Title: Management of pain and cachexia in pancreatic cancer: Systematic reviews of randomised controlled trials and network meta-analysis
Funder: Department of Health and Social Care

Abstract: Research question What is the best treatment and NHS care pathway to decrease pain and cachexia, and improve health-related quality of life, and other patient-reported outcome measures in people with pancreatic cancer? Background In the UK, 11,400 people were diagnosed and 10,000 people died with pancreatic cancer in 2018. The incidence of pancreatic cancer is increasing in the UK and if the trend continues, pancreatic cancer will become the third commonest cause of cancer death in the UK. The major symptoms related to pancreatic cancer, particularly in those with unresectable cancers are pain, cachexia, and jaundice. There is considerable uncertainty on the management of people with pancreatic cancer pain and/or cachexia and prevention of cachexia. Addressing these uncertainties are some of the top research priorities in pancreatic cancer. Objectives Primary objectives: To compare the benefits and harms of different treatments for pancreatic cancer pain through network meta-analyses (NMA) and to generate rankings of the different treatments according to their safety and efficacy. To compare the benefits and harms of different interventions in the prevention and treatment of pancreatic cancer cachexia through a systematic review (and meta-analysis when possible). Secondary objectives: Identify gaps in the existing research that cause uncertainty in decision making (based on the systematic review and/or NMA). Develop a pathway for management of pain and for prevention and treatment of cachexia (using evidence collected as part of primary objectives), through surveys, and focus group discussions. Methods We will perform a systematic literature review of important medical literature databases and trial registers. Two people will independently screen the search results, identify relevant RCTs, and extract relevant data from the studies. We will perform NMA for pancreatic cancer pain and systematic review (and meta-analysis if possible) for prevention and treatment of pancreatic cancer cachexia. We will also develop a pathway for management of pain and for prevention and treatment of cachexia using evidence collected as part of primary objectives, surveys, and through focus group discussions involving people with pancreatic cancer, their carers, and healthcare professionals. Research timetable (all timelines from start of grant) Finalise protocols and PROSPERO registration: 3 months Ethical approval: 12 months Data collection and resolving the differences: 15 months Data analysis and interpretation: 18 months Focus group meetings to develop an acceptable clinical pathway, and final report: 24 months. Anticipated impact and dissemination The evidence-based clinical care pathways for the management of pain and cachexia in people with pancreatic cancer in the NHS developed as part of this project will help streamline the care of people with pain and cachexia resulting from pancreatic cancer. It will also provide the information necessary for shared decision making in people with pain and cachexia resulting from pancreatic cancer and lead to more primary research in areas where there is an evidence gap. The team will disseminate the findings of the research through patient group websites, social media groups, conferences, publish the findings in peer-reviewed journals, and via Pancreatic Cancer UK influence on NHS decision makers.

Lay abstract: Aims of the research To find out the benefits and harms of different treatments for people with pain and cachexia (weakness and wasting of the body) due to pancreatic cancer, and develop effective routes for treatment (clinical care pathways) which are based on evidence. Background to the research In UK, 11,400 people were diagnosed and 10,000 died from pancreatic cancer in 2018. Numbers are rising and pancreatic cancer is likely to become the third commonest cause of cancer death by 2030. Approximately two-thirds of people with pancreatic cancer seek medical help for tummy or back pain. Treatments include drugs called opioid pain-killers for example morphine, non-opioid pain-killers like ibuprofen or paracetamol, and destroying the nerves behind the pancreas (nerve block). Currently it is unclear which treatments work best. More than half of people with pancreatic cancer have cachexia (weakness and wasting of the body). There is uncertainty about which treatments (if any) help in either prevention or treatment of cachexia in pancreatic cancer. Randomised controlled trials (RCTs) are clinical studies that provide the best information about the benefits and harms of treatments, when conducted well. We will assess the quality of RCTs using standard tools available for this purpose. Design and methods used We will review the different treatments for pain and cachexia due to pancreatic cancer. We will search medical literature thoroughly for RCTs on this topic ( systematic review ).We will use advanced methods that allow us to compare many different treatments at the same time ( network meta-analysis ).This research will identify treatments most likely to benefit people with pain or cachexia due to pancreatic cancer. Clinical care pathways are ways to ensure healthcare is provided to the same standards wherever a person is receiving NHS treatment. We will use surveys and focus group discussions involving patients, carers, and healthcare professionals to develop care pathways that are acceptable for patients and realistic for delivery in the NHS. Patient and public involvement Patients and carers were involved in identifying the top 10 research priorities for pancreatic cancer treatment. A carer of a person with lived-in experience of pancreatic cancer was involved in developing this grant application. They reviewed the plain English summary to ensure that it can be understood by non-experts. They will also be involved in looking at the research findings and developing the clinical care pathways. Dissemination We will publish the results in written reports in medical journals, present them at conferences, display them on patient group websites, and share them through NHS cancer networks and social media. Pancreatic Cancer UK (supporting this application) have well established links with NHS policy makers. As such, they are able to effectively promote the best treatment approaches to be adopted by the NHS.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: CANCER AND NEOPLASMS