134 research outputs found

    Identification of dose constraints and evaluation of optimal planning technique for radical thoracic re-irradiation for non-small cell lung cancer

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    Background There are approximately 48,000 new diagnoses of lung cancer in the United Kingdom. It is one of the most lethal cancers, with a 10% chance of survival at 10 years. A third of patients receive radiotherapy a part of the primary treatment for lung cancer. However, there is an approximately 30% local recurrence rate after radical radiotherapy for non-small cell lung cancer, and there is a 14% risk at 10 years of developing a second lung cancer. There are no treatment guidelines for patients who are diagnosed with intra-thoracic relapsed disease. Radical thoracic re-irradiation for non-small cell lung cancer has been performed in selected patients from the 1970s with promising efficacy. However, re-irradiation is associated with increased risk of toxicity compared to de novo radiotherapy. Re-irradiation is being delivered more frequently due to the advances in radiotherapy technology and better detection of recurrent disease, despite the lack of evidence in how to deliver re-irradiation safely, or any recent prospective studies that demonstrate efficacy. Aim of thesis The aim of this thesis is to investigate how to optimise the safety of radical thoracic re-irradiation, in preparation for a future prospective clinical trial. Methods (i) An international Delphi consensus process with thoracic oncologists was performed to identify current practice in thoracic re-irradiation, patient selection, develop dose constraints and radiotherapy planning strategies. (ii) A retrospective review of 39 patients who underwent re-irradiation in the Beatson West of Scotland cancer centre was conducted. Clinical outcomes and cumulative dosimetric information were analysed. Image and dose registration strategies were developed to account for the previous dose delivered from initial radiotherapy with the re-irradiation dose. (iii) A literature review was performed to collect information (including toxicity, cumulative dose, interval between treatments and use of chemotherapy) about thoracic re-irradiation. This was divided into five datasets for the organs at risk in the chest (spinal cord, oesophagus, lungs, proximal bronchial tree, and aorta) and logistic regression modelling was performed to determine cumulative dose constraints. (iv) A literature review was performed to collect information (including cumulative dose, local control, and overall survival rates) from thoracic re-irradiation for non-small cell lung cancer. Logistic regression modelling was performed to determine the dose required for 50% rates of 2-year local control and overall survival. (v) A radiotherapy planning study using the 39 Beatson patients was conducted using volumetric arc therapy (VMAT) and multi-criteria optimisation (MCO). Patients were re planned to the cumulative dose constraints and the models developed in sections (iii) and (iv) were applied to assess if the re-planned re-irradiation was safer. (vi) Patients who had completed a course of radical lung radiotherapy were recruited into a qualitative interview study to explore patients’ perspectives on re-irradiation. The interviews were transcribed and underwent thematic analysis. Results (i) Fifteen lung oncologists participated in the Delphi process. Patients being considered for radical re-irradiation should be PS 0-2, and radical resection should be discussed. Staging with PET-CT and brain imaging was endorsed. Consensus dose constraints based on clinician expertise were agreed upon for the oesophagus, spinal cord, brachial plexus and aorta. There was no consensus for lung and proximal bronchial tree doses. (ii) Clinical outcomes and cumulative dose of 39 patients from the Beatson were analysed and divided into patients with local recurrence and second primary lung cancers. The 2-year OS rate was 38.5% in the local recurrence group, and 69.2% in the SPLC group. Sixteen patients (41%) experienced grade 3 toxicities and one patient (2.6%) had fatal haemoptysis. A reproducible process to accumulate dose was developed, which identified that using the whole lung for image registration was the optimal strategy. (iii) The literature search identified 55 studies with the cumulative dose and toxicity required for modelling. Dose/toxicity models were developed using logistic regression for the spinal cord, oesophagus, the mean lung dose, the lung V20Gy, the proximal bronchial tree and aorta. There was insufficient data to model the heart, chest wall and brachial plexus dose. For the spinal cord, oesophagus, proximal bronchial tree and aorta, the maximum likelihood 5% risk of grade 3 toxicity was seen at 77.2Gy, 94.3Gy, 157.5Gy and 142.5Gy respectively (all doses in equivalent dose in 2-Gray fractions, median values used if other variables were included in the model). The mean lung dose and V20Gy associated with 20% grade 3 toxicity were 19.3Gy and 28.4% respectively. These models were validated on the Beatson data, and dose constraints developed. (iv) The literature search identified 21 studies with 2-year local control or overall survival data and cumulative dose to the tumour. Dose/outcome models were developed using logistic regression modelling. The modelling predicted a 50% 2-year local control rate at 67.8Gy using a median planning target volume of 112cc. The predicted dose to the tumour for a 50% 2-year overall survival rate was 76.5Gy. A sub-study to assess if 13 locally recurrent patients from the Beatson cohort could have dose escalation identified six patients where their re-irradiation dose could potentially be increased. (v) The planning study identified 15 patients from the 39 patients in the Beatson cohort that breached the re-irradiation dose constraints. These patients mostly had locally recurrent disease. Seven patients were replanned using VMAT and MCO and met the dose constraints. The remaining eight patients required alternate strategies (such as a change in dose fractionation or modification of the planning target volume) to meet the constraints. Six patients were able to be safely replanned with these alternate strategies. The combination of VMAT and MCO was superior to VMAT alone when planning re-irradiation for sparing the serial organs at risk in the chest. (vi) Eight patients participated in a qualitative interview exploring their perspectives on radical re-irradiation. Thematic analysis identified two main themes from the interviews: fear and control. The key finding was that all patients would consider re-irradiation. A common reason given was they were not afraid of it having experienced radiotherapy before. Each patient had a very different attitude to risk, with some patients stating that they would accept high risk treatment if the outcomes were better, whereas others preferred to prioritise avoiding toxicity. Conclusions The research detailed in this thesis contributes to the delivery of safe re-irradiation in several ways. The consensus statements provided guidance for the selection and staging of patients to be considered for radical re-irradiation, ensuring that only suitable patients proceed with high-risk treatment. The dose constraints developed from the dose/toxicity can be used to limit severe re-irradiation toxicity and allows patients to be better counselled prior to treatment. The dose/outcome study identified that recurrent disease required higher doses for disease control, and that dose escalation may be possible in selected patients. The planning study identified that the optimal planning technique is VMAT with MCO. The qualitative study demonstrated that patients may consider re-irradiation and require individual counselling regarding their acceptance of risk. This research provides insights to the inclusion criteria, dose constraints, radiotherapy planning technique and the patient and public involvement necessary for a prospective clinical study of re-irradiation

    Applications

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    Volume 3 describes how resource-aware machine learning methods and techniques are used to successfully solve real-world problems. The book provides numerous specific application examples: in health and medicine for risk modelling, diagnosis, and treatment selection for diseases in electronics, steel production and milling for quality control during manufacturing processes in traffic, logistics for smart cities and for mobile communications

    Systematic Approaches for Telemedicine and Data Coordination for COVID-19 in Baja California, Mexico

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    Conference proceedings info: ICICT 2023: 2023 The 6th International Conference on Information and Computer Technologies Raleigh, HI, United States, March 24-26, 2023 Pages 529-542We provide a model for systematic implementation of telemedicine within a large evaluation center for COVID-19 in the area of Baja California, Mexico. Our model is based on human-centric design factors and cross disciplinary collaborations for scalable data-driven enablement of smartphone, cellular, and video Teleconsul-tation technologies to link hospitals, clinics, and emergency medical services for point-of-care assessments of COVID testing, and for subsequent treatment and quar-antine decisions. A multidisciplinary team was rapidly created, in cooperation with different institutions, including: the Autonomous University of Baja California, the Ministry of Health, the Command, Communication and Computer Control Center of the Ministry of the State of Baja California (C4), Colleges of Medicine, and the College of Psychologists. Our objective is to provide information to the public and to evaluate COVID-19 in real time and to track, regional, municipal, and state-wide data in real time that informs supply chains and resource allocation with the anticipation of a surge in COVID-19 cases. RESUMEN Proporcionamos un modelo para la implementación sistemática de la telemedicina dentro de un gran centro de evaluación de COVID-19 en el área de Baja California, México. Nuestro modelo se basa en factores de diseño centrados en el ser humano y colaboraciones interdisciplinarias para la habilitación escalable basada en datos de tecnologías de teleconsulta de teléfonos inteligentes, celulares y video para vincular hospitales, clínicas y servicios médicos de emergencia para evaluaciones de COVID en el punto de atención. pruebas, y para el tratamiento posterior y decisiones de cuarentena. Rápidamente se creó un equipo multidisciplinario, en cooperación con diferentes instituciones, entre ellas: la Universidad Autónoma de Baja California, la Secretaría de Salud, el Centro de Comando, Comunicaciones y Control Informático. de la Secretaría del Estado de Baja California (C4), Facultades de Medicina y Colegio de Psicólogos. Nuestro objetivo es proporcionar información al público y evaluar COVID-19 en tiempo real y rastrear datos regionales, municipales y estatales en tiempo real que informan las cadenas de suministro y la asignación de recursos con la anticipación de un aumento de COVID-19. 19 casos.ICICT 2023: 2023 The 6th International Conference on Information and Computer Technologieshttps://doi.org/10.1007/978-981-99-3236-

    Virginia Commonwealth University Graduate Bulletin

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    Graduate bulletin for Virginia Commonwealth University for the academic year 2022-2023. It includes information on academic regulations, degree requirements, course offerings, faculty, academic calendar, and tuition and expenses for graduate programs

    Non-canonical Kinases and Substrates in Cancer Progression

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    This book is a printed edition of the Special Issue "Non-canonical Kinases and Substrates in Cancer Progression" that was published in the scientific journal Cancers. It was edited by Francisco M. Vega, Ph.D. from the University of Seville in Spain. It brings together the latest views and original research on non-canonical protein kinases, substrates, and scaffold

    An Approach Based on Particle Swarm Optimization for Inspection of Spacecraft Hulls by a Swarm of Miniaturized Robots

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    The remoteness and hazards that are inherent to the operating environments of space infrastructures promote their need for automated robotic inspection. In particular, micrometeoroid and orbital debris impact and structural fatigue are common sources of damage to spacecraft hulls. Vibration sensing has been used to detect structural damage in spacecraft hulls as well as in structural health monitoring practices in industry by deploying static sensors. In this paper, we propose using a swarm of miniaturized vibration-sensing mobile robots realizing a network of mobile sensors. We present a distributed inspection algorithm based on the bio-inspired particle swarm optimization and evolutionary algorithm niching techniques to deliver the task of enumeration and localization of an a priori unknown number of vibration sources on a simplified 2.5D spacecraft surface. Our algorithm is deployed on a swarm of simulated cm-scale wheeled robots. These are guided in their inspection task by sensing vibrations arising from failure points on the surface which are detected by on-board accelerometers. We study three performance metrics: (1) proximity of the localized sources to the ground truth locations, (2) time to localize each source, and (3) time to finish the inspection task given a 75% inspection coverage threshold. We find that our swarm is able to successfully localize the present so
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