Cancers are often treated with external beam radiotherapy. Current radiotherapy treatments are performed using computed tomography (also known as CT) scans which may not always clearly identify the cancer. In some instances, magnetic resonance imaging (MRI) may be able to better identify cancers. Therefore, efforts are currently underway to use the MRI scans to improve radiotherapy treatments or eventually even use radiotherapy equipment that only uses MRI scans to guide treatments. This new technology that will only use MRI scans to guide treatments is called the Linac-MR (linear accelerator with an MRI). This new Linac-MR is a unique innovation at the Cross Cancer Institute, with theoretical advantages over other Linac-MR machines that are being tested elsewhere in the world. This feasibility study is being done as a first step in clinical development of the Linac-MR, as this new technology has to be tested to see if it is acceptable to both doctors and participants. The purpose of this Phase I/II study is (1) to verify treatment completion as intended and scheduled the oncology team, and (2) to evaluate treatment effects, including any expected or unexpected radiation side effects and cancer response to radiation. This study will allow the researchers at the Cross Cancer Institute to develop this technology further by conducting additional studies to take advantage of MRI scanning on tumor tracking during radiation treatments.

This prospective, open-label, Phase I/II, clinical trial is feasibility study to evaluate MR-guided radiotherapy with the Alberta linac-MR P3 system in adult patients with cancer that are treated with external beam radiotherapy in four graduated stages (described below), progressing from palliative participants with simple techniques to curative participants with complex techniques, with progression to each stage determined by an internal SAFE review committee. Conventional treatment margins and doses will be utilized, with the MR being utilized in place of CT based imaging. The intent is to replicate current CT based treatments on the Alberta linac-MR P3 system using MR guided imaging, planning and treatment delivery. MR imaging will be utilized for simulation, planning and image guidance. Dosimetry will be done as per standard of care. MRI contrast may be used, as applicable. Adverse events will be collected weekly during RT, and participants will complete one questionnaire at the end of their RT treatment. Follow-up will consist of adverse event assessment at 1, 6, and 12 months following completion of RT, and may be assessed annually via chart review for up to 1 year. Survival status will be assessed at 12 months following completion of RT, and then annually for up to 1 year.

In stage 1, 4 to 15 participants with incurable malignancies that require palliative radiotherapy with parallel-opposed pair beam arrangements will be enrolled. These will be patients with bone or brain metastases from their malignancies that require either a single fraction or multiple fractions of radiotherapy. The treatment will be a simple opposed pair beam arrangement to a dose of a single 8 Gy or to a dose of 20 Gy over a course of 5 fractions. Once some initial treatments are completed, and at the discretion of an internal SAFE review committee, additional treatment sites will be permitted (i.e. lung, abdomen, etc.) that are also utilizing a simple opposed pair beam arrangement with the above doses.

In stage 2, 10 to 28 participants with malignancies (curative or palliative treatments) that require multi-field arrangement for their external beam radiotherapy will be enrolled. Initially, 4 field techniques (anterior, posterior, right lateral, left lateral) will be utilized to treat central tumors using fractionation schemes that are currently considered standard of care. Patients with pelvic malignancies (i.e. prostate cancers, rectal cancers, cervical cancers, endometrial cancers) or other malignancies requiring simple four field techniques will be identified for this stage.

In stage 3, 5 to 28 participants with malignancies (curative or palliative) that require more complicated multi-field 3DCRT treatments (not requiring IMRT) to a high radiation dose for their external beam radiotherapy (i.e. lung, brain, etc.) will be enrolled. This will include the use of field-in-field techniques such as step-and-shoot techniques to allow for modulation of the radiation beam during treatment.

In stage 4, 10 to 28 participants with malignancies (curative or palliative) that require more complicated multi-field IMRT treatments for their external beam radiotherapy (i.e. prostate, head and neck, lung, brain, etc.) will be enrolled.

Inclusion Criteria:

• Adults ≥ 18 years of age
• Patients deemed fit to undergo external beam radiation therapy by their attending radiation oncologist
• Accessible for follow-up

Exclusion Criteria:

• Patients with contraindications for MRI
• Patients who are unable to lie flat and still for the duration of the expected scan acquisition and treatment
• Patients who are unable to provide informed consent
• Patients with clinically significant inferior treatment plans compared to standard CT based external beam plans. For example, plans that generate hot spots of > 110% or other unacceptable treatment plans that would not otherwise arise with standard CT based external beam plans.
• Pregnancy