Chemo-radiotherapy as Main Treatment Strategy for Rectal Cancer. Can we Provide a More Precise and Effective Treatment

Chemo-radiotherapy as Main Treatment Strategy for Rectal Cancer. Can we Provide a More Precise and Effective Treatment

The purpose of this project is to obtain important information about the tumour and surrounding organs during preoperative chemo-radiotherapy for patients with adenocarcinoma of the rectum. The knowledge generated in this project has the potential to make future radiotherapy treatments (RT) of rectal cancer patients more precise, with less side effects. This could lead the way to make chemo-radiotherapy the main treatment modality and spare a large group of patients from the risk of severe complications after surgery. Specifically, we aim to obtain:

• A characterization of systematic and random changes in position and shape of tumours and surrounding organs during RT.
• A patient-specific pre-treatment characterization of random uncertainties in position and shape of the tumour during radiotherapy. This will be used to create and assess an individual, patient-specific treatment strategy, with the possibility to implement an adaptive RT strategy using the information obtained from the MRI-scans during treatment.
• Information about treatment response and local toxicity from morphological and functional data before, during and after CRT.

Patients diagnosed with locally advanced adenocarcinoma of the rectum are treated with concomitant chemo-radiotherapy (CRT), with the aim of reducing local recurrences. Depending on tumor location, this is a pre-operative procedure prior to total mesorectal excision or partial mesorectal excision. The surgery is associated with a high risk of postoperative morbidity, however, especially when combined with CRT. Consequently, recent years have seen an increasing focus on other therapeutic approaches, such as "watch and wait", where the aim is to treat some patients with definitive CRT alone. The success of these new approaches directly relies on the effectiveness of the radiotherapy (RT) treatment and thereby on the level as well as the accuracy of the delivered dose to the tumor.

Standard treatment today is based on a single set of CT- and MRI-scans, which are insufficient to estimate the organ motion during RT. Precise knowledge about the variation in position and shape of the tumor using multiple MRI scans before and during RT will have the potential to make future radiotherapy treatments more precise with less side effects.

The investigators will conduct a prospective study of sequential MRI scans before and during CRT. Patients will be MRI scanned six times in addition to the standard MRI-scan appointments and follow-up. This will provide a total of 9 MRI-scans of each patient; 3 before RT, 3 during RT and 3 during follow up. The information gained from these additional scans will provide a much better understanding of the tumor and organs during RT.

This project's overall focus is to make future RT treatments of rectal cancer patients as precise and efficient as possible. This could contribute to and aid the paradigm shift of making chemo-radiotherapy the main treatment strategy for some rectal cancer patients. This has the potential to spare patients of the severe morbidities associated with surgery, as well as the need for stomas.

Inclusion Criteria:

All patients referred to standard chemoradiotherapy for locally advanced rectal cancer.

Exclusion Criteria:

• Prior surgery in pelvic minor region
• Pacemaker
• Neurostimulator
• Other non MR-compatible implants
• Pregnancy
• Incapable of undergoing MRI
• Incapable of understanding the patient information
• Allergic to contrast agent
• Contraindication for Buscopan
• Reduced renal function (GFR < 50 ml/min) Patients who cannot tolerate the contrast used for DCE-MRI (due to allergies, contraindications for Buscopan or reduced renal function (GFR < 50 ml/min)) will still be offered inclusion in the study, but without the contrast-based MRI scans.