Written by an international collaboration of clinicians and physicists, the review explores the opportunities, benefits and challenges of MRI-guided adaptive radiotherapy of the prostate and describes the current state-of-the-art (Int. J. Radiat. Oncol. Biol. Phys. doi: 10.1016/j.ijrobp.2017.10.020). The authors include researchers from sites involved in research using the Unity MR-linac and MRIdian treatment systems from Elekta and ViewRay, respectively, the two companies with MRI-guided radiotherapy technology in clinical use (see: First patient treated on the Unity MR-linac; Henry Ford treats first patient with MRIdian linac).

For some time, MRI has been regarded by many in the radiation oncology community as the future of image guidance. The high soft-tissue contrast images that it provides of the patient on the treatment couch is a key advantage over conventional X-ray guided linacs. Exploiting such information to adapt plans over the course of treatment is a critical step forward, according to first author Angela Pathmanathan, a clinical fellow at the Institute of Cancer Research and the Royal Marsden Hospital in London.

"By acquiring MR images prior to