NIHRDataInsights/HRCSData huggingface dataset:
Title: Cemiplimab for treating cutaneous squamous cell carcinoma (CDF review of TA592) [ID3883]
Funder: Department of Health and Social Care

Abstract: Cutaneous squamous cell carcinoma (SCC) is a non-melanoma form of skin cancer that starts in the cells lining the top of the epidermis (the outer layer of the skin), their role is to produce keratin which protects the outer layer of the skin. The skin constantly sheds these cells.[1] Cutaneous SCC presents itself on the surface of the skin as a firm pink lump with a rough surface and are tender to touch.[1] There is a small risk (up to 5%) for cutaneous SCC lesions to spread but if they do, then they spread deeper into layers of the skin as well as metastasise across the body.[2]_x000D_ _x000D_ Cutaneous SCC accounts for about 20% of skin cancers[2] and 23% of nonmelanoma skin cancers[3] . Around 122,000 cases of non-melanoma skin cancer were registered in 2015 in England. [2] Deaths from cutaneous SCC are rare, however the prognosis for metastatic cutaneous SCC is poor, with a median overall survival of less than 2 years.[4]_x000D_ _x000D_ Surgery is the main treatment for non-melanoma skin cancer. For locally advanced and metastatic disease, the European consensus-based interdisciplinary guideline[4] suggests alternative treatment options if surgery is not feasible such as radiotherapy and chemotherapy (e.g. cisplatin, carboplatin, 5-fluorouracil and bleomycin). In addition, electrochemotherapy can be used for locally advanced lesions and EGFR inhibitors (e.g. cetuximab) can be considered as second line treatments after chemotherapy.[4] The treatment used will depend on the type, size and location of the nonmelanoma skin cancer.[1]_x000D_ _x000D_ References_x000D_ 1. NHS Choices (2017) Non-melanoma skin cancer [accessed at 05/02/2018] https://www.nhs.uk/conditions/non-melanoma-skin-cancer/_x000D_ 2. Cancer Research UK (2017) Skin cancer_x000D_ 3. National cancer Intelligence Network (2013) Non-melanoma skin cancer in England, Scotland, Northern Ireland, and Ireland_x000D_ 4. Stratigos A, Garbe C, Lebbe C et al. ‘Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline’. Eur J Cancer. (2015)_x000D_ Volume 51, Issue 14, Pages 1989–2007. http://www.eado.org/medias/Content/Files/2015-StratigosEurGuidelineSCC-EJC.pdf [Accessed at 24/08/2018]

Lay abstract: To appraise the clinical and cost effectiveness of cemiplimab within its marketing authorisation for treating cutaneous squamous cell carcinoma.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Durvalumab for maintenance treatment of unresectable non-small-cell lung cancer after platinum-based chemoradiation: CDF review of TA578 [ID3885]
Funder: Department of Health and Social Care

Abstract: Lung cancer falls into 2 main histological categories: around 85–90% are nonsmall-cell lung cancers (NSCLC) and the remainder are small cell lung cancers. NSCLC can be further classified into 3 histological sub-types of large-cell undifferentiated carcinoma, squamous cell carcinoma and adenocarcinoma. Most lung cancers are diagnosed at an advanced stage, when the cancer has spread to lymph nodes and other organs in the chest (locally advanced disease; stage III) or to other parts of the body (metastatic disease; stage IV)._x000D_ _x000D_ Cancer cells expressing an immunologic marker called programmed cell death 1 ligand (PD-L1) are believed to suppress certain immune responses and cause increased tumor aggressiveness. The proportion of NSCLC that is PD-L1 positive in England is unknown._x000D_ _x000D_ In 2018, around 35,000 people were estimated to be diagnosed with NSCLC in England. [1],[2] Around 22% had stage III disease.[1] The prognosis for people with NSCLC is generally poor. Between 2013 and 2017 around 40% of people with lung cancer survived for 1 year or longer and only 16% survived for 5 years or longer.[2]_x000D_ _x000D_ NICE guideline 122 (NG122) recommends chemoradiotherapy as an option for people with stage II or III unresectable NSCLC. There is currently no national clinical guidance on maintenance therapy for people who do not progress following chemoradiotherapy._x000D_ _x000D_ This review of technology appraisal guidance 578 only covers the population eligible for treatment according to that guidance (that is, adults with locally advanced unresectable NSCLC whose tumours are PD-L1 positive and whose disease has not progressed after concurrent platinum-based chemoradiation)._x000D_ _x000D_ References_x000D_ 1. National lung cancer audit 2018 (2021) Royal college of Physicians. Accessed November 2021._x000D_ 2. 2 Cancer survival in England: adult, stage at diagnosis and childhoodpatients followed up to 2018 (2019) Office for National Statistics. Accessed November 2021

