NIHRDataInsights/HRCSData huggingface dataset:
Title: Combining diet and symptom management for earlier detection of cancer using transactional data
Funder: Cancer Research UK

Abstract: Background Improvement of early-stage cancer diagnosis when patients have better treatment options remains a significant challenge. The Cancer Loyalty Card Study (CLOCS) has obtained transactional data from ovarian cancer (OC) patients and women without OC and has shown that patients are likely treating symptoms at least eight months before diagnosis. The use of transactional data to better understand self-care in the patient interval is only the beginning of how this data can be used for understanding cancer risk and health behaviours, such as diet, and the potential it has to improve earlier diagnosis for individuals experiencing non-specific cancer symptoms. Aims The aims of this project are to 1) use transactional data to examine the association of diet exposures and OC among existing CLOCS participants and 2) investigate the use of transactional data for early detection of cancer types that commonly exhibit non-specific symptoms as well as test the effectiveness of participant recruitment through primary care based text messages. The final aim of the project focuses on career development, where the lead researcher will complete an intensive course in data science to further enhance analysis of the transactional data. Methods For the first aim, we will identify diet exposures related to OC risk and develop a transaction cancer symptom score that incorporates dietary risk, change in dietary behaviour, and symptom management behaviour. Secondly, we will conduct a pilot case-control study with recruitment of patients diagnosed with eight novel cancer types using a text message invitation from primary care. The predictive cancer symptom score developed in the first aim will be tested and validated among more participants in the CLOCS multi-cancer case-control study. How the results of this research will be used The results from this project will inform future CLOCS research where 500 patients with colon, oesophageal, and pancreatic cancer will be recruited for case-control analysis. If this pilot study shows evidence for self-management of symptoms before diagnosis of stomach, liver, bladder, vulval, and uterine cancers, then these cancer sites can be added for future research into the use of transactional data to improve earlier diagnosis. If the transactional cancer symptom score is found to indicate a signal that someone should seek medical attention, then the next stage of research would be to understand the possible routes of using this score to decrease the patient interval.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Dinutuximab -Beta as the theragnostic vector for non-invasive molecular imaging and radiatiotheray for high risk neuroblastoma
Funder: Neuroblastoma UK

Abstract: Creating and evaluating new radioactive compounds for scanning and treating children with high -risk neuroblastoma


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: MIGRATES: Multi-centre deployment of preclinical multi-modal imaging-guided radiotherapy
Funder: Cancer Research UK

Abstract: This project supports the overall aim of CRUK RadNet to improve the treatment of cancer patients with radiation. Treating cancer with X-ray radiation needs clear images of the cancer to aim the beam. The machines used to treat animal models of cancer cannot always give good enough images for this, so images are taken on other machines and transferred to the radiation treatment machine. This work will design and build cradles and holders to support and transfer the animals between different machines while they are still anaesthetised and unable to move. It will also improve monitoring of their temperature and breathing. The cradles and new computer programs will make it easier to combine images from different machines to aim the beams more accurately, killing more of the cancer and doing less damage to healthy parts of the body close to the cancer. This will be tested first in Cambridge, then shared with researchers across the country (in Glasgow, Leeds, Manchester & London) so the same high standards can be met at all the sites. This will improve studies of new treatments with radiation or radiation combined with new drugs. This will give better guidance to future clinical trials and lead to better patient treatment.


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: Novel decision support intervention to support choice in cervical screening modality
Funder: Cancer Research UK

Abstract: Background: Cervical cancer is the second most diagnosed cancer in individuals with a cervix under 45 years of age in the UK. Cervical screening using HPV testing is routinely offered to individuals with a cervix between the ages of 25 and 64 years in the UK via the NHS cancer screening programmes. The cervical screening eligible population could for the first time have a choice of cervical screening modality; in-clinic or self-sampling for Human Papillomavirus (HPV). To date, no intervention has integrated behaviour change techniques with decision support principles to support equitable participation in cervical screening, whilst also promoting informed screening modality choice. Aims: This project aims to identify optimal methods of communicating cervical screening programme changes, and to understand the needs of individuals with a cervix regarding a combined behaviour change and preference-based decision support tool when presented with a choice of cervical screening method. Methods: A qualitative co-production approach will be used to: 1. explore communication preferences and decision support needs in a diverse sample of the cervical screening-eligible population (particular focus on underserved populations) using semi-structured interviews (up to 30); 2. examine stakeholder perceptions regarding the practical implications of choice on the service journey for users using semi-structured interviews (up to 20), and 3) develop a novel theory-informed Logic Model of the active components required to develop an intervention for preference-based decision support about screening modality. Qualitative interview recruitment will be guided by the concept of ‘information power’ and will continue until no significant new themes are identified. Data transcribed verbatim and will be thematically analysed. How results of this research will be used: Outputs will build the platform for future research by identifying a logic model, communication strategy and stakeholder consortium for the subsequent development of novel integrated behaviour change and decision support interventions to support cervical screening decisions within new screening programme provision. The stakeholder consortium will work collaboratively to develop a research grant application to CRUK’s Early Detection and Diagnosis Project Awards focusing on using the novel logic model to form and pilot test a decision support intervention.


Research activity codes: 4.3 INFLUENCES AND IMPACT
Health categories: CANCER AND NEOPLASMS
Title: Early Detection with Urine and Cognitive Assessment Multiplex (The EDUCAM study)
Funder: Cancer Research UK

Abstract: Background: Cancer screening has demonstrated efficacy in reducing cancer burden. However, methods used are unsuitable for brain cancer due to its low incidence, the risks (e.g radiation)/costs associated with repeated imaging and the indistinct signal obtained with cell free DNA (cfDNA) mutational analysis. Recent molecular analysis of IDH wild-type low grade gliomas as an ‘early detected’ glioblastoma with an improved prognosis (versus glioblastoma) has renewed interest in the efficacy of brain cancer screening. Up to 20% of patients with systemic cancers will develop brain metastasis, for which the incidence is increasing, and no screening test is currently available. Recent studies have identified cognitive deficits in newly diagnosed brain and breast cancer patients. Moreover, we have demonstrated efficacy in urine cfDNA identification of brain cancer. We propose that by combining these techniques we can improve detection sensitivity and specificity. Our truly non-invasive approach will make multi-test paradigms more feasible and genome wide DNA assessment, incorporating multiple disease-specific signatures (e.g. urine cfDNA epigenome analysis) will further boost statistical power and therefore improve sensitivity and specificity. Aims: 1) Multi-modal assessment (cognition assessment and urine cfDNA analysis) for early detection of brain cancer in the ACED cohort. 2) As above but for systemic cancer Methods: We will recruit all participants (~1000) to the ACED clinic Cambridge during their baseline visit to the EDUCAM study. Participants will undergo a 5 minute cognitive test using a tablet computer based application. Subsequently a sample of urine (~100mls) will be collected. The cognitive data metrics will be used to stratify participants into groups from higher to lower risk of cancer on the basis of performance. Urine samples will be batched, DNA extracted and fragmentation, mC pulldown signatures and mutant allele fraction obtained. Epigenomic/mutational signatures and cognitive data will be used for machine learning modelling to identify whether and how these non-invasive sources can be used additively to predict cancer diagnosis. Confirmation through the collection of ‘ground truth’ follow up data for the duration of the ACED clinic recruitment will be utilised. Use: We will have identified whether cognitive tests and urine cfDNA are useful for early cancer disease detection. We plan to follow up ACED participants and obtain subsequent samples/information on future diagnoses. This data will inform a larger clinical trial comparing these techniques with other early detection paradigms guiding subsequent broader implementation across the NHS.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Improving myeloma diagnosis using a simple rapid test
Funder: Cancer Research UK

Abstract: Background Of the major cancers, myeloma ranks worst for diagnostic delays; this causes substantial morbidity and early mortality. Every year, 3,100 patients die of myeloma in the UK, where the route to diagnosis is well-defined by multiple primary care consultations, emergency presentation to acute services and intra-hospital delay. Myeloma comes at not only substantial costs to the patient but also the NHS, consuming approximately £148 million of budget each year. In LMIC, limited access to the specialised laboratory testing currently required to diagnose myeloma means most patients present with advanced disease and multiple complications. There are two laboratory blood tests (serum free light chains [sFLC] and m-protein) that can identify myeloma and their wider use could reduce delays in diagnosis. We have published a strategy using these biomarkers to sensitively and specifically identify myeloma from other conditions. However, currently these tests can only be carried out in large clinical chemistry departments/specialised laboratories. To truly tackle delayed diagnosis in the UK and to improve ability to diagnose myeloma in LMIC, these biomarkers need to be translated into a simple, easy to interpret, rapid and low-cost test. Aims Our project seeks to technically and clinically validate a Myeloma Lateral Flow (MLF) test. The ultimate objective is an MLF test which is ready to be used at the point of care/rapidly available in the laboratory, which will drive progress in early detection via increased access to and speed of testing. Methods We have developed a MLF prototype that measures sFLC and m-protein using a qualitative colour-change format. The project will use an industry expert to manufacture our MLF test. The university of Birmingham team will then perform I) extensive technical validation and II) clinical accuracy studies using our large well-characterised sample biobank, including a range of patient samples (monoclonal gammopathies and other conditions) and healthy controls. How the results of the research will be used The project will generate an evidence base for the clinical utility of our test. This will be utilised to develop a commercial partnership and take the test forward into trials in clinical practice in the UK and LMICs.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: PRISM - Machine Learning for Discovery of Pre-neoplastic signature in Mesothelioma
Funder: Cancer Research UK

Abstract: Background: Malignant pleural mesothelioma (MM) is a highly aggressive cancer and has a five-year survival rate of less than 10% from diagnosis. The prognosis of patients with MM is poor since most of the patients are diagnosed at an advanced stage when MM is resistant to current treatment options MM is mainly caused by exposure to asbestos. Mesotheliomas arise most commonly from the mesothelial cells that line the pleura. To diagnose MM, a biopsy is taken, which can be either in the form of pleural tissue (for histopathology) or pleural fluid (for cytology) or both. By identifying early cancer changes and preneoplastic changes, at risk patients can be entered into a surveillance programme allowing earlier diagnosis of MM. There is a strong clinical priority to develop novel systems that can analyse and detect pre-neoplastic changes in mesothelial cells for early cancer detection, improved patient stratification and preneoplastic biomarker discovery. Aims: The aim of this proposal is to use machine learning techniques to identify phenotype markers of pre-malignant change in mesothelial cells. This will create a basis for tool development for early cancer detection in mesothelioma. Methods: A data lake will be constructed containing clinical data, follow up data and Whole Slide Images from approximately 2050 MM cases, 360 atypical mesothelial proliferation and 3000 cases with normal or reactive mesothelial samples with WSI using H&E sections of biopsy and cytology samples available from the Royal Brompton and Harefield Hospitals NHS Trust (RBHT), Basildon and Thurrock Hospitals NHS Trust (BTHT), MESO bank (14), St George’s Hospital University of London (SGUL) and the Medizinische Hochschule Hannover (MHH). Recent advances in deep learning neural networks have led to the possibility to integrate heterogeneous feature data, to label unlabelled data and to classify with noisy labels. All these techniques will be investigated, enhanced and applied in this project. Deep learning techniques will applied such as data integration using heterogeneous feature space learning for discovery of MPM signatures, Data labelling for unlabelled data employing semi-supervised or transductive learning and learning with abstention. Outcome: This will create a basis for tool development for early cancer detection in mesothelioma. Features extracted from MM can be used as markers for surveillance of pre-malignant changes in mesothelial cells and subsequently aid identification of early stage cancers when treatments can be more effective. This will be the first machine learning method to identify pre-malignant changes in mesothelioma from digital pathological images.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Point-of-care-Based Electrochemical Sensing for Human Papillomavirus Detection
Funder: Cancer Research UK

Abstract: The early detection challenge of cervical cancer will be addressed through the development of a low-cost, point-of-care (PoC) device that has the potential to improve clinical outcomes for patients in both developed and developing countries while overcoming key barriers linked to screening uptake and limited infrastructure, which has impeded progress till date. Cervical cancer caused by certain genotypes of human papillomavirus (HPV) is the fourth most frequent cancer among women globally with approximately 570,000 new cases diagnosed in 2018; where 90% of deaths reported in low and middle-income countries are linked to limited prevention, screening, and treatment options. The mortality rate was estimated at 6.7 per 100 000 women in Europe compared to global mortality rate of 6.8 per 100 000 women. Vaccination and screening have the potential to reduce the incidence rate of cervical cancer to 4 per 100 000 women globally. Recently, the uptake of cytology-based screening has fallen below the 80% standard due to concerns about the sampling collection procedure and cultural barriers, among others. Recent advances in personalized medicine and biosensing technologies has influenced the paradigm shift to PoC diagnostics from cytology-based screening and HPV testing that require advanced instrumentation, centralized laboratories, and experienced operators. However, few PoC devices have been translated from research laboratories to clinical use, due to overcoming challenges including low levels of sensitivity and specificity in clinical samples, system integration and signal readout requirements. Currently, there are no World Health Organisation prequalified PoC tests for HPV detection. We therefore now propose an interdisciplinary project bringing together researchers from chemistry, engineering, biomedical science, and medicine necessary to develop rapid PoC diagnostic tools with improved sensitivity and specificity for early detection of HPV genotypes via electrochemical biosensing. In summary, the project seeks to facilitate the early detection of high-risk HPV genotypes, especially in both developing and developed countries with limited infrastructure and declining uptakes rates, respectively, while improving health and well-being which is the third UN Sustainable Goal.


Research activity codes: 3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION)
Health categories: CANCER AND NEOPLASMS
Title: CRUKD/17/020 CRISP: A phase Ib of crizotinib either in combination or as single agent in pediatric patients with ALK, ROS1 or MET positive malignancies (Study ITCC 053)
Funder: Cancer Research UK

Abstract: Background Novel approaches are required to address the significant unmet medical need for certain relapsed/refractory paediatric malignancies such as neuroblastoma (NBL) and rhabdomyosarcoma (RMS) in which prognosis is dismal, and in anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumours (IMT) where less toxic therapies are required. The CRISP trial builds on an extensively-studied biological rationale to utilise a novel tyrosine kinase inhibitor –the ALK/MET/ROS1 inhibitor crizotinib – to selectively target known genetic aberrations in these paediatric tumour types. Crizotinib has been licensed in ALK-positive non-small cell lung cancer in adults. In a single agent phase I trial in children whose tumours harboured relevant aberrations, tolerability and anti-cancer activity results were promising. However, some showed less response to crizotinib than expected given the likely oncogenic (cancer-driving) nature of the aberrations and it is anticipated that greater activity will be seen through administration of combination therapies. This hypothesis is supported by robust preclinical data. Aims CRISP aims to establish the safety profile, recommended phase II dose (RP2D) and activity of crizotinib given in combination with disease-relevant combination partners in ALCL, NBL and RMS harbouring ALK/ROS1/MET aberrations, and to explore single agent crizotinib in any other solid tumours with relevant molecular abnormalities. Methods CRISP is a European, multicentre, non-randomised, open-label prospective trial that will treat children and young adults in 3 groups: - Stratum 1: phase Ib study to determine the RP2D of vinblastine in combination with a fixed dose of crizotinib in relapsed/refractory ALCL with ALK aberrations, followed by a cohort expansion to evaluate preliminary activity - Stratum 2: phase Ib study to determine the RP2D of crizotinib in combination with a fixed dose of temsirolimus in patients with relapsed/refractory NBL or RMS with ALK-or MET-aberrations, followed by a cohort expansion to evaluate preliminary activity (RMS patients will only be included in the expansion if a significant response is seen during the dose escalation phase) - Stratum 3: phase Ib/II exploratory cohort study determining the safety and preliminary activity of single-agent crizotinib in patients with IMT or other ALK-, MET- or ROS1-aberrrant tumours with no known superior therapeutic options available Impact of results The anticipated future benefits are improved outcomes, without significant toxicity, in children and young adults with diseases displaying apparently actionable genetic aberrations in ALK/ROS1/MET, and currently largely associated with a poor prognosis or (in the case of IMT) requiring unacceptably morbid surgery in an attempt to effect cure.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Combining Radiation with JAK inhibitors as a novel therapeutic strategy for rectal cancer
Funder: Cancer Research UK

Abstract: Background In addition to the use of neoadjuvant radiotherapy (RT) little progress has been made over the past 20 years for treatment of locally advanced rectal cancer. Novel RT-based combination therapies are highly sought after to improve treatment responses and expand organ preservation. Our data demonstrates that in rectal cancer patient specimens IL6 expression and activation of the STAT3 pathway are associated with poor patient prognosis, also RT induces up-regulation of IL6 expression and STAT3 activation and patient derived organoids (PDO) treated with JAK inhibitors +/- RT undergo cell death. Taken together this supports inhibition of the IL6/JAK/STAT3 pathway as a therapeutic approach for rectal cancer. However, the optimal scheduling of RT and JAK inhibitors is not yet clear, and the subgroups of patients that will gain most benefit from this therapeutic strategy is yet to be defined. Aims We hypothesis that “RT via stimulation of IL6 production in the tumor microenvironment will sensitize rectal cancer to inhibition of the IL6/JAK/STAT3 cascade.” In order to test this hypothesis we will establish if up-regulation of IL6/JAK/STAT3 signaling in rectal cancer patient specimens is influenced by rectal cancer phenotype. We will also establish what the optimal scheduling is for RT/JAK inhibition combination therapy and to what patients it should be administered. Methods We will utilize 2 patient rectal cancer cohorts, from both Glasgow and Oxford. Using pre and post RT treatment biopsies, RNAScope and IHC will be employed to establish if IL6 expression and STAT3 activation increases in response to RT. This will be combined with genomic, transcriptomic and histological data to establishing if RT increases IL6 resulting in STAT3 activation in all rectal tumors or those from one particular genetic background, consensus molecular subtype (CSM), histological subtype (GSM) and stem cell index. Mouse and PDO models will be employed to establish the optimal combination therapy of RT and JAK 1/2 inhibitor Ruxilitinib or JAK2/3 inhibitor Tofacitinib at a range of concentrations plus and minus 5FU. Again a range of genetic background, CSM, GSM or stem cell index will be used to determine if response to combination therapy is observed across all or are particular subtype of rectal cancer. How the results of this research will be used. This project will harness expertise across 3 RadNet centers to provide evidence that repurposing of JAK inhibitors could be utilized in rectal cancer, identify predictive biomarkers and provide data for future grant applications .


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;6.1 PHARMACEUTICALS;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS