NIHRDataInsights/HRCSData huggingface dataset:
Title: Complex Cochrane Systematic Reviews in prioritised brain tumour areas in collaboration with NCRI & NICE
Funder: Department of Health and Social Care

Abstract: Annually there are 11,000 new brain/intracranial tumours in the UK (1). Symptoms initially can be vague leading to late diagnosis. Referral guidelines and protocols to improve early diagnosis have not been systematically reviewed. Changes in the WHO classification of tumours 2016 emphasise the importance of molecular markers in LGG and GBM but there are multiple methods to test these that vary in cost and availability. Technologies to maximise tumour resection are common but are costly with uncertain impact. Advanced research MRI scanning in LGG surveillance may detect early transformation, but are costly and not in routine use. Clinical trials show early radiotherapy and chemotherapy for LGG improves survival but possibly at the expense of late harms. In the elderly and after 2nd recurrence, survival with GBM is poor and treatment may not be in the patients’ best interests, but are increasingly prescribed. All are priority areas for systematic reviews for JLA/NCRI and NICE guidelines. The theme is to facilitate strategic primary brain tumour clinical goals through collaboration to produce high quality prioritised systematic reviews. In May 2015 at a clinical research strategy meeting, including stakeholders from Cochrane, NCRI, NICE, NIHR, CRUK, Research Design Service, charities and patients agreed to work collaboratively to ensure JLA Neuro-oncology prioritised topics would be the focus of well-designed systematic reviews and clinical studies to inform NICE guidelines(2). The scope is to evaluate complex evidence around management of primary brain tumours including early diagnosis, molecular markers and most effective treatments in LGG and GBM. We will collaborate with NCRI, NICE/National Guideline Alliance (NGA) , EPPI-Centre, CRSU and Newcastle University Health Economic Group to produce high quality Cochrane reviews to inform decision-making. These include network meta-analyses, DTA reviews and evidence on harms and of relative efficiency of current treatments.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: CANCER AND NEOPLASMS
Title: Nivolumab for treating advanced or recurrent gastric cancer [ID1118]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of nivolumab within its marketing authorisation for previously treated gastric or gastro-oesophageal junction cancer.

Lay abstract: Stomach cancer is a malignant tumour arising from cells in the stomach. The most common type of stomach cancer is gastric or gastro-oesophageal junction adenocarcinoma, which affects about 95% of people with the disease (1). It is more common in men than women, with approximately 4,600 cases diagnosed in men, and 2,500 cases in women in 2013 (2). Around half of all new cases of stomach cancer are diagnosed in people aged over 75 years (2). Initial symptoms of disease are vague and are similar to other stomach conditions but advanced stages of cancer may include a lack of appetite and subsequent weight loss, fluid in the abdomen and blood in the stool. Because of the nature of symptoms, stomach cancer is often diagnosed at an advanced stage, with around 14% diagnosed at stage 3 (locally advanced), and 80% diagnosed at stage 4 (metastatic)3. Once the stage of the cancer has been established the main treatment option, if appropriate, is surgical resection of the tumour with or without adjunctive chemotherapy; these include cisplatin, capecitabine, fluorouracil and FOLFOX (folinic acid, fluorouracil and oxaliplatin). Radiotherapy may be used palliatively with or without chemotherapy. At advanced stages of the cancer surgery may not be an option at first but may potentially be operable after chemotherapy has down-staged the tumour. The aim of treatment in advanced gastric or gastro-oesophageal junction cancer is primarily palliative; to prevent progression, extend survival and relieve symptoms with minimal adverse effects. NICE technology appraisal 191 recommends capecitabine in combination with a platinum-containing agent as a first line option for advanced cancer. Other options include combination regimens, such as epirubicin with a platinum-containing agent and capecitabine or fluorouracil, docetaxel and irinotecan, FOLFIRI (irinotecan and fluorouracil), and if people are HER2-positive; then NICE technology appraisal 208 recommends trastuzumab in combination with cisplatin and capecitabine or fluorouracil. There is no standard treatment for previously treated advanced disease. People may be treated with taxane (docetaxel or paclitaxel) monotherapy or combination therapy once again at second line, but beyond second line there is no evidence on the effective use of these agents. NICE technology appraisal 378 does not recommend ramucirumab for treating advanced gastric cancer or gastro-oesophageal junction adenocarcinoma previously treated with chemotherapy. References 1. Types of stomach cancer (2016). Cancer Research UK. Accessed December 2016 2. Stomach cancer statistics. Cancer Research UK. Accessed December 2016. 3. Survival statistics for stomach cancer. Cancer Research UK. Accessed December 2016.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Gemtuzumab ozogamicin for treating early untreated acute myeloid leukaemia [ID982]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of gemtuzumab ozogamicin within its marketing authorisation for untreated acute myeloid leukaemia.

Lay abstract: Acute myeloid leukaemia is a cancer of the blood and bone marrow. It is characterised by the overproduction of early immature myeloid cells (blasts). Acute myeloid leukaemia is classified into several types. In most types of acute myeloid leukaemia, the cancer cells are immature white blood cells. In other less common types, immature platelets or immature red blood cells form the leukaemia cells. Anaemia, bleeding problems, serious infections, fatigue, weakness, breathlessness, fever, night sweats, weight loss and bone, joint or muscle pain are common symptoms in acute myeloid leukaemia. The incidence of acute myeloid leukaemia has increased by 8% in the UK over the last decade. There were 2,590 new diagnoses of acute myeloid leukaemia and 2,127 deaths registered in England in 2014.(1) In the UK in 2012-2014, more than half (55%) of new diagnoses were in people aged 70 and over.(1) Acute myeloid leukaemia typically develops rapidly and can be fatal unless treated. For people who are fit enough, intensive treatment is available. It is conducted in 2 phases: induction chemotherapy is given to achieve a remission, followed by consolidation therapy which is given to reduce the risk of leukaemia recurring. Drugs that may be used for intensive treatment include amsacrine, cytarabine, daunorubicin, etoposide, fludarabine, idarubicin, mitoxantrone and thioguanine.(2) Fludarabine does not currently have a marketing authorisation in the UK for treating acute myeloid leukaemia. A combination of fludarabine, idarubicin, cytarabine and granulocyte colony stimulating factor (G-CSF) can also be used in ‘poor risk’ patients classified according to cytogenetic profile or in patients for whom a rapid response is needed. In some circumstances, people may be offered haematopoietic stem cell transplantation. NICE technology appraisal guidance 218 recommends azacitidine for adults who are not eligible for haematopoietic stem cell transplantation and have acute myeloid leukaemia with 20–30% blasts and multilineage dysplasia, according to the World Health Organization classification. NICE technology appraisal guidance 399 does not recommend azacitidine for treating acute myeloid leukaemia with more than 30% bone marrow blasts in people of 65 years or older who are not eligible for haematopoietic stem cell transplant. References: 1. Cancer Research UK (2014) Acute myeloid leukaemia (AML) statistics. Accessed September 2017. 2. Cancer Research UK (2016) Chemotherapy for acute myeloid leukaemia (AML). Accessed September 2017.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Lenvatinib for treating first line, advanced unresectable or metastatic hepatocellular carcinoma [ID1089]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of lenvatinib within its marketing authorisation for advanced hepatocellular carcinoma not previously treated with systemic therapy.

Lay abstract: Hepatocellular carcinoma (HCC) is the most common form of liver cancer in England, accounting for 55% of primary liver cancer diagnoses in men and 28% of diagnoses in women (1). It is commonly associated with cirrhosis (scarring of the liver), which can be caused by excessive alcohol intake, viral infections such as hepatitis B or C, or other conditions that result in chronic inflammation of the liver (2). There were 2,456 people diagnosed with HCC in England in 2015(3). The risk of developing HCC increases with age, with the average age at diagnosis being 66 years(2). Treatment for HCC depends on the location and stage of the cancer, and how well the liver function is preserved. Early stage hepatocellular carcinoma may be treated with potentially curative surgery (hepatic resection), or percutaneous radiofrequency/thermal ablation in patients with well-preserved liver function, or liver transplantation for those with impaired liver function. However, treatment is palliative rather than curative for people with more advanced disease. Treatment options include interventional procedures such as transarterial chemoembolisation (using doxorubicin or cisplatin) or selective internal radiation therapy, and external beam radiotherapy. People for whom these treatments are not suitable, or those with metastatic disease, are treated with sorafenib (a multi-kinase inhibitor). Some people with HCC are treated with best supportive care. NICE Guidance TA474 (Cancer Drugs Fund reconsideration of TA189) recommends sorafenib as an option for treating advanced HCC only for people with Child-Pugh grade A liver impairment. Sorafenib was available for people with both Child-Pugh grade A and B advanced HCC via the Cancer Drugs Fund. The indication for people with Child-Pugh grade B liver function was removed from the Cancer Drugs Fund on 5th November 2017.(4) References 1. National Cancer Registration and Analysis Service (2010) Trends in incidences in primary liver cancer subtypes. Accessed July 2017 2. Patient (2015) Hepatocellular carcinoma. Accessed July 2017 3. Office for National Statistics (2015) Cancer registration statistics. Accessed September 2017. 4. Cancer Drug Fund (2017) National Cancer Drug Fund List ver1.41. Accessed September 2017.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Magnetic resonance perfusion for differentiating low grade from high grade gliomas at first presentation
Funder: Department of Health and Social Care

Abstract: Brain tumours affect 1 person every hour and 11,000 each year in the UK. They are the most common cancer killer of children and young adults. On average brain tumours reduce life expectancy by 20 years - the highest of any cancer. In 2015 a priority setting exercise in collaboration with the James Lind Alliance identified a number of questions relevant to our DTA review, specifically relating to the uncertainty and variability in diagnostic imaging and follow-up protocols. We anticipate our DTA review will make a significant impact on improving care by expediting timely intervention when required and enabling safe observation when appropriate. To help achieve this objective we hope to prepare our review in time for the updated NICE guidelines in neuro-oncology, due to be published in July 2018. While this DTA review is a first in neuro-oncology it is already apparent that DTA reviews are likely to be a significant growth area. Oncology and neurosciences are already two of the most imaging intensive specialties, and research priorities have changed focus from novel interventions to disease subtyping. Therefore, it is high priority that our group develops expertise in DTA reviews.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Lipsomal cytarabine with daunorubicin for first line treating patients aged 60 years or older with acute myeloid leukaemia [ID1225]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of liposomal cytarabine and daunorubicin within its marketing authorisation for untreated, high risk, acute myeloid leukaemia.

Lay abstract: Acute myeloid leukaemia (AML) is a bone marrow cancer characterised by the overproduction of early immature myeloid cells (blasts). Myeloid neoplasms with more than 20% blasts in the peripheral blood or bone marrow are considered AML. AML is classified into several different types. In most types of AML, the leukaemia cells are immature white blood cells. In other less common types, too many immature platelets or immature red blood cells form the leukaemia cells. Anaemia, bleeding problems and serious infections are common symptoms in AML. The incidence of AML in the UK is about 3100 cases per year. Around three quarters of all cases occur in people over 60 years and 55% of all cases occur in people over 70 years1. AML is slightly more common in men than in women. AML is classified according to the World Health Organisation (WHO) classification which takes into account morphology, cytochemistry, immunophenotype, cytogenetics and clinical information and categorises AML into several clinically distinct types. Cytogenetics is the most important prognostic factor and classifies patients into ‘favourable, intermediate or adverse risk’ groups based on the presence or absence of specific chromosomal patterns. Poor prognostic factors, including intermediate and adverse risk cytogenetics, are more common in older people and make treatment more challenging. AML typically develops rapidly and can be fatal unless treated. People for whom intensive chemotherapy is suitable are treated with cytotoxic agents such as an anthracycline in combination with cytarabine to induce remission. People who cannot tolerate or do not wish to receive intensive chemotherapy may have non-intensive chemotherapy such as low dose cytarabine2. NICE technology appraisal 218 recommends azacitidine for adults with acute myeloid leukaemia with 20–30% blasts and multilineage dysplasia (AML that has developed from a myelodysplastic syndrome), according to the WHO classification and who cannot have haematopoietic stem cell transplantation. Azacitidine is not recommended by NICE for people with more than 30% blasts (NICE technology appraisal 399). If a person’s leukaemia is in remission they may receive consolidation therapy or a haematopoietic stem cell transplant if suitable2. Other aspects of care include blood product replacement for anaemia and thrombocytopenia, antibiotics and antifungals for infections and intermittent low dose chemotherapy with hydroxycarbamide to keep the peripheral blood blast count low.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Cabozantinib for treating advanced or metastatic renal cell carcinoma [ID1208]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of cabozantinib within its marketing authorisation for untreated, intermediate or poor risk, locally advanced or metastatic renal cell carcinoma.

Lay abstract: Renal cell carcinoma (RCC) is a cancer that usually originates in the lining of the tubules of the kidney (the smallest tubes inside the nephrons) that help filter the blood and make urine. RCC is the most common type of kidney cancer (more than 80% of the cases)(1). There are several types of RCC. The main ones are clear cell (accounting for approximately 75% of cases),(1) papillary and chromophobe. RCC is graded into stages I to IV. Stage III denotes disease that is locally advanced and/or has spread to regional lymph nodes. Metastatic RCC, in which the tumour has spread beyond the regional lymph nodes to other parts of the body, is defined as stage IV. Early small RCC tumours are usually asymptomatic; the diagnosis of early RCC is often incidental after abdominal scans for other reasons. The most common presenting symptoms of advanced RCC are blood in the urine (haematuria), a palpable mass in the flank or abdomen and abdominal pain. Other non-specific symptoms include fever, night sweats, malaise and weight loss. Localised radical approaches including nephron-sparing surgery, radical nephrectomy and ablative therapies may be curative in people with localised tumours. However, around half of those who have surgery develop advanced disease later on. In 2015, 10,507 new kidney cancers were diagnosed in England.(2) In 2014, approximately 44% of people diagnosed with kidney cancer had stage III or IV disease and 25% to 31% had metastases.(3) The 5-year relative survival rate for stage IV RCC is approximately 6%.(4) The aim of treatment is to prevent the growth and survival of cancer cells within the tumour. In untreated RCC, NICE technology appraisal guidance 169 recommends sunitinib as a ‘first-line treatment option for people with advanced and/or metastatic renal cell carcinoma who are suitable for immunotherapy and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.’ NICE technology appraisal guidance 215 recommends pazopanib as a ‘first-line treatment option for people with advanced renal cell carcinoma who have not received prior cytokine therapy and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1’. References 1. Cancer Research UK (2016) Types of kidney cancer. Accessed July 2017. 2. Office for National Statistics (2017) Cancer Registration Statistics. Accessed July 2017. 3. Cancer Research UK (2017) Kidney cancer incidence statistics. Accessed July 2017. 4. Cancer Research UK (2016) Kidney cancer survival statistics. Accessed July 2017.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Durvalumab after chemoradiation for treating non-small-cell unresectable lung cancer [ID1175]
Funder: Department of Health and Social Care

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.

Lay abstract: Lung cancer falls into two main histological categories: around 85–90% are non-small-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). 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. In 2015, around 33,000 people were estimated to be diagnosed with NSCLC in England.(1),(2) Around 21% had stage III disease.(1) The prognosis for people with non-small-cell lung cancer is generally poor. Between 2011 and 2015 around 39% of people with lung cancer survived for 1 year or longer and only 15% survived for 5 years or longer.2 NICE clinical guideline 121 (CG121) recommends chemoradiotherapy as an option for people with stage II or III unresectable non-small-cell lung cancer. There is currently no national clinical guidance on maintenance therapy for people who do not progress following chemoradiation therapy. References 1. National lung cancer audit 2016 (2017) Royal college of Physicians. Accessed October 2017. 2. 2 Cancer survival in England: adult, stage at diagnosis and childhood- patients followed up to 2016 (2017) Office for National Statistics. Accessed October 2017

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Encorafenib in combination with binimetinib for treating malignant BRAFV600 unresectable metastatic melanoma [ID923]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of encorafenib with binimetinib within its marketing authorisation for treating advanced unresectable or metastatic BRAF V600 mutation-positive melanoma

Lay abstract: Melanoma is a cancer of the skin. In its early stages, melanoma is normally asymptomatic and can often be cured by surgery (resection). However, it can spread or metastasise to nearby lymph nodes (stage III) or to other parts of the body (stage IV). Most melanomas occur in people with pale skin. The risk factors are skin that tends to burn in the sun, having many moles, sun exposure and sunburn. There were 13,356 new diagnoses of melanoma in England in 2015.(1) Approximately 60% of new diagnoses were in people aged 60 and over.(1) In England in 2012-2015, 7.5% of cases were diagnosed at stage III or IV.(2) There were 1,937 deaths registered in England in 2016.(3) A mutated form of the BRAF gene is found in 40% to 60% of melanomas; 80% to 90% of these are BRAF V600 mutations.4 Mutated BRAF genes activate the RAF-MEK-ERK pathway, leading to uncontrolled cell division and growth of the tumour. Treatment options for advanced melanoma depend on the person’s BRAF mutation status and treatment history. In clinical practice, for people with BRAF mutation-positive advanced melanoma, a BRAF inhibitor is the usual first-line treatment. For BRAF V600 mutation-positive unresectable or metastatic melanoma, NICE technology appraisal guidance recommends the BRAF inhibitor, dabrafenib alone (TA321) or with the MEK inhibitor, trametinib (TA396) and the BRAF inhibitor, vemurafenib alone (TA269). Dabrafenib with trametinib is considered the standard of care in clinical practice, replacing the use of targeted BRAF inhibitor monotherapy. NICE technology appraisal guidance 414 does not recommend the use of vemurafenib with the MEK inhibitor, cobimetinib, for treating BRAF V600 mutation-positive advanced melanoma. Immunotherapy is also recommended for advanced melanoma. References 1. National Cancer Registration and Analysis Service. Routes to diagnosis 2006-2016 workbook (a). Accessed June 2018. 2. National Cancer Registration and Analysis Service. Routes to diagnosis 2006-2016 workbook (b). Accessed June 2018. 3. Cancer Research UK (2014) Skin cancer statistics. Accessed June 2018. 4. Vora NL. (2016) Melanoma and BRAF. Medscape. Accessed January 2018.

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