluded that required clinical accuracy can be achieved in radiotherapy treatment, but needs careful control at all stages of the radiotherapy process. In addition a previously-designed geometric phantom, developed for a UK national dosimetry intercomparison and audit system has been used to extensively test achievable accuracy of dosimetry and some basic treatment planning parameters and processes in one department. This has been used as the basis to develop an interdepartmental audit in Scottish and other radiotherapy centres (the so-called Scottish+ audit group, within the UK radiotherapy dosimetry audit network). Also a semianatomic phantom has been developed to allow reasonably realistic audit of various representative treatment sites. This has been constructed from epoxy-based tissue substitute phantom materials. It has been extensively tested before audit use, by measuring the whole range of possible irradiation situations on five megavoltage photon beams, calculating dose distributions using the Edinburgh in-house treatment planning system and CADPLAN, and comparing measured results to expected values. Some small differences can be linked to the phantom materials. Others can be linked to small discrepancies in the testing department, for example in planning data, machine performance, etc.
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Cecconi, Agnese <1979>. "Stereotactict body radiotherapy (SBRT)." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4317/1/Cecconi_Agnese_tesi.pdf.
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Purpose: evaluation and comparison of volumetric modulated RapidarcTM radiotherapy (RA-IMRT) vs linac based Stereotactic body radiotherapy (SBRT) in the salvage treatment of isolated lymph node recurrences in patients affected by gynaecological cancer.
Materials and Methods From January 2010 to September 2011, 15 patients affected by isolated lymph nodes recurrence of gynaecological cancer underwent salvage radiotherapy after conventional imaging staging with CT and 18-FDG-PET/CT. Two different radiotherapy techniques were used in this study: RA-IMRT (RapidarcTM implemented radiotherapy Varian Medical System, Palo Alto, CA, USA) or SBRT (BrainLAB, Feldkirchen, Germany).
Five patients underwent CT scan and all patients underwent 18FDG-PET/CT for pre-treatment evaluation and staging.
The mean total dose delivered was 54.3 Gy (range 50-60 Gy with conventional fractionation and 27.4 Gy (range 12-40 Gy hypofractionation) for RA-IMRT and SBRT respectively.
The mean number of fractions was 27.6 fractions (range 25-31) and 3-4 fractions , the mean overall treatment duration was 40.5 days (range 36-45) and 6.5 days (range 5-8 days) for RA-IMRT and SBRT respectively.
Results:
At the time of the analysis, October 2011, the overall survival was 92.3 % (80% for RA-IMRT and 100% for SBRT). Six patients are alive with no evidence of disease and also six patients are alive with clinically evident disease in other sites (40% and 50% patients RA-IMRT vs SBRT respectively, one patient died for systemic progression of disease and two patient were not evaluable at this time.
Conclusions: Our preliminary results showed that, the use of RA-IMRT and SBRT are an excellent local therapy for isolated lymph nodes recurrences of gynaecological cancer with a good toxicity profile and local control rate, even if any long term survivors would be expected. New treatment modalities like Cyberknife are also being implemented.
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Cecconi, Agnese <1979>. "Stereotactict body radiotherapy (SBRT)." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4317/.
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Purpose: evaluation and comparison of volumetric modulated RapidarcTM radiotherapy (RA-IMRT) vs linac based Stereotactic body radiotherapy (SBRT) in the salvage treatment of isolated lymph node recurrences in patients affected by gynaecological cancer.
Materials and Methods From January 2010 to September 2011, 15 patients affected by isolated lymph nodes recurrence of gynaecological cancer underwent salvage radiotherapy after conventional imaging staging with CT and 18-FDG-PET/CT. Two different radiotherapy techniques were used in this study: RA-IMRT (RapidarcTM implemented radiotherapy Varian Medical System, Palo Alto, CA, USA) or SBRT (BrainLAB, Feldkirchen, Germany).
Five patients underwent CT scan and all patients underwent 18FDG-PET/CT for pre-treatment evaluation and staging.
The mean total dose delivered was 54.3 Gy (range 50-60 Gy with conventional fractionation and 27.4 Gy (range 12-40 Gy hypofractionation) for RA-IMRT and SBRT respectively.
The mean number of fractions was 27.6 fractions (range 25-31) and 3-4 fractions , the mean overall treatment duration was 40.5 days (range 36-45) and 6.5 days (range 5-8 days) for RA-IMRT and SBRT respectively.
Results:
At the time of the analysis, October 2011, the overall survival was 92.3 % (80% for RA-IMRT and 100% for SBRT). Six patients are alive with no evidence of disease and also six patients are alive with clinically evident disease in other sites (40% and 50% patients RA-IMRT vs SBRT respectively, one patient died for systemic progression of disease and two patient were not evaluable at this time.
Conclusions: Our preliminary results showed that, the use of RA-IMRT and SBRT are an excellent local therapy for isolated lymph nodes recurrences of gynaecological cancer with a good toxicity profile and local control rate, even if any long term survivors would be expected. New treatment modalities like Cyberknife are also being implemented.
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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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Steenbakkers, Roel Johannes Henricus Marinus. "Optimizing target definition for radiotherapy." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2007. http://dare.uva.nl/document/40825.
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Cufflin, Rebecca Sian. "Verification of Intensity Modulated Radiotherapy." Thesis, Cardiff University, 2012. http://orca.cf.ac.uk/25873/.
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The main aim of this work was to develop accurate and efficient methods for the verification of Intensity Modulated Radiotherapy (IMRT). IMRT is an advanced form of radiotherapy demanding extensive verification procedures to ensure treatments are delivered accurately. This requires comprehensive sampling of the complex dose distributions impacting on the tumour volume and radiationsensitive ‘organs at risk’. This work has focused on the use of electronic portal imaging devices (EPIDs) for verification purposes. Modern EPIDs are composed of a scintillator and an amorphous silicon detector panel with an array of photodiodes and thin film transistors. They are primarily used to verify the patient position during treatment by capturing transmission images, but they also have the potential to be used as efficient dose verification tools of high spatial resolution. Two complementary dose verification methods have been developed. One approach involves the calculation of portal dose using Monte Carlo (MC) methods. A MC model of the linear accelerator, in combination with the EPID, enables the dose to the detector to be predicted accurately and compared directly with acquired images. An alternative approach has also been developed. This utilises a clinical treatment planning system (TPS) to calculate the dose at the detector level, and convert this to predicted EPID intensity by application of a series of derived correction factors. Additionally, there have been numerous publications in the literature detailing problems in dosimetry caused by non-uniform backscatter to the imager from the model of detector support arm used in this work. Two novel methods to correct for this issue have been developed, a MC modelling solution and a matrix-based correction. These developed methods for IMRT dose verification have been applied both prior to and during treatment. When applied to pre-treatment verification, the MC solution is accurate to the 2%, 2 mm level (an average of 96% of points passing gamma criteria of 2%, 2 mm) and the TPS based method is accurate to the 3%, 3 mm level (an average of 98% of points passing gamma criteria of 3%, 3 mm). Both verification methods achieve acceptable verification results during treatment at the 5%, 5 mm level (average gamma pass rates of 97% and 96% being achieved for the MC and TPS based solutions respectively). Furthermore, in initial clinical studies, both techniques have identified dose delivery errors due to changes in patient position or patient anatomy.
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McMahon, S. J. "Heavy Atom Radiotherapy Dose Enhancement." Thesis, Queen's University Belfast, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.527871.
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Lewis, R. D. "Monte Carlo modelling for radiotherapy." Thesis, Swansea University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.637892.
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The Monte Carlo code MCNP-4B has been utilised to investigate the origins of radiation dose perturbation in the head and neck region, arising from natural heterogeneities, the changing external contours of the patient, boundaries between materials of different atomic number and prosthetic implants. MCNP-4B was used to develop a simple model of a linear accelerator treatment head which incorporated the electron target, primary collimator, beam flattening filter and the secondary collimators. The model was used to calculate the energy spectra and angular distribution of the x-ray beam from a 4 MV Philips SL 75/5 and a 10 MV SL 15, and then tested by using these data to compute the central and off-axis x-ray beam profiles for various field sizes in water. Monte Carlo simulations using the calculated spectra were used to assess the dose distribution of treatment plans obtained in a simple heterogeneous phantom by several commercially available treatment planning systems. Practical measurements were undertaken using film dosimetry. The dose distributions were calculated for a variety of irradiation conditions designed to show the effects of surface obliquity, inhomogeneities and missing tissue above tangential beams. The results show maximum differences of 47% between some planning algorithm and film. Overall, the dose distribution obtained from film was most faithfully reproduced by the MCNP. The dose due to backscatter and lack of forward scatter from a metal implant within a head and neck phantom has been shown vary with atomic number, field size, surface obliquity, implant thickness, variations in secondary electron transport and the presence of teeth.
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Johnson, Kerstie Anne. "Predicting radiotherapy toxicity in patients treated with radical radiotherapy using predictive assays and circadian rhythm." Thesis, University of Leicester, 2018. http://hdl.handle.net/2381/40982.
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Radiotherapy is a fundamental cancer treatment and plays a pivotal role in the improving outcomes for the disease. Depending on the cancer site and organ at risk rates of moderate to severe acute toxicity range between 15 to 30 percent and rates of late toxicity between 5 and 15 percent. If a patient’s individual risk of radiotherapy toxicity could be predicted then their treatment could be tailored appropriately. In this thesis two cohorts have been used to analyse predictive measures for acute and late radiotherapy toxicity: the REQUITE cohort (prospective international observational study of breast, prostate and lung cancer patients) and the LeND cohort (retrospective local study of breast cancer patients). Three main areas have been examined to establish whether they can be used to predict for radiotherapy reactions. In the prostate and lung patients associations between clinical and treatment variables and acute toxicity were reviewed. The second area was predictive assays: DNA damage and repair were assessed using the comet and γ-H2AX assays and apoptosis in lymphocytes using the RILA (radiation induced lymphocyte apoptosis assay). Finally the effect of circadian rhythm and its underlying genetics on radiotherapy toxicity were assessed. Many of the variables were significantly associated with increased toxicity on univariate analysis. Three were significantly associated with toxicity on multivariate analysis. Acute toxicity in prostate patients was associated with intended duration of hormones (p=0.05) and V50 bladder (p=0.01)). Morning radiotherapy was associated with increased overall bivariate STAT score (p=0.03) in the LeND volunteers. The results of this study indicate clinical and genetic variables and the use of predictive assays can be utilised to create more personalised radiotherapy treatments that strive for better cancer and quality of life outcomes for patients.
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Bär, Werner. "Optimized delivery of intensity modulated radiotherapy." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=965610934.
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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.
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Rojas, Callejas Ana Maria. "ARCON in experimental and clinical radiotherapy." Doctoral thesis, Umeå : Univ, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-207.
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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.
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Yin, Zaizhe. "Solid state detectors in radiotherapy dosimetry." Thesis, University of Birmingham, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288576.
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Gulliford, Sarah Louise. "Artificial neural networks applied to radiotherapy." Thesis, Institute of Cancer Research (University Of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404474.
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Grellet, Sophie. "Optimisation of gold nanoparticles for radiotherapy." Thesis, Open University, 2018. http://oro.open.ac.uk/57326/.
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Radiotherapy is currently used in around 50% of cancer treatments. Although highly effective it is also damaging to surrounding healthy tissues and needs to be improved by better targeting of cancer cells. Improved radiotherapy outcomes can be achieved by using nanoparticles, especially those with high atomic number (Z), that interact with ionising radiation to generate secondary electrons and reactive species that increase cellular damage. One of the most promising elements to use is gold, in the form of gold nanoparticles (AuNPs) because of its biocompatibility and amenability to surface modification. For example, surface modification of AuNPs with simple sugars can improve their solubility and cellular uptake. Furthermore, positively charged AuNPs are thought to have an improved cellular uptake because of their interactions with negatively charged cell membranes. This thesis is focussed on two research areas: (1) the development of dual action chemo-radiosensitising AuNPs and (2) the development of oligonucleotide-AuNPs for radiosensitisation. (1) It is shown that sugar-PEGamine coated AuNPs demonstrate selective uptake and toxicity toward skin cancer cells with an IC50 of 1 μg/ml [Au], without damaging normal skin cells at this concentration. Oxidative stress and caspase-dependent apoptosis both play a key role in the toxicity of these AuNPs. Moreover, AuNPs coated with sugar and PEGamine show a strong radiosensitisation effect in combination with kilovoltage X-rays and a smaller effect with megavoltage X-rays. (2) Oligonucleotide-phosphine-coated AuNPs are shown to demonstrate a limited uptake in the cellular cytoplasm compared to the previous AuNPs but increase AuNPs uptake into the cell nucleus. The limited uptake into the cells, as well as the DNA triplex forming oligonucleotides (TFOs) attached to the AuNPs, is still responsible for a radiosensitisation effect, although smaller than with sugar:PEGamine AuNPs. In the future, the uptake of the oligonucleotides AuNPs may possibly be improved by varying their size (from 3.5 to 2 nm) and/or adding a spacer between the NP and the TFO.
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Ahbabi, Salma Saeed Al. "Achievable accuracy and reproducibility in radiotherapy." Thesis, University of Surrey, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.616955.
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The use of Volumetric Modulated Arc Therapy (VMAT) is expected to increase, largely due to development of helical tomotherapy. VMAT minimises the occurence of hotspots and inadiation of critical organs, providing more uniform dose while sparing critical organs. Two important characteristics of VMA T are its dynamic nature and dosimetric variability in radiation delivery. These present considerable challenge for clinical physicists as the implementation of the process contains a number of sources of uncertainty and thus require robust QA.
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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.
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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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Sandberg, Linnea. "Quality assurance of a radiotherapy registry." Thesis, Umeå universitet, Institutionen för fysik, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-176779.
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The radiotherapy clinics in Sweden have been without a functioning national platform consisting of dose data from patients undergoing radiotherapy. A national collaboration between clinics will improve the quality of radiotherapy since clinics will be able to compare dose data from treatment plans between clinics. It will also help and improve future researches in radiotherapy. A new national quality registry for radiotherapy in Sweden is under development and is located on the INCA platform. The aim of this study is to do a quality assurance of the INCA registry. The data stored in the registry are calculated from the treatment plans stored locally at the clinics. The quality assurance of the registry is done by creating a program run by Python code and by using Streamlit as the graphical user interface. The program takes dose and volume data from the dose volume histograms located in treatment plans from the INCA database and compares it with the dose and volume data from the local clinics' treatment planning system. The different treatment planning systems considered in the program are Oncentra(Elekta, Sweden), Eclipse(Varian, U.S.), RayStation(RaySearch Laboratories, Sweden) and Monaco(Electa, Sweden). The compared absorbed doses are the dose to 99% of the structure volume(D99%), D98%, D50%, D2% and D1%. The program generates how much the INCA data differs from the TPS data in percent and is named QARS(Quality Assurance of the Radiotherapy Database in Sweden). A verification of the created program and a preliminary evaluation is done on a limited dataset containing three patient groups(prostate patients, lung patients and head and neck patients) with five patients in each group. The dataset is run through the program with patient data from both Oncentra and Eclipse. The result indicates that all the near-maximum doses, D2% and D1% in INCA are very close to their corresponding TPS dose. There is a more noticeable difference in the near-minimum doses, D99% and D98% but also for some D50% where the difference seems to increase in larger structure volumes with very low doses and in very small structure volumes, smaller than 0.01 cm3. It is compared how well INCA agrees with Oncentra and Eclipse respectively and it is clear that Eclipse has a smaller difference to INCA than Oncentra for structures with very small volumes and larger structures with low doses. To summarise the study, it generates a program for quality assurance of the national quality registry for radiotherapy in Sweden which hopefully can help improve the quality of radiotherapy and help future researches in the field.
