NIHRDataInsights/HRCSData huggingface dataset:
Title: Development and validation of a risk assessment tool to improve early detection of childhood, adolescent and young adult cancer
Funder: Cancer Research UK

Abstract: Background: Cancer is the commonest cause of mortality among children and young people in the UK. Delayed cancer detection is a known contributing factor to this healthcare challenge, with the UK continuing to have longer diagnostic intervals across childhood cancers compared to other high-income countries. The rarity of childhood, adolescent and young adult cancers makes diagnosis difficult. National awareness initiatives have attempted to address this challenge; however, general practitioners report ongoing difficulties in early diagnosis and young people experience ongoing delays. There is a clear gap in our early diagnostic strategies for childhood, teenage and young adult cancers. New approaches need to be explored to supplement current pathways. Aims: To explore ways to improve early childhood, teenage and young adult cancer detection through further characterisation of pre-diagnostic presenting features and development of a novel risk prediction tool. Methods: Using QResearch Database, the largest linked primary care database in the UK, clinical presenting features of three common childhood and TYA cancers (acute lymphoblastic leukaemia, central nervous system tumours and lymphomas) will be explored in a case-control study. For each case, ten age, sex and GP-practice matched controls will be included. Pre-diagnostic features occurring in more than 1% of cases or controls will be explored. The association between any pre-diagnostic feature and subsequent diagnosis of cancer, according to age, sex, tumour grade and stage will be investigated. Combination of features will be explored. A timeline of these features prior to diagnosis will be established. Development of the risk prediction tool will include fitting of pre-diagnostic clinical features and other known risk factors into a penalised regression model using a derivation cohort. Subsequently, a validation cohort will be used to assess measures of discrimination and calibration. How the results of this research will be used: We anticipate that the findings of this study will advance our understanding of person-specific and cancer-specific clinical features important in the diagnostic pathway of childhood, teenage and young adult cancers, making it a useful resource to the scientific community to drive future research. Our risk prediction tool carries large translational potential and is likely to influence the quality of early cancer diagnosis services provided to children, teenage and young adults in general practice. We aim that our prediction tool will facilitate risk assessment and early referrals for suspected cancers.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Bladder Cancer Prognosis Programme (BCPP)
Funder: Cancer Research UK

Abstract: The overarching objective of this application is to optimise the linkage of existing and future Bladder Cancer Prognosis Programme clinical- and laboratory-based (omics and digital pathology) datasets through the creation of a searchable and user-friendly BCPP ‘data warehouse’. We will achieve this by: • Curation of the current data; • Implementation of a curation pipeline for future data; • Initial normalisation steps to make BCPP ready for AI/Deep Learning applications


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Novel tools for molecular imaging of pancreatic preneoplasia - ACEDFR3_0620I14P016
Funder: Cancer Research UK

Abstract: Advanced pancreatic cancer (PC) is a debilitating and often lethal disease and one of the leading causes of cancer-related death. Early PC is difficult to diagnose using anatomical imaging. The disease is often asymptomatic and early lesions are frequently missed. Currently, there are no molecular imaging tools that can provide clinical information on early pancreatic cancer development. Our objective is to meet the urgent requirement for new diagnostic techniques for detection of the early stages of PC, potentially enabling curative surgery. We propose targeting PC-associated glycans for the development of new imaging techniques that can be translated to the clinic for improved detection of early stage disease.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Improving neo-adjuvant therapy in high-risk sarcomas - Studentship
Funder: Cancer Research UK

Abstract: The vision is to deliver datasets, data mining tools and patient-derived models that will drive the development of a stratified medicine approach for personalised NCT in high-risk STS patients. This will be achieved through 3 interrelated programs.1)Develop a common data platform to enable standardised clinicopathological and imaging data collection and curation of STS clinical specimens. 2)Generate molecular datasets and models that shed light on the biological processes impacting tumour response to NCT and 3)Develop a suite of data mining tools to facilitate analysis and integration of clinical and molecular data for use by the sarcoma community.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: Development of a myeloma case-finding approach for higher-risk patients: analysis of routine blood tests
Funder: Cancer Research UK

Abstract: Background Myeloma, a type of blood cancer, is one of the hardest cancers to diagnose. It is relatively rare and the main presenting symptoms, including back pain, bone pain, tiredness and repeated infections, are non-specific and common to many non-cancer conditions that occur in the elderly. Diagnosing myeloma early is important to prevent disease-related complications which can impact on quality of life and survival. Aims The project is aimed at improving the early diagnosis of myeloma. The specific aim is to develop a myeloma case-finding approach for higher-risk patients based on routine blood tests. The rationale for this approach is that many myeloma patients will have numerous blood tests in the years before diagnosis (e.g. blood counts, renal and liver function, inflammatory markers), predominantly for reasons unrelated to myeloma, and that people at higher-risk of myeloma can be identified from these tests and their evolution over time. Methods A nested case-control study will be conducted using de-identified data from Leeds Teaching Hospitals Trust including pathology, clinical and demographic data for myeloma patients and non-myeloma controls. We will consider as a separate group, patients with the myeloma precursor monoclonal gammopathy of undetermined significance (MGUS). We will compare and describe the number and type of blood test conducted in patients subsequently diagnosed with myeloma, MGUS and non-myeloma controls, as well as plotting trajectories of the blood test results in these three groups. A risk prediction model will be developed and internally validated to identify people at high-risk of having myeloma based on these results and clinical data. We will develop an early economic model to explore whether an automatic triage testing pathway for those at high risk of myeloma has the potential to be cost-effective. How the results of this research will be used Following algorithm development, future funding would be sought to conduct a prospective multi-centre study aiming to implement the algorithm and reflex-test individuals identified at higher-risk of myeloma. This would be with the aim of determining the impact on time to diagnosis, patient outcomes including quality of life and estimated costs to the NHS. Assessment of overall benefits and harms of earlier diagnosis, including a potential increase in MGUS cases would also be performed. If successful, there is clear line of sight to implementation within the clinical setting, capitalising on the existing healthcare infrastructure with the potential for a paradigm shift in the diagnostic pathway for myeloma.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Single molecule mass photometry for the early detection of cancer.
Funder: Cancer Research UK

Abstract: The transformation of cells leads to changes in proteins expressed both within the malignant cells and on the surface. Circulating Tumour cells (CTC) leave the primary tumour and drive metastasis. They are therefore a critical target for early detection methodologies and can be obtained using minimally invasive liquid biopsies. Therefore, the sensitive, rapid and correct detection of cancer cell specific markers is critical for medical diagnosis. Single molecule methodologies provide an absolute level of detection – a individual molecule which is a critical early detection advantage. However, these methods are rarely applied for screening and molecular recognition. The key challenge with single molecule approaches is to utilize a suitable contrast mechanism to detect the molecules against a complex background. Fluorescence-based single molecule methods are frequently employed but fluorescent methods are subject to significant limitations which include high-background and non-specific signals. Overall, this renders detection within complex samples, such as cell lysates or blood technically challenging, or impossible. Non-fluorescent, label-free microscopy methodologies such as light-scattering based interferometric scattering (iSCAT) microscopy, alleviates some of these challenges. There is a linear relationship between molecular volume and refractive index. This relationship means that the signal within an iSCAT microscope is directly proportional to molecular mass. This has led to the development of Mass Photometry by Refeyn. With this approach, we have the ability to detect single molecules without modifying the target, using minimal concentrations and volumes, within a short timescale, and with the ability to determine mass of the target. Here, we will develop a novel single molecule screening application based on mass photometry. Targets of interest will be surface captured by antibodies in minimal volumes. The target-capture approach enables a universal format where it would be possible to detect low levels of circulating protein marker in a blood sample. This project describes the proof-of-concept experiments which is focused on optimizing antibody capture then detecting targets from cell and tissue lysates. The final assay would be based around isolating CTC then screening for protein markers. This would be a transformative technology enabling the rapid detection of circulating biomarkers within blood samples.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: How does the Zika virus kill Neuroblastoma cells? A potential new oncolytic virotherapy for neuroblastoma
Funder: Neuroblastoma UK

Abstract: A study to understand the molecular mechanisms underlying the oncolytic response in Neuroblastoma induced by the Zika virus


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: CANCER AND NEOPLASMS
Title: Gains in life expectancy as tangible metrics for improvement assessment
Funder: Cancer Research UK

Abstract: Background Many early diagnosis initiatives focus on the evaluation of process measures, such as improvement in the public’s awareness about symptoms or increases in the number of primary care referrals. While these measures can be considered to represent surrogates of improved survival, it is nonetheless optimal to also evaluate the impact of interventions on survival directly. There are a number of challenges for survival-based metrics in this context; the impact of lead time and the challenge in attributing improvements to the initiative alone. Methodological developments are necessary to offer easier comparisons of the likely benefit of early diagnosis initiatives or policy implementations on life expectancy. Aim We aim to further develop statistical methods for estimating gains in life expectancy due to earlier cancer diagnosis with the view to provide easy to interpret measures capable of assessing (i) the potential for future early diagnosis initiatives and (ii) measuring the impact of completed early diagnosis initiatives. Important methodological issues are incomplete data on stage, and the relatively short follow-up on data with sufficient completeness. We aim to further develop existing approaches to overcome these difficulties and provide a unified framework for early diagnosis initiative assessment. Methods A number of methodological extensions are necessary in order to adopt a lifetime-based metric using stage-specific data. The first consideration is that missing data for stage is an issue and our approaches will need to be combined with appropriate imputation techniques. Secondly, the data with sufficient completeness on stage at diagnosis is not mature, and so the extrapolation needed for estimating life expectancy based metrics will need to be longer and entail more assumptions. We will develop approaches for multiple imputation to deal with incomplete stage information and also utilise a period analysis approach to minimise the impact of incomplete data and to also provide the most up-to-date survival estimates possible. How the results of this research will be used. This project will have wide-ranging benefits across the policy/practice landscape; offering a sound methodological approach for making informed comparisons of the likely lifetime impact of early diagnosis initiatives. The approach can be applied in the planning stage to show the hypothetical impact of an intervention, or could be applied following an intervention to assess the observed benefit. This will allow the prioritisation of early diagnosis initiatives by highlighting where the highest impact can be made in terms of reducing inequalities and extending cancer patients’ life expectancy.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Screening Trial Surrogate Endpoints: Systematic Review
Funder: Cancer Research UK

Abstract: A comprehensive systematic review and meta-analysis of cancer screening randomised controlled trials (RCTs) will establish the strength of the evidence to support using intermediate outcomes as surrogate endpoints in future trials, for two purposes: 1. Futility of continuing/starting RCTs. Knowledge that the size of effect on the surrogate is small enough to rule out a clinically-significant effect on mortality would enable researchers and funders to identify ineffective tests, prevent funding similar trials, and stop trials early (entirely, or by dropping the least promising interventions in multiarm-multistage trials). 2. Sufficiency of the effect on the surrogate to conclude that screening is very likely to have a clinically-significant impact on mortality. This would enable policy-makers to plan for potential implementation, and start pilot programmes and implementation research whilst awaiting mortality outcomes. Research Questions Systematic review, to assess whether in RCTs of cancer screening: 1. Late-stage cancer is a sufficient surrogate to predict differences in cancer-specific mortality between trial arms and/or to predict the futility of continuation to mortality outcomes (overall, by modality, by cancer site, by site-modality combination). 2. Same as question 1, but for other pre-specified surrogates. Data from trials combined with other studies, to assess: 3. The potential utility of predicted mortality as a surrogate endpoint.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Understanding public receptiveness to risk-based approaches for cancer prevention and early diagnosis
Funder: Cancer Research UK

Abstract: Background Recent advances in understanding of the evolution of cancer and the development of new screening and diagnostic tests and approaches mean that in the future there are likely to be new innovations that have the potential to stratify individuals, or groups of individuals, based on their risk of having an undiagnosed cancer or their risk of developing cancer in the future. Understanding the perspectives of target populations and society more broadly is essential to ensure that such risk-based approaches can be communicated and implemented in a way that optimises acceptability and uptake while minimising potential inequalities. Aims The overall aim of the research is to develop a detailed understanding of public attitudes towards new and emerging risk-based cancer prevention, screening and diagnostic approaches and technologies. Specific objectives are: 1. To explore the views of the public on future risk-based technologies and risk stratification in cancer prevention and early diagnosis at a societal level 2. To explore in-depth public attitudes and receptiveness to risk-based innovations at an individual level and identify key barriers and enablers towards uptake 3. To describe and quantify public attitudes and receptiveness to risk-based innovations and how these are influenced by individual level characteristics and attitudes towards risk of cancer 4. To quantify the relative importance of different attributes of risk-based technologies amongst members of the public and their potential impact on uptake Methods We will conduct four linked studies using novel and complementary approaches: a community jury study; a think-aloud study in which participants will complete an online survey about their attitudes and receptiveness to risk-based innovations while “thinking-aloud” about their internal judgmental processes; an online population-based survey using the same survey as for the think-aloud study; and a discrete choice experiment. In all four studies we will use exemplars of potential future risk-based innovations identified and prioritised at a workshop at the start of the research with representatives from Cancer Research UK and leading experts in cancer early detection and diagnosis. We will synthesize the findings from all four studies using the Theoretical Framework of Acceptability and COM-B frameworks. What value will the programme of work deliver? Together, these four studies will enable us to describe the barriers and facilitators to engagement with future risk-based innovations, both at societal and individual level, and provide recommendations for evidence-based policy, communications and implementation approaches to improve public receptiveness and increase motivation to engage with new interventions.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS
Title: Development and application of methods to assess the impact of stage differences and potential changes in the stage distribution on cancer survival.
Funder: Cancer Research UK

Abstract: BACKGROUND Early diagnosis is a key aspect of improving cancer survival and a strategic aim of CRUK and the NHS. When comparing cancer survival between population groups a proportion of the difference in survival will often be due to differences in the stage of disease at diagnosis. Such differences have been seen at the national level when comparing deprivation groups, sex, regions and internationally when comparing the UK with other countries. However, stage specific survival within these population groups still varies and more advanced stage is likely to only explain a proportion of the differences in cancer survival. Understanding how improvements in the stage distribution would impact on survival is a form of mediation analysis. Such methods are complex and it is essential that the methods are appropriately used and their assumptions understood. AIMS We will combine methodological development, novel applications of new methods, software development and educational material to transfer methods in to practice. Specific Aims. 1. Further develop and apply statistical methods to quantify the impact of differences in the stage distribution between population groups. 2. Produce various measures that quantify these differences, including avoidable/postponable deaths. 3. Produce software and tutorials to enable other researchers to implement the methods. METHODS We will extend and apply mediation analysis methods in order to quantify the impact of stage at diagnosis on survival differences and the potential impact of interventions to shift the distribution of stage at diagnosis. We will present methods using easy to understand metrics, such as the number of “avoidable” deaths. We will clarify the assumptions required when performing such analysis. We will use the methods in two applied studies using NCRAS data with a more detailed colorectal cancer study using CORECT-R. To ensure that the methods are transferred to applied research we will develop user-friendly software, teach methods on courses/workshops and develop a tutorial website. HOW THE RESULTS OF THIS RESEARCH WILL BE USED? This is primarily a methods project but has important benefits in increasing understanding of the potential impact of earlier diagnosis. The ultimate aim is to improve epidemiological cancer research by getting the methods used by other research groups worldwide.


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