NIHRDataInsights/HRCSData huggingface dataset:
Title: EBV@50, Views from the Past, Views of the Future: The International Meeting to Mark the 50th Anniversary of the Discovery of Epstein-Barr virus
Funder: Cancer Research UK

Abstract: This historic conference marks the 50th anniversary of the discovery of EBV, the first human tumour virus. It will be held in Keble College, Oxford, exactly 50 years after the virus’ discovery was first announced by Epstein, Achong and Barr in a letter to The Lancet in March 1964. The conference will include invited reviews by current leaders in the field, plus selected oral presentations by junior investigators. Both days will include time for round table discussions and will finish with historical talks. Keynote speakers include Professor Sir Anthony Epstein, Professor George Klein and, to represent the Henle Laboratory, Nobel Laureate Harald zur Hausen.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: Outcome of cancer patients with critical illness admitted to Intensive Care
Funder: Cancer Research UK

Abstract: Background As the outcomes for cancer improve it is no longer considered the terminal disease it once was. However, the Intensive Care (ICU) community remains prejudiced against this group of patients as, although ICU survival is comparable with the non-cancer population, there are concerns that longer term outcomes do not justify the risks and burdens of an ICU admission. It is difficult to identify which patients are likely to benefit from ICU intervention and it may be that ICU is being withheld based on inaccurate perceived futility. Aims We will compare the survival of ICU patients with cancer to cancer patients who did not require ICU admission and to ICU patients without cancer. We will describe determinants of survival by demographic, cancer type, cancer stage and other clinical risks (such as biochemical markers of inflammation or disease treatments). Methods We will link the West of Scotland cancer registry database with local intensive care (ICU) and national mortality databases to identify patients with cancer who have been admitted to ICU. We will then match these patients to patients with cancer without ICU admission, and to ICU patients without cancer. How results will be used We are seeking to identify groups of patients with cancer who would have previously been considered inappropriate for ICU in whom long term outcomes are not significantly altered by an ICU admission. With an enhanced understanding of what happens to cancer patients with critical illness we would be in a better position to give prognostic information regarding illness trajectory following ICU admission. This would facilitate open discussion and better inform patients and clinicians when considering different treatment options.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS
Title: Cambridge Cancer Research UK Centre (Bridging Funding)
Funder: Cancer Research UK

Abstract: The launch of the Cambridge Cancer Centre puts Cambridge at the forefront of cancer research, bringing benefits to patients in the South East. The Centre is a major new research collaboration which exists though a unique partnership between Cancer Research UK, Cambridge University, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Health Partners. The Centre will be funded by Cancer Research UK to the tune of £2 million a year and joins our specialist network of cancer Centres across the UK. Researchers at the Centre will concentrate on understanding the biology of how and why cancers develop, particularly breast, lung, ovarian, pancreatic, oesophageal, blood and prostate cancers. Scientists will also focus on developing new ways to detect cancer though cutting-edge imaging techniques.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Improving the intra-operative diagnosis of high-grade glioma using a fluorescence biomarker
Funder: Cancer Research UK

Abstract: IMPROVING THE INTRA-OPERATIVE DIAGNOSIS OF HIGH-GRADE GLIOMA USING A FLUORESCENCE BIOMARKER Background: Intrinsic brain cancers (Gliomas) are classified as low and high-grade tumours. Correctly distinguishing high-grade glioma (HGG) from low-grade glioma (LGG) during surgery can influence the surgical procedure, enhancing resection and improving survival. An ongoing CRUK phase I study (GALA-5) is evaluating combining fluorescence with intra-operative chemotherapy in patients with glioblastoma (GBM), the most aggressive type of HGG. In 4 out of 45 patients with visible fluorescence during surgery peri-operative tissue analysis was unable to confirm HGG so no chemotherapy was delivered. Subsequent histopathology confirmed that all patients had a GBM. To date there is no biomarker available to aid decision making in real time during surgery. Improving diagnostic accuracy is important because knowing that a tumour is high-grade will aid surgical decision-making. Nests of HGG can be “hidden” in some tumours that appear less aggressive. Because the nests cannot be seen they may be missed at surgery. Aims: We propose to prospectively investigate whether sampling visible tumour fluorescence improves the diagnostic accuracy during surgery. Currently the error rate for missing high-grade diagnoses for patients with visible fluorescence intra-operatively is around 10%. The proposed surgical biomarker will be acceptable in practice if the error rate is 1%. We will recruit 80 patients with visible fluorescence into the study. With =78 patients confirmed high grade, we could conclude that the diagnostic error rate is 1%, verses 10%, with a 1% significance level and 95% power. Methods: Previously stored tissue samples cannot be evaluated for fluorescence. Therefore samples must be collected prospectively and correlated with peri-operative and post-operative histological evaluation. Samples of visibly fluorescent tumour will be taken. The fluorescent sample will be divided into two parts; one part is sent for peri-operative histopathological analysis the other part is sent for post-operative histopathological analysis. All analyses will be in accordance with established histopathology protocols. How the results will be used: This diagnostic surgical biomarker project will establish the relationship between the biomarker (visible fluorescence) and the gold standard diagnostic practice (peri-operative histopathology) (BIDD BM discovery stage 2). The project will confirm that the assay is fit for purpose (BIDD assay development stage 3) and define the performance of the biomarker in comparison with the gold standard prospectively (CTAAC/BIDD BM Qualification Stage 1). This will ensure a rapid translation into routine clinical practice in the UK.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: The role of faecal Volatile Organic Compounds (VOCs) as a non-invasive diagnostic biomarker of colorectal cancer: feasibility study.
Funder: Cancer Research UK

Abstract: Background The vast majority of Colorectal Cancers are sporadic, developing from adenomatous polyps which had been present for many years beforehand. The existence of such a pre-cancerous lesion, which can be readily identified and removed, mostly during a single colonoscopy procedure, gives a powerful argument for a screening programme. In the UK, this is currently achieved through the use of a combination of Faecal Occult Blood (FOB) testing and colonoscopy. FOB has a generally high specificity but very low sensitivity. Thus a new screening test which improves upon the sensitivity and specificity of FOB testing, while also detecting FOB-negative neoplasia, would be invaluable in reducing the cost burden of colonoscopy upon the NHS and the number of patients exposed to the risks of the procedure (0.2% perforation risk and 0.006% mortality rate). Over the past few years there has been a great swell of interest in the use of “electronic noses” to detect the “smell” of disease. This arises from the many anecdotal reports of both dogs and humans associating specific smells with disease states such as Clostridium Difficile infection, melaena and the Fetor Hepaticus of Chronic Liver Disease. The Volatile Organic Compounds (VOCs), which create the smell are produced by a combination of host and gut bacterial metabolism. VOCs can be sampled from a variety of modalities - such as blood, urine, breath, faeces - and identified using gas chromatography-mass spectrometry (GC-MS). VOCs emitted from faeces have shown remarkable correlation with gastrointestinal health and between different diseases. The frequency of these compounds and their concentration can be compared between states of health and disease to give a quantifiable measure of the “smell” of the sample and diagnose the underlying condition. Aims Identification of a pattern of VOCs in faecal occult blood-positive that is predictive of the presence of polyps, colorectal cancer or no cancerous lesions. this is a pilot study to inform the design of a later PhD proposal. Methods VOCs can be sampled and identified using GCms We will collect 100 faecal samples from patients presenting for colonoscopy as part of the Bowel Cancer Screening Programme and measure the VOCs, looking for appropriate correlation. Utilisation of results. GC-MS machines are available in many hospital laboratory settings. Once validated, our pattern of VOCs could be swiftly incorporated to improve the accuracy of screening techniques for colorectal cancer.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: CRUK/13/007: A randomised phase two-arm phase II study of Trametinib alone and in combination with GSK214795 in patients with advanced uveal melanoma (International Rare Cancers Initiative Trial - IRCI 005) (Supported by Stand Up To Cancer)
Funder: Cancer Research UK

Abstract: Background Advanced uveal melanoma represents an orphan disease area with a median survival of less than 6 months. Uveal melanoma is the most prevalent primary intraocular malignancy in adults and the development of metastasis in this disease is common; occurring in approximately 50% of patients with posterior uveal melanoma within 15 years after the initial diagnosis and treatment. Uveal melanoma is thought to be particularly resistant to systemic treatment, and no systemic therapy has yet been demonstrated to improve survival. However, our increasing understanding of the underlying biology of uveal melanoma has led to the identification of a number of novel and promising therapeutic strategies that warrant investigation, including Trametinib (GSK1120212) and GSK214795 which inhibit the MEK and AKT pathways respectively. Aims This trial will primarily investigate the Progression-Free Survival (PFS) of good performance status patients treated with Trametinib or Trametinib plus GSK214795. Overall Survival (OS), Overall Response (OS) and toxicity assessment are the secondary endpoints. Exploratory endpoints include the correlation of clinical outcome with Gnaq/11 mutational status. Methods This randomised phase II trial will recruit 80 patients across several international sites (site selection is ongoing, estimate 10 sites in total) over a 2 year period. Patients will be stratified based on ECOG performance status (0/1 versus 2) and LDH (normal versus ULN). Key Inclusion criteria: histologically proven advanced uveal melanoma, ECOG performance status 0 to 2 and Bilirubin = 1.5 mg/dl, AST = 2.5 x ULN and ALT = 2.5 x ULN or AST = 5 x ULN, ALT = 5 x ULN depending on presence of liver metastases. Patients will be randomised to receive Trametinib 2 mg PO QD or Trametinib 1.5 mg PO QD in combination with GSK214795 50 mg PO QD until disease progression, unacceptable toxicity or withdrawal of consent. At time of progression, patients randomised to Trametinib who remain eligible for therapy may be offered treatment with Trametinib plus GSK214795. Tissue and blood sample collection for translational analyses will also be completed. How the results of this research will be used The results of this research will be presented at national and international meetings and published in peer reviewed journal.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: CRUK/13/008: A Single Arm Phase II trial of BMN673 for inoperable, advanced endometrial cancer with retrospective PTEN, MSI and MRE11 analysis (Supported by Stand Up To Cancer)
Funder: Cancer Research UK

Abstract: Background: There is no standard of care for the treatment of inoperable, advanced or metastatic endometrial cancer. Platinum/taxane combination chemotherapy is often used but response rates are low, generally of short duration and survival remains poor. The therapeutic alternatives to chemotherapy are very limited and neither endocrine therapy nor novel targeted agents evaluated to date have demonstrated a survival benefit. In addition, there are no validated predictive markers to select patients for systemic therapy in this setting. There is therefore a significant unmet need for effective, tolerable systemic therapy in a heterogeneous patient population that would benefit from predictive biomarkers to select for treatment benefit. PTEN inactivation, microsatellite instability (MSI) and MRE11 mutation (a target of MSI) have all been implicated as sensitisers to PARP inhibition through interaction with DNA repair mechanisms Each of these evaluable molecular abnormalities are all relatively common in endometrial cancer caused by a variety of mechanisms and thought to be functionally significant in endometrial carcinogenesis. Therefore, retrospective correlation of PTEN, MRE11 and MSI in endometrial cancer with outcome to PARP inhibitor therapy is justified. Aims: The aim of this study is to evaluate the efficacy and safety of single agent PARP inhibition with BMN673 for inoperable, advanced or metastatic endometrial cancer and to retrospectively determine whether the status of PTEN, MSI or MRE11 modifies response to single agent BMN673 and may be used in future studies for patient selection. Methods: This will be a single arm multicentre Phase II trial conducted in the UK recruiting up to 80 patients. The primary endpoint will be response rate. Patients will have inoperable, advanced endometrial cancer and will be unsuitable for treatment with chemotherapy in the first line setting or receiving subsequent line therapy. All histological subtypes of endometrial cancer will be included. Results will be stratified according to previous chemotherapy exposure, platinum sensitivity (if previous chemotherapy), PTEN, MSI and MRE11 status and histological type (endometrioid or non-endometrioid). How results will be used: The results of this study will be used to determine whether a Phase III trial of single agent BMN673 is indicated in this patient population and whether selecting patients according to PTEN, MSI or MRE11 molecular status warrants further investigation.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Stratification of adjuvant chemotherapeutic response to allow personalised choice of pyrimidine prodrug: based on levels of transporters and enzymes involved in initial metabolism
Funder: Cancer Research UK

Abstract: Background: The standard form of adjuvant chemotherapy for pancreatic cancer is gemcitabine, but ESPAC-3(v2) has shown that there is no significant difference in survival benefit between treatment with gemcitabine and 5-fluorouracil (5FU). Both drugs are pyrimidine analogues but gemcitabine is a nucleoside and 5FU is a nucleobase. Our hypothesis is that differences in tumour biology mean that patients will be more responsive to either nucleobase or nucleoside therapy. We have shown, with samples from ESPAC-3(v2), that high hENT1 levels are associated with better survival with gemcitabine but not 5FU. Aim: To identify a personalised approach for the choice of pyrimidine to use for adjuvant chemotherapy of pancreatic cancer. Methods:Initial metabolism of pyrimidine analogues within the cell is controlled by deoxycytidine kinase (gemcitabine), cytidine deaminase (gemcitabine), thymidine phosphorylase (5FU) and dihydropyrimidine dehydrogenase (5FU). The project will involve measurement of the level of these enzymes in resected tumour samples from patients who were on ESPAC-3. Commercial antibodies will be validated according to the protocols of the ESPAC translational steering committee. Data are available on hENT1 levels in samples from 352 ESPAC-3 patients. This will be extended to further patients and stratified according to staining with the antibodies indicated above. A specific hENT1 inhibitor will be used in combination with gemcitabine, 5FU and SiRNA reduction of nucleoside transporters and drug metabolising enzymes. Intracellular levels of 5FU and gemcitabine will be assayed along with response to the drugs. The response to gemcitabine and gemcitabine eladiate will be compared in cell lines with different levels of transporters. Adjuvant abraxane in combination with pyrimidine analogues will soon be trialled in pancreatic cancer. Stromal SPARC levels influence abraxane efficacy and stromal density may determine access of prodrugs to tumour. SPARC level will be analysed in ESPAC patients to determine if prodrugs affect its prognostic value and a novel method of measuring stromal density will be applied. Use of results: Other drugs will be offered to the set of patients with low levels of tumoral hENT1, rather than gemcitabine. Further stratification of patients will be possible allowing some patients with high hENT1 to be given other drugs and some with low hENT1 to be given gemcitabine dependent on IHC for enzymes involved in drug metabolism. As abraxane becomes more commonly used in adjuvant therapy, SPARC levels will be used in combination with assay of hENT1 and other proteins to decide on the appropriate combination therapy.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: Epigenetic modification of the BRCA1 promoter and breast cancer phenotype
Funder: Cancer Research UK

Abstract: Background Tumours associated with mutations in the Breast Cancer susceptibility 1 gene, BRCA1, are associated with a higher rate of particularly aggressive, overlapping subtypes of breast cancers called the Triple Negative (TN) and basal phenotypes. TN cancers do not express oestrogen, progesterone or ERBB-2 (HER-2) receptors and are associated with a poor prognosis compared with many of the other subtypes. Overall the TN subtype accounts for around 16% of all breast cancers whereas in BRCA1 carriers it accounts for over 50% (Rummel, Varner et al. 2012). It has also been noted that the BRCA1 associated TN phenotype is common in women with a family history of breast cancer where no genetic mutation has been identified (Wong, Southey et al. 2011). This has led to the hypothesis that other mechanisms of inactivation of the BRCA1 gene may be important, with a particular focus on epigenetic gene silencing through aberrant methylation of the BRCA1 promoter. A number of small studies suggest that methylation of the BRCA1 promoter, detected in peripheral blood mononuclear cell (PBMC) DNA is associated with TN phenotype cancers (Snell, Krypuy et al. 2008) and that the level of methylation correlates with number of BRCA1 morphological features (Wong, Southey et al 2011). We have preliminary data from 310 women with breast cancer, including 52 with TN breast cancer, that hypermethylation of two individual CpG sites within the BRCA1 promoter in PMBC DNA may distinguish TN from non-TN tumours. Aims Our aims are firstly to determine the relationships between lymphocyte DNA methylation of the BRCA1 gene and (a) BRCA1 methylation in the tumour, (b) BRCA1 protein levels in the tumour, (c) tumour phenotype and behaviour. Secondly we aim to characterise the distribution of BRCA1 methylation in healthy control subjects. Methods Pyrosequencing of bisulphite treated DNA will be used to determine methylation levels at distinct methylation sites (CpGs) using PBMC DNA from 500 cases and 500 control subjects, and matched FFPE tumour samples. Immunohistochemistry will be used to look for BRCA1 protein expression in the tumour specimens. Tumours will also be scored for the presence of BRCA1-like morphological features. Further questions arising from the work that could be addressed as part of a PhD project include development of PBMC methylation levels as biomarkers and mechanistic studies to investigate how BRCA1 is inactivated and how this leads to particular tumour phenotype.


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: Impact of a previous cancer referral that did not result in a cancer diagnosis: patient attitudes and help-seeking for subsequent possible cancer symptoms
Funder: Cancer Research UK

Abstract: Background Diagnostic and treatment delay have been associated with more advanced disease in studies focusing on different cancers. Addressing diagnostic delay among patients with possible cancer symptoms is particularly important given that around 90% of patients are diagnosed following symptomatic presentation rather than screening. Patients’ experience during medical encounters may influence attitudes, risk perception and help-seeking if they subsequently develop new cancer symptoms Limited data are available on the consequences of previous cancer examinations on attitudes and help-seeking for patients with potential cancer symptoms Delay in help-seeking has been associated with the distress caused by a previous ‘false alarm’ but also with reassurance from a previous benign diagnosis. One commonly reported barrier in the UK is patients' perception of "wasting the doctor's time", but that has not been studied in relation to a previous false alarm. Aims The purpose is to collect preliminary data and conduct a feasibility study for the evaluation of factors influencing attitudes and help-seeking for cancer symptoms among patients who have previously undergone cancer examinations which did not result in a cancer diagnosis (here called false alarm). Methods The project will include a scoping study and preliminary data collection for evaluating attitudes and help-seeking among patients with a previous false alarm. The project includes: 1) A systematic review of the literature to examine evidence on specific cancers (e.g. breast, colorectal, melanoma), psychological, clinical, socio-demographic and health-care factors related to delay. 2) A pilot study based on in-depth interviews with 20 individuals who have experienced health examinations in the past due to possible cancer symptoms Face-to-face or telephone interviews will investigate patient experiences, attitudes and behaviours regarding symptomatic presentation following the false alarm. 3) A scoping study exploring approaches for recruiting patients having undergone cancer examinations that resulted in a false alarm. Meetings with GPs and secondary care personnel from cancer MDTs, and semi-structured interviews with 8-10 clinicians will be used to collect data on physician-perceived barriers and facilitating factors potentially influencing help-seeking among patients with a previous false alarm. How the results will be used The project will provide information for designing a future large-scale study, identifying issues that should be addressed in order to optimize the data collection methodology. The findings will be relevant for enhancing help-seeking and early diagnosis among people with a previous false alarm should they develop new cancer symptoms


Research activity codes: 4.3 INFLUENCES AND IMPACT
Health categories: CANCER AND NEOPLASMS