NIHRDataInsights/HRCSData huggingface dataset:
Title: Energy Balance and Cancer Risk
Funder: Cancer Research UK

Abstract: Background: Epidemiological evidence indicates that inactivity, poor diet and obesity are significant risk factors for cancer as well as influencing survival after a cancer diagnosis. Their high prevalence places them second only to tobacco in terms of attributable risk. Advancing cancer prevention science requires a better understanding of the biological pathways, and effective strategies for behaviour change. Aims: This research programme has three aims: i) to increase understanding of the associations between energy balance and cancer risk, ii) to test the effect of weight loss on molecular pathways hypothesised to underlie the association with cancer, and iii) to develop a cost-effective behavioural intervention that can set the stage for studies of the effects of lifestyle change on cancer survival. Methods: Three projects are proposed. INTERCEPT (Intervening to reduce cancer risk) is a two-arm RCT randomising obese individuals (n=300) to intensive, diet-induced weight loss or healthy dietary advice, and examining effects on biomarkers of cancer risk in serum and colorectal tissue. ASCOT (Advancing Survival after Cancer: Outcomes Trial) aims to develop a cost-effective, self-help based, healthy lifestyle programme for cancer survivors with the ultimate aim of improving survival. Materials will be theory-based and developed through reviews of the literature and patient and health professional surveys. Efficacy for behaviour change in cancer survivors will be tested in an individually-randomised pilot trial (n=600) of the ASCOT intervention vs. usual care. Success in the pilot trial will set the stage for a large-scale cluster-randomised trial with cancer-related outcomes. The third project will exploit existing data from the English Longitudinal Study of Ageing and its sister studies in the US and Europe. Secondary analyses of these datasets will examine associations between health behaviours, biomarkers, health status, and cancer in population-representative samples of older adults. How the results of the research will be used: The results of this research will contribute significantly to our understanding of the relationship between energy balance and cancer risk, and extend existing research to discover whether modifying energy balance reduces risk. Clear evidence for a cancer-protective effect of weight loss is likely to be motivating for obese people, and we will disseminate the results widely through our contacts in the Department of Health and the voluntary sector. A successful, self-help-based behavioural intervention for cancer survivors can be disseminated in clinical settings and through cancer organisations to the more than two million cancer survivors in the UK today.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: CANCER AND NEOPLASMS
Title: Cancer Communication and Screening
Funder: Cancer Research UK

Abstract: Background: Screening and early diagnosis are key to improving cancer outcomes. In the UK, uptake of breast screening is high. However, cervical screening rates are falling in younger women, colorectal cancer screening uptake is low, and there is evidence for delays in symptomatic presentation. A better understanding of how people make decisions about early detection, and especially how they integrate information on benefits and harms, is important for achieving informed decision-making while maximising uptake across all sectors of the community. Cancer’s uniquely feared status is an added complication; with evidence that fear can both motivate and deter early detection. Integrating theories and methods from psychology, epidemiology and public health offers the opportunity to build a powerful research programme with the capacity to promote the early detection of cancer. Aims: This research programme has three main aims The first is to improve uptake of colorectal cancer screening and reduce inequalities. The second is to unravel the complex motivational effects of cancer fear. The third is to discover how to promote informed choice without deterring screening participation among groups for whom information can be off-putting. Methods: Project 1 will use population-level colorectal cancer screening data to examine uptake by broad socio-demographic variables and across all stages of the programme, and new survey data to explore potential psychosocial predictors. In-depth interviews with selected groups will be used to compare the beliefs and expectations of people showing differing patterns of adherence across the screening programme. Project 2 will use qualitative methods to investigate cognitive and affective responses to cancer. These will inform the development of a multi-dimensional measure of cancer fear which will be used in a population sample to examine the predictors and behavioural consequences. Project 3 will apply decision-theory approaches, using qualitative and quantitative methods, to understand preferences for informed decision-making, and to investigate how people integrate information on harms and benefits of screening. The annual ABACUS survey, sampling older and general-population samples in alternate years, will support all three projects. How the results will be used: We will use our links with CR-UK’s Health Information and Cancer Data Department, the NHS Cancer Screening Programmes, the Policy Research Unit on Cancer Awareness, Screening and Early Diagnosis, and the National Awareness and Early Diagnosis Initiative, to ensure that our findings inform efforts to optimise screening attendance and promote timely symptomatic presentation.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: CANCER AND NEOPLASMS
Title: Smoking cessation: population and clinical approaches
Funder: Cancer Research UK

Abstract: Background: Tobacco smoking remains by far the largest preventable cause of cancer. Reducing uptake and promoting cessation are both important: this programme focuses on cessation. Considerable scientific advances have been made in methods of encouraging and helping smokers to stop but in the UK only 36% of smokers try to stop each year and less than 5% of these succeed long term. New findings and recent developments in behaviour change theory offer the opportunity to advance the science and practice of smoking cessation considerably over the next five years. Aims: This research programme is aimed at three key targets: 1) increasing the rate at which smokers try to stop and use the most effective methods of stopping; 2) maximising the benefit smokers get from existing smoking cessation interventions; 3) developing more effective interventions. Within these targets we will address 12 topics that build on the work of the current programme and we believe offer the greatest opportunity for impact on smoking while advancing our understanding of the process of behaviour change. Methods: Eighteen studies are proposed under the 12 topics. Two major data sources will be used (The Smoking Toolkit Study and data from the English Stop-Smoking Services) to be supplemented by other data sets (e.g. The Health Improvement Network) and randomised controlled trials. Studies will include: a) evaluations of national-level events and b) evaluations of specific interventions. The events include: changes to incentive payments to GPs for giving advice on smoking, No Smoking Day, measures to increase the cost of smoking, and changes to the NHS stop-smoking services. The specific interventions include: an online training course on brief advice for GPs, a theory-based DVD to promote quit attempts and use of effective methods of quitting, theory-based behaviour change techniques for face-to-face behavioural support for cessation, point-of-sale information to promote effective use of NRT bought over the counter, use of glucose tablets as an adjunct to medication and behavioural support, personal monitoring of expired-air carbon monoxide concentrations to achieve radical smoking reduction, improvements to an internet-based smoking cessation intervention. How the results will be used: Through close links with the Department of Health, the National Institute for Health and Clinical Excellence, the Framework Convention on Tobacco Control Article 14 implementation team, the NHS Stop-Smoking Services, and the NHS Centre for Smoking Cessation and Training, the results will feed into guidelines and directly into implementation nationally and internationally.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CANCER AND NEOPLASMS
Title: Lifestyle and biological determinants of cancer: the European Prospective Investigation into Cancer in Norfolk population study
Funder: Cancer Research UK

Abstract: Background EPIC-Norfolk is a prospective population study of 30446 men and women aged 40-74 years resident in East Anglia recruited at a baseline survey in 1993-97, of whom 25,639 attended a clinic examination, and who have been followed up to present for cancer incidence, survival and other health events. While part of the ten country European Prospective Investigation into Cancer collaboration on diet and cancer with half million participants, data collection in EPIC-Norfolk was substantially expanded to enable much more detailed and accurate assessment of lifestyle (diet, physical activity and psychosocial factors) and biological measures. These include two subsequent detailed follow up examinations including biological sample collection to enable longitudinal assessment of biomarkers and changes not available in other cohorts. Aims The objectives of the European Prospective Investigation into Cancer (EPIC) are to identify dietary, other lifestyle and biological determinants of cancer and quantify the magnitude of any associations to inform interventions for prevention and treatment. Methods For the next five years the aims of the EPIC-Norfolk cancer programme are: (i) to continue follow up for cancer incidence in the Norfolk cohort and to obtain more detailed phenotyping through medical records linkage and tissue banks (ii) to continue development of innovative methodology in diet, exercise, biomarkers and psychosocial measures while maintaining the substantial biological bank (iii) to identify intermediate biomarkers of cancer risk such as mammographic changes, measures of inflammation and glucose metabolism and endogenous hormones (iii) to use nutritional biomarkers to clarify the relationship between diet, intermediate biomarkers and cancer risk (iv) to build on the work identifying genetic susceptibility variants to examine interactions between diet, other lifestyle factors and risk biomarkers with gene variants and cancer risk (v) To continue to contribute to the Europe wide EPIC as well as other collaborations including the UK Dietary Cohorts Consortium and genetic association studies How the results will be used We will continue to contribute to the scientific evidence to improve understanding of causes of cancer in the population to inform and improve interventions for cancer prevention and treatment. [Cancer focus: breast, colorectal, prostate, all sites]


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: CANCER AND NEOPLASMS
Title: Symptom prevalence and help seeking among patients at risk of lung cancer: an exploratory feasibility study in a primary care population
Funder: Cancer Research UK

Abstract: Background: Cancer survival rates remain poor among patients with lung cancer, and late diagnosis is an important factor. There is a dearth of research into help-seeking prior to lung cancer diagnosis, the prevalence of symptoms that might indicate lung cancer in primary care populations, or how individuals behave in relation to these symptoms A factor in delayed presentation is that individuals fail to recognise symptoms and therefore do not seek professional help. The applicants have previously developed a self-completion symptom and risk assessment questionnaire (IPCARD). This study proposes to assess the feasibility of using a brief version of the questionnaire to identify individuals potentially experiencing symptoms so that early intervention can take place. The feasibility study will: 1) explore the help-seeking behaviours of symptomatic individuals and the factors that promote or inhibit help seeking; 2) examine the feasibility of administering the symptom and risk assessment screening questionnaire in a primary care population, by evaluating response rates to the questionnaire and prevalence rates of symptoms reported that warrant GP review; and 3) examine the behaviour of individuals experiencing symptoms such as the rate and outcome of GP consultations among symptomatic patients. Methods: The first phase of the study involves the administration of IPCARD to identify patients with symptoms indicative of lung cancer, and to inform a purposive sample for Phase 2. Descriptive and multivariate analysis will determine: the prevalence of symptoms indicative of lung cancer within the primary care population; variables most predictive of higher consultation rates amongst such patients; and the relationships between symptoms and socio-demographic backgrounds. Focus groups (n=2) will be held with primary care staff to elicit their views on the analysis and define thresholds at which patients should be called in for review. We will use multivariate Poisson regression analyses with outcome defined as 'number of consultations per year' to develop a predictive model for consulting behaviour. The second phase will involve selection of a purposive patient sample (n=45) from amongst questionnaire (IPCARD) respondents, who will be invited to participate in a semi-structured interview, to better understand the help-seeking behaviour of these individuals, and reasons for their not seeking help. Qualitative data will be analysed using Framework Analysis: a matrix based approach for collating, reviewing and understanding data. Improved understanding of barriers to help-seeking will enable us to develop interventions to overcome these barriers, especially in groups at high risk of delay.


Research activity codes: 4.3 INFLUENCES AND IMPACT;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: CANCER AND NEOPLASMS
Title: CRUK/11/030: The UK-R2W study Subcutaneous Bortezomib, Cyclophosphamide and Rituximab versus Fludarabine, Cyclophosphamide and Rituximab for initial therapy of Waldenstrom macroglobulinaemia: a randomised phase II study.
Funder: Cancer Research UK

Abstract: Background Treatment for Waldenstrom macroglobulinaemia (WM) is currently unsatisfactory in that there is no standard of care and complete responses (CR) are rarely seen. Clinical trials have historically been of small size and since there is no established first line therapy, it remains difficult to choose one first line agent or regimen over another. This study builds on recent data demonstrating improved response rates, including achievement of CR, with bortezomib and rituximab combination therapy. The proposed novel regimen of bortezomib, cyclophosphamide and rituximab (BCR) is designed to be disease specific and target both cellular components within the tumour which give rise to the clinical manifestations relating to disease bulk and / or the physicochemical properties of the IgM paraprotein. Aims and Objectives To examine the safety and efficacy of the addition of cyclophosphamide to subcutaneous bortezomib and rituximab versus fludarabine, cyclophosphamide, rituximab (FCR), which serves as the control arm to avoid selection bias, in the initial therapy of previously untreated patients with symptomatic WM. To determine whether the addition of cyclophosphamide to subcutaneous bortezomib and rituximab improves the CR rate, kinetics of the response, duration of remission and time to next treatment. To determine whether assessment of response can be improved. Methods A safety run-in of 6 patients, to ensure that the 3-drug combination of BCR is sufficiently tolerable followed by a multicentre randomised non-comparative phase II study of BCR versus FCR of 50 patients, to receive up to 6 cycles of treatment. They will be evaluated for response and toxicity. A detailed clinicopathological assessment of response will be undertaken incorporating multiparametric flow cytometry and serum free light chain assays. Use of results This study will provide the efficacy and safety data to determine whether BCR warrants further investigation as the experimental arm of a randomised phase III with FCR as the comparator arm. It also has the potential to improve the assessment of response for WM.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Development and testing of a new tool to measure the diagnostic interval in cancer research
Funder: Cancer Research UK

Abstract: Background Research on early cancer diagnosis relies upon the accurate measurement of diagnostic intervals – it is important, for example, to establish the time taken for patients to report symptoms, and for primary care to respond to these symptoms Yet there is little consistency in approach to measurement of key timepoints and intervals in existing early diagnosis research. Our group has recently completed a project which has produced guidance and a checklist on definitions and measurement of early cancer diagnosis timepoints and intervals (the AARHUS Statement); building on this work, we now wish to develop a data collection tool to assist researchers, and promote consistency and quality. The tool will focus on the diagnostic interval from time of first presentation to primary care to the point of diagnosis (the ‘diagnostic interval’). It will also examine a sub-set of this interval, the ‘primary care interval'. Aims & Objectives We wish to identify the key, essential domains of enquiry in a data collection tool targeting the diagnostic and primary care interval in early diagnosis research. We further propose to test the validity (face, content) and reliability of this tool, and establish its acceptability for end-users. Methods Our tool development strategy will comprise item generation (based on existing work), question development and refinement (utlising focus groups), and item selection and validity testing (based on participant feedback at an expert group meeting). The draft tool will then be piloted amongst a group of 30 patients with colorectal cancer in SE Scotland. How the results of this research will be used The end product of this work will be a data collection tool which will be available for use by early diagnosis cancer researchers in the UK and internationally. Development of a tool based on clear definitions of timepoints and intervals, and robust principles of measurement, will help promote consistency and methodological quality in early cancer diagnosis research.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Sheffield Cancer Research UK Centre (Core)
Funder: Cancer Research UK

Abstract: Research at the Sheffield Centre will cover many different types of cancer, although there is particular interest in breast and lung cancers. There is also a strong focus on cancers affecting the bones, especially secondary bone tumours caused by cancer cells that have spread from elsewhere in the body. Many researchers at the Sheffield Centre are investigating the fundamental biology of cancer, understanding how the disease starts and how it grows and spreads. In particular, several scientists at the centre are studying how cancers interact with the cells and tissues that surround them, and how they grow a blood supply. By understanding this ‘tumour micro-environment’, researchers are developing exciting new approaches for treating cancer. Importantly, the Sheffield Cancer Research Centre will act as a focus for training the next generation of cancer researchers through prestigious studentships and fellowships. Finally, the centre will also foster strong links with the local community, increasing awareness of the world-class research taking place right on their doorstep.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: CANCER AND NEOPLASMS
Title: Sheffield Cancer Research UK Centre (Non-Clinical Training Account)
Funder: Cancer Research UK

Abstract: Non-clinical training associated with the Centre: Research at the Sheffield Centre will cover many different types of cancer, although there is particular interest in breast and lung cancers. There is also a strong focus on cancers affecting the bones, especially secondary bone tumours caused by cancer cells that have spread from elsewhere in the body. Many researchers at the Sheffield Centre are investigating the fundamental biology of cancer, understanding how the disease starts and how it grows and spreads. In particular, several scientists at the centre are studying how cancers interact with the cells and tissues that surround them, and how they grow a blood supply. By understanding this ‘tumour micro-environment’, researchers are developing exciting new approaches for treating cancer. Importantly, the Sheffield Cancer Research Centre will act as a focus for training the next generation of cancer researchers through prestigious studentships and fellowships. Finally, the centre will also foster strong links with the local community, increasing awareness of the world-class research taking place right on their doorstep.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: CANCER AND NEOPLASMS
Title: Proof-of-concept oncology target validation for retinoblastoma protein activation screen (Rb screen) hits.
Funder: Cancer Research UK

Abstract: The vast majority of human cancers contain genetic alterations that remove controls resulting in an ability of cancer cells to divide in an uncontrolled and limitless manner. Amongst these alterations is the loss INK4a/CDKN2A tumour suppressor, which inhibits the activity of two closely related D cyclin activated protein kinases, which in turn cause inactivation of the cell cycle regulating retinoblastoma protein. With the aim to identify means that could repair the lack of control of these kinases we tested 6895 gene functions by eliminating these functions using small interfering RNA and searched for targets that delivered retinoblastoma protein dependent cell cycle arrest hence phenocopying the action of the INK4a/CDKN2A tumour suppressor. INK4a/CDKN2A is mutated or lost with high frequency in a substantial number of cancers types including pancreatic cancer, melanoma, glioma, non–small cell lung cancer and colon. Therapeutic inhibition of the identified functions may be suitable to compensate for such loss, thereby providing cancer therapeutic utility in such cancers. Amongst the targets identified we selected four on which we are seeking to undertake proof of concept preclinical analysis with the aim to demonstrate that inhibition of these functions delivers cancer therapeutic activity. The overall aim of the proposed work is to provide sufficient validation around these gene functions to justify initiation of a discovery programme for small molecule inhibitors for the treatment of cancer.


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