Technology in Radiotherapy Feasibility Studies

The context of the research:Approximately one in three people will develop cancer at some point in their lives. Technical improvements in diagnosis and treatment have significantly contributed to improved survival in recent years: the 5 year rate is now 50% and the 10 year rate has doubled in the last 30 years. It is in this context that our research group operates, particularly with reference to radiotherapy, which treats 40% of patients.Each proposing institute has an established track record of delivering innovative research, both individually and as a consortium. Indeed, we jointly created the Engineering & Computational Science for Oncology Network (ECSON), with the aim of establishing a basis for free exchange of cross-disciplinary expertise and knowledge to expedite technical solutions to problems in cancer therapy. Funded by the EPSRC Collaborating for success through people programme, ECSON is a formidable hub composed of 24 leading academic, research, commercial and clinical institutions from 6 European countries.Whilst the majority of physics/engineering activity in oncology is focused on delivering translational research that will be beneficial to patients in the short-term, this feasibility account presents an opportunity to explore some of the riskier ideas, with the potential to engender significant changes in long-term knowledge and treatment, that have emerged from the rich breeding ground of ECSON.The aims and objectives:The proposed research has the potential to open unexplored avenues of investigation of particular relevance to radiotherapy. However the tools and techniques we hope to create may provide the means for other investigators to conduct studies that could well be tangential to our aims.There are 4 themes to our proposal, drawing on different strengths of the proposing institutes:-We aim to investigate the bio-mechanical properties of healthy and cancerous cells when subjected to radiation exposure. We think this could provide evidence implicating the cellular structure as a whole in their response to radiation, as opposed to just the nuclear DNA.-We will investigate subtle structure in 3D/4D (i.e. moving 3D) medical images that we think clinicians may sub-consciously refer to when looking at images. This is particularly relevant to modern image guided radiotherapy where image quality is poor in comparison with diagnostic data.-We will model the complex cytoskeletal structure in cells. We believe this structure is implicit in a cell's mechanical strength, so understanding its structure fully will enable scientific, evidence-based analysis of its contribution. Also we will investigate how it varies in cancerous cells and cells exposed to radiation.-We will measure the 3D movement and articulation of head and neck radiotherapy patients' faces. We hope that we will be able to identify early predictors of treatment complications that can result in loss of facial function.Potential applications and benefits:Each of these themes constitutes an exciting, high-risk, but potentially very rewarding avenue of investigation. If realised, our research aims could, in the medium to long term, bring about very significant benefits in the radiotherapy process. We think they could lead to the introduction of new procedures, improvement in existing treatment methods, or even the dawn of a completely new ways of understanding the manner in which radiation interacts with healthy and diseased cells - i.e. the way in which radiotherapy works! Beyond radiation therapy, we hope that any tools we might develop, or discoveries we might make, during the proposed research could open up a number of new topics for academia. In this respect we are well placed, as the cross-disciplinary nature of the ECSON network provides the means to rapidly communicate findings outside our traditional subject areas. We believe that this work could provide immense gains across all medical fields.

If successful the proposed research presents the medium to long term possibility of bringing about very significant benefits to the patients and clinical staff across the radiotherapy process, as well as to relevant manufacturing sectors. Who will benefit from this research and how ? Patient Beneficiaries: Nearly half of all cancer patients have radiotherapy and the proposed research has the potential to majorly impact this process. The research on biomechanical properties of cells can have significant future impact on the delivery of radiotherapy. If mechanical properties do indeed alter as a result of radiation insult for mammalian cells, as it is hypothesised, it would radically change the conventional views on how ionising radiation kills both healthy and pathological cells and as a consequence would lead to improved treatment procedures. Quantifying clinical image structural content, as proposed, will be instrumental in limiting the additional radiation dose delivered to patients. A formal, quantifiable, understanding of cytoskeletal structure would bring closer the goal of being able to model the cell as a chemo-mechanical system. Such a model would be a major tool in studying drug and radiation insult to cells, where structure change plays a significant role - e.g. cancer, and Alzheimers disease, etc. If the proposed feasibility studies show a potential for using facial scans to measure a radiation-induced damage, then this would be likely to open a completely new way of non-invasive monitoring of radiotherapy for head and neck patients. Furthermore, it would be of benefit to other patients, such as stroke patients, enabling early detection of symptoms and better patient care. Clinical Staff Beneficiaries: Clinical experts are pressed for time to accurately define tumour position during pre-treatment planning, let alone on each day of treatment. The clinically oriented image metrics investigated in the proposed research will provide the potential for simplified, automated procedures for treatment monitoring, freeing-up the valuable time of clinical staff. Drug design is one area in which biomolecular computer modelling is becoming more prevalent. For cellular diseases such as cancer, where therapeutic drugs often work by interaction with the cytoskeleton, e.g. tomoxifen, the ability to accurately model cytoskeletal structure in healthy and diseased cells would be of inestimable benefit. For facial dysfunction assessment, there exists no robust and quantitative measurement of facial articulation, other than subjective judgement. The proposed research will contribute to the development of objective standards, by discovering possible metrics for changes in facial symmetry and weakness, leading to a reduction in precious clinicians' time that currently spent in visual examination and diagnosis. Manufacturers: Radiotherapy is a technology driven activity, so with the proposed standardised clinical image quality measures, manufacturers of imaging modalities and treatment planning systems would be in a better position to respond to clinical needs. Research on cell biomechanics and facial scans, if successful, would have very significant effects on manufacturing industry, e.g. by opening completely new markets for dynamic 3D scanners, or atomic force microscopes. Action plan to ensure that beneficiaries will have the opportunity to benefit from the project As the proposed project consists of feasibility studies, it is very difficult to predict their outcomes and consequently plan for their exploitation, but whatever outcomes will be achieved, they will be communicated to the wider research community, clinicians, patient groups, and relevant manufacturing sectors, through dissemination of the results. Feasibility account results will also be presented at public events, open days, etc. This will include the creation of CDROM 'story-boards' to share scientific concepts and their clinical applications.