NIHRDataInsights/HRCSData huggingface dataset:
Title: Improving earlier diagnosis and precision medicine for reduced mortality of breast cancer in Kenya
Funder: Medical Research Council

Abstract: Data and key priority setting is desperately needed to inform prevention, diagnosis and improved treatment strategies in Kenya. To tackle the increasing incidence and high mortality of breast cancer in Kenya, this pump-priming award would develop a new UK-Kenya partnership to investigate the molecular epidemiology of breast cancer. Building off a recently funded grant by the Kenya National Research Fund by co-investigator PI: F. Makhoka--Genomic Approaches for Understanding Breast Cancer Progression in Kenyan Patients--this proposal would enhance success of this work by providing key research staff and contemporary methodologies for molecular assays. Specific aims are: 1) Develop a new partnership between the University of Edinburgh and Mount Kenya University. PI: Dr. J. Figueroa has over a decade of experience in molecular epidemiology and pathology studies of breast cancer, including conduct of a large multidisciplinary study in Ghana, west Africa (Brinton...Figueroa International Journal Cancer 2017) . 2) Design data collection pipelines for molecular pathology studies of breast cancer and mortality outcomes--which are desperately needed to inform what the key barriers and challenges are for breast cancer surveillance, diagnosis and treatment. 3) Exchange knowledge of contemporary molecular subtyping methods for breast cancer, and perform a pilot study to assess whether we can collect and quantify cell free DNA (cfDNA) tumour fraction at the time of breast cancer diagnosis and the relationships with clinics-pathological characteristics of breast cancer tumours for (N=100 cases)-for potential earlier diagnosis of breast cancer. 4) Using pilot data collected in this study, engage key stakeholders (e.g. physicians, ministry of health, policy makers) to prioritise the key areas needed for long term planning to enhance capacity to tackle the increasing burden of breast cancer in Kenya


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Methods for analysing national routine electronic records for cancer patients in England
Funder: Medical Research Council

Abstract: Cancer causes 28% of deaths in the UK. Cancer patients near the end of life would ideally be managed solely using planned care-a combination of primary care, hospital outpatient services, community nursing, and palliative care. However, most cancer patients have unplanned hospital care near the end of life. In the last six months of life, 77% of colorectal cancer patients have at least one emergency hospital admission, with unplanned hospital stays totalling 15 days, on average, during this period. Electronic hospital records (EHRs) contain large amounts of sociodemographic, administrative, diagnostic, treatment, and organisational data linked for each patient along the care pathway. These records provide rich information to understand why some patients use unplanned hospital care more than others near the end of life. Study population - Patients who died from colorectal cancer in England, according to the National Cancer Registry and Office for National Statistics death register. Outcome variables - 1) Visits to emergency departments, 2) unplanned hospital admissions, and 3) intensive care unit admissions, in England in the last six months of life. These variables will be derived from Hospital Episode Statistics. Advanced statistical methods (e.g. cross-classified multi-level models and instrumental variable analysis) will be used to investigate variation in emergency hospital visits based on: Patient and diagnostic information - Patient characteristics, such as age and area of residence, are recorded in several datasets, including the National Bowel Cancer Audit. Cancer details (e.g. staging) are recorded in the National Bowel Cancer Audit and National Cancer Registry. Treatment and healthcare information - Hospital Episode Statistics, the National Radiotherapy Dataset, and the Systemic Anti-Cancer Therapy dataset contain administrative, surgical, radiotherapy and chemotherapy records.


Research activity codes: 7.2 END OF LIFE CARE
Health categories: CANCER AND NEOPLASMS
Title: PhD studentship - head and neck squamous cell carcinoma and two tier control in the skin
Funder: Medical Research Foundation

Abstract: Dr Patel’s group investigates the Fanconi anaemia DNA repair pathway, specifically the role of that the enzyme ALDH2 and the gene FANCD2 play in repairing damaged DNA pathways. Patel has proposed that the human body has a two tier repair system and the failure of this in patients with Fanconi anaemia (i.e. lacking ALDH2/FANCD2) results in physical developmental abnormalities, leukaemia and bone marrow failure. Additionally they are 500-700 times more likely to develop cancers in epithelial cells in the oral/anal region, and these cancers are the seventh most common worldwide. The student’s graduate research project will establish whether epidermal stem cells are also reliant on the two tier protection system and therefore its failure leads to these cancers.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Specificity of fibroblast growth factor-induced signalling pathways in human tumours – identification of novel therapeutic targets?
Funder: Medical Research Scotland

Abstract: Ovarian cancer is difficult to treat – it is often widespread at diagnosis, and treatment is palliative rather than curative. Ovarian cancer patients are primarily treated by chemotherapy, although response is unpredictable, and often limited by the development of drug-resistant disease. There is therefore an urgent clinical need to understand how ovarian tumours spread and become drug resistant, and to develop better treatments. Many new drugs in development are targeted to “growth factors”, specialised proteins produced by tumours, which promote cell growth. We are interested in fibroblast growth factors (FGFs) – we have shown that the amount of a protein called fibroblast growth factor 1 (FGF1) varies widely, and is increased in more advanced ovarian tumours. We have created novel experimental models with different amounts of FGF1, and shown that the amount of growth factor produced determines whether tumours respond to cisplatin and carboplatin, the chemotherapy drugs most commonly prescribed to ovarian cancer patients. In this project, we will further investigate FGFs and related proteins in ovarian and other common tumours including breast and colorectal cancers. We will identify additional chemotherapy drugs, where tumour growth factors influence response, and will investigate whether blocking growth factor production can halt tumour spread and/or influence response to chemotherapy.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Spatially-resolved, highly multiplexed, digital-characterization of protein distribution and abundance in tissue sections using optical barcoding
Funder: Medical Research Scotland

Abstract: Precise information, derived from measurement of markers in cancer tissue, helps decide who will benefit from new and invariably expensive anti-cancer treatments. Cancers are not uniform; the amount and distribution of markers are important. Currently, testing cancers either disrupts the tissue giving accurate quantification of many markers, or retains structure but only looks at a few markers giving a subjective description including variability but only guessing quantity. This project represents a paradigm shift in how to use tissue for diagnosis and in predicting correct treatment. It combines the use of very high resolution microscopes to collect information from tissue; a brand new way of looking at many different markers simultaneously in a single tissue sample without destroying the tissue geography - each one uniquely labelled with its own optically readable barcode; computer analysis to accurately quantify precisely how much marker is present and where it is in relation to other markers; and state of the art statistical techniques to use all of the relevant information to derive the best information to guide diagnostic, treatment and prognostic information for individual patients. We will study kidney cancer because it is becoming commoner and new drugs are becoming available; current tests are inadequate.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Rapid development of kinase inhibitors that cross the blood brain barrier and target brain malignancies
Funder: Medical Research Scotland

Abstract: Glioblastoma multiforme is the most common and aggressive cancer that begins within the brain. Without treatment the average survival following diagnosis is merely 3 months, while with the best available surgical and adjuvant therapies can only be extended to 12-14 months. Pharmacological treatment of this incurable disease is severely limited by the lack of drugs capable of reaching the brain at therapeutic levels. Using a cost-effective drug discovery strategy recently developed by researchers at the Cancer Research UK Edinburgh Centre of the University of Edinburgh, an innovative programme of research is proposed to generate novel drug candidates that are able to penetrate the brain and specifically target brain cancer growth and survival. Due to its clinical importance, successful project outcomes will be protected under patent and progressed towards commercialization as appropriate by IOmet Pharma, a Scotland-based life sciences company specialized on the development of anticancer drugs. In addition, the PhD student will receive invaluable training in multiple cutting-edge techniques at the interface of chemistry and biomedicine within a world-class research environment that will significantly promote his / her professional career


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Idelalisib for refractory indolent non-Hodgkin's lymphoma [ID1379]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of idelalisib within its marketing authorisation for refractory indolent non-Hodgkin's lymphoma.

Lay abstract: Lymphomas are cancers of the lymphatic system, which is part of the body’s immune system. They are divided into Hodgkin’s and non-Hodgkin’s lymphomas. Non-Hodgkin's lymphomas are a heterogeneous group of conditions ranging from ‘indolent’ (low-grade) to ‘aggressive’ (high-grade) depending on the rate at which the abnormal lymphocytes divide. Indolent lymphomas are slow growing, with long median survival times but are less likely to be cured by treatment. Follicular lymphoma is the most common type of indolent non-Hodgkin’s lymphoma. Patients with follicular lymphoma typically present with painless, swollen lymph nodes in the neck, armpit or groin. Lymphomas are commonly staged I (best prognosis) to IV (worse prognosis). The stage of the lymphoma reflects how many groups of lymph nodes are affected, where they are in the body, and whether other organs such as the bone marrow or liver are affected. Most people (80%) present with advanced disease (stage III to IV). In 2015, approximately 11,700 people were diagnosed with non-Hodgkin’s lymphoma in England, of whom around 20% had follicular lymphoma. (1). The 5- year survival rate for people with follicular lymphoma is 87% and 20-year survival rates have been reported to be as high as 44%.(2) Most people with advanced follicular lymphoma will have initial treatment with chemotherapy in combination with rituximab, often followed by maintenance therapy with rituximab. However, most people’s lymphoma will relapse after the initial response, and treatment is often characterised by multiple lines of treatment as the disease responds and relapses. Cancers that do not respond to rituximab or relapse soon after finishing treatment are termed ‘rituximab refractory’. Treatment options for rituximab-refractory follicular lymphoma include single- or multi-agent chemotherapy (for example, including cyclophosphamide, fludarabine, bendamustine or chlorambucil) and best supportive care. Obinutuzumab in combination with bendamustine followed by obinutuzumab maintenance treatment has also been recommended for use within the Cancer Drugs Fund as an option for treating follicular lymphoma that did not respond or progressed during or up to 6 months after treatment with rituximab or a rituximab-containing regimen (NICE TA 472). References 1. Office for National Statistics (2015) Cancer registration statistics, England, 2013. Accessed February 2016. 2. Cancer Research UK (2014) Non-Hodgkin lymphoma survival statistics. Accessed February 2016.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Brentuximab vedotin for treating CD30-positive Hodgkins lymphoma (published TA446) [ID1366]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of brentuximab vedotin within its marketing authorisation for treating people with CD30-positive Hodgkin’s lymphoma.

Lay abstract: Hodgkin's lymphoma is a cancer of the lymphatic system which arises from cancerous B lymphocyte cells (also known as Reed-Sternberg cells). Some tumours express the integral membrane antigen CD30. The initial symptom of Hodgkin’s lymphoma is swelling of lymph nodes in the neck, armpit or groin. Other symptoms include recurring fever, night sweats, weight loss, cough, breathlessness, abdominal pain, and itching. Hodgkin’s lymphoma accounts for around 20% of all diagnosed lymphomas. In England, there were 1517 people diagnosed with Hodgkin’s lymphoma in 2011 and 256 registered deaths from Hodgkin’s lymphoma in 2012. The age- specific incidence of Hodgkin’s lymphoma shows two peaks, one in people aged 20–25 years and the second in people aged over 70 years. Current first-line treatment for Hodgkin’s lymphoma is chemotherapy alone or chemotherapy combined with radiotherapy. Between 15 and 30% of people with Hodgkin’s lymphoma do not achieve long-term remission with these therapies. For these people, high-dose chemotherapy followed by autologous stem cell transplant is a potentially curative treatment that is effective in approximately 50% of people. However, autologous stem cell transplant may not be an option in some circumstances; for example, if the disease is refractory to chemotherapy, or if the person’s age or co-morbidities prohibit this intervention. Following autologous stem cell transplant, people are considered to be at ‘high risk’ of residual disease if they have any of the following: • primary refractory disease • disease relapse within 1 year of completing first-line treatment • a positive PET scan prior to autologous stem cell transplant • extra-nodal involvement at the time of relapse prior to autologous stem cell transplant. There is no standard therapy administered after autologous stem cell transplant to delay disease progression. People whose disease relapses after ous stem cell transplant may be treated with single or combination treatment regimens that may include chemotherapy such as gemcitabine, vinblastine, or vinorelbine (alone or in combination) or ChlVPP (chlorambucil, vinblastine, procarbazine and prednisolone). Some chemotherapy regimens are used outside their marketing authorisation.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: 177Lu-dotatate for treating unresectable or metastatic neuroendocrine tumours in people with progressive disease [ID1224]
Funder: Department of Health and Social Care

Abstract: This project will review and appraise the evidence presented to the National Institute of Health and Care Excellence (NICE) on the clinical effectiveness and cost-effectiveness of everolimus, lanreotide, lutetium-177 DOTATATE and sunitinib for treating unresectable or metastatic neuroendocrine tumours with disease progression.1

Lay abstract: The aim of this project is to review the clinical effectiveness and cost effectiveness of everolimus, lanreotide, lutetium-177 DOTATATE, and sunitinib for treating unresectable or metastatic neuroendocrine tumours with disease progression in a multiple technology appraisal. The medical benefits and risks associated with these treatments will be assessed and compared across the treatments and against available standard treatments.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Abiraterone for treating newly diagnosed hormone-naive metastatic prostate cancer [ID945]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of abiraterone within its marketing authorisation for treating newly diagnosed high risk metastatic hormone-naive prostate cancer.

Lay abstract: Prostate cancer is a disease in which tumours develop in the prostate, a gland in the male reproductive system. Its cause is thought to be multi-factorial, involving both environmental and genetic factors. (1),(2) The incidence of prostate cancer increases with age and is higher in men of black African-Caribbean family origin and people with a family history of the disease (1). In England, there were over 40,000 people newly diagnosed with prostate cancer and over 9500 deaths from prostate cancer in 2014.(3) Prostate cancer often leads to bone metastases, typically in the spine, pelvis and rib cage. In 2015, 21% of patients diagnosed in England with prostate cancer had metastatic disease.(4) Hormone-naïve refers to people that are about to start (or who have started within the last 12 weeks) treatment with androgen deprivation therapy for the treatment of metastatic prostate cancer. For metastatic prostate cancer, NICE clinical guideline 175 recommends androgen deprivation therapy, specifically, bilateral orchidectomy (removal of the testicles) or continuous luteinising hormone-releasing hormone agonist therapy. For people who are willing to accept the adverse impact on overall survival and gynaecomastia (breast swelling) in the hope of retaining sexual function, the guideline recommends offering anti-androgen monotherapy with bicalutamide. NHS England commissions docetaxel chemotherapy for treating metastatic prostate cancer in people w o are about to start, or who recently started, androgen deprivation therapy. References 1. Cancer Research UK. About cancer. Prostate cancer risks and causes. Accessed November 2017. http://www.cancerresearchuk.org/about- cancer/type/prostate-cancer/about/prostate-cancer-risks-and-causes 2. Macmillan Cancer Support. Cancer information. Risk factors and causes of prostate cancer. Accessed November 2017. http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Prostate/Abo utprostatecancer/Causes.aspx 3. Cancer Research UK. Cancer stats. Prostate cancer mortality statistics. Accessed November 2014.. http://www.cancerresearchuk.org/cancer- info/cancerstats/types/prostate/mortality/ 4. National Prostate Cancer Audit. Annual report 2015. Accessed October 2016. http://www.npca.org.uk/annual-report-2015/

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Blinatumomab for treating acute lymphoblastic leukaemia for people with minimal residual disease activity in remission [ID1036]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of blinatumomab within its marketing authorisation for treating acute lymphoblastic leukaemia for people with minimal residual disease in remission.

Lay abstract: Acute lymphoblastic leukaemia (ALL) is a cancer of lymphocyte-producing cells. Lymphocytes are white blood cells that are vital for the body's immune system. In ALL there is an excess production of immature lymphocyte-precursor cells, called lymphoblasts or blast cells, in the bone marrow. This affects the production of normal blood cells and there is a reduction in the numbers of red cells, white cells and platelets in the blood. ALL is most common in children, adolescents and young adults, with 65% of cases diagnosed in people aged under 25 years1. A second increase in incidence is observed in people aged over 60 years1. In England, 654 people were diagnosed with ALL2, and 201 people died from ALL3, in 2014. The aim of treatment in ALL is to achieve a cure. Treatment can take up to 3 years to complete and is generally divided into 3 phases; induction phase, consolidation and maintenance. The choice of treatment can depend on the phase. During induction, newly diagnosed ALL is generally treated with chemotherapy combinations including vincristine, an anthracycline, corticosteroids and asparaginase, with or without cyclophosphamide or cytarabine. NICE technology appraisal 408 recommends pegaspargase as part of an antineoplastic combination therapy for untreated, newly diagnosed ALL. During the consolidation phase, intensified chemotherapy is used, which may include high dose methotrexate with mercaptopurine, asparaginase, or a repeat of the induction therapy. During the maintenance phase low dose chemotherapy is used, which typically consists of weekly methotrexate and daily mercaptopurine for an extended period of time to prevent relapse. Many of the patients that achieve a complete remission will experience a recurrence of disease. Relapse is thought to result from residual leukaemia cells that remain. Minimal disease diagnostics are used to detect these remaining cells and guide treatment response. Treatment depends upon the degree of residual activity and may require more intensified further treatment (that is, commencing induction therapy once again, which includes high dose chemotherapy).

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS