Title: MRI scans with respiratory Immobilisation to Contour Radiotherapy Organs at risk using oral Contrast of Hypo or hyper intense fluids Including the Patient perSpective: The MICROCHIPS study.
Funder: Health Education England

Abstract: Background Incidence rates of primary liver cancer in the UK are projected to rise by 38% by 2035 because of increasing prevalence of chronic liver disease due to viral infection, obesity, diabetes and/or alcoholic liver disease. Radiotherapy (high-dose radiation) is used to treat cancer. Imaging advances have enabled a new radiotherapy technique, using higher and more targeted radiation doses: Stereotactic Ablative Body Radiotherapy (SABR). SABR is increasingly used as a treatment option for liver cancers, but its use is challenging because: Respiratory/organ motion Poor visualisation of the tumour and surrounding healthy tissue.These increase the risk of damaging healthy tissue, limiting the radiation dose that can be safely delivered, compromising cure. If we can reduce these problems, we can increase the accuracy of SABR and the chances of cure. Research question Is it possible to increase the accuracy of liver SABR by improving the visualisation of normal and abnormal tissues in the upper-abdomen using imaging and motion management techniques in a way that is clinically acceptable and practicable for liver cancer patients? Aim and objectives The aim is to improve liver SABR accuracy by reducing organ motion and improving the visualisation of healthy and unhealthy tissues using practices adopted from diagnostic radiology, in an acceptable way to patients.The following objectives will achieve this: Compare interventions to reduce motion and improve tissue visualisation in healthy volunteers Ask patients and staff to select combined interventions to test Conduct a proof of concept effectiveness study in liver cancer patients to: Compare the intervention's impact on liver SABR accuracy against the existing standard of care (SOC) Determine patient acceptability of the interventions. Methods A two-stage study following the R-IDEAL framework (Radiotherapy - Idea, Development, Exploration, Assessment and Long-term evaluation) using a quantitatively driven concurrent design, will evaluate methods to improve the accuracy of liver SABR. Stage 1: Efficacy study in 12 healthy volunteers to evaluate tissue conspicuity using oral contrasts and breath-hold immobilisation interventions. Interventions will be compared using a primary outcome measure of the Dice coefficient, an established volume analysis comparison metric. Secondary outcome measures include: motion analysis, contouring time, visual grading analyses and healthy volunteer questionnaires. An adaptation of the Nominal Group Technique will be used with a group of patients and staff, to select the most appropriate interventions to be tested in Stage 2. Stage 2: Proof of concept effectiveness study comparing interventions against SOC in 12 liver cancer patients, each receiving SOC and the interventions. Quantitative outcome measures performed in Stage 1 are repeated in Stage 2 with an evaluation of potential changes in radiation dose to normal tissues and semi-structured patient interviews. Anticipated impact and dissemination By optimising immobilisation and normal tissue visualisation we can avoid more healthy tissue while treating patients with liver cancer, increasing chances of cure while maintaining quality of life. The interventions could also be used in oesophageal and pancreatic cancers. Outcomes will be disseminated through journals, conference presentations, social media, public events and communications with charities.

Lay abstract: Background Liver cancer is a disease where cells that are not normal, grow and spread very fast in the liver. Deaths from liver cancer in the UK have increased by almost 80% over the last ten years and are still rising. Surgery or a liver transplant can be used to cure people with liver cancer. Sadly, surgery and liver transplants cannot be used on all patients because of other health problems meaning that an operation would be too risky. Radiotherapy is another treatment option which uses high-energy x-rays to kill cancer cells, but it can hurt normal cells near the cancer too. If we can be very precise at targeting the cancer cells we can use a new type of radiotherapy, called stereotactic ablative body radiotherapy (SABR), which uses much bigger doses of radiation to a small target to give a better chance of cure. Magnetic resonance imaging (MRI) scans help us plan liver SABR treatments, but it can be hard to see the differences between the liver and bowel or the liver and the cancer. To make sure we can treat the cancer we often have to treat more normal cells than we would like because we can't see where the cancer is precisely. Two main reasons for this are: Even when you lie still, the liver moves around when you breathe and digest food It can be hard for doctors to see the difference between cancer and normal cells and be sure which parts of the body we need the SABR to hit or miss.Fixing these problems can improve the accuracy of SABR and may allow higher doses to improve the chance of cure. Aim To make liver SABR more precise by limiting the amount the cancer can move and helping doctors see the difference between cancer and normal cells better, using methods taken from diagnostic radiology. Design and Method A mixed-methods study containing two stages is planned: Stage 1: Twelve healthy volunteers will have four separate MRI scans to compare three different ways of holding your breath combined with drinking water, milk, or juices to help doctors see the difference between the liver and bowel (known as regions of interest (ROI). For each MRI scan, doctors will draw around the ROI and I will compare them against the usual method, which is an MRI taken without drinks using a plate put on the patient's tummy and tightened with a screw to limit how much the patient can breathe (see Figure 1). A group of patients and staff will review the results from Stage 1 and agree the best method to take forward to Stage 2. Stage 2: The method chosen by the group will be tried and compared to the usual treatment method in 12 liver SABR patients to find out if doctors can see and plan more precise treatments with higher SABR doses to liver cancers. Interviews will be done to explore patients' views of treatment. Patient and Public Involvement (PPI) PPI is important because there is no detailed research of patient views on liver SABR. To help define my research question, I talked with patients who had liver SABR, who told me about their experiences and difficulties while having treatment. PPI will help select the method for Stage 2, design the interviews and help share the results. Dissemination The results will be shared by research papers in journals and at national and international conferences. I will inform the wider public of results via the British Liver Trust, twitter, the University website and public events like Pint of Science and Be Curious (University of Leeds).

Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS