NIHRDataInsights/HRCSData huggingface dataset:
Title: Improving Cancer Survivorship Care Through Theory-Based, Tailored eHealth Interventions.
Funder: Chief Scientist Office, Scotland

Abstract: In the UK, the number of cancer survivors is expected to grow every decade from 2.1 million in 2010 to 5.3 million in 2040. Cancer survivors have a range of unmet health and practical needs. eHealth has huge potential to improve the quality of health care. eHealth has not fulfilled its promise so far because interventions have failed to address problems faced by patients, and there have been many technological issues. This programme of research will develop eHealth cancer digital support for people with colorectal and prostate cancer. The research will involve collaboration between patients, healthcare professionals, researchers, NHS eHealth, charities, design professionals, and commercial technology experts. The first stage will be to investigate the workload of managing health after a diagnosis of prostate or colorectal cancer (treatment burden). Treatment burden will be investigated through scientific literature review, interviews with patients, carers, and healthcare professionals, a questionnaire, and analysis of routinely collected healthcare data. Our understanding of treatment burden and the problems faced by patients will be fed into design events, during which our collaborators will come together to develop interventions that meet the needs of people undergoing follow up for prostate and colorectal cancer. We will test the potential of our cancer digital support systems with around fifty patients. We will deliver the interventions securely on-line. Our ambition is that our new systems of cancer digital support will become widely available throughout the NHSs.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS
Title: Development and Evaluation of Novel Treatment Strategies Using Immuneoncology Agents in Combination with Radiotherapy in Rectal Cancer.
Funder: Chief Scientist Office, Scotland

Abstract: Rectal cancer affects 14,000 people in the UK each year. The standard treatment for many patients is radiotherapy to shrink tumours so that surgery has the highest chance of cure. This major surgery unfortunately has a significant risk of complications and is associated with long-term bowel, urinary and sexual dysfunction. Over two thirds of patients require a stoma at the time of surgery which, for one third of patients is permanent. Recent years have seen a paradigm shift in rectal cancer management with appreciation that, in a small proportion of patients (10-20%), the radiotherapy component of treatment can completely eradicate the cancer. This has allows the concept of ‘organ preservation’ to develop where patients are managed non-operatively with active surveillance instead of surgery. For 75% of these patients, they achieve long term rectal preservation without the need for surgery. My previous research has identified that the immune system may play a role in how tumours respond to radiotherapy. The idea is that radiotherapy may charge the immune system making immunotherapies more effective in mounting an anti-tumour response. There is a rationale for assessing this treatment, and I am leading a trial of Durvalumab immunotherapy in combination with radiotherapy in rectal cancer. However other immune cell types and their interaction with tumour cells are likely to be important and may lead to the development of other new treatments. During this fellowship I will develop new strategies to better target and eradicate rectal cancer in combination with radiotherapy. My ultimate goal is to enable more patients to be managed with organ preservation strategies. I will study biopsy specimens from patients receiving radiotherapy to better define the immune and molecular changes related to treatment response and at the same time I will work with state-of-the-art pre-clinical laboratory based models of rectal cancer in which changes in the immune response to radiotherapy will be defined and harnessed for treatment benefit using immunotherapy treatments. Through these techniques I aim to develop strategies that can be used in clinical trials with patients.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: A new image processing method for Ultrasound Imaging to diagnose prostate tumours.
Funder: Chief Scientist Office, Scotland

Abstract: Prostate cancer incidence and deaths from the disease have both significantly increased in recent years. Current diagnostic approaches are unpleasant, costly and invasive. Additionally, many men undergo radical treatments that can have long-term detriment on their quality of life because current methods to characterise these tumours are not always able to predict the patient’s likely disease progression with sufficient confidence. We propose a new image analysis method based on diagnostic ultrasound in order to find prostate disease early. Since cancer has different blood flow compared to normal prostate the proposed technology aims to provide a 10-fold improvement in the detail in mapping the blood flow (i.e. from half a millimetre to a 20th of a mm). This unique method will help determine the state of a tumour. We will use images from volunteer prostate patients in order to develop our image analysis method and subsequently assess its potential for prostate cancer diagnosis.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Understanding resistance to targeted therapies in Oesophageal Squamous Cell Carcinoma as a foundation to developing new precision medicine approaches
Funder: Chief Scientist Office, Scotland

Abstract: Oesophageal squamous cell carcinoma (OSCC) is a type of cancer of the oesophagus (food-pipe), associated with social deprivation and poverty, and a key public health concern for Scotland where the incidence in women is the highest in the world. Current treatments are not very effective and most patients die within 1 year. Our previous research suggests that OSCC patients who have tumours with too much of the EGFR protein benefit from drugs which specifically block EGFR and stop EGFR-positive tumours growing. This research lays the foundations for personalised precise treatment. However, all OSCC tumours eventually become resistant to anti-EGFR drugs and tumours regrow. To overcome this major barrier to effective treatment we have carried out laboratory studies which show that resistance to EGFR inhibitors is often linked to the action of proteins in the PI3K/AKT/mTOR pathway which help tumour cells survive during anti-cancer treatment. Combining medicines to block both EGFR and PI3K/AKT/mTOR at the same time could improve treatment for OSCC patients and overcome drug resistance. This project extends our previous studies to provide the data needed to deliver clinical trials using our established research networks and will accelerate the development of effective, personalised and precise treatments for OSCC patients.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Comprehensive longitudinal characterisation of refractory and relapsing oropharyngeal squamous cell carcinoma by tumour and blood-based genome sequence analysis.
Funder: Chief Scientist Office, Scotland

Abstract: Cancers of the throat, oropharyngeal squamous cell carcinoma (OPSCC), are highly prevalent across Scotland. Over the past 10 years, both global and Scottish cases of OPSCC have increased, particularly those associated with human papillomavirus (HPV). However there has been little change in techniques for diagnosis and monitoring. Although imaging technologies are improving, results of imaging are often indeterminate and clinicians require additional tools to make informed decisions. With this in mind our research team have established a range of blood based tests which detect and monitor cancer DNA fragments shed by tumours into the blood stream in OPSCC patients. Our initial studies have shown that such tests, which are minimally invasive compared to surgical biopsy, hold the potential to provide an accurate, “real-time” method to monitor patient response to treatment, identify early relapse and assist in clinical decision making. We aim to expand these results to assist clinical decisions for both virally associated and non-viral associated OPSCC. Following this, we will focus on the poorest prognosis OPSCC group (non HPV tumours) by applying state-of-the-art DNA detection and sequencing technologies to analyse tumour-derived DNA fragments in the bloodstream, to follow treatment response and to develop new methods for detecting relapse and resistance to treatment in OPSCC. Ultimately, we envisage that the implementation of such genetic assays of tumours and the fragments that they release into the bloodstream will provide a transformative shift in the clinical assessment and quality of life of OPSCC patients in Scotland


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: CANCER AND NEOPLASMS
Title: Developing representative models of the blood-tumour barrier to enhance drug development for glioblastoma.
Funder: Chief Scientist Office, Scotland

Abstract: Glioblastoma (GBM) is an incurable, aggressive brain tumour that affects all age groups. No new treatments have been approved since 2005, and numerous new drugs that showed promise in the laboratory have failed to improve outcomes for patients. The brain is protected from circulating chemicals by the ‘blood brain barrier’ (BBB), which plays an important role in the healthy brain but unfortunately prevents many drugs from getting into brain tumour cells at sufficiently high levels to kill them. However, previous research has shown that GBM cells cause changes to the BBB that increases its leakiness and could be used to improve drug delivery. Now we need more information about these changes in order to design drugs that will cross the ‘leaky’ BBB and penetrate brain tumour cells more effectively. To obtain this information we will (1) establish how GBM cells affect the BBB, using existing patient samples and laboratory models of GBM; and (2) measure drug levels in GBM and the surrounding brain to understand how changes in the structure of the BBB affect drug delivery to the tumour cells and the normal brain. In the longer term we will use this information to develop new laboratory models of the ‘leaky’ BBB that exists in GBM, and use them to develop drugs that are much more likely to get into brain tumour cells at high enough levels to kill them.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Robust EArly Detection of bReast cancer in hIgh-riSK premenopausal population using novel lipid based imaging methods (READ RISK)
Funder: Chief Scientist Office, Scotland

Abstract: Breast cancer is a major and growing health challenge, and the leading cause of cancer in Scottish women. As population obesity rates increase, the number of new cases continues to rise, and despite treatment advances, it remains an important cause of premature mortality, taking women in the prime of life. Although underlying susceptibility caused by mutation in the genes BRCA1/2 and TP53 is increasingly identified, current pre-symptomatic screening for the general population and those at high genetic risk remains sub-optimal, with high false negative and positive rates. Alteration of breast lipid composition has been observed by us and others in patients with breast cancer and is thought to precede onset. We have developed and tested a novel system to allow a standard 3T MRI scanner to perform quantitative 3D mapping of specific lipid molecules in the breast. We have already shown that we can visualise altered levels of peri-tumoural lipids in surgically removed breast specimens and have successfully demonstrated the technique in vivo in pre-treated postmenopausal breast cancers. Here we seek funding to see if this method can detect very early breast cancers. We will compare the amount and spread of lipid composition in breast tissue of premenopausal women with breast cancer, obese women without cancer, and those with very high genetic risk of breast cancer. Subsequently we will work with our industrial partner to develop a prospective clinical trial to inform the development of better breast cancer screening for young women at high risk of breast cancer.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Dissecting the transcriptomic and phenotypic reprogramming of myeloid cells that mediate chemoresistance in cholangiocarcinoma
Funder: Chief Scientist Office, Scotland

Abstract: Cholangiocarcinoma (CCA) is an aggressive disease for which therapeutic options are limited. Although some CCA patients show poor response to chemotherapy, a sub-group of patients who have long term benefit from anticancer therapies does exist. We will study the group of patients with a durable response to therapy and we will compare them with patients whose tumours grow quickly during chemotherapy to understand what makes the treatment effective. Our previous studies suggest that drug response in CCA depends not only on cancer cells, but also on the surrounding non-cancer cells, especially a subtype called myeloid cells. Here, we will investigate how myeloid cells differ between responders and non-responders to chemotherapy; we will grow these myeloid cells with mini-tumour replica established directly from patients’ cancers and we will assess how the myeloid cells can change the way cancer cells respond to chemotherapy drugs


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Opportunity-Led - Develop, test and evaluate an online resource of patient experience narratives before and after surgery for oral cancer
Funder: Public Health Agency, NI

Abstract: This project will build on evidence generated from previous studies in this programme of work. An online resource will be developed, producing data prospectively through filming of patient experience narratives at three key junctures of the cancer journey, namely 1) after diagnosis but before surgery, 2) early post-treatment and 3) one year following diagnosis. Patients and their families can benefit from this patient-centred resource as they conduct their independent online searches for information before and after treatment for oral cancer. This online resource will also facilitate consultations with the healthcare team, through provision of realistic patient-focused information and informed decision-making. Shared decision-making and informed consent is when patients and healthcare professionals work together, placing the patient at the centre of decisions about their own treatment and care. It is vitally important that care and treatment options, to include the long-term impacts are shared in an accessible patient-centred way (NICE 2016, NCRI 2018). Having demonstrated the current void of rigorously developed and accessible online resources containing narratives of peoples’ lives before and after treatment for oral cancer, the aim of this project is to develop, test and evaluate such a resource using the ‘person-based approach’ (Yardley et al 2015). This online resource with patient experience narratives filmed will provide patients and their families with accurate, patient-centred information and support, to aid decision-making, informed consent and preparedness for the impact of surgery to subsites within the oral cavity.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: CANCER AND NEOPLASMS
Title: Opportunity-Led - H2020: Evaluation of Dyadic Psychoeducational Interventions for People with Advanced Cancer and their Informal Caregivers (DIAdIC)
Funder: Public Health Agency, NI

Abstract: The DIAdIC project is an interdisciplinary, cross-national project to evaluate Dyadic psychosocial Interventions for people with Advanced cancer and their Informal Carers. As cancer is a chronic disease affecting millions of Europeans each year, the provision of support for both patients and their frequently overburdened informal carers is highly relevant from an economic, a healthcare and a prevention perspective.Aims:The project aims to evaluate the effectiveness and cost-effectiveness of two existing psychosocial dyadic (i.e. aimed at patient and informal caregiver together) interventions, one web-based e-health and one nurse-led face-to-face. In addition, the project aims to assess the interventions’ effects on vulnerable subgroups (eg people with a lower socioeconomic position), their effectiveness in different healthcare systems, and their suitability as perceived by end-users.Concept and methods:The two interventions are tailored to dyads’ needs and have been shown to improve quality of life of both patient and informal caregiver in trials in the USA, but are yet to be tested in Europe. They will be adapted for the healthcare and cultural context of six European countries, as well as made compatible with modern existing e-health systems. The effectiveness of the interventions (compared to each other and to care as usual) will be assessed by way of an international randomized controlled trial in people with advanced cancer and their primary informal carers. The project includes a full health-economic evaluation, being the first to do so when comparing e-health and face-to-face dyadic interventions, and a thorough implementation evaluation Impact: The project advances the state of the art in several ways, eg by providing tailored health care interventions (including an eHealth solution) suitable for implementation across diverse healthcare systems. The use of public involvement ensures input of stakeholders throughout the project and enhance


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS
Title: Opportunity- Led - ECMC TARGET Study
Funder: Public Health Agency, NI

Abstract: The majority of patients referred for consideration of Phase I clinical trials have advanced cancer and have typically failed available standard of care therapies (or have no standard care therapies available). While tumour type, prior therapies and available pre-clinical and clinical research data will be considered when considering an individual patient for trials, for most patients this remains a ‘best guess’ approach. Consequently response rates to treatment in this patient population are low, traditionally reported at 5-10%. There is therefore a need to better ‘match’ patients to trials which may be met by molecular profiling to identify actionable genomic or transcriptional alterations. A range of genomic alterations are already tested for within routine cancer treatment pathways where these have licensed companion therapeutics or have established prognostic significance. However, broad genomic profiling across all tumour types is not yet routine practice in all UK centres. A number of precision medicine trials have attempted to explore whether high throughput sequencing approaches could address this and ultimately provide individualised treatment. While these studies have been heterogenous in terms of patient populations and genomic platforms used, a number of them suggest improved response rates to treatment and progression-free survival in the matched patient group:


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: 2019 Doctoral Fellowship: Understanding risk factors, treatment choices and survival rates for the rising number of young-onset colorectal cancer patients
Funder: Public Health Agency, NI

Abstract: Background: The incidence of colorectal cancer is rising in younger adults under the age of 50. From 1993 to 2015, incidence rates in people aged 25 to 49 years have increased by 33% in the UK, whereas incidence rates in age groups over the age of 50 have remained stable or decreased. There is an urgent need to better understand the underlying risk factors driving this increase. Further research is also required to evaluate the molecular basis pathogenesis of seemingly non-hereditary young-onset colorectal cancer, and to determine if there are differential survival, and treatment experiences for younger compared with older patients with colorectal cancer. Methods: Several epidemiological approaches will be employed to evaluate four aims: (i) Secondary data analysis of a Northern Ireland Cancer Registry cohort of colorectal cancer patients aged <50 years (n>1,500 have been diagnosed since 1993 to date), linked to the Child Health Systems to investigate perinatal risk factors for young-onset colorectal cancer (ii) UK Biobank cohort data analysis (n=500,000) to evaluate environmental factors, genetic variants and biomarkers related to young-onset colorectal cancer risk, with a particular emphasis on obesity and alcohol-related exposures. (iii) Molecular characteristics and obesity/alcohol-related biomarkers in an existing population-based cohort of n=661 stage 2 and 3 colon tumours, comparing their prevalence between younger and older patients, and exploring impact on survival. (iv) Survival outcomes, treatment experience and decisions faced by young-onset colorectal cancer patients. Collaborations with research teams in Scotland and Germany will provide opportunities to validate findings from the above studies. Impact: Identification of novel risk factors and molecular features underpinning young-onset sporadic colorectal cancer development will help to inform future preventative strategies. Increasing knowledge of determinants of survival and treatment choices will help to improve clinical management and outcomes for this patient group.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: CANCER AND NEOPLASMS