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Leite, Rocha Pedro. "Novel approaches to radiotherapy treatment scheduling." Thesis, University of Nottingham, 2011. http://eprints.nottingham.ac.uk/12281/.
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Radiotherapy represents an important phase of treatment for a large number of cancer patients. It is essential that resources used to deliver this treatment are used efficiently. This thesis approaches the problem of scheduling treatments in a radiotherapy centre. Data about the daily intake of patients are collected and analysed. Several approaches are presented to create a schedule every day. The first presented are constructive approaches, developed due to their simplicity and low computational requirements. The approaches vary the preferred treatment start, machine utilisation reservation levels, and the frequency and number of days in advance with which schedules are created. An Integer Linear Programming (ILP) model is also presented for the problem and used in combination with approaches similar to the ones above. A generalisation of the constructive utilisation threshold approach is developed in order to vary the threshold level for each day according to how far it is from the current day. In addition, the model is evaluated for different sizes of the problem by increasing the rate of patient arrivals per day and the number of machines available. Different machine allocation policies are also evaluated. An exact method is introduced for finding a set of solutions representing the whole Pareto frontier for integer programming problems. It is combined with two robust approaches: the first considers known patients before they are ready to be scheduled, while the second considers sets of predicted patients who might arrive in the near future. A rescheduling approach is also suggested and implemented. A comparison is made amongst the best results from each group of approaches to identify the advantages and disadvantages of each. The robust approaches are found to be the best alternative of the set.
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Howarth, Ashley L., Joshua R. Niska, Kenneth Brooks, Aman Anand, Martin Bues, Carlos E. Vargas, and Raman C. Mahabir. "Tissue Expanders and Proton Beam Radiotherapy." LIPPINCOTT WILLIAMS & WILKINS, 2017. http://hdl.handle.net/10150/625389.
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Proton beam radiotherapy (PBR) has gained acceptance for the treatment of breast cancer because of unique beam characteristics that allow superior dose distributions with optimal dose to the target and limited collateral damage to adjacent normal tissue, especially to the heart and lungs. To determine the compatibility of breast tissue expanders (TEs) with PBR, we evaluated the structural and dosimetric properties of 2 ex vivo models: 1 model with internal struts and another model without an internal structure. Although the struts appeared to have minimal impact, we found that the metal TE port alters PBR dynamics, which may increase proton beam range uncertainty. Therefore, submuscular TE placement may be preferable to subcutaneous TE placement to reduce the interaction of the TE and proton beam. This will reduce range uncertainty and allow for more ideal radiation dose distribution.
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Elmpt, Wouter Johannes Catharina van. "3D dose verification for advanced radiotherapy." Maastricht : Maastricht : Universitaire Pers ; University Library, Universiteit Maastricht [host], 2009. http://arno.unimaas.nl/show.cgi?fid=14960.
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Nyholm, Tufve. "Verification of dose calculations in radiotherapy." Doctoral thesis, Umeå : Umeå University, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1931.
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Varas, Jaime Armando. "Spectral unfolding of radiotherapy photon beams." Thesis, The University of Sydney, 2008. https://hdl.handle.net/2123/28131.
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An iterative folding method was used to unfold a 6 MV and 18 MV photon en—
ergy spectra from depth dose measurements. By developing a response matrix that
included photon beam attenuation in water, electron disequilibrium and contamination,
and phantom scatter factors; we unfolded the spectra from a Siemens Primus 6
MV and 18 MV radiotherapy photon beams.
The unfolding algorithm was initially applied to open fields, where we looked at
five different field sizes for each energy. Their resulting spectra were then analyzed,
our results showing a broadening of the beam spectra with increasing field size, and
an overall increase in the spectral mean energy as a function of field size for both
energies. This was attributed, in part, to the increased collimator scatter, SC, arising
from the changing field size and the dependence of the amount of flattening filter area
exposed on the field size setting.
Next we applied the unfolding algorithm to hard and soft wedges for three field
sizes, and five different wedge angles. The response matrix had to be modified, adding
an extra factor to account for wedge scatter. The results for the hard wedges showed
that though effects such as flattening filter and collimator scatter are still present in
the wedged spectra, they are dominated by the attenuation properties of the hard
wedges, with the wedge angle and field size determining the spectral distribution.
For the soft wedges, which are formed via a combination of dose rate adjustment
and jaw movement rather than the attenuation of the beam, the results were similar
to those of the hard wedges. The field size dominated the spectral distribution, with
wedge angle exerting no major effect.
For both wedge modes, the spectral change along the wedge gradient axis was
examined. It was found that there was a considerable shift in the spectrum from the
thin end of the wedge to the thick end. For the hard wedge this was expected, but a
similar result was noted for the soft wedge. The effective change in field size in the
formation of the soft wedge was noted as the cause of this effect.
The unfolding algorithm was also applied to carbon fiber inserts. These devices
are routinely used in radiotherapy, and are known to increase surface dose to patients.
By analyzing the spectrum of a 6 MV beam attenuated by a carbon fiber insert, we
were able to surmise that the increased dose was due in part to a build-up effect, and
partially due to a biased attenuation of the linac head—scatter by the carbon fiber
insert.
Noting that thermoluminescent dosimeters, TLDs, are routinely used for in vivo
measurements with soft wedges, we analyzed the effect of the changing spectrum of
a soft wedge along the gradient axis on TLDs. By using the unfolded spectrum with
EGSnrc Monte Carlo, we were able to show that the TLDs did over respond when
measuring dose of a soft wedge. This was due to the changing spectrum of the soft
wedge, and was contradictory to common belief concerning soft wedges.
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Canada, Justin M. "Impaired Cardiorespiratory Fitness Following Thoracic Radiotherapy." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5499.
Full textAbstract:
Cancer (CA) is the second leading cause of death in the United States preceded only by cardiovascular disease (CVD). Over the past 30 years, the 5-year survival rate for all cancers combined has increased by more than 20%. This improved survival rate is due to early diagnosis and advances in treatment involving a multimodality treatment approach that includes radiotherapy [RT] with about half of all CA patients receiving some type of RT sometime during the course of their treatment. Cardiotoxicity is one of the most important adverse reactions of RT and leads to a meaningful risk of CVD-related morbidity and mortality. Radiotherapy-related cardiotoxicity is a heterogeneous clinical syndrome characterized by symptoms related to impaired cardiac function due to radiation-injury to one or more cardiac structures. Furthermore, the relative risk of CVD increases with increasing incidental radiation dose to the heart.
There is not a unified consensus on the definition of CA-related cardiotoxicity although most trials have focused on changes in resting systolic function, and/or development of cardiac symptoms.Commonly used tools to assess cardiac function are insensitive to minor injury hence subtle changes may go unnoticed for many years. Cardiotoxicity definitions should include a dynamic functional assessment of the CV system. This may allow detection of latent CV abnormalities before the precipitous decline of resting myocardial function or the development of CV symptomology that may impact quality of life.
Cardiopulmonary exercise testing (CPET) including measurement of peak oxygen consumption (VO2) is the gold standard for the assessment of cardiorespiratory fitness (CRF). Cardiorespiratory fitness is a strong, independent predictor of mortality, CVD-related mortality, HF-related morbidity and mortality, CA-related mortality and may be involved in the pathophysiologic link between anti-CA related treatments and the increased risk of late CVD events. Emerging evidence indicates CRF may be reduced in CA survivors and have utility to detect subclinical cardiotoxicity, but this has not been evaluated in CA survivors treated with RT with significant heart involvement. This dissertation consists of one literature review and one comprehensive paper that will examine the ability of CPET to detect subclinical cardiotoxicity.
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Jayasekera, Piyakeerthi Mangala. "Practical aspects of radiotherapy gel dosimetry." Thesis, Queensland University of Technology, 2000.
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Smith, Shaun T. "Development of gel dosimetry for radiotherapy." Thesis, Queensland University of Technology, 2017. https://eprints.qut.edu.au/102759/1/Shaun_Smith_Thesis.pdf.
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Gel dosimeters have the potential to track radiation beams, improving safety and treatment effectiveness for radiotherapy patients, however despite extensive research over the last three decades, gel dosimeters have yet to achieve widespread clinical acceptance. In this research, a new version of the ‘Fricke’ gel dosimeter was developed which is more clinically viable. The method performs chemical manipulations on the gel ingredients to eliminate the blurring effect of dose information, which is their primary drawback.
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Morrey, D. "Aspects of computer automation in radiotherapy : A system for prescription, calculation, verification and recording of radiotherapy treatments." Thesis, Bucks New University, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376420.
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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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Jena, Rajesh. "Optimisation of radiotherapy for patients with high-grade glioma using diffusion tensor imaging and intensity modulated radiotherapy." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.614124.
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Lewis, Benjamin C. "Radiotherapy Response Using Intravoxel Incoherent Motion Magnetic Resonance Imaging in Liver Patients Treated with Stereotactic Body Radiotherapy." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5821.
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Magnetic resonance imaging is utilized as an important tool in radiation oncology for delineation of healthy and cancerous tissues, and evaluating the functionality of those tissues, structures, and organs. Currently, the clinical imaging protocol at Virginia Commonwealth University includes anatomical imaging for tissue and structure delineation, and to observe treatment induced changes. Diffusion weighted imaging (DWI) is also acquired for calculation of apparent diffusion coefficient (ADC) values to provide quantitative information on tissue diffusivity and microstructure. However, anatomical images and ADC values may not display the true extent of changes in tissue. This work seeks to further utilize the capabilities of MRI and expand its role in treatment response monitoring for liver cancer patients treated with stereotactic body radiotherapy (SBRT). To do so, an imaging protocol and image analysis methodology to evaluate treatment changes on pre- and post-treatment image sets was developed. An extension of DWI, termed intravoxel incoherent motion (IVIM) imaging, was utilized to quantitatively assess levels of perfusion and diffusion within the liver and tumor. Acquisition of high-quality diffusion weighted images of the liver necessitated the development of an MR safe respiratory motion management device, which was designed, constructed and evaluated in this work. An imaging protocol was developed providing anatomical and functional images of the liver, acquired under breath hold, utilizing the respiratory motion management device. An IVIM parameter calculation and texture analysis workflow was developed using MATLAB, and applied to acquired data sets from multiple studies, including past clinical cases, investigator, healthy volunteer, and liver cancer patient . Differences in IVIM and texture analysis parameters were investigated for healthy and diseased tissue, and for select dose regions from pre- and post-treatment imaging sessions. Significant differences, at a voxel level, were found between healthy and diseased tissue, and pre- and post-treatment volumes, for multiple parameters, including apparent diffusion coefficient, pure diffusion, and perfusion, as well as for various texture features. Overall, this study showed the potential of IVIM and texture analysis to be used for discriminating between healthy and diseased tissues in the liver, and for indication of treatment response.
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Lin, Lan. "Development and clinical application of an integrated treatment planning platform for 4D radiotherapy : a dissertation /." San Antonio : UTHSC, 2007. http://proquest.umi.com/pqdweb?did=1400966621&sid=1&Fmt=2&clientId=70986&RQT=309&VName=PQD.
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Olofsson, Jörgen. "Developing and evaluating dose calculation models for verification of advanced radiotherapy /." Umeå : Strålningsvetenskaper Radiation Sciences, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-841.
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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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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.
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Gilbert, L. "Improving the safety of radiotherapy treatment delivery." Thesis, Coventry University, 2015. http://curve.coventry.ac.uk/open/items/58d00757-edad-48c5-8676-9f5bf07ffd7c/1.
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Errors during radiotherapy treatment can cause severe, and potentially fatal, patient harm. The final check immediately prior to treatment delivery, whereby two radiographers ensure that the dose about to be delivered corresponds with the prescription, is the last defence against error. The aim of this research was to increase understanding of this final treatment check and factors affecting error detection, in order to improve the safety of radiotherapy treatment delivery. The research adopted a mixed methods approach, combining qualitative and experimental studies to investigate the interaction of factors affecting accuracy during the final treatment checks. The qualitative interviews and task analysis pointed to difficulties maintaining attention and variation in how these checks are conducted. The interface used to conduct the final treatment check was also recognised to have usability issues. The laboratory-based experimental studies results indicated that a structured form of double checking, called challenge-response, is most effective at error detection, when compared to single or unstructured double checking. Furthermore, it was found that alternating the roles of challenger and responder, and the order parameters are checked in, significantly increases accuracy during repeated treatment checks. The original contribution of this research was a detailed investigation of a previously understudied aspect of radiotherapy treatment. The results informed the design of an original, evidence and theoretical based two-person checking protocol for use during the final treatment check. Qualitative evaluation indicates that it would be well received as a standardised method of treatment checking. Furthermore, an alternative interface design has been proposed, specifically for use during the final treatment check. This was comparatively tested against the most frequently used software package within the UK and found to have a significant positive impact upon user’s accuracy. An additional output is a series of practice based recommendations to improve accuracy during repeated treatment checking. This research has concluded that implementation of the practice recommendations, checking protocol and interface design should help maintain radiographers’ attention during repeated final treatment checks, thereby preventing errors passing undetected. Future research into the radiotherapy interface design and implementation of the standardised final treatment check protocol have been identified.
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Wyer, J. A. "Radiolysis of Molecules of Interest in Radiotherapy." Thesis, Queen's University Belfast, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492265.
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The use of highly-energetic iOIl: beams for treating cancerous tumours is of increasing importance. In this study the damage caused to plasmid DNA by HO and H+ beams was investigated. Damage to dry DNA samples as a function of dose was assessed using gel electrophoresis. Results show enhanced levels of damage relative to that of x-rays and demonstrate an increase in damage with beam energy. Additionally, a considerable dependence on sample structure was shown. X-ray irradiation work has shown that doping samples with gold nanoparticles greatly enhances DNA damage and could enhance the effectiveness of cancer treatment. Hence in this study, damage to DNA samples containing gold nanoparticles was investigated, however, no enhancement was observed. TOF-MS was used to investigate fragment damage profiles at a molecular level. High-mass fragments corresponding to basal cleavage were not observed. Significant buffer residues in the dried samples were seen and identified. A model of DNA damage as a function of dose was constructed, providing quantitative conclusions about the effects of both gold nanoparticles and the different buffers used. Most of the energy deposited in the body by ionising radiation is absorbed by water molecules, leading to radical formation and, potentially, subsequent DNA damage. Current damage models use information on energy loss rates with penetration depth instead of information on radical production. In this work, fundamental fragmentation processes of water molecules irradiated with H+, HO and carbon ions and atoms were investigated. It was shown that it is imperative to consider the damage caused by fast neutrals in any dose profile modelling. Additionally, results for the ion production rate, to which free-radical production relates directly, show it is actually relatively uniform at a region where the ions come to rest and is not as sharply localised as suggested by the Bragg peak energy loss profiles.
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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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Moerland, Marinus Adriaan. "Magnetic resonance imaging in radiotherapy treatment planning." [S.l.] : Utrecht : [s.n.] ; Universiteitsbibliotheek Utrecht [Host], 1996. http://www.library.uu.nl/digiarchief/dip/diss/01760825/inhoud.htm.
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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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Curtin-Savard, Arthur. "Dose delivery uncertainty in photon beam radiotherapy." Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=22856.
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It is known that slight variations in total dose delivered to the patient in external beam photon radiotherapy can significantly alter the probability of tumour control. For this reason, ICRU has recommended a goal of $ pm$5% precision in the dose delivery to the target volume. Several investigators have analyzed the degree of precision routinely achieved and have come to the conclusion that ICRU's goal can be attained, but in practice this is just barely so.We have measured the degree of precision which exists in our institution by examining each step of the radiotherapy process on a cobalt unit and a 10 MV linear accelerator. Our study finds beam intensity uncertainties of $ pm$3.8% (one standard deviation) and beam positional uncertainties of $ pm$5.5 mm (one standard deviation). The effect of these uncertainties on the dose to the patient is illustrated for a typical case.