The Microbrect-FFC Study

Sixty patients with locally advanced rectal cancer who require neoadjuvant chemoradiotherapy will be included. Patients will be identified at the Colorectal Cancer (CRC) Multidisciplinary Team (MDT) meeting when a diagnosis of rectal cancer is made. Patients will then meet the consultant to confirm the standard plan for treatment. An out-patient appointment will be arranged for the patient to see a clinical oncologist. At this appointment the rationale, practical aspects and potential side effects of pre-operative therapy will be discussed. At this point the consultant will make the patient aware of the study. A written patient information sheet will be given to the patient to consider at home. Patients will be asked to contact a member of the team if they wish to take part. If the participant agrees to take part written informed consent will obtained at their next hospital visit. Emphasis will be made to the patient that this study will not change the clinical management of their cancer. Pelvic radiotherapy is given as an out-patient. The first step is contouring the relevant anatomy, including tumour and associated lymph nodes, as well as normal organs that we want to limit the dose of radiation received. This contouring and preparation of a radiotherapy plan (for VMAT) can take up to two weeks so there is plenty of time for the first FFC scan and sampling to be done before treatment commences. For patients who decide to enter the study, their first FFC imaging scan will be performed before starting the pelvic radiotherapy as an out-patient. The FFC imaging scans will take place in the PEDRI unit of the Biomedical Physics Building, Foresterhill, Aberdeen. All participants will complete an MRI safety screening form before having the scan. As for conventional clinical MRI scans, time and privacy will be given for the participants to change clothes and a safe will be provided to store their valuables during the scan. The scanning procedure will be explained to them before the scan, and they will be in audio contact with the scan controller for the duration of the scan. An alarm bell will be provided for them to signal any problems. The scan will be interrupted any time that a participant asks, and they will be able to stop the procedure and leave whenever they want to, without being asked for a reason. The FFC imaging procedure will take up to 60 minutes and will include calibrations, navigator images and a T1 dispersion sequence, which will measure the T1 maps between 200 millitesla and 20 microtesla. After the scan, the participants will be given privacy to get dressed and will have access to the safe to collect their belongings. This scan will not delay the start of their clinical therapy and will occur in the two-week gap of radiotherapy planning required by the oncology team. The oral sample will be collected in the radiotherapy department prior to the first NaT treatment, and the patient can choose to collect the faecal sample either at home or in the clinic, both on the day they are due to start the chemoradiotherapy. Sample kits will be provided to those who wish to collect their sample at home. On the next visit, the patient will receive treatment as normal. On completion there will be a 7 to 8 week wait to allow the treatment to have an effect on the tumour, as well as allowing for any side effects to settle. After this gap, the patient will have their second FFC scan and will be asked to provide their second faecal and saliva sample. They will also have a pelvic MRI scan which will be reviewed at the Multi-Disciplinary Team, to assess if operation planes are now clear, allowing the patient to proceed to potentially curative surgery. Patients with a clear CRM will be asked to undertake their last FFC scan prior to surgery. During surgery a specimen will be collected from theatre and brought directly to the pathology department as per standard practice. The tumour itself will be assessed using a standardised approach, and any response graded using a validated and published system 6, 13. Patients who do not undergo surgery will be assumed to have a complete response and placed in this group for analysis