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Case Study 4. Improving chemotherapy, radiotherapy and patient outcomes for colorectal cancer through patient-focused integrated clinical trials

Summary of the impact

Colorectal cancer is a common disease, which frequently causes death or morbidity, either because of failure to control the primary tumour or failure to prevent distant metastases. Leeds researchers have devised new treatment approaches using chemotherapy and radiotherapy and tested them in large randomised controlled trials which have led to major changes in clinical practice in the management of rectal cancer and advanced colorectal cancer (aCRC), driving clinical decision-making and improving outcomes for patients. This includes better-evidenced treatment for elderly patients and patient stratification on the basis of molecular biomarkers.

Submitting Institution

University of Leeds

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Oncology and Carcinogenesis

Stratification of treatment for adult patients with acute leukaemia

Summary of the impact

Research conducted at UCL/UCLH over the last 20 years has enabled the identification of adults with acute leukaemia who are most likely to benefit from the use of stem cell transplantation, i.e. those with acute leukaemia in first remission. The treatment is highly intensive, potentially toxic and expensive high-dose chemotherapy followed by haemopoietic stem cell transplantation, and is inappropriate for some patients. The work has made a major contribution to the development of guidelines worldwide for the treatment of this disease. Improved patient selection for transplantation results in improved survival, less toxicity with improved overall quality of life, and a more appropriate use of NHS resources.

Submitting Institution

University College London

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Oncology and Carcinogenesis

Systemic therapies for ovarian cancer

Summary of the impact

University of Glasgow research has led to the adoption of first-line chemotherapy for ovarian cancer, which has improved patient survival by 11% and has been used to treat 66% of women with ovarian cancer since January 2011 in the West of Scotland Cancer Care Network alone. These therapies are recommended by guidelines for ovarian cancer treatment in the USA, Europe and the UK. The USA guidelines are disseminated to 4.3 million people worldwide and the European guidelines reach 15,000 health professionals. The UK guidelines are used to identify those drugs that are funded by the NHS and used in NHS hospitals.

Submitting Institution

University of Glasgow

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences, Oncology and Carcinogenesis

Study A leads to changes in Tuberculosis treatment guidelines

Summary of the impact

Prior to the change in WHO recommendations which occurred following this study many patients in Africa and other developing countries were receiving an inferior regimen for the management of tuberculosis, a consequence of which meant that many had to be retreated. Since the implementation of the revised WHO Guidelines in 2010 almost all countries have now switched to the gold standard tuberculosis treatment regimen based on 6 months of isoniazid and rifampicin

Submitting Institution

University College London

Unit of Assessment

Public Health, Health Services and Primary Care

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences, Oncology and Carcinogenesis, Public Health and Health Services

Overcoming barriers to clinical trial recruitment in cancer with educational interventions

Summary of the impact

Research on professionals' discussions about clinical trials of cancer therapy has identified the major barriers to patient recruitment to clinical trials. This research was used to create an educational intervention to improve patient experiences and willingness to participate in a variety of clinical trials worldwide, resulting in increased participation in prostate, colorectal, renal and breast-cancer trials. It also involved educating members of UK cancer teams to the best ways to approach, communicate and maximise trial planning.

Submitting Institution

University of Sussex

Unit of Assessment

Psychology, Psychiatry and Neuroscience

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences, Oncology and Carcinogenesis, Public Health and Health Services

A: The GRACE risk score: a reference standard for the management of acute coronary syndrome

Summary of the impact

Impact: Health and welfare; the GRACE risk score (derived using data from 102,000 patients with acute coronary syndrome (ACS) in 30 countries) identifies high-risk ACS patients more effectively than do alternative methods.

Significance: GRACE is now a reference standard and has resulted in international guideline changes. It is estimated to save 30-80 lives for every 10,000 patients presenting with non-ST elevation ACS.

Beneficiaries: Patients with ACS; the NHS and healthcare delivery organisations.

Attribution: All work was led by Fox (UoE) with co-chair Gore (University of Massachusetts) and was developed from Edinburgh-based studies.

Reach: Worldwide: guidelines adopted in more than 55 countries; >10,000 downloads of app.

Submitting Institution

University of Edinburgh

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Public Health and Health Services

Reducing the toxicity of pemetrexed treatment in malignant pleural mesothelioma.

Summary of the impact

Malignant pleural mesothelioma (MPM) is a treatable but incurable cancer that originates in the cells lining the lungs. Over 14,000 people worldwide are diagnosed annually with MPM. Antifolates are often used in cancer therapy, but side effects are a major issue. A retrospective analysis of cancer trials and phase 1 trial of MPM patients, carried out by Newcastle in collaboration with Eli Lilly Pharmaceuticals, determined that plasma homocysteine levels were a good predictor of drug toxicity in cancer patients treated with the antifolate pemetrexed, and that this drug was well tolerated by patients with low homocysteine levels. It was also determined that pemetrexed treatment should be supplemented with vitamin B12 as well as folic acid, to reduce drug toxicity. Ultimately, this permitted the continued development of pemetrexed, which otherwise would have been too toxic for clinical use. It is now the only licensed drug for MPM treatment in combination with platinum-based chemotherapy.

Submitting Institution

Newcastle University

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences, Public Health and Health Services

UOA01-16: The International Subarachnoid Aneurysm Trial: Changing Clinical Practice

Summary of the impact

The University of Oxford's International Subarachnoid Aneurysm Trial (ISAT) changed clinical practice worldwide by showing that endovascular coiling is a more effective and safer treatment than neurosurgery following subarachnoid haemorrhage, with fewer complications and improved quality of life. Subarachnoid haemorrhages account for 1 in 14 strokes and are caused by bleeding in and around the brain; approximately 85% occur when cerebral aneurysms rupture. ISAT was the first trial to compare neurosurgery, or neuroradiological endovascular coiling in patients with ruptured cerebral aneurysms causing acute subarachnoid haemorrhage.

Submitting Institution

University of Oxford

Unit of Assessment

Clinical Medicine

Summary Impact Type

Political

Research Subject Area(s)

Engineering: Biomedical Engineering
Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences

Improving the safety of aminoglycoside antibiotics in cystic fibrosis

Summary of the impact

Research from the University of Nottingham on aminoglycoside antibiotics in cystic fibrosis (CF) has changed clinical practice and improved patient safety internationally. There are over 70,000 people with CF worldwide. Most require frequent and prolonged intravenous courses of aminoglycoside antibiotics (which can cause kidney damage) to treat chronic lung infection with Pseudomonas aeruginosa. This infection may lead to respiratory failure and death. Our research has influenced national and international guidelines, and changed practice, such that once-daily aminoglycosides (less toxic to the kidneys) are now used. We have also stopped the use of gentamicin, in favour of less toxic aminoglycosides.

Submitting Institution

University of Nottingham

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services

3. A New Standard of Care for Locally Advanced Prostate Cancer

Summary of the impact

Locally advanced prostate cancer (where a tumour has extended outside the prostate gland to surrounding tissues) will affect around 20,000 men per year in the US, and 4,000 men per year in the UK. Prior to the underpinning research, there was no consensus on the standard of care, with hormone therapy often being given alone. The International randomised clinical trial, led by Cardiff researchers showed that treating locally advanced disease with a combination of radiotherapy and hormone therapy halved the risks of dying of prostate cancer. Consequently, it is now a standard of care, enshrined in European and North American guidelines, that all such patients who are fit enough to receive it, should now be offered combined modality radiotherapy plus hormone therapy.

Submitting Institution

Cardiff University

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences, Oncology and Carcinogenesis, Public Health and Health Services

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