NIHRDataInsights/HRCSData huggingface dataset:
Title: Epidemiology, aetiology and genetics of solid tumours in children, teenagers and young adults
Funder: Cancer Research UK

Abstract: 1. Background and Relevance to Cancer Cancer is the most common disease-related cause of death in children, Teenagers and Young Adults (CTYAs). However, over 75% of cancers arise in persons aged over 50 years, following decades of exposure to causative factors. Alternative exposures, pathways and mechanisms must be sought to understand why CTYAs develop cancer. 2. Aims and Objectives To analyse data and other material on a large population-based series of CTYAs with solid tumours and their families and investigate the role of genetic predisposition in aetiology. The contribution of transplacental and other environmental exposures will be considered. Germline TP53 mutations predispose to specific childhood cancers. Families with such mutations will be analysed to determine correlations between cancer phenotype and mutant protein structure and function. 3. Methods 3.1. Comprehensive data on 882 children with sarcomas, Wilms, hepatoblastoma and adrenocortical tumours and their extended families were collected. Cases included in the Manchester Children’s Tumour Registry from 1954 to 2008 were eligible. Interviews were conducted and oncology, obstetric and GP records abstracted. Cases, parents and siblings are followed-up prospectively. Standard statistical methods will be applied to these data to analyse familial cancer risks, congenital anomalies, birthweights and inter-relationships between these. Frequencies of known syndromes and residual cancer clustering will be assessed. 3.2. Over 3,400 children with solid tumours plus their parents are flagged to give continuous follow-up on cancer occurrence and deaths from all causes. Cancer incidence and mortality rates by cause will be analysed and compared with those expected in the general population. Cancer patterns in case-parent trios will be assessed for familial predisposition. In addition we shall seek excesses of cancers and non-cancer causes of death in parents which may be consistent with transplacental carcinogenesis in the case-child e.g. via parental smoking or occupational exposures. Exposure-related carcinogen fingerprints will be sought by analysis of TP53 mutations in tumour tissue from 450 selected index cases. 3.3 Confirmed cancer diagnoses are available on 61 extended families with germline TP53 mutations. Population-based, morphology-specific relative frequencies and absolute cancer risks will be calculated overall and by mutation type. Classes of mutation defined by IARC will be applied. Studies of LOH and immunohistochemical staining for p53 in tumour and normal tissue will be carried out. Results will be used to generate hypotheses about genotype-phenotype correlations. These will be tested against families included in the IARC database. 4. Results will have clinical and molecular biological applications.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.4 SURVEILLANCE AND DISTRIBUTION;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Improving the understanding of the results from population-based cancer studies
Funder: Cancer Research UK

Abstract: 1) Background (including relevance to cancer)_x000D_ This research stems from two common themes for population-based cancer research in the UK. Firstly, data collection mechanisms for UK cancer registry data have come under recent scrutiny. Secondly, a more widespread theme for population-based cancer research is the desire to provide simple measures for patients and clinicians to understand the output from complex statistical analyses._x000D_ _x000D_ 2) Aims & Objectives_x000D_ The main objectives are:_x000D_ 1) To investigate data quality issues in population-based cancer studies by performing a detailed simulation study to make an assessment of the extent to which potential inaccuracies in cancer registration may bias estimates of survival for the UK cancer registry statistics._x000D_ 2) Improving quantification of survival outcomes. This will be mainly through the use of flexible parametric survival models to estimate the number of “avoidable” deaths and the loss in expectation of life. _x000D_ 3) Applying and extending recently developed methodology for obtaining future prediction of incidence. _x000D_ _x000D_ 3) Methods_x000D_ We will simulate data from two "perfect" registries having exactly the same survival, but then make one of the registries "imperfect" by generating incorrect dates of diagnosis and missed individuals according to some realistic criteria. This will allow an assessment of the impact on survival rates caused by the errors that are likely to exist in the UK data. _x000D_ We will use the flexible parametric modelling framework to extend methods for estimating the number of “avoidable” deaths and the loss in expectation of life. _x000D_ We will apply recent developments in incidence modelling to UK data and assess the potential to jointly model incidence and survival using individual-level data._x000D_ _x000D_ 4) How the results of this research will be used_x000D_ The results of the simulations will be used to assess how much of an effect the level of “imperfections” in the UK cancer registry data will have in terms of international comparisons. The work on providing simple measures for quantifying differences between groups will be applicable in a wide range of settings. The cancer incidence (and prevalence) projections will be useful for estimating future planning needs for UK health authorities. Finally, the measures for loss in expectation of life will provide new and simple techniques for assessing the impact of cancer on society, which will be of benefit for the planning of cancer care.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: CANCER AND NEOPLASMS
Title: Cancer symptom appraisal in everyday life: psychological and demographic influences
Funder: Cancer Research UK

Abstract: Background: Failure to recognise symptoms as cancer is a key factor associated with patient delay and may contribute to more advanced disease at presentation. Previous research has investigated symptom appraisal specifically in the context of cancer, which may bias help-seeking reports. <br/><br/>Relevance to cancer: By understanding the symptom appraisal process in everyday life, this research aims to improve our understanding of cancer symptom appraisal. This will help identify targets for intervention to reduce appraisal delay and ultimately to save lives. <br/><br/>Aims &amp; Objectives: This research aims to understand the psychological and demographic correlates of symptom appraisal without explicit mention of cancer, using a theoretical model (Psycho-Physiological Comparison Theory; PPCT) to guide research. The primary objectives are: i) To investigate symptom reports in the general population and predictors of appraisal delay, including sex, age, SES, number of symptoms, perceived consequences and knowledge. A secondary objective is to investigate the role of individual characteristic variables, such as anxiety, time perspective, self-efficacy and type of information-seeker. ii) To conduct in-depth qualitative interviews with a sub-sample of patients reporting possible cancer symptoms in Study 1 to explore potential explanations for sex and SES differences (e.g. differences in optimism, normalisation). iii) To use a novel methodology to provide further information about the relative importance of symptom attributes (identified from Studies 1 and 2) on cancer attribution. <br/><br/>Methods: Mixed methods will be used to achieve the objectives; i) a quantitative population-based survey to assess symptom prevalence and appraisal according to demographic and psychological characteristics ii) a qualitative study for in-depth exploration of explanations for demographic differences and iii) a behavioural economic study using discrete choice experiments to assess the importance of specific symptom attributes for a cancer attribution.<br/><br/>How the results of this research will be used: The results of the research will be published in peer-reviewed journals and will be used to inform the development of interventions aimed at reducing appraisal delay. This study is unique because it will provide information on symptom appraisal in everyday life and will explore potential explanations for demographic differences.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS
Title: Drug Development and Human Clinical Evaluation of Small Molecular PARP Inhibitors
Funder: Cancer Research UK

Abstract: The Translational Cancer Research Prize recognises a team who have made a significant impact on the continuing effort to prevent, diagnose and cure cancer, and whose research is at the cutting edge of scientific novelty. The team receives a research grant of £25,000, a commemorative glass trophy, and free attendance at the NCRI Annual Conference for up to five members of the team. In 2010, the Prize was awarded to a team from Newcastle University for their work on a class of compounds called PARP inhibitors. About the Newcastle PARP inhibitor study team: The story of the Newcastle PARP inhibitor study team's achievement begins in 1980 with an initial scientific observation by Dr Barbara Durkacz, a group leader at Newcastle University, that there was a poly-ADP ribosylation reaction, catalysed by a protein called PARP, associated with DNA damage. If this reaction was blocked, it increased the killing effect of the DNA damage on cancer cells. In 1990, the newly formed Newcastle drug discovery team undertook its first project - the development of a PARP inhibitor. Over the subsequent 20 years, the team has made significant contributions to compound identification, preclinical biology and testing, design of clinical trials and biomarkers and the subsequent clinical development of multiple compounds in this exciting new class of drugs. This prize recognises the ability of this team to take a scientific concept through medicinal chemistry and preclinical work, right through to first-in-human clinical studies. All of this was done in a single location, with input from a wide range of research fields. The members of the winning team at Newcastle University are: Prof.s Barbara Durkacz, Ruth Plummer, Hilary Calvert, Nicola Curtin, Bernard Golding, Roger Griffin and Herbie Newell.


Research activity codes: 5.1 PHARMACEUTICALS;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: MRI biomarkers of low grade glioma growth and infiltration.
Funder: Cancer Research UK

Abstract: Background<br/>There is still a need for accurate and objective biomarkers that aid characterization of low grade gliomas (LGG) for delineation of tumour infiltration and early identification of malignant progression. We are investigating the role of the advanced MRI methods of 1H Magnetic Resonance Spectroscopic Imaging (MRSI) and Diffusion Tensor Imaging (DTI) in the diagnosis and management of adult brain tumours. The combination of MRI markers relating to tissue metabolism and structure offer a powerful tool to non-invasively identify biomarkers directly related to the biological processes of tumour growth and invasion and to enable patient and tumour-specific evaluation and treatment. We have successfully developed novel automated algorithms for objective analysis of data from both modalities. Our initial analyses demonstrate glioma grading and depiction of heterogeneity by MRSI and DTI measurements provide markers that may objectively detect subtle changes in tumour malignancy, growth and infiltration.<br/><br/>Aims<br/>To further develop our novel pattern recognition analysis of MRSI and DTI data of brain tumours by combining multimodal MRI data (diffusion tensor imaging, perfusion imaging and 3D metabolite mapping). To test how well the individual and combined biomarkers predict malignancy and tumour growth pattern for LGG. To develop 3D visualizations of such data that delineates the tumour-brain interface and tumour growth pattern and can be used within a routine radiological clinical environment.<br/><br/>Methods<br/>DTI, 1H MRSI and relative cerebral blood volume (rCBV) data will be acquired from low grade glioma patients at 6 monthly intervals over a 3 year period. Pattern recognition of DTI (k-means clustering of the p and q diffusion components) and MRSI (independent component analysis and mixture model analysis) will be combined for characterization of bulk tumour and surrounding infiltrative tissue regions. Coregistered longitudinal image data will be used to determine which biochemical and structural characteristics of tissue are best predictive of progression by comparison to conventional MRI and rCBV.<br/> <br/>How the results of this research will be used.<br/>Biomarkers developed in this study will relate to the earliest transforming tumours (i.e. those within 2 years of diagnosis) in the patient cohort. We would aim a follow up study of patients with later transforming tumours to further assess biomarker validity. We would aim to design a multi-centre trial to evaluate the biomarker and 3D visualization software within a clinical environment and determine the generalisability of our results, and refine the algorithms for use on different MR systems


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: Prospective evaluation and refinement of a targeted on-site monitoring strategy for multi-centre cancer clinical trials
Funder: Cancer Research UK

Abstract: Background:_x000D_ Most academic-led cancer trials are conducted in the National Cancer Research Network (NCRN) and test licensed oncology drugs outside their licensed indication. As resources are limited, monitoring strategies for these trials must be cost effective and efficient, and balanced against the assessment of trial participants’ safety, and data accuracy and validity. However, no empirical evidence currently exists to guide the nature and extent of this monitoring. _x000D_ _x000D_ On-site monitoring, at which source data verification takes place, is frequently used but is a major cost-driver. Proven cost-effective and efficient monitoring strategies would enable more good quality trials to be conducted, to the ultimate benefit of more cancer patients._x000D_ Triggered monitoring (where on-site monitoring takes place only after the site meets a certain trigger identified through central monitoring at the coordinating centre), may be particularly useful for the QA/QC of cancer trials which typically have a large number of sites and limited trial management resources. We therefore propose to conduct a prospective evaluation of a triggered monitoring strategy in four UK cancer trials. _x000D_ _x000D_ Aims and Objectives:_x000D_ To assess:_x000D_ a)if a triggered monitoring strategy is effective at distinguishing cancer trial sites at which critical/major site monitoring findings are more likely to be identified_x000D_ b)which triggers are most discriminatory_x000D_ c)if triggers can improved so that the visits that are performed are warranted_x000D_ d)the costs and benefits of different triggering strategies_x000D_ _x000D_ Methods:_x000D_ During this study, all sites meeting one or more of the pre-defined triggers will undergo a site monitoring visit, and an additional control site, matched for number of patients and time since accrual of first patient, but not meeting triggers at that time, will also be visited. The number of critical, major and “other” findings will be noted on a standard monitoring report, and reviewed by an endpoint review committee blinded to study group. The proportion of sites with at least one critical or major finding, and the number of such findings, will be compared across the triggered and untriggered sites._x000D_ _x000D_ How the results of this research will be used:_x000D_ If effective, implementation of the strategy will ensure that in large low- or medium risk trials with limited resources, a scientifically assessed, cost effective and efficient monitoring strategy is being used to protect participant safety and the accuracy of results. It will be one of the first studies to evaluate different monitoring strategies, increasing methodological knowledge in the field.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: CANCER AND NEOPLASMS
Title: Quantitative Fitness Analysis to understand the Schizosaccharomyces pombe telomere
Funder: Cancer Research UK

Abstract: Background: Functional telomeres permit cell division and help maintain genetic stability. To better understand telomere function we will systematically measure genetic interactions in fission yeast cells with telomere defects. This will help define conserved eukaryotic responses to telomere failure, the basis for variations among species, and has the clear potential to help cancer diagnosis or treatment._x000D_ _x000D_ Relevance to Cancer: In most human somatic cells insufficient telomerase is expressed to maintain telomere length through successive rounds of DNA replication. Short, defective telomeres stimulate cell cycle arrest, senescence or apoptosis, processes that simultaneously promote aging and protect against cancer. Telomere failure also induces genetic instability if defective telomeres are &quot;repaired&quot; as if they were Double Strand Breaks (DSBs) leading, for example, to cycles of chromosome fusion and breakage. Finally, in order to become immortal any cancer cell has to deal ultimately with the end replication problem by somehow stabilizing telomeres. To help understand carcinogenesis, and to target treatments to cancers arising from cells with defective telomeres, it is critically important to understand the structure and properties of functional telomeres, defective telomeres and the spectrum in between. Eukaryotic telomere structure is conserved across evolution and therefore we propose to study telomere function in the experimentally tractable model organism fission yeast.br/br/Aims of research: We have shown that by measuring the fitness of budding yeast strains with telomere defects we gain important insights into telomere structure. We now aim to extend this approach to the fission yeast Schizosaccharomyces pombe, as this model system combines the potential for quantitative genome-wide analysis with telomere structures that are more similar to those of human. There are four specific aims br/br/1. Optimize synthetic genetic array (SGA) procedures for S. pombebr/br/2. Perform SGA experiments to understand the telomerebr/br/3. Establish Quantitative Fitness Analysis (QFA) procedures for S. pombebr/br/4. Perform QFA analysis on strains with taz1 deletion or temperature sensitive pot1ts mutationsbr/br/Outcomes: We will establish robust procedures to determine the fitness of systematic libraries of S. pombe yeast strains with telomere defects. These approaches will address important questions about fission yeast telomere structure and function. Comparison of these results with analogous experiments performed in budding yeast will reveal conserved and non-conserved aspects of these responses, with significant implications for human telomere biology. Finally, the methods we establish will be of use to others studying other aspects of S. pombe cell biology.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: CANCER AND NEOPLASMS
Title: Prospective evaluation of smooth muscle actin (SMA) expression in predicting oral cancer aggression
Funder: Cancer Research UK

Abstract: Background: The UK incidence of oral cancer (OSCC) has risen significantly since the 1970s, to ~5300 cases annually, and is estimated to rise further over the next decade. OSCC is an heterogenous disease, staged currently using the TNM classification, supplemented with pathological information from tumour and loco-regional lymph nodes. Although patients with advanced disease show reduced survival, there is no single pathological or molecular feature that identifies aggressive tumours at an early stage._x000D_ Preliminary data: We conducted a retrospective study of 282 OSCC patients from two London hospitals (1992-2005), and analysed data on clinical, pathological and molecular features in relation to OSCC mortality (120 deaths; Marsh et al., 2010). We found that the best independent risk factor of early OSCC death was a feature of tumour stroma rather than tumour cells. High stromal smooth muscle actin (SMA) expression produced the highest adjusted hazard ratio (3.06, 95% CI 1.65-5.66; p=0.002), and highest likelihood ratio (3.6; Detection rate:False positive rate) of any feature examined, and was strongly associated with mortality regardless of disease stage. These data highlighted the limited prognostic value of TNM staging, and suggest that stromal SMA is a highly effective marker for identifying a significant group of patients with aggressive tumours._x000D_ Aims: The aim of this study is to evaluate in a prospective cohort of OSCC patients, the usefulness of SMA immunostaining in identifying clinically aggressive disease, and to determine the clinical progression of SMA-positive tumours._x000D_ Methods: We aim to recruit 306 patients from 5 UK centres over 15-18 months. We will carry out SMA immunostaining on a single tissue section from paraffin-embedded material from the patient’s diagnostic biopsy or surgical resection specimen. The cost is relatively cheap (~£15 per patient). Tumours will be scored for SMA-positivity by a pathologist as high, moderate or low. We will generate a patient database containing detailed clinical, pathological and immunochemical data, enabling us to record comprehensively the natural progression of SMA-positive tumours. Patients will be followed up for 2 years._x000D_ Utility: If SMA expression is validated as the best predictor of OSCC mortality, then routine SMA immunostaining of tumours would be a highly cost-effective method for identifying clinically aggressive OSCC. Understanding how such tumours progress, will suggest how current patient management can be modified to improve patient survival. _x000D_


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: MRes Pathology Students
Funder: Cancer Research UK

Abstract: MRes in Pathology associated with the CRUK Centre. Researchers at the Cancer Research UK West of Scotland Cancer Centre are particularly focusing on bowel cancer and leukaemia, although their work will touch on many other cancer types. Scientists at the Centre also have considerable expertise in studying how cancer cells break away from a tumour and spread through the body - their work is paving the way for new treatments to halt this process. The Centre builds on Glasgow's excellent track record in developing new drugs for cancer. Scientists, doctors and nurses are working together to understand the molecular faults that lie at the heart of cancer, and find new drugs to target them. Researchers at the Centre also have the expertise to take exciting new treatments out of the lab and into the clinic, testing them in early-stage clinical trials with patients. To ensure that Glasgow continues to be a focus for cancer research for years to come, the Centre will play an important role in recruiting and training the next generation of cancer researchers. The staff at the Centre will reach out to the local community, highlighting the importance of a healthy lifestyle in cutting the chances of cancer, and how to spot the early signs of the disease (http://aboutus.cancerresearchuk.org/what-we-do/research/research-near-you/glasgow/science-research/)


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: CANCER AND NEOPLASMS