Title: Mri-only treAtmeNT planning for Anal and Rectal cAncer radiotherapY (MANTA-RAY)
Funder: Health Education England

Abstract: It is widely recognised that the greatest challenge in providing precision radiotherapy is the accurate definition of cancerous tissues, with the uncertainty in target volume definition often leading to the unnecessary treatment of healthy tissues. Anorectal cancers are particularly prone to this, due to the similarity in density of healthy tissues near to the cancer. As a consequence, radiotherapy treatments of these cancers often result in significant healthy organ toxicities. Attempts to improve target definition in the radiotherapy planning process have been hindered by the poor soft-tissue contrast of CT scans. This is because of the necessity to use CT scans for radiotherapy treatment planning because they provide the patient density information required to calculate radiation dose in tissue, without which no treatment can be planned.This study aims to develop and validate a new method of radiotherapy treatment planning using only an MRI scan (MRI-only planning) rather than a CT scan for anorectal cancer patients. The potential benefit to patients, in terms of a reduction in dose to the healthy tissues and organs for anorectal radiotherapy treatments, will then be measured. If this study quantifies a clinically significant benefit to patients through the reduction in radiation dose to healthy organs, this technique could be translated into the standard protocol for anorectal cancers.This project will recruit a minimum of 60 anorectal cancer patients. Inclusion criteria require each participant to already be consented to receive radiotherapy as part of their standard treatment, which will not be impacted by this study. These patients will undergo an MRI scan in addition to their radiotherapy CT treatment planning scan. An MRI-only radiotherapy solution will be produced which involves the generation of pseudo-CT datasets from the patient MRI scans. This will allow radiation dose calculations to be performed without the need for a radiotherapy planning CT scan to be acquired. The MRI-only planning solution will be analysed to determine its clinical validity in terms of electron density and dosimetric calculation accuracy. The benefit to patients in terms of the reduction in radiation dose to healthy tissues, which in the literature has been shown to correlate with reduced toxicity, will be determined through a comparison study between CT and MRI planned treatments. The differences in the radiation doses to healthy tissues and organs will be quantified, including a statistical analysis. The MRI workflow will be validated for use as the on-set patient positioning system. The patient position accuracy will be compared in 3-dimensions when using CT and MRI data for positioning.

Lay abstract: Radiotherapy is used in the treatment of the cancers that are found at the lower end of the bowel, known as rectal and anal cancers. For rectal cancer, radiotherapy is used before surgery to make the cancer smaller and easier to remove. For anal cancer, radiotherapy is used in combination with drugs (chemotherapy) to treat and cure the cancer without needing surgery. However, the radiation that treats the cancer can also damage the healthy organs in the body, which can lead to side effects such as diarrhoea and incontinence. These side effects can be permanent and can have a big impact on day-to-day life. Currently when patients are going to undergo radiotherapy treatment they have a CT (Computed Tomography) scan. The CT scan is used to plan how to deliver the radiation so that it successfully treats the cancer but delivers the smallest amount of radiation to the healthy organs close to the cancer. This is to reduce the risk of side effects as much as possible. CT scans are used because they provide information about the density of the muscles, bones and organs in the body. This density information is needed to calculate the amount of radiation dose that will be delivered to patients during radiotherapy. However many cancers are difficult to see on a CT scan. This means that a bigger area is usually treated (including parts of the body that do not have cancer in them) to make sure all the cancer is treated.It is much easier to see cancer on a Magnetic Resonance Imaging (MRI) scan. If we could plan radiotherapy treatments on an MRI scan, it would allow the cancer to be seen, and therefore treated, more accurately. This would also mean that the amount of healthy tissue, including organs and muscle, treated with radiation could be reduced as we would know exactly where the cancer was. MRI scans do not measure the density information that is needed for calculating radiation dose. This means MRI scans cannot be used to plan radiotherapy treatments. However new technology allows pseudo-CT scans (computer generated CT scans), which do provide the needed density information, to be generated from MRI scans. This new technology could allow MRI scans to be used for radiotherapy treatment planning, improving our ability to see the cancer and therefore improving these treatments.This project aims to test this new method of using MRI and pseudo-CT scans, instead of CT scans, for radiotherapy treatment planning to see if a) it can calculate the radiation dose as accurately as a CT scan does, b) it could reduce the radiation dose to the healthy organs surrounding the cancer and c) it can be used in a clinical radiotherapy department to plan patient cancer treatments.Thirty rectal cancer and thirty anal cancer patients who are already receiving radiotherapy as part of their treatment will be recruited for this study. These participants will receive an MRI scan in addition to their normal treatment. This study will have no impact on the participant's treatment. The MRI scan will be used to compare the new method of treatment planning with the current method used routinely in patient care.This study will be divided into three parts. In part one, each MRI scan will be used to create a pseudo-CT scan. Each pseudo-CT scan will then be compared to its corresponding CT scan to assess whether it is accurate enough for planning radiotherapy treatments. In part two, radiotherapy treatments will be planned on the MRI and pseudo-CT scans and the MRI-based and CT-based treatment plans will be compared. This will determine whether the dose to healthy organs would be reduced by planning the treatment using an MRI scan. In part, three pseudo-CT data will be tested to see if it can be used to check that patients are in the correct position before their treatment is delivered.This research will be undertaken with support from a group of five members of the public. This group will meet with me every six months and at other key stages of the study to discuss the development of the study, for example the development of the MRI scan pathway for participants. Two members of the group will also join the study steering group to make sure that the patient perspective is listened to throughout the study.The findings of this study will be publicised in research journals, at workshops and conferences and in direct presentations to relevant staff and public groups.

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