Lay abstract: To appraise the clinical and cost effectiveness of durvalumab within its marketing authorisation for the maintenance treatment of locally advanced unresectable non-small-cell lung cancer that has not progressed following platinum-based chemoradiation therapy.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Regulatory gap analysis of the Plexaa preconditioning device
Funder: Department of Health and Social Care

Abstract: The number of women undergoing breast reconstruction following mastectomy is increasing 1&ndash;3. However the rate of complications following breast reconstruction remain relatively high: 1 in 3 patients experience a complication and 1 in 5 require a reoperation 4. Complications cause delayed discharges, returns to theatre, suboptimal aesthetic outcomes, an impact on psychosocial well-being and potentially readmissions, increasing the overall cost of breast reconstruction 5. Between 2015-2018 an NIHR RfPB funded RCT called preHEAT was undertaken at St Thomas Hospital. We investigated the beneficial effects of supraphysiological preconditioning the breast skin pre-operatively (the night before surgery) with heat to reduce surgical complications. Preconditioning increases the blood supply to the skin to protect it against complications. Our study demonstrated a 13% reduction in mastectomy skin flap necrosis; a 50% reduction in reoperation rates; and a 70% reduction in follow-up appointments 6. We used hot water bottles to precondition however these lose heat and being unmonitored can pose a risk to patients who have had radiotherapy &ndash; the very patients where preconditioning could help the most. Plexaa was built as the safe, scalable solution to providing preconditioning to all breast reconstruction patients. Plexaa is an app and sensor controlled, fully automated, ultra-precise, wearable device that can be sent directly to the patient to perform preconditioning the night before surgery at home. Now patented, we have built a fully functioning MVP that we want to get ready for regulatory approval. This funding is required now to help accelerate the adoption of Plexaa into the NHS by helping us identify our regulatory gap. The NHS is looking for new technologies to help address the backlog created by the pandemic and we firmly believe that Plexaa can be adopted quickly to help reduce complications, outpatient follow ups and length of stay for breast reconstruction patients.


Research activity codes: 5.4 SURGERY
Health categories: CANCER AND NEOPLASMS
Title: The gut microbiome and response to neoadjuvant chemotherapy in breast cancer.
Funder: Chief Scientist Office, Scotland

Abstract: Within our gut there are lots of bacteria, which play important roles in keeping us healthy. We believe that these bacteria may also determine which patients achieve the best response to chemotherapy. We know that diet and other interventions can change the bacteria. In this research we hope to identify certain patterns in the bacteria that link with what type of response a patient has to chemotherapy. To do this we will look at blood, stool and tumour samples from women who are having a course of chemotherapy before surgery for breast cancer. We will look into the role that the immune system, gut products and tissues surrounding the cancer may have in working alongside the bacteria. We will try to understand how the bacteria are linked with chemotherapy side effects. Overall, we hope to identify specific trends in the gut bacteria, which are associated with a better response to chemotherapy. With future research we would then hope to determine how to recreate these favourable gut bacterial trends in patients, to help them achieve the best response to chemotherapy


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: A novel model of the breast cancer liver metastatic niche: tackling metastatic recurrence.
Funder: Chief Scientist Office, Scotland

Abstract: Breast cancer is the most common cancer in women but despite advances in screening and treatment in the early stages, the cancer can return years later in other organs. Approximately 50% of these women will develop secondary tumours in the liver. This is associated with a limited life expectancy as their condition is no longer curable. Therefore, preventing secondary breast cancer formation in the liver is key to improving the long-term survival of breast cancer patients. Secondary tumours result from cancer cells escaping into the blood supply during the early stages of primary cancer formation. Some of these cancer cells travel to other organs, such as the liver, where they subsequently grow to form secondary tumours. In order for the cancer cells to grow, they must first survive and then settle in their new environment. This process is known as ‘metastatic colonisation’ and relies on supportive signals from the liver cells. There is evidence to suggest that some cancer cells can hide in the new organ for many months or years by becoming inactive and remaining inactive until the environment is favourable for colonisation. The process of metastatic colonisation is not yet well understood but is essential in discovering ways of preventing the formation of secondary tumours. Liver disease can be studied and new treatments tested by growing liver as 3D cultures in a laboratory dish. I will mix breast cancer cells with these liver cultures to replicate breast cancer cells that have spread to the liver in a patient. I will study the complex interactions that occur between the breast cancer cells and liver cells. I will also test chemical substances and drugs to look for treatments that could prevent breast cancer cells in the liver from forming new tumours. The model is ideal for these experiments because identical copies of it can be produced at a low cost and at a large scale, which will allow multiple substances or drugs to be tested rapidly and efficiently in one go. My project will improve understanding of the genes and pathways that play a role in formation of secondary tumours in the liver, help discover new drugs that target the interactions between breast cancer and liver cells in order to prevent formation of secondary breast cancer in the liver. Preventing this process from occurring will have a huge impact on women with breast cancer by reducing the rates of secondary tumours and thereby improving survival.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: How Should Scotland Respond to the Challenge of Lung Cancer Screening? A Mixed Methods Feasibility Study.
Funder: Chief Scientist Office, Scotland

Abstract: Lung cancer is a major cause of death in Scotland; our rates are higher than many other European countries and it is usually diagnosed at a late stage. Studies in Europe and the US have shown that offering screening with a CT scan can reduce deaths from the disease – but only amongst those at highest risk. We need evidence from Scottish research which examines the effectiveness of this kind of screening in our population - which includes areas of high deprivation, and is more dispersed in rural locations than the rest of the UK. We propose a study which will examine how we can best identify those at the highest risk of lung cancer in the Scottish population, and offer them a medical check on their ‘lung health’, and screening using CT if their risk of cancer is high enough. We will see how acceptable people find this kind of screening, and how we could improve our processes to meet the needs of the Scottish population. Our findings will help us design a much larger study which will be able to examine the impact of screening on improving outcomes in Scottish lung cancer patients


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: The impact of primary care led, FIT-based, triage of new onset colorectal symptoms on diagnostic service demand and the diagnosis of colorectal cancer
Funder: Chief Scientist Office, Scotland

Abstract: Symptoms poorly predict colorectal (bowel) cancer (CRC). Patient awareness initiatives (e.g. Detect Cancer Early) led to a rapid increase in ‘suspected cancer’ colonoscopy referrals but the yield of CRC remained low at ~5%. An effective means of triage of symptomatic patients is required to avoid unsustainable pressure on diagnostic services and the unintended consequence of delaying diagnosis of CRC. Measurement of the patient’s faecal haemoglobin (FHb) concentration (amount of blood in the stool) with a FIT (Faecal Immunochemical Test) is now recommended in UK guidelines. Patients with undetectable FHb carry an extremely low risk of CRC and may not need investigation. However, there remains debate around whether the FIT test should be deployed by GPs (with fears that referrals will increase, or that CRC may be missed) or should only be used in patients after referral to secondary care. Furthermore, NICE suggests FIT testing should be reserved for ’low-risk’ symptoms, but recent large studies have challenged this. NHS Tayside pioneered GP led, FIT-based triage of all patients with new bowel symptoms in December 2015 and more than 60,000 FIT samples have been analysed. We wish to take the FIT laboratory results and, using the patients’ unique CHI number, link them with the corresponding electronic patient record to note the clinical details, blood results, subsequent referral, investigations performed, and final outcomes, and link to the Scottish Cancer Registry to determine the impact of FIT triage in primary care on referral rates, diagnostic service demand, and the timely diagnosis of CRC


Research activity codes: 4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: Manipulating the Immune Microenvironment in Malignant Pleural Mesothelioma (MPM).
Funder: Chief Scientist Office, Scotland

Abstract: MPM is caused by asbestos exposure, usually through work in trade industries such as shipbuilding. Asbestos exposure causes chronic inflammation which promotes tumour formation. The UK has the highest death rate from Mesothelioma in the world- it is resistant to all chemo and radiotherapy. Research until now has focused largely on the cancer cell but it is becoming clear that the surrounding cells and the immune system are crucial in allowing tumour initiation and progression. New treatments called immunotherapies reveal previously hidden cancers to the immune system, or activate immune cells directly to fight cancer. For example, drugs that disrupt the PD1 “immune checkpoint” system have shown great promise, but only work in around 20% of patients with MPM. Macrophages are an immune cell which initiate and establish inflammation in the lining of the lung, which precedes MPM in most patients. They make up 20-30% of all the cells present in human MPM tumours and studies show that macrophage programming is important in influencing the immune response to cancer and may be involved in resistance to standard treatments. As a result, new drugs which directly target macrophages are in clinical trials for other cancers. We believe that targeted treatment of macrophages in MPM may result in new and highly effective MPM therapies. In particular, based on previous studies, we anticipate that macrophage treatment may be effective as a single agent and increase the number of responders to standard chemotherapy and/or anti-PD1 immunotherapy. We will have the opportunity to interrogate a new, unique, mouse model of MPM. This means we can test these questions before any patients are exposed to new drugs in clinical trials. Our model combines asbestos driven inflammation with state-of-the-art genetic engineering. Importantly, our mice have normally functioning immune systems. In this study we will inject macrophage treatments (CSF-1R or CD98 inhibitors) directly into the pleural cavity of MPM bearing mice. We will then measure the effect of these treatments on the activity and death rate of the tumour cells, and the length of time the mice survive


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: The role of NFκB signalling in immune checkpoint expression and myeloid cell function in colorectal cancer.
Funder: Chief Scientist Office, Scotland

Abstract: Colorectal cancer is a major source of death in Scotland, and despite successful outcomes after surgery in early stages, 5-year survival for all patients remains around 60%. Patients with more advanced cancer, even if it is able to be removed by surgery, undergo chemotherapy as they are at higher risk of recurrence. However, this treatment is not effective for everyone. Depending on the tumour type, some patients can benefit from targeted therapy. Immunotherapy, drugs that activate the immune system, have revolutionised cancer treatment but for colorectal cancer only 10-15% of patients will respond. We know that cancers that have increased levels of inflammation are often more aggressive and our data shows that increases in a specific pathway of inflammation, NFB, is associated with more patients vulnerable to dying of their cancer. Our data also shows a link between this inflammation pathway and certain markers for immunotherapy treatments including PD-L1. This research project is designed to investigate this link between the NFB pathway in cancer cells and how the surrounding immune cells behave to support progression of the cancer. I am interested in studying one of the most important types of immune cell in fighting off cancer, like it does with infection, called the macrophage. By closely studying immune cell functions in the environment surrounding cancer tissue, we hope to better understand whether this NFB pathway causes worse inflammation, stops these macrophages from working properly and causes cancer progression. We want to find out if treatments to block this inflammation pathway (NFB) will influence the function of macrophages and stop tumour growth. I will assess if using immunotherapy (anti PD-L1) is more effective in boosting the immune cells to fight off the cancer


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: The relationship between the tumour phenotype, JAK/STAT signalling, systemic inflammation, body composition and survival in patients with operable colorectal cancer.
Funder: Chief Scientist Office, Scotland

Abstract: The aim of this study is to establish an overarching explanation for muscle loss and reduce ability to perform activities of daily life seen in patients with cancer. Many attempts to address muscle loss, anorexia and reduced physical function, termed cachexia, have been made over the years. These include nutritional support programs and targeted exercise regimes. However, most of these interventions have at best only produced a minor improvement in patient weight loss and have not improved patient quality of quantity of life. We think that the body’s own immune system is critical in this but we need to fully understand this. Using a specific type of cancer, bowel cancer, as our test cancer, we will examine how the immune system influences loss of muscle and other factors in cachexia. There are currently medications in use to treat different medical problems such as arthritis and in patients with advanced cancers which act on the immune system. In addition, several animal based studies have shown the importance of the immune system in cancer cachexia. This study will allow us to understand this interaction between the immune system and muscle. This could potentially allow us to use existing medications to treat cancer cachexia to improve both the length and quality of patients lives and to allow interventions such as nutritional and exercise support mentioned above to become more effective.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: The role of cancer associated fibroblast heterogeneity in determining metastatic patterns in pancreatic and oesophageal adenocarcinoma.
Funder: Chief Scientist Office, Scotland

Abstract: Pancreatic and oesophageal cancer remain major causes of cancer death in Scotland, and the Western world, with less than 8% and 20% of patients alive 5-years after diagnosis for each respectively. Almost all patients with these cancers die from the cancer spreading to other organs, usually the liver or lung. Even when the original tumour is diagnosed early, and patients have surgery to remove the tumour, most patients have their cancer coming back and often in a different place in the body. I believe non cancer cells, called fibroblasts, in the tumour, can direct the spread of cancer cells. Using new, state-of-the-art technologies, I hope to study the behaviour of these fibroblasts at a detail that has never been done before to identify new treatments to prevent these cancers from spreading or coming back after surgery to remove them. I will investigate the unique organisation of these fibroblasts in the original tumour, and in some, in the sites where it has spread to. I believe that this will allow me to determine how these fibroblasts enable cancers to spread to other organs, and why they select specific organs such as the liver in some patients and the lung or other sites in others. This will allow me to identify new treatments that target these fibroblasts and other immune cells to help prevent, and treat, pancreatic and oesophageal cancer from spreading to distant sites.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS