NIHRDataInsights/HRCSData huggingface dataset:
Title: The role of GAS5 lncRNA in the development and therapy resistance of castrate-resistant prostate cancer.
Funder: Prostate Cancer UK

Abstract: The newly reported functional importance of long non-protein coding RNAs in the control of cell fate and oncogenesis presents previously unexplored avenues for developments in the therapy and prognosis of castrate-resistant prostate cancer. GAS5 lncRNA in particular, is down regulated both in clinical samples of advanced prostate cancers and during the development of castrate-resistant prostate cancer in a (LNCaP-based) mouse model system. GAS5 lncRNA has also been shown to control cell proliferation and cell death in cancers derived from other tissues. This pilot project will modulate GAS5 lncRNA expression levels in both castrate-resistant prostate cancer cell lines and in cell lines derived from early stages of prostate cancer, in order to determine the functional importance of this molecule in producing the drug resistance displayed by advanced prostate cancers. The project will also analyse the role of GAS5 lncRNA in modulating the androgen receptor signalling pathway, which is of crucial importance in in most castrate-resistant prostate cancers, and will identify the region of the GAS5 lncRNA responsible for these effects. These studies will form the basis for therapeutic targeting of this pathway as well as allowing its potential in prognosis of castrate-resistant prostate cancer to be assessed.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Mutation of Duffy Antigen Receptor for Chemokines (DARC) as an indicator of prostate cancer severity in Afro- Caribbean men
Funder: Prostate Cancer UK

Abstract: Afro-Caribbean men are three times more likely to develop prostate cancer than Caucasian/Asian men and this cancer is more severe than in other ethnicities. The causes for this are as yet unknown. However, one hypothesis is that this is due to mutation of DARC (duffy antigen receptor for chemokines),a receptor on red blood cells and endothelium which clears angiogenic chemokines: Several angiogenic chemokines (bound by DARC) including MCP-1 and IL-8 promote prostate cancer. Malarial parasites can also infect red blood cells through DARC . Up to 90% of Afro-Caribbeans lack DARC on red blood cells and have a form of endothelial DARC(b+) binding more weakly to chemokines than the form (a+) commonly found in Caucasian/Asian populations. In this project we will analyse DARC DNA and proteins in blood and prostate cancer tissue from black and white men diagnosed with prostate cancer, to determine correlations between the DARC gene sequence (leading to aberrant forms of the receptor), levels of chemokines in blood, and prostate cancer severity (measured by Gleason score, TNM and PSA). We propose that DARC genotyping will distinguish men more likely to develop aggressive disease so they can be targeted for active treatment rather than watchful waiting/ surveillance.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Targeting microRNA regulation of metabolism in prostate cancer
Funder: Prostate Cancer UK

Abstract: Altered cell metabolism in tumours is now a recognized "hallmark of cancer" and presents many new opportunities for diagnosis, prognosis and therapy. However the normal prostate has a particular metabolism compared to other tissues, e.g. it is characterized by a truncated TCA cycle and secretion of citrate by the glandular epithelium into prostatic fluid. Furthermore, several genes directly regulated by the androgen receptor have been recently reported to play a specific role in prostate cancer metabolism and growth (e.g. GNMT, PFKFB4, CAMKK2). Hence there is need for a prostate-specific understanding of the evolution of metabolic behavior in cancer. In this pilot project we aim to use metabolomics and novel cellular models to explore the role of an AR-regulated oncogenic miRNA, miR27a, in determining prostate tumour cell metabolism. Specifically we will define the effects of miR27a and prohibitin (a known target) on metabolic phenotype;test for miR27a targeting of cancer-associated metabolic enzymes suchas ATP-citrate lyase; determine if interference with miR-27a metabolic regulation can inhibit tumour cell growth or sensitize tumour cells to drug therapy. Thus we will generate key evidence for metabolic regulation by miR-27a and how this may be exploited in prostate cancer therapy.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: The effect of neo-adjuvant chemotherapy on exercise capacity and outcome following upper gastrointestinal cancer surgery.
Funder: Department of Health (England)

Abstract: Background Neo-adjuvant chemotherapy (NAC) prior to surgery for upper gastrointestinal (oesophageal and gastric) cancer is associated with improved survival. We have pilot data showing that NAC in this context results in reduction in objectively measured exercise capacity (fitness). The literature suggests that a lower level of exercise capacity is associated with a high risk of adverse outcome (death and serious complications) after major surgery. We wish to explore whether the benefits of NAC are outweighed by the harm associated with reduced exercise capacity in some patients undergoing upper gastrointestinal cancer surgery. Aims The aim of this project is to explore the hypothesis that the decrease in exercise capacity (fitness) associated with neo-adjuvant chemotherapy (NAC) prior to upper gastrointestinal cancer resection may outweigh the benefits (duration of survival) achieved by NAC in some patients. This proposal therefore outlines a study to explore the primary hypotheses that: 1. Neo-adjuvant chemotherapy will result in a decrease in exercise capacity (defined as Lactate Threshold measured using Cardiopulmonary Exercise Testing) prior to upper gastrointestinal cancer surgery. 2. The fall in Lactate Threshold associated with NAC will be associated with increased harm following surgery. We also aim to answer the clinically important question: “can we use CPET to select patients for NAC?” Plan of Investigation We propose a prospective blinded observational cohort study of patients patients undergoing NAC prior to elective upper gastrointestinal cancer resection (oesophagectomy and gastrectomy) in three NHS teaching hospitals. Exercise capacity (fitness) before and after NAC will be assessed using CPET and the relationship between the derived variables (LT, VO2 peak) and clinical outcomes will be described. Postoperative outcomes will be objective recorded and clinically meaningful and will include mortality 1 year after surgery and short term postoperative harm described by the Post-Operative Morbidity Survey (POMS) as well as generic PROMS and resource use (e.g. hospital bed utilisation). The relationship between changes in exercise capacity and clinical outcomes will be explored. ?? Potential Impact If the hypotheses being investigated are supported by the study results: Patient outcomes may be improved (longer survival) due to better patient selection. Patient information will be improved. Patient choice will be facilitated. Resource use (e.g less unnecessary or potentially harmful courses of NAC and reduced bed usage due to improved outcome following surgery) may fall. ????


Research activity codes: 6.4 SURGERY;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Development and Evaluation of an Intervention to Assist Lay Carers to Provide Physical Care to Family Members with Cancer at End-of-Life
Funder: Department of Health (England)

Abstract: Background Systematic and narrative reviews of the needs of lay carers (henceforth carers) of family members with advanced cancer at end-of-life document their need for a range of information of a practical nature (i.e. pain and other symptom management, hydration, feeding, positioning). Most studies of caregiving at the end-of-life however, focus on information and psychosocial needs of patients and/or carers with little attention to the practical knowledge and support carers need. Problems in providing physical care often results in expensive and unwanted hospital admissions, giving up plans for a home death, and psychological distress for patients and carers. Thus, any intervention which improves patients’ physical care may result in improved outcomes for patients as well as carers. Aims Objectives: 1. Develop an intervention, based on available evidence and input from family carers, recently bereaved carers and health care personnel, to address carers’ needs for practical information, support and skills. 2. Conduct a pragmatic evaluation of the intervention as to its: i) acceptability to family carers, ii) acceptability to health care personnel and feasibility to adopt into their everyday practice in interacting with patients and carers, and iii) outcomes to family carers (e.g. caregiver burden and satisfaction, competence, preparedness to care). Plan of Investigation This study builds on our earlier narrative and systematic reviews. The research is situated within a participatory action research framework which will involve family carers in developing, using and evaluating the intervention (the developmental phase of MRC guidance on developing and evaluating complex interventions). Data collection includes focus groups/interviews with carers to develop the intervention; questionnaires administered to carers pre and post intervention; semi-structured interviews with carers and nurses. Interviews and focus groups will be tape recorded, transcribed and analyzed using framework analysis. Pre and post intervention change scores will be examined and potential for measuring efficacy assessed. Potential Impact The output will be a well designed practical educational package to assist lay carers in gaining knowledge and practical skills when providing home care for people with a terminal illness. The potential impact is considerable if adopted by district nurses, specialist palliative care nurses and general practitioners into their every day practice with carers. It has the potential to increase carer and patient satisfaction with care and wellbeing, and decrease carer burden without additional resources. It may also reduce resources if less community input and hospitalisations are required. Also, it may help some patients, who desire a home death, to achieve this. The package may also provide a template for developing resources for other patient groups (i.e. stroke).


Research activity codes: 7.2 END OF LIFE CARE
Health categories: CANCER AND NEOPLASMS
Title: South-West Mesothelioma and Radiotherapy Trial (SMART trial) - RCT evaluating whether prophylactic radiotherapy to biopsy sites in pleural mesothelioma reduces chest wall tumour seeding
Funder: Department of Health (England)

Abstract: Background Malignant pleural mesothelioma is an aggressive universally fatal tumour causing one death on average every 4 hours in the UK, median survival is Aims This trial will assess whether prophylactic radiotherapy to large biopsy tracks prevents PTM and therefore leads to improvements in patients’ symptoms and QoL. At present the medical community is in equipoise with regard to whether or not this treatment is useful and practice varies accordingly. The results of a small RCT by Boutin over a decade ago have led guidelines to recommend its routine use, although techniques have since altered. Two recent underpowered studies were however negative. Our primary aim is to undertake a suitably powered RCT to address this issue and lead to change in NHS practice. Plan of Investigation Design: RCT to evaluate whether use of prophylactic radiotherapy to large pleural intervention biopsy tracks prevents procedure track metastases (PTM) compared to no intervention (1:1) Primary endpoint: The proportion of patients who develop chest wall metastasis around the site of pleural intervention within 12 months of diagnosis. Secondary endpoints: Proportion on symptomatic PTM. Mean monthly chest wall pain scores VAS, QoL (EQ5D) Setting : Patients will be identified from respiratory & oncology clinics across the SW region, Oxford and Portsmouth. Time scale: Complete recruitment within 15 months and follow up period 12 months. Comparison of the outcomes will define whether prophylactic radiotherapy to large intervention sites prevents PTM. Potential Impact This trial will answer the important question of whether NHS resource should be spent on prophylactic radiotherapy to biopsy sites in patients with mesothelioma. At present across the UK approximately 50% of hospitals are performing this routinely and the rest are not. No study to date has been suitably powered to answer this question. We believe, whatever the outcome, the results of this trial will lead to practice changes across the UK. If it is positive it will lead to more patients getting the treatment they require. If negative, it will lead to NHS savings and avoid the need for vulnerable and distressed patients to make onerous hospital visits for their prophylactic radiotherapy.


Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: Optical diagnosis of small colorectal polyps in routine clinical practice (Detect Inspect Characterise Resect and Discard; DISCARD 2 trial)
Funder: Department of Health (England)

Abstract: Background Colorectal cancer (CRC) is the second most common cause of cancer death in the UK. Removal of adenomatous (pre-cancer) polyps reduces CRC risk by 80% but most polyps are small ( Aims DISCARD 2 is a multi-centre study which will assess the accuracy and acceptability of NBI optical diagnosis. Its blinded calibration study design will compare NBI optical diagnosis with the reference standard of routine histology for small polyps ( The primary outcome of the study is test sensitivity: the proportion of all patients requiring surveillance that are correctly identified by NBI optical diagnosis. A range of secondary analyses will describe test performance. Focus groups and forums will be used to establish patient and clinician views of moving to optical diagnosis-led care. Cost and cost-effectiveness analyses will help inform NHS decision making. Plan of Investigation Consenting patients presenting for colonoscopy in 6 sites in the Northern Region will be recruited. NBI optical diagnosis will be compared to reference standard histopathology. A 20% sample of NBI optical and histopathological findings will be independently reviewed to assess inter-rater reliability. Patients (N=2500) will receive routine, standard colonoscopic procedure and subsequent care pathway; the only addition is the use of NBI during the colonoscopy. Out-patient appointments, timing of results and surveillance intervals will not be influenced by the study, which involves no additional follow-up. A series of patient and clinical focus groups, and patient forums, will explore future implications of NBI, using a phenomemological approach. Potential Impact In addition to current bowel cancer screening, from 2012 a new national flexible sigmoidoscopy screening programme will be introduced for all 55 year olds. Around 500,000 patients will be screened annually, of whom around 75,000 will have at least one polyp. Findings from this study have the potential to detect adenoma accurately while reducing substantially the use of histology. This would reduce the number of unnecessary polypectomies and allow patients to receive an immediate diagnosis: an initial estimate suggests net cost savings would be achieved. If successful, NBI optical diagnosis would be used routinely in patients at risk of CRC to reduce potential harm as well as aid timely decision making and choice of surveillance.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: PIT - A phase III trial of Prophylactic Irradiation of Tracts in patients with malignant pleural mesothelioma following invasive chest wall intervention.
Funder: Department of Health (England)

Abstract: Background Invasive chest wall diagnostic/ therapeutic procedures in malignant mesothelioma (MM) can encourage tumour seeding along the tract resulting in the development of subcutaneous chest wall metastasis, usually within 6 months of the procedure. It has been widespread practice in the UK to prophylactically irradiate intervention sites post procedure, a practice known as prophylactic irradiation of tracts (PIT). A recent UK survey showed the use of PIT varies depending on locality. This reflects the lack of a robust evidence base from 3 previous, underpowered randomised controlled trials with conflicting results. Furthermore, patients are now offered effective chemotherapy for MM. The efficacy of PIT, in the new era of effective chemotherapy for MM, needs to be determined. Aims The primary objective of this study is to determine whether mesothelioma patients benefit from PIT, as assessed by the rate of chest wall metastasis in MM in the era of effective palliative chemotherapy. The secondary objectives are to describe the toxicity of PIT, to determine the impact of PIT on time to the development of chest wall metastasis, and to assess pain from chest wall metastasis. Plan of Investigation A 2-arm, multi-centre randomised trial comparing radiotherapy vs no radiotherapy in patients with a histological diagnosis of MM following chest wall intervention. Patients will be stratified by the type of chest wall intervention, histological subtype, and intention to give chemotherapy. Patients will be offered chemotherapy after PIT if deemed suitable by their local oncologist. Out-patient follow-up will be at 6 weeks, 12 weeks, and 26 weeks post-randomisation. Patients will also receive monthly telephone follow-up for 12 months from a dedicated study nurse but will also be reviewed at the next available clinic if a skin nodule is detected. Based on a rate of chest wall metastses of 15 vs 5%, using a 5% significance level, 2-sided test, and 80% power this would require 374 patients. Potential Impact Over 2300 patients per year are diagnosed with MM in the UK and the incidence is rising. This study will finally determine whether PIT significantly reduces the incidence of chest wall metastasis for these patients. If PIT is shown to be beneficial, the study will standardise the use of PIT in the UK, resulting in a rationalisation of limited NHS resources. If no benefit is demonstrated, it will ensure that MM patients, who are often unwell and have a limited life expectancy, do not continue to receive an ineffective treatment with the associated inconvenience of extra hospital visits, and ensure NHS resources are not used on an inffective therapy.


Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: Understanding the communication processes engaged in cancer telephone helpline work: A qualitative case study
Funder: Department of Health (England)

Abstract: BACKGROUND: There are 1500+ UK helplines in operation, yet we have scant knowledge about the process of delivering and seeking cancer related telephone help. We know from the face-to-face communications literature that sometimes patients do not get the information or supportive care that they need. We also know that very simple alterations to communication behaviour can improve patient outcome (such as satisfaction, eliciting concerns).Without empirical evidence it is hard to precisely determine whether this research applies to helpline work and what in particular contributes to effective helpline communication. AIM: Using Macmillan Cancer Support (hereafter MCS) as a case study, address the research question of ‘How do parties to helpline talk communicate, what communication approaches contribute to effectiveness, and can real transcribed interaction help improve effectiveness through the training of helpline call-takers?’Objectives: Phase 1: Conduct the 1st UK empirical study of telephone based help for those affected by cancer.Phase 2: Conduct interviews with key stake holders (e.g. callers/calltakers) (Dimbleby Cancer Care or in place of Phase 4).Phase 3: Hold expert panels to generate feedback on early analysis of Phase 1 & early training solutions for Phase 4.Phase 4: Use findings to develop Training Information Package for call takers.Phase 5: Synthesise findings for key stakeholders through oral and written dissemination.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: CANCER AND NEOPLASMS
Title: Using computerised clinical data to investigate the links between long-term drug treatments and cancer risk
Funder: Department of Health (England)

Abstract: There are concerns that some widely-used drug treatments might be linked to an increase in the risk of cancer. To investigate such concerns requires data on large numbers of patients observed for several years. By using routinely collected healthcare data, recorded in large electronic databases, I will be able to investigate associations between: (i) angiotensin receptor blockers and cancer; (ii) pioglitazone and bladder cancer; (iii) insulin glargine and breast cancer; (iv) finasteride and breast cancer in men. The research will help patients, doctors, and regulators to weigh up the benefits of treatment with these drugs against the potential harms


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Improving breast cancer screening detection rates through understanding, modelling, and adapting patterns of radiologist performance
Funder: Department of Health (England)

Abstract: “This research aims to reduce cancer mortality by improving breast screening practice. We know that screening performance can be affected by interruptions, breaks and fatigue. Therefore, the first study uses a Randomised Controlled Trial to test whether changing mammogram reading order can improve screening performance. We also know that computer-aided detection has the potential to improve screening, but includes pop-up prompts which cause interruptions. The second study will investigate the effects of pop-ups on screening performance using a controlled experiment with test cases. Modelling of the outcomes of both studies will provide important information for future policy, practice, and research.“


Research activity codes: 4.4 POPULATION SCREENING;4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Evaluating treatment response of whole-body metastases with multi-modality imaging.
Funder: Department of Health (England)

Abstract: Untreated cancers can eventually spread (metastasize) to other parts of the body such as the bones, leaving patients with low chances of survival. Although many new treatments for bone metastases are becoming available, clinicians will hit a snag: there is currently no way of visualizing if a patient is getting better. In this project, I will investigate the combination of PET, CT and MRI imaging techniques for providing a ‘biological map’ of the body that shows the effects of treatment on both the disease volume and biology of tumour cells, providing clinicians with a much better understanding of treatment effects.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS