NIHRDataInsights/HRCSData huggingface dataset:
Title: Choice and Competition - Does provider choice improve quality outcomes for cancer patients?
Funder: Department of Health (England)

Abstract: This research will assess whether NHS Choice and Competition influences treatment decisions and improves quality outcomes for patients with cancer. It will utilise a mixed methods research design. The patient cohort will be defined from the National Prostate Cancer Audit, which will collect information on all newly diagnosed prostate cancer patients in England and Wales. It will identify the proportion of cancer patients choosing alternative cancer care providers, their socio-demographic profile and characteristics of providers that gain or lose patients. The outcomes are expected to provide guidance on the organisation and delivery of specialist cancer services in the NHS.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: CANCER AND NEOPLASMS
Title: Predicting acute radiosensitivity in breast cancer: an exploratory study incorporating the patient’s perspective
Funder: Department of Health (England)

Abstract: After surgery, radiotherapy is the second most commonly used treatment for breast cancer. However, radiotherapy causes side-effects to the body’s normal tissues. Some patients even experience severe acute reddening and peeling of the skin, which can considerably affect their quality of life. There are various known pre-disposing factors, but research has also shown that an individual’s sensitivity to radiation is influenced by their genes. The aim of this study is to find out how this information can be used to predict more accurately who is at risk of radiotherapy side-effects and to develop a decision-making tool for breast cancer patients.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Addressing treatment switching within Health Technology Assessment: Development, evaluation and application of methods of adjustment
Funder: Department of Health (England)

Abstract: Treatment switching is when patients switch treatments during a Randomised Control Trial (RCT). This often occurs on disease progression when the experimental treatment is more effective than the control. If treatment switching is not accounted for, the difference in the effectiveness of the treatments is reduced. While patients in the RCT benefit from switching treatments, other patients may be denied the experimental treatment on the NHS if it is not judged cost-effective because of the reduced difference between the treatments. This project develops and evaluates new methods to address treatment switching, and ensuring better healthcare decisions to be made.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: CANCER AND NEOPLASMS
Title: 2011 Doctoral Fellowships: Differences in gene methylation due to human papillomavirus infection in oropharyngeal squamous cell carcinoma
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Introduction and Aim It has been established that abnormal methylation is an epigenetic mechanism that can lead to neoplasia. The direct relevance of this is not well understood in head and neck cancer, and the aim of this study is to increase knowledge on patterns of methylation with regard to human papillomavirus (HPV) infection. Objectives The study will identify genes and pathways whose expression has been altered by methylation, and whose functional significance may be of interest for future clinical studies. Design Retrospective study with matched case-control design Methodology 60 OSCC samples (from the pathology department of Belfast HSC Trust between 2000 and 2008) of adequate size for nucleic acid extraction will be examined. DNA and RNA will be isolated from formalin-fixed paraffin-embedded human tissue and the methylation of CpG island amplification and microarray (MCAM) technique will be performed. Following this, the HPV status and subtype will be determined. Genes that are differentially methylated in association with HPV infection will be examined in more detail, and the results of the MCAM analysis will be validated with pyrosequencing. The results of the methylation study will be related to clinical parameters and linked to five-year survival statistics. Opportunities of the Study The use of microarray technology enables high throughput analysis of valuable human tissue, which can then direct further work looking at individual genes in detail. It is hoped that this work will identify novel predictive biomarkers and potential molecular targets for the development of new treatments in head and neck cancer.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: 2011 Doctoral Fellowships: Molecular Characterisation of poor Prognosis triple negative Breast Cancers
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Aims: The aim is to identify a panel of markers capable of distinguishing good from poor prognosis triple negative breast cancer and characterize the biology driving the poor prognosis phenotype. Objectives •Perform gene expression Prof.iling of ‘poor’ versus ‘good’ prognosis triple negative breast tumours. Undertake supervised and unsupervised analysis to classify poor versus good prognosis tumours and identify novel biomarkers that correlate with prognosis. Characterize the functional pathways that define poor versus good prognosis triple negative breast cancer in cell line models. Design: We have identified 300 triple negative breast cancers with linked survival data. We will perform microarray based expression Prof.iling from 10 micron FFPE sections from a discovery set selected from the cohort. We will Prof.ile 50 poor prognosis and 50 good prognosis samples matched for stage, grade, age and nodal status using the Almac Diagnostics Breast Cancer DSA that has been designed for Prof.iling from FFPE derived RNA. The resulting data will be analysed to identify markers linked to poor prognosis and the key genes driving the poor prognosis phenotype at a functional level. Scientific and Medical opportunities of the study: The major opportunity is the development of a Qrt-PCR or IHC based assay capable of differentiating good from poor prognosis triple negative breast cancer. This assay would have significant clinical utility by highlighting a sub-population of triple negative breast cancers that are at significantly higher risk of relapse and should be considered for additional novel treatments.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: 2011 AIIHPC Doctoral Fellowship: Developing a Cancer Cachexia Rehabilitation Intervention for People with Inoperable Advanced Non Small Cell Lung Cancer
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Pain, fatigue, anorexia and weight loss are some of the most prevalent physical symptoms in advanced non small cell lung cancer (NSCLC). Control of cancer pain has improved considerably with standardised guidance for assessment and treatment. Optimal management of fatigue, anorexia and weight loss is still to be determined. These three symptoms are components of cancer cachexia syndrome. The aim of this proposal is to develop and test a cancer cachexia rehabilitation intervention to reduce symptom burden and improve quality of life in individuals with NSCLC. User, healthcare professional (HCP) and personal and public involvement (PPI) perspectives will be uniquely combined to ensure that the intervention is considerate of the barriers and enablers to effective adherence and implementation. A fixed exploratory sequential mixed methods design will be employed, modelled on the Medical Research Council (MRC) framework to complex interventions. •Phase 1: Up to 20 people with advanced NSCLC will be interviewed on their experiences of living with and managing symptoms of cancer cachexia •Phase 2: Up to 20 HCPs working in cancer centres and hospices in Belfast and Dublin will be invited to share their views on current and ideal practice for managing symptoms of cancer cachexia within multidisciplinary focus groups •Phase 3: Synthesis of user and HCP perspectives to develop a cancer cachexia rehabilitation intervention •Phase 4: Testing feasibility of the intervention with 30 people who have advanced inoperable NSCLC People with a lived experience of lung cancer will be involved throughout the research.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: CANCER AND NEOPLASMS
Title: 2013 Doctoral Fellowship: Characterising the cell of origin of high grade serous ovarian cancer (HGSOC)
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Serous ovarian cancer is the most common type of epithelial ovarian cancer and has subdivisions of high and low grade (HGSOC and LGSOC, respectively). These differ in underlying pathogenesis, molecular events, behaviour and prognosis. HGSOC is more common, clinically more important and has a worse prognosis. It has been postulated to arise from either the ovarian surface or the distal fallopian tube (FT) with the proposed precursor lesion being serous tubal intraepithelial carcinoma (STIC). Defining the cell of origin is highly important in investigating the underlying biology of this aggressive disease. To do this, we performed a pilot study involving gene expression profiling of tissue from 6 cases of HGSOC: normal fallopian tube epithelium, ovarian surface epithelium (OSE), STIC, HGSOC and omental metastases. Initial unsupervised clustering analysis has revealed that the molecular profile of HGSOC is more similar to the FT than the OSE. In addition, the STIC lesions appear to cluster more closely to HGSOC. This supports our hypothesis that the fallopian tube is the cell of origin of HGSOC. We now propose to identify genes that are commonly and also differentially regulated between the FT, serous TIC and HGSOC. We hope this will identify target genes and molecular pathways which are reflective of the pathogenic events occurring when serous TIC transforms into HGSOC. Finally, we plan to generate a tissue microarray containing all of these ovarian tissues in order to perform immunohistochemical based validation of any novel gene targets or mutations that we identify in this study.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Next generation intraoperative lymph node staging for stratified colon cancer surgery.
Funder: Department of Health (England)

Abstract: Research Design: A prospective multi-centre evaluation of 5-ALA fluorescence diagnosis (FD) for patients with colon cancer. Study population: Inclusion criteria: right or sigmoid colon cancers amenable to laparoscopic resection. Exclusion criteria: transverse/left colon cancers; metastatic disease (evaluation phase only); history of hypersensitivity reactions porphyria renal or hepatic impairment synchronous colorectal tumours co-existent colonic pathology. Planned interventions: A pre-operative CT scan will be assessed for lymph node metastases. Patients will undergo colonoscopy with peritumoral injection of colorimetric dye (India ink) and administered oral 5-ALA. At operation a Storz D-Light laparoscope will be used for FD of involved lymph nodes. Patients resection of colorectal cancer with D3 lymphadenectomy. Lymph nodes will be mapped according to their anatomical location and fluorescence status and subjected to in-depth histological analysis. Proposed outcome measures: Developmental phase - primary outcome: an optimised protocol for colorimetric dye/5-ALA FD; secondary outcomes: standardisation of D3 resection and histopathology. Evaluation phase- primary outcome: diagnostic accuracy of 5-ALA FD as compared to histopathology; secondary outcomes: comparison of 5-ALA FD with CT staging comparison of standard and in-depth histological analysis ability of 5-ALA FD to stratify patients for D3 resection and 30-day safety. Assessment and follow-up: Data collected for 30-days to include demographics CT staging operative details including 5-ALA FD histological assessment and safety. Proposed sample size: 300 patients required to provide a to provide a 95% confidence interval of +/-7 to 9.2% for sensitivity estimates between 80 and 90% and +/-5.4 to 6.1% for specificity estimates between 70 and 80% and to detect a 15-21% difference in sensitivity/specificity between CT and 5ALA lymph node staging (80% power 5% significance). Statistical analysis: Sensitivity specificity positive and negative predictive values and 95% confidence intervals for 5-ALA FD and CT staging compared with histology will be calculated using the Wilson Score method. These values will be compared for CT and 5-ALA FD using McNemar’s chi-squared test. Project timetables including recruitment rate: Developmental stage - at least 40 patients from 2 centres over 18 months. The milestone will be optimisation of protocols for colorimentric/5-ALA FD which will constitute a Go/No-Go decision point. Evaluation phase – 300 patients recruited over 24 months from 10 centres. Milestones include recruitment of 100 patients at 12 months.


Research activity codes: 6.4 SURGERY;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Spin Dynamics - from quantum theory to cancer diagnostics
Funder: Engineering and Physical Sciences Research Council

Abstract: This project addresses a long-standing problem in the physics and chemistry of magnetic phenomena -- the lack of efficient simulation algorithms for quantum spin dynamics.All magnetic processes can be traced back to a property of elementary particles called 'spin', but until recently the calculations of realistic systems could only be done for less than ten spins - a major limitation, particularly in chemical and biological magnetic spectroscopy, where the molecules often contain hundreds of spins.We recently solved this theoretical problem and will now proceed to implement and use the resulting high-efficiency algorithms to boost a number of research projects in magnetochemistry and biological magnetic resonance.Specifically, biological magnetoreceptors (some migratory birds feel the Earth's magnetic field and use it for navigation) can now be simulated and analysed, and so can paramagnetic cancer diagnostics agents, which are currently used in early cancer detection by MRI (magnetic resonance imaging). We have published a number of research papers in both areas and expect these research fields to benefit significantly from the expanded simulation capabilities.There are also a number of long-standing problems within chemistry itself, which can be solved now that large spin systems can be simulated -- protein structure determination can be streamlined and simplified, the analysis of magnetic spectroscopy experiments is no longer constrained by the available computer power, the questions about the possible chemical and biological effects of mobile phones and power transmission lines can be evaluated using quantum mechanical simulations of spin dynamics. Last, but not least, money can be saved and animal lives spared by theoretical pre-screening of molecules before running an experiment.On the practical level, the research programme will include:1. Theoretical segment: further investigation and optimization of high-efficiency spin dynamics simulation algorithms2. Software segment: creation and testing of powerful user-friendly open-source software package for spin dynamics simulation of chemical and biological systems3. Applications segment: application of the resulting theory and software to the investigation of magnetic phenomena in chemistry and biology.We believe this is an exciting and timely research project that will bring direct benefits to the society by creating powerful and efficient tools for fundamental and applied research as well as by addressing current questions and concerns relating to magnetism.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Interaction of metal complexes with DNA and proteins: towards a new generation of therapeutic and imaging agents
Funder: Engineering and Physical Sciences Research Council

Abstract: The search for new chemicals that have therapeutic properties is a lengthy and costly process that continuously looks for chemical diversity. While organic compounds have been extensively studied in this context far less is known about the therapeutic properties of metal complexes. In spite of the great success of some metallo-pharmaceuticals such as cis-platin in cancer therapy, and gadolinium complexes in Magnetic Resonance Imaging (MRI), medicinal inorganic chemistry has received comparatively very little attention from the pharmaceutical industry and in general from the medicinal chemistry community. However, the structural and electronic versatility of metal centres provide a unique opportunity to explore chemical diversity for the rational design of drugs. Furthermore, metals often have attractive optical and magnetic properties that are ideally suited for the development of molecular probes for bio-imaging. The project herein presented aims at developing novel metal complexes as potential anticancer drugs. In particular, we will aim to develop complexes that can selectively interact with a specific type of DNA (named quadruplex DNA which in recent years has been increasingly associated with regulatory processes in the human genome and has emerged as a novel and distinctive target for the development of anticancer drugs). To realize the full therapeutic potential of the compounds developed, their interactions with proteins relevant to transport and delivery will be studied. Besides the potential therapeutic properties of the compounds developed (with the obvious implications to a range of beneficiaries) we will also aim to develop molecular probes that can be used to gain a better understanding of the interaction of small molecules and quadruplex DNA.Metal-containing compounds have been overlooked for a long time by the pharmaceutical industry and medicinal chemistry community. However, their distinctive structural and functional properties provide a unique opportunity for the development of new therapeutic agents and imaging tools. The vision of this project is to demonstrate that metal complexes that interact with quadruplex DNA, can be excellent candidates for the development of anticancer drugs and also unique probes for bio-imaging.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Multimodality Techniques for Cancer Diagnosis and Therapy
Funder: Engineering and Physical Sciences Research Council

Abstract: Many of the key opportunities that currently exist for improving the diagnosis and treatment of cancer are cross-disciplinary. Imaging now crucially underpins all therapeutic procedures. The Joint Department of Physics has developed and implemented methods for accurately delivering different radiation therapies to tumours using CT, Magnetic Resonance (MR) and/or ultrasound (US) imaging, but the use of emerging molecular imaging techniques (such as Positron Emission Tomography (PET), functional MR, US and optoacoustic imaging) will give us the opportunity to define targets according to biochemical or metabolic function. A major challenge in therapeutics is organ motion: here, for example, we are developing methods for pre-treatment modelling using MR, real-time US and intelligent x-ray tracking to guide radio- and US therapy. There are significant challenges in developing cross-disciplinary projects. These include training and retention of staff with the key combination of skills in imaging physics, therapy and clinical application, and the development of specialist multi-modality equipment, molecular imaging probes and histological techniques to support pilot studies. For example, satisfying the needs of both x-ray imaging and MR compatibility, can be challenging. A particular challenge in this sector is the translation of laboratory research to a stage where it may be tested in clinical trials. We are uniquely placed for addressing these. Platform funding will help us to retain researchers with the highly specialist key skills, to fund the pilot work for multi-modality applications and to allow translation of research results to a stage where they are ready for exploitation either in our clinics or by collaboration with industry.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: Development of Theranostic Nanoparticles; MRI-responsive, thermosensitive drug carriers activated by MRg FUS for local tumour drug release
Funder: Engineering and Physical Sciences Research Council

Abstract: Our proposed research program is concerned with how to mobilize physical science and engineering innovation in nanoparticle drug carrier design from basic science laboratory to medical application. In order to do this, Prof Miller's chemistry team (Imperial) with expertise in nanoparticle technologies, will collaborate closely with Dr Maya Thanou's pharmaceutical sciences team (Kings) in the design, formulation and characterization of MRI-responsive thermosensitive drug carrier nanoparticles (theranostic ABC nanoparticles) that have the capacity to accumulate in cancerous lesions (fibroids or tumours), in real time post administration in vivo (as observed by MRI). Thereafter, we will collaborate with and make use of the expertise of the research teams of Prof Gedroyc and Dr Stebbing (Imperial, Medicine) to demonstrate that these nanoparticles can then be activated by means of magnetic resonance guided focused ultrasound (MRgFUS) to release drug locally at sites of nanoparticle accumulation within the relevant lesion. This combined process should be able to deliver a powerful anti-cancer effect that also improves radically on local drug bioavailability (specific only to tumours) and drug efficacy while minimizing systemic drug toxicity. Nanoparticle modelling and fluid dynamics studies will then be performed by the team of Prof Xu (Imperial, Chemical Engineering) in order to improve our understanding of the delivery barrier and drug release and uptake process. Thereafter we shall seek to take this understanding to optimize MRgFUS-activated theranostic nanoparticle mediated drug delivery of actives in vivo provided by our healthcare partner Antisoma. We anticipate that Antisoma and our other healthcare partners [the Focused Ultrasound Surgery (FUS) Foundation and MacMillan Nurses] will assist us with the commercialization process thereafter including providing some of their novel anti-cancer compounds for local delivery, to increase efficacy and decrease toxicity.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS