EMERALD - Pancreas
Research type
Research Study
Full title
Evaluation of hypofractionated adaptive radiotherapy using the MR Linac in localised pancreatic cancer
IRAS ID
279946
Contact name
Somnath Mukherjee
Contact email
Sponsor organisation
University of Oxford, Research Governance, Ethics and Assurance
ISRCTN Number
ISRCTN10557832
Duration of Study in the UK
2 years, 5 months, 31 days
Research summary
Research Summary:
Localised pancreatic cancer has a poor outlook. The best radiotherapy dose for pancreatic cancer that is safe and effective is unknown. Radiotherapy aims to deliver a high dose to the cancer and avoid the surrounding normal organs as much as possible. This gives the best combination of getting the highest chance of treating the cancer with the lowest risk of toxicity.
Radiotherapy for pancreatic cancer is usually given in 25-30 daily treatments combined with chemotherapy. More recently, high-dose precision radiotherapy called stereotactic radiotherapy has been shown to be similarly effective when delivered in 1-5 treatments. However, although the tumour and surrounding organs is clearly visualised on the planning CT scan, day-to-day variation during treatment is difficult to visualise on the current CT-guided radiotherapy, which causes some inaccuracy. Furthermore, some organs in the body move all the time- as we breathe and as food moves through the intestines. These impact on the dose the cancer and normal organs gets. We are using a machine which combines Magnetic Resonance Imaging(MRI) with a radiotherapy machine(MR-linac). The MR-linac allows us to see the cancer and surrounding organs more accurately and use that information to update the radiotherapy plan one each treatment day. Also, during treatment the cancer is imaged continuously and if it moves out of the treatment field the machine switches off, and switches back on when the cancer moves back within the field.
Our initial research using planning scans shows that, higher doses could be delivered to the tumour on the MR-linac over 5, 3 and 1 treatments without over-dosing the normal organs. This research study aims to see if we can safely deliver this in actual patients. This could improve cancer control. In future, this may also allow us to explore combining radiotherapy with other treatments to improve pancreatic cancer outcome.
Summary of Results:
EMERALD Trial Lay Summary Purpose/Objective Doctors can treat localised pancreatic cancer, who cannot have an operation, with high dose radiotherapy called stereotactic radiotherapy (SABR), which is usually given after a course of chemotherapy. Treatment is usually given in 5 treatments (fractions) on daily or on alternate days over 1 to 2 weeks. This is a standard treatment option.
Giving a higher dose of radiotherapy or in fewer fractions would mean fewer visits to the hospital and may improve tumour control.
Before using these treatments researchers need to find out whether they might cause more or worse side effects. The aims of the EMERALD study were to find out whether they can: safely increase the dose of radiotherapy and give a high dose in fewer treatments.
High dose radiotherapy (SABR) in 5 treatments can sometimes cause serious damage to the bowel in 1 in 10 people. This is because the pancreas is very close to the stomach and intestines. If SABR treatment can be given with MRI guidance (Stereotactic MRI-guided Adaptive RadioTherapy, SMART), the treatment can be given even more precisely, because the tumour and other organs can be seen more clearly, each treatment can be planned individually, and the tumour can be monitored live during treatment, so that the treatment is directed only at the tumour. This means a bigger dose can be given with less risk of damage to the bowel. This treatment can be given on a MR Linac radiotherapy machine.
However, SMART treatment requires a lot of specialist staffing; it requires oncologists and physicists to be present at daily treatment, the treatment itself takes about 1 hour each day (compared to standard CT guided SABR which takes 10-15 mins) and availability of MR Linacs are limited, with currently 3 MR Linacs available for NHS patients in the UK. The EMERALD trial was designed to find out whether it is possible and safe to treat pancreatic cancer with high dose radiotherapy or in fewer number of treatments via SMART (1 or 3 instead of 5 treatments).Material/Methods
The research took part at the Churchill hospital, and Genesis Care in Oxford. There are 3 groups in this study and no placebo. These were:
- Level 1: High dose (50Gy) given in 5 treatments on daily or alternate days. Five treatments are standard. This level was there to act as ‘control’ to compare side effects with 5 treatments compared to 3 and 1 treatments.
- Level 2: High dose radiotherapy (39Gy) dose given in 3 treatments on alternate days and
- Level 3: High dose (25Gy) radiotherapy dose given in 1 treatment.
The main aim of the study was to see if the treatment could be given without severe side effects that would limit how much treatment can be given safely. Patients were followed up for a minimum of 3 months to look out for these severe side effects. If patients were to develop upper gastro-intestinal bleeding, development of gastro-intestinal fistula (perforation of bowel, connecting to other organs), severe nausea/vomiting, inflammation of the pancreas (pancreatitis) and non-tumour-related blood vessel damage (dose limiting toxicity/DLT) at any dose level, the investigators would declare that regimen as unsafe and not suitable for further testing.
The trial also looked at any other early (within 3 months) or late (after 3 months) side-effects to the treatment, as well as how well the cancer was controlled and the survival of the patient.
Trial registration number: ISRCTN10557832.Results
25 patients took part between 25 August 2022 and 04 October 2023. 20 patients received the treatment (SMART).
Of these 20 patients, the average age was 71 years (range 58-85 years), and all patients were either fully active or well enough to do light housework. 12 patients had a tumour at the top of their pancreas, this was the most common location of pancreatic tumours. All but 1 patient had received chemotherapy, before taking part. Four patients were treated at level 1, and 8 patients each at level 2 and level 3. There were no side effects that limited the treatment (DLTs). Severe side effects (grade 3 and above) were fatigue for 3 patients, obstruction to the bile duct for 2 patients and duodenal obstruction for 1 patient. One patient died from a gastrointestinal bleed, more than 3 months after SMART was given. The relationship to treatment (SMART) could not be ruled out. Patients were followed up for between 3.5 to 20.3 months from the first treatment with SMART.
The average follow up period for all patients was 9.8 months. In Level 2, 18-month overall survival (OS) of patients was 85.7% and Local progression free survival (LPFS) of patients was 72.9%. In Level 3, the 18-month OS was 26.3% and LPFS was 28.1%Conclusion
EMERALD demonstrates that SMART for localised pancreatic cancer can be given in single and three fraction (treatments) with acceptable side effects and health results. This shows further investigation in bigger (phase II/III) trials to test health benefit and cost effectiveness is needed.REC name
West Midlands - Black Country Research Ethics Committee
REC reference
22/WM/0122
Date of REC Opinion
7 Jul 2022
REC opinion
Further Information Favourable Opinion