NIHRDataInsights/HRCSData huggingface dataset:
Title: PET biomarkers for tumour hypoxia and radiosensitivity
Funder: Cancer Research UK

Abstract: Background Tumour hypoxia is acknowledged as being a key determinant of cancer prognosis and has been shown to decrease the therapeutic efficacy of radiation treatment. Non-invasive methods for hypoxia measurement are sought that will identify patients with hypoxic tumours and provide a rapid assessment of hypoxia modification strategies. Aim The overall aim of the fellowship is to develop a PET biomarker that shows selective uptake by hypoxic tumour cells at the pO2 at which tumour cells become radioresistant. Plan .. From a library of Cu-ATSM analogues, select tracers with hypoxia selectivity for further evaluation in animal models using microPET. .. Use an in vitro model to directly link radiosensitivity with intracellular tracer uptake, removing uncertainty over how to interpret oxygen concentration definitions that may differ between different models and different techniques. .. Choose the tracer with the most favourable biodistribution and tumour uptake in animal models and intracellular uptake at the pO2 threshold of radioresistance in vitro, for further evaluation in a human study involving colorectal cancer patients. .. Produce data to support a follow up study in patients to validate correlation of tracer uptake with response to radiotherapy and to hypoxia modification strategies.


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: EORTC Liaison Officer
Funder: Cancer Research UK

Abstract: The European Organisation for Research and Treatment of Cancer (EORTC) founded in 1962 is an international research organisation based in Brussels, Belgium which aims to develop, conduct, coordinate, and stimulate laboratory and clinical research in Europe to improve survival and quality of life for cancer patients. The EORTC is establishing a network of Liaison Offices to promote and facilitate collaboration between clinical cancer research groups across Europe. Liaison offices exist in Sweden, France and the UK. Further information about the EORTC, their trials, processes and associated groups can be found here http://www.eortc.be/ UK-EORTC Liaison A UK-based EORTC Liaison Office, jointly supported by EORTC, NCRN and Cancer Research UK, was established in September 2007. The purpose of this post is to foster and help co-ordinate collaborative clinical research in cancer between the UK and other international cancer research organisations, with a particular focus on that conducted by the EORTC. The NCRN and the EORTC have similar missions in their respective localities and partially overlapping memberships. Similarly, their research activities are sometimes joint and sometimes separate. However, the structures and many of the standard procedures of the two organisations are very different because they are subject to different national regulations. This makes for a complex environment that is difficult for clinician investigators to navigate. The primary goal of the liaison office is to bring together the relevant procedural knowledge of NCRN and EORTC and develop standard practices that will streamline the collaborations between the two trial organisations. Last updated / /


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: CANCER AND NEOPLASMS
Title: CRUK/08/025: AML 17: A trial for Acute Myeloid Leukaemia and high risk Myelodysplastic Syndrome in younger patients.
Funder: Cancer Research UK

Abstract: Younger patients with Acute Myeloid Leukaemia and high risk Myelodysplastic syndrome have a high level of complete response to modern chemotherapy but 50% die, mostly due to relapse. The AML study group conducts the largest trials in the world to address a number of issues in these patients and recruits around 60 patients per month with over 80% of patients in the UK entering the national trial in this age group. The AML17 trial will compare 2 induction chemotherapy (DA vs ADE) schedules which will be combined with one of two dose levels of the immunoconjugate Mylotarg which we have just shown in low dose to significantly reduce the risk of relapse and improve disease free survival . Following induction, patients will be assessed for relapse risk. Patients with a FLT3 mutation will receive chemotherapy with or without the FLT3 inhibitor (CEP-701), those with high risk disease based on a new risk index that we have prospectively validated, will be randomised to receive either conventional chemotherapy (FLAG-Ida) or a novel combination of daunorubicin and the novel agent clofarabine, with the intention of going on to allogeneic transplant.. Other standard risk patients will receive chemotherapy with or without the mTOR inhibitor Temsirolimus. All patients who are not high risk will be randomised to receive a total of 3 versus 4 courses of treatment. The impact of minimal residual disease monitoring on survival will be assessed by randomising patients to monitor or not to monitor disease. In patients with the APL subgroup the Italian AIDA protocol (ATRA with Anthracycline) will be compared with the chemo-free treatment with ATRA and Arsenic Trioxide. This will be a trial in collaboration with the Italian GIMEMA study group and German study Groups


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: CRUK/09/011: 111 Testis: A single arm multi-centre study evaluating a single cycle of BEP as adjuvant chemotherapy in high risk, stage 1 non-seminomatous germ cell tumours of the testis (NSGCTT).
Funder: Cancer Research UK

Abstract: Background: In 1996 a single arm UK trial of 2 cycles of BEP chemotherapy showed that recurrence rate was reduced from an expected &#126;45% to <2% in high-risk stage 1 non-seminoma germ cell tumours of the testis (NSGCTT). This is now standard practice in many parts of the world. Some data suggest that a single chemotherapy cycle might be as effective but the evidence is not strong enough to change practice. Relevance: Halving the number of chemotherapy cycles would reduce short- and longterm toxicity and young men would return to normal life more quickly. In addition it would reduce the overall burden of chemotherapy and healthcare resource usage. If effective, the trial is likely to lead to change in practice globally. Aims: To demonstrate that one cycle of adjuvant BEP reduces recurrence rate to less than 5% in high-risk (vascular invasion positive) stage 1 NSGCTT, with acceptable shortterm toxicity. Methods: 111-Testis is a single arm trial of one cycle of BEP chemotherapy with a primary endpoint of tumour recurrence. The minimum sample size is 236 patients which is sufficient to exclude a recurrence rate of 5% or more. Events will be closely monitored and the trial terminated should the predicted recurrence risk equal or exceed 5%. Last updated 21/07/2010


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: The role of the bone marrow fibroblast as a determinant of tumour cell survival in paraproteinaemia
Funder: Cancer Research UK

Abstract: Multiple myeloma is an incurable malignant disease of plasma cells and represents the most severe form of paraproteinaemia. Benign forms of paraproteinaemia (termed MGUS) are also observed in many elderly individuals and progress to myeloma at a rate of approximately 1% each year. Both primary and malignant plasma cells have an absolute requirement for localization within the bone marrow niche. Moreover, co-culture of tumour cells and stroma taken from patients at different stages of disease demonstrates that it is the stroma, rather than the tumour cell, that acts as a major determinant of disease progression. The nature of the critical interactions between tumour cell and microenvironment have yet to be determined in detail but are likely to offer novel therapeutic potential. In addition, our group and others have demonstrated that T cells specific for tumour-specific cancer testis antigens are present in many patients with myeloma but are clearly inadequate to control disease progression. Again, the microenvironment is likely to play a major role in tumour resistance, either through action mediated via plasma cell survival or directly on leucocyte function. Fibroblasts are emerging as the predominant regulators of stromal architecture and our group has demonstrated that these cells carry a distinct tissue-specific phenotype that is retained during proliferation and regulates a number of functions including leucocyte migration. Very little is known concerning the physiological activity of bone marrow fibroblasts and, perhaps surprisingly, fibroblasts have never been specifically studied in patients with paraproteinaemia. Here we propose to study fibroblast phenotype and function in patients at different stages of paraproteinaemia in order to determine the potential importance of fibroblasts in disease progression. Bone marrow and serum will be collected from normal donors, and from patients with benign monoclonal gammopathy or multiple myeloma. Primary fibroblast cultures will be obtained from marrow and the phenotype and transcriptome of these cells will be determined and compared between the patient groups. This analysis should identify potential molecules that can be targeted through antibody blockade or siRNA. The functional activity of fibroblasts will be determined by co-culture with primary myeloma cells in order to address if such co-culture can support plasma cell survival. In addition, fibroblasts will be cultured with primary tumour-specific T cells in order to assess they potential to impair T cell proliferatin or function. Bone marrow and plasma serum will also be used in proteomic and metabolomic studies to determine if differences in soluble stromal mediators are observed at different stages of disease.


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: Tumour Microcirculation
Funder: Cancer Research UK

Abstract: Pericyte-stabilised tumour vessels tend to be resistant to vascular-targeted treatment, leading to the concept of exploiting the later stages or ‘maturation phase’ of tumour angiogenesis for therapy. However, this phase is complex and poorly understood. We have found that alternative splicing of the VEGFA gene influences tumour vascular maturation and impacts on vascular disrupting therapy, specifically using the tubulin-binding agent, CA-4-P. Further understanding of the processes involved in maturation and how existing vascular disrupting drugs interfere with them, should provide new treatment avenues. Vascular-targeted treatments need to be combined with conventional ones. For radiotherapy, it will be important to understand the effects of radiation on tumour blood vessels that may influence subsequent vascular-targeted therapy. We aim to: 1. Determine the mechanisms by which VEGF188/9, in particular, impacts vascular maturation. It is hypothesised to influence pericyte recruitment by preferentially activating VEGFR-1 on various cell types. Results will determine the therapeutic potential of inhibiting VEGFR-1 ± tubulin-binding agents and inform on the relationship between vascularity and blood flow. 2. Determine the influence of adherens junctions on tumour vascular integrity and response to vascular disrupting therapy. CA-4-P is hypothesized to disrupt tumour adherens junctions in vivo, with VEGF188/9 opposing this effect. Results will determine whether junctional disruption is the main way that tubulin-binding agents cause blood flow shutdown. 3. Investigate the interaction of radiation with vascular disrupting agents. It is hypothesised that more mature tumour blood vessels are relatively resistant to radiation damage; and radiation-induced vascular effects can be modified to increase sensitivity to VDAs. Results will provide potential routes for optimising this treatment combination. Vascular maturation processes will be studied at the cellular and whole animal levels. We will utilise transgenic animals, e.g. to visualise pericytes in vivo. Intravital microscopy (conventional and multi-photon fluorescence) will be used for detailed analysis of vascular morphology, function and blood oxygenation, supplemented with well-established techniques for measuring nutritive blood flow rate and vascular volume (contrast agent uptake). 3-D co-culture of different cell types will be used to investigate specific interactions and cell signaling pathways. Therapeutic response will be assessed by conventional techniques. Most experiments will be undertaken in genetically modified transplantable tumours. However, where appropriate, primary tumour models will be used. Anti-angiogenics are finding a place in cancer therapy. Results will provide insight into the maturation phase of tumour angiogenesis, with the potential for developing new vascular disrupting strategies and optimizing them for combination with radiotherapy.


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: The influence of a negative FOBT on the response of screening invitees and healthcare providers to symptoms of colorectal cancer
Funder: Cancer Research UK

Abstract: Background Bowel cancer screening, which has the potential to significantly reduce mortality from colorectal cancer, is being introduced across the UK. However, approximately 40% of cancers will not be detected by the FOBt, and therefore there is a need for awareness of the symptoms of colorectal cancer in the general population, and for primary care to respond effectively to symptomatic patients, whether or not they have been screened. Preliminary work from our group has demonstrated a high rate of bowel cancer symptoms in FOBt screening invitees in the Scottish arm of the UK pilot, and we have shown that significant numbers of invitees believe that a one-off test confers long-term protection from the disease. Relevance to cancer Colorectal cancer is a significant cause of mortality and morbidity in the UK population. Specific aims of the research To determine whether the pattern of symptom presentation to primary care differs between individuals who have accepted offers of FOBt screening and those who have not yet been invited (i.e are awaiting their invitation in an area which has already rolled out)? To determine whether amongst FOBt screening participants who developed ‘interval cancers’ (that is, had a diagnosis of colorectal cancer after a negative FOBt), if their response to any bowel symptoms was influenced by their test result. To understand how GPs respond to bowel symptoms in patients who have had a recent negative FOBt. To determine whether ethnicity, socio-economic status or GP characteristics moderate how patients or professionals respond to bowel symptoms in screen-negative individuals. To explore the key elements of an information package which would reduce any adverse consequences of FOBt screening on bowel symptom awareness and symptom-based diagnosis in primary care. Outline plan of research The study will have three components: 1) a linkage analysis of Pilot screening databases and primary care encounter/morbidity databases in England and Scotland, 2) a ‘pathway to diagnosis’ study amongst 50 patients with interval cancers (25 in England, 25 in Scotland) and their health care providers, and 3) a qualitative study of 50 participants in the English and Scottish programmes who have had negative test results.


Research activity codes: 4.3 INFLUENCES AND IMPACT;8.2 HEALTH AND WELFARE ECONOMICS
Health categories: CANCER AND NEOPLASMS
Title: A study of the barriers to early presentation and diagnosis with breast cancer in black African, black Caribbean and white women
Funder: Cancer Research UK

Abstract: BACKGROUND_x000D_ Breast cancer is one of the most common cancers to affect UK women. Women from black ethnic groups diagnosed with breast cancer tend to have more advanced disease and are less likely to survive than white women. It is suggested black women have lower breast cancer awareness, and different cultural values to white women, resulting in their taking longer to seek medical help after discovering breast symptoms, or choosing not to take up breast screening. Most evidence underpinning these beliefs comes from the US and fails to consider the influence of delays in primary or secondary care. Little research has been undertaken in the UK. Before interventions to promote early presentation in these groups can be developed, we need to understand why delays arise. _x000D_ _x000D_ AIMS_x000D_ The research will investigate barriers to early diagnosis with breast cancer in black African and black Caribbean women by exploring: _x000D_ • Awareness of breast cancer symptoms in these groups_x000D_ • Barriers to early presentation _x000D_ • Perceptions of, and attitudes to, breast cancer screening_x000D_ • The process of being diagnosed with breast cancer_x000D_ • Why delays in presentation and diagnosis occur_x000D_ • How perceptions of breast cancer, and attitudes to early diagnosis, impact on early presentation._x000D_ _x000D_ Through recruiting a group of white women diagnosed with breast cancer the research will:_x000D_ • Understand how experience of breast cancer diagnosis varies within and across white and black African and black Caribbean women_x000D_ _x000D_ OUTLINE OF RESEARCH_x000D_ The research will be undertaken in three related phases. Phase 1 will comprise a systematic review of research exploring barriers to early presentation and diagnosis with cancer in black African and black Caribbean women. Phase 2 will entail in-depth unstructured interviews with black and white women diagnosed with breast cancer in London. These will explore experiences of diagnosis, and both barriers to, and facilitators of, early presentation and diagnosis. Grounded Theory methodology will be utilised to analyse data and generate in-depth understanding of factors impacting on early presentation with, and diagnosis of, breast cancer both unique to black women and common across cultures. Phase 3 will explore the conceptual understanding gained in Phase 2 through recruiting a further sample of women to participate in focus groups from areas outside London - Bristol, Birmingham and Manchester. These groups will allow the saliency of the account generated in Phase 2 to be determined. Data will be analysed using Framework Analysis.


Research activity codes: 4.3 INFLUENCES AND IMPACT
Health categories: CANCER AND NEOPLASMS
Title: Evaluating the acceptability and feasibility of a gynaecological cancer information leaflet
Funder: Cancer Research UK

Abstract: Background: The incidence of all gynaecological cancers combined is second only to breast cancer, but women are relatively unaware of these cancers and the subject is often taboo. Delay in presentation is common. Relevance to awareness and early diagnosis of cancer: Data from population surveys and interviews with patients indicate that patient delay is related both to failure to recognise the seriousness of symptoms and reluctance to visit the GP. There is an urgent need to identify strategies that can increase patients’ recognition of symptoms, improve attitudes to help-seeking, and ultimately demonstrate effects on delay. Aims: This study aims to: i) evaluate a simple educational intervention (leaflet) that can be sent to all women to increase gynaecological symptom awareness and reduce perceived barriers to GP presentation, ii) gain support from primary care for use of the leaflet and demonstrate patient acceptability, and iii) demonstrate that mailing the leaflet to all women in a general practice is feasible, does not create a problematic increase in unnecessary consultations, and is associated with trends indicating an increase in diagnostic referrals. Outline plan: The work will be carried out in three stages. Stage 1 will develop and refine the leaflet using psychological theory, health professional expertise, and information from patients. Short-term impact will be demonstrated in experimental studies assessing change in awareness, attitudes and intentions as a result of exposure to the leaflet. Stage 2 will investigate GPs’ responses to the proposal to educate women about the value of early presentation and assess women’s reactions to receiving the leaflet in a single practice. Stage 3 will pilot the mail-out of the intervention and the recording of outcome data (patient attendances and referrals) in a pilot study across 5 practices to demonstrate that the intervention can increase attendance at the GP with gynaecological symptoms that deserve attention without problematic increases in unnecessary GP visits.


Research activity codes: 4.3 INFLUENCES AND IMPACT;3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;7.3 MANAGEMENT AND DECISION MAKING;4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Understanding healthcare utilisation of responders and non-responders to the bowel screening programme in Wales before and after invitation to screening in order to improve early detection either through screening or opportunistic testing
Funder: Cancer Research UK

Abstract: Background In order to be effective at a population level, national screening programmes need to achieve a high uptake. The bowel screening programme in Wales has been established for two years and its uptake is about 58%. Unlike other cancer screening tests, the sample is taken at home and does not require a visit to a clinician. Little is known about the characteristics of non-responders to understand why they do not access the opportunity for prevention or early detection of bowel cancer and whether there may be opportunities to improve uptake through opportunistic contact with health care professionals. Previous work on non-responders to other screening programmes have focussed on socio-demographic and adaptive factors. The role of co-morbidities and hence opportunities for intervention at other points of contact with healthcare services has not been examined. Aims This study aims to compare the engagement of responders and non-responders to the bowel screening programme with health care services in the year before invitation and in the two years following invitation. We will explore the engagement with primary and secondary care and infer contact with pharmacies using data linkage. Method The SAIL project has the necessary raw data from the Welsh bowel screening programme, GP practices and all hospital contact already held securely, with established governance procedures in place to permit researchers to undertake epidemiological investigations on anonymised data. Our research group, a collaboration between Cardiff and Swansea Universities (EPI-SCREEN) has successfully used the SAIL project to research screening related issues in large epidemiological studies. We plan to link information from several sources to compare morbidity, measured by GP consultations, hospital outpatient, elective and emergency admissions, both before and after invitation to the screening programmes. Use of results The information on healthcare contact will be useful for targeting interventions aimed at improving uptake. We would plan to publish results in peer-reviewed journals. If further action is appropriate, the Principal Investigator is part of the management structure for the screening programmes in Wales and so recommendations can be implemented and evaluated with inferences made more generally for the UK.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: CANCER AND NEOPLASMS