NIHRDataInsights/HRCSData huggingface dataset:
Title: ICR-CTSU Clinical Trial Fellowship: Efficient assessment of toxicity related outcomes in pelvic radiotherapy clinical trials.
Funder: Cancer Research UK

Abstract: Background Toxicity is a key outcome in clinical trials of radiotherapy. Late toxicity, occurring months or even years after the immediate post-treatment period can be debilitating and limits dose escalation which may lead to improved disease control. Ongoing assessment for toxicity is therefore a key feature of clinical trials investigating new radiotherapy schedules, techniques or technologies. Whilst assessment of safety of new treatments is paramount, collection, central curation and management of repeated and detailed toxicity assessment data on all clinical trial participants, often over many years, can be burdensome for patients, clinical/research teams at clinical trial sites and for clinical trials unit (CTU) staff. The fellowship will explore approaches to the efficient assessment of toxicity related outcomes in pelvic radiotherapy clinical trials, using bladder cancer as a model. Aims To explore the need to collect both patient reported outcomes (PRO) and clinician reported outcomes (CRO) for trial participants. To define optimal time-points of collection of toxicity outcome data. To use routinely collected data to ascertain late normal tissue effects. To test methodology for use of electronic patient reported outcomes (ePRO) in clinical trials. Methods Associations and areas of concordance/discordance between clinician and patient reported outcomes will be explored to determine optimal assessment methods. Associations between presenting clinical and sociodemographic features, dosimetry, acute toxicities and development of late effects will determine factors predictive of late toxicity to support design of risk-based follow-up schedules, i.e. to identify subgroups of patients in whom less/more intense or shorter/longer follow-up is recommended. Existing clinical trial datasets will be linked to routinely collected datasets to develop and test algorithms to identify late events. Data from a number of national bladder cancer clinical trials collecting clinician and patient reported outcomes will be used for statistical analysis. A focus group will inform methodology for integrating electronic patient reported outcomes into clinical trial follow-up and a pilot study will be conducted. Further pelvic radiotherapy clinical trials currently in set up at ICR-CTSU provide opportunities for novel prospective trials methodology research using a studies within a trial (SWAT) approach. How results of this research will be used The Fellowship will provide a thorough grounding in clinical trials methodology and lead to a thesis for PhD submission. Research outputs will be integrated into methodology for ongoing follow up in existing trials and will inform the design of future trials for patients undergoing pelvic radiotherapy.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: CANCER AND NEOPLASMS
Title: Young people's response to e-cigarettes and emerging nicotine products and their marketing
Funder: Cancer Research UK

Abstract: Background Since their introduction in 2011, the e-cigarette market has continued to develop rapidly, including the recent introduction of Juul to the UK. Additionally, the emergence of new nicotine products such as Heat not Burn (HnB) products, which share similarities with e-cigarettes, have the potential to cause confusion in distinguishing different types of alternatives to smoking. Given this changing nicotine environment, there is an urgent need to monitor young people’s interest in and understanding of these products, the messages conveyed to young people through their marketing, the extent to which HnB and other new nicotine products are perceived as similar to, or distinct from, e-cigarettes and tobacco cigarettes, and to ensure collection of valid survey data Aims This research aims to 1) explore young people’s response to e-cigarettes and their advertising, alongside response to emerging nicotine devices and 2) develop validated survey questions which accurately represent the changing nicotine market. Method The study involves two work packages. Work Package 1 will comprise two phases of qualitative research, taking the form of 10 focus groups, with 11 to 24 year olds, in 2020 and a further 10 focus groups in 2022. They will explore awareness and understanding of different product types and response to examples of advertising for these products. Work Package 2 will involve developing and testing survey questions to examine response to and understanding of different product types. Survey questions will undergo thorough piloting before being inserted in an online survey. How the results will be used Dissemination will be via journal articles, presentations, teaching, and meetings. Data from this study will provide an insight into young people’s perceptions, understanding and response to e-cigarettes and new and emerging nicotine devices. It will show the extent to which these products, and the marketing of these, are seen as similar or distinct. This study will inform policy by examining the adequacy or otherwise of marketing controls and the need for any consumer education on the differences between products and any differences in product harms. The development and testing of survey questions, along with data collected via an online survey will provide validated questions to monitor prevalence of e-cigarette use and use of new and emerging alternatives to smoking, to ensure that surveys collect valid data and avoid ambiguity about the type of device being asked about. These questions will have potential to be used in national surveys thereafter.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CANCER AND NEOPLASMS
Title: A programme for a broad-based training in clinical trials at the CRUK Clinical Trials Unit in Leeds, with a focus on biomarker-driven trials in colorectal cancer
Funder: Cancer Research UK

Abstract: Background: Christopher Williams is a medical oncology registrar, currently completing a PhD examining predictive and prognostic biomarkers in colorectal cancer at the University of Leeds. His work involves developing novel biomarkers to help patients navigate treatment decisions and optimise outcomes. Within this field, he has a particular interest in using clinical trials to validate putative biomarkers to progress them towards use in clinical practice. Aims: Through the proposed fellowship at the CRUK CTU at Leeds Clinical Trials Research Unit, CW aims to acquire a comprehensive training in clinical trials in order to design and deliver practice changing cancer research as a future chief investigator, with a focus on biomarker-driven clinical trials. Key outcomes will include an ability to: - Lead teams in devising, securing funding for, and delivering novel clinical trials - Strategically plan the onward progression of a research portfolio - Build upon existing, and develop new links with commercial and academic partners - Develop data-rich sample collections to maximise the translational output of current and future trials - Disseminate findings to a broad audience and transfer lessons learned across tumour types Methods: CW will work closely with his supervisors and mentors to embed himself in a broad selection of projects at the Leeds CTRU. Training will be through a combination of formal courses, practical trials experience, observation of key committees, and laboratory meetings. A three-year fellowship is proposed with a focus on formal training and work within established trials in the initial years, progressing towards the development of CW's own project proposals in the later stages. Involvement as the Trial Physician for the ARIEL trial (biomarker-driven trial in colorectal cancer) and as Associate PI lead in the FOxTROT trials (neoadjuvant therapy in colon cancer) is initially proposed. CW then plans to work up proposals for biomarker-driven trials incorporating EGFR ligand immunohistochemistry to predict benefit from anti-EGFR therapy, and an artificial intelligence-driven IHC immune biomarker to predict outcomes from immunotherapy. These projects will be developed in collaboration with senior colleagues at Leeds CTRU and partners at other institutions. How the results of this research will be used: It is hoped that the knowledge, skills and connections developed during this fellowship will provide CW with the ability to lead on future project proposals within the Leeds CTRU among a broad-based network of collaborators. Through biomarker research, CW aims to help patients and physicians navigate treatment decisions to their best advantage.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: CANCER AND NEOPLASMS
Title: Variation in timeliness of diagnostic investigations for symptomatic patients and effect on cancer outcomes: facilitating the implementation of Faster Diagnosis Standards
Funder: Cancer Research UK

Abstract: Background: Early-stage cancer diagnosis and reducing emergency presentations are key targets of the NHS Long Term Plan. The recent Faster Diagnosis Standards aim to ensure that cancer is ruled in or out within 28 days for patients referred for suspected cancer. The COVID-19 pandemic, during which cancer investigations have decreased, highlights the urgent need to identify patients at higher risk of adverse outcomes, who could most benefit from timely investigations. Evidence on the use and timeliness of hospital-based investigations (imaging, endoscopies) by patient characteristics and their impact on cancer outcomes can guide interventions to improve diagnostic pathways, considering limited healthcare resources and possible risks associated with invasive investigations. Aims: To help improve diagnostic pathways, we aim to characterise patient groups at risk of prolonged diagnostic intervals, identifying where delays occur and their impact on cancer outcomes. We aim to answer the following questions: 1. Does the use of specific hospital investigations and their timeliness differ by patient clinical and socio-demographic characteristics? 2. What are the effects of different types of investigations and their timing on stage at diagnosis, emergency presentations and short-term survival? 3. What are the mechanisms linking clinical characteristics to diagnostic timeliness and cancer outcomes? Methods: Focusing on patients with possible lung and gastro-intestinal cancer symptoms recorded 2011-2020, we will use linked primary care, hospital and cancer registration data to examine a) the use of investigations (endoscopies/imaging) and b) time intervals from first GP-recorded symptom to referrals/investigations (and where applicable, to cancer diagnosis) by patient characteristics (aim 1). Among patients diagnosed with cancer, multivariable analysis will be used to examine the effect of patient and tumour characteristics and use of specific hospital investigations on the risk of emergency and advanced-stage cancer diagnosis and survival, accounting for variations by GP practice through multi-level modelling (aim 2). Causal inference counterfactual-based mediation analysis will be used to reveal underlying mechanisms (aim 3). Comparisons between pre- and post-COVID-19 periods (pre/post-March 2020) will highlight processes affecting cancer outcomes and underlying mechanisms. How the results will be used: We will characterise patient groups at higher risk of prolonged diagnostic intervals, because appropriate tests were not used or were used late and estimate the frequency of such occurrences. This will inform guidelines and healthcare policies on referrals/access to investigations for optimizing diagnostic pathways and help reduce advanced stage and emergency cancer diagnoses.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: CANCER AND NEOPLASMS
Title: Interventions to encourage early diagnosis of future cancer after a negative urgent referral
Funder: Cancer Research UK

Abstract: BACKGROUND More than 90% of those referred for suspected cancer on urgent two-week wait (TWW) pathways do not have cancer diagnosed. Yet patients may be at risk of developing a future cancer. However, patients with new or ongoing symptoms may not return promptly to their doctor because they were reassured following their previous referral, unsure how to respond, or they don’t want to bother their doctor. This can result in delays in diagnosis. There is scope to provide support to those who are initially discharged without a cancer diagnosis to ensure subsequent cancers are diagnosed at an early stage. AIMS Workstream 1: Investigate the occurrence of cancer in each of the 5 years after an initial negative diagnosis (defined as no cancer in first year after referral) following referral for suspected cancer on the main TWW pathways. This will highlight specific pathways where practice change could be most beneficial. Workstream 2: Investigate the feasibility and acceptability to patients and providers of receiving/providing support to encourage early diagnosis of cancer after a negative diagnosis following a TWW referral. METHODS Workstream 1 will involve linking a cohort of TWW referrals (using Cancer Waiting Times data) to National Cancer Registration data to determine the cancer type and stage of cancer of any cancers occurring in each of the following 5 years for those with a negative diagnosis. Workstream 2: will involve: • Semi-structured interviews with providers (n=30) connected to the TWW pathway in order to gain in-depth insights into provider experiences and views on the feasibility and acceptability of providing advice and support for early diagnosis of cancer following a negative diagnosis after a TWW referral. • Patient and public involvement in developing the format(s), target group(s), and content of interventions to encourage early diagnosis of future cancer. • A cross-sectional survey of patients (n=1200) who have received a negative diagnosis following referral for suspected cancer to quantify patient’s prospective acceptability of different approaches to provision of advice and support, stratified by TWW pathway. HOW THE RESULTS OF THE RESEARCH WILL BE USED Workstream 1 will allow identification of those on TWW pathways who may be at higher risk of subsequent cancer. Workstream 2 will ensure interventions are designed to be implementable within an NHS setting and acceptable to patients. This proposal has the potential to make an important, rapid and significant impact to the millions of patients going through suspected cancer pathways.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS
Title: Investigating the conversion rate of routine referrals for patients presenting with symptoms of possible cancer
Funder: Cancer Research UK

Abstract: Background The Two Week Wait pathway for suspected cancer is generally considered the optimum referral route for patients presenting with symptoms of possible cancer to primary care. However, many patients receive routine referrals, either when indicated as appropriate within guidelines, or despite guidelines recommending other actions. Routine referrals generally result in later cancer diagnoses than Two Week Wait referrals which may affect treatment options and survival. Thus, it is important to understand for which patients routine referrals represent the most appropriate action. Aims For a range of exemplar symptoms we will assess the extent to which patients presenting to their GP with a symptom of possible cancer receive a routine referral. We will establish which of the considered symptoms and which patient characteristics are associated with higher or lower chances of receiving a routine referral. We will quantify how many patients who receive a routine referral go on to be diagnosed with cancer (the conversion rate) according to symptom and patient characteristics. Methods Our study population will include patients presenting to primary care with one the following symptoms for the first time during 2016-2017: dysphagia, weight loss, anaemia and abdominal pain (oesophago-gastric cancers); back pain (myeloma); jaundice, weight loss and abdominal pain (pancreatic cancer); lumps/masses and weight loss (lymphoma); haematuria and recurrent urinary tract infection (bladder cancer); breast lumps (breast cancer) and post-menopausal bleeding (endometrial cancer). These include symptoms where routine referral is recommended and symptoms where urgent referral or primary care investigations are recommended, but a routine referral may have been made. We will use linked primary care (Clinical Practice Research Datalink), secondary care (Hospital Episode Statistics) and cancer registry data. Routine referrals following presentation will be identified from secondary care data. Logistic regression will be used to examine which patient factors (symptoms, age, gender, deprivation and co-morbidities) predict the use of routine referral and a diagnosis of cancer (during the year following the first relevant appointment) once a routine referral has been made. How the results of this research will be used This study will quantify the percentage of referrals resulting in a cancer diagnosis for a given symptom and patient group. This information could help identify which patients are most likely to benefit from different referral pathways and facilitate a tailored reconfiguration of cancer diagnostic services or changes to referral guidelines in an evidence-based manner.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: CANCER AND NEOPLASMS
Title: CRUK/11/027: POUT SC - The collection of biospecimens from patients eligible for the "POUT" clinical trial in upper urinary tract urothelial carcinoma
Funder: Cancer Research UK

Abstract: POUT is a multicentre randomised controlled phase III trial of adjuvant chemotherapy versus observation in transitional cell carcinoma of the upper tract. 345 patients who have undergone nephroureterectomy, who are surgically staged as pT2-pT4 N0-3, or who are node positive and are fit for adjuvant chemotherapy, will be randomised to four cycles of adjuvant platinum based chemotherapy (experimental group) or surveillance (control group). The primary endpoint is disease-free survival, and secondary endpoints include toxicity and quality of life. POUT opened to recruitment in May 2012. We intend to collect a number of different biospecimens longitudinally (both pre-operatively and post-operatively) from patients eligible and subsequently recruited for POUT. The biospecimens include blood, urine and tissue, and will provide a valuable resource of international significance for future research and analysis. Such future research could advance our understanding of disease pathogenesis, identify novel targets or discover biomarkers. Such biomarkers could, for example, be used for accurate monitoring of response to therapy or interventions, or for long-term surveillance for early detection of recurrence. The biospecimen collection will be administered, co-ordinated and stored by the Human Biomaterials Resource Centre at the University of Birmingham, a Human Tissue Act licensed facility.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Aspirin Esomeprazole Chemoprevention Trial - EXension Long-term (AspECT EXceL); for the definitive risks vs. benefits
Funder: Cancer Research UK

Abstract: Background. Follow up of the cohort in AspECT EXceL is needed even more now, as all the other large studies still can’t define either the optimum age to start aspirin therapy, the optimal dose or duration of therapy. Indeed AspECT Excel is the only trial to show a net benefit of aspirin use because the benefits, (number needed to treat of 1 in 43), were not offset by serious complications especially gastrointestinal bleeding. In fact less than 1% of trial patients had serious side effects and those that could be attributable to bleeding in the GI tract, probably because all patients were on proton pump inhibitors. Aims. a. To see if aspirin AND PPIs effectiveness increases long term (we found both worked and were synergistic). b. To see if aspirin effectiveness increases as predicted. c. To see if any complications from PPI occur over a longer period of follow up. Methods. AspECT centres. 80 out of 84 have written to confirm a wish to enter the AspECT EXceL trial. We plan to reconsent these patients; there remain approximately 2000 patients from the AspECT trial eligible for follow up at present. We propose a 6 month set up phase, a 1 year feasibility recruitment phase (to recruit 30% of recruitment target 400-500 patients), a 5 year main trial allowing 2 cycles of 3 yearly endoscopy (over 6 years), followed by a 6 month close down stage (7 years in total). Interventions and schema for Follow up. This would mean endoscopy every 3years (which is now normal NHS practice). We anticipate minimal excess treatment costs. Where variance (deviation from the initial randomisation) occurs we will monitor treatments received, disease progress and demographics. The Trial Team. This includes experts in aspirin chemoprevention from around the UK and overseas. The UCL Trial Centre is well placed to do this as it runs the on-going ADD-ASPIRIN Trial. It is felt this co-ordinating centre will best manage the various unique issues that arise. Use of Results. The data will be used to inform on clinical practice by several go=vernment organisations in the EU and USA. Specifically the National Institute for Health and Care Excellence has indicated it is following AspECT closely. If longer follow up was available it would give more power to the primary outcomes enabling evidence to be presented for a change in National Guidelines. Patients will be informed by letter and newsletter.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: CANCER AND NEOPLASMS
Title: Understanding the DNA Damage Driven Immune Response in Oesophageal Adenocarcinoma (OAC): Opportunities for Improved Stratification and Treatment
Funder: Wellcome Trust

Abstract: Oesophageal cancer is the sixth most common cause of cancer death worldwide. Even when treated with chemotherapy and surgery aiming to cure the disease, eight out of ten patients do not respond to chemotherapy and most patients relapse. We have shown previously that genetic changes within the tumour can influence whether chemotherapy is effective. We showed that a group of patients have tumours which respond better to chemotherapy than others. This group is called ‘DNA damage immune response (DDIR) positive’. DDIR negative patients have worse outcomes. In this project, we aim to use genetic information about DDIR positive patients who benefit from chemotherapy to improve outcomes for those who do not. We will initially analyse genetic information from 548 oesophageal tumours. We will identify the most common genetic changes in patients who benefit from chemotherapy. We then plan to model these changes in the laboratory in oesophageal cancer cells which are relatively resistant to chemotherapy to find out if they respond. We will confirm our findings in a range of laboratory models. We expect that the knowledge gained will play a role in identifying new combinations of treatment to improve response to chemotherapy in patients who currently have poor outcomes.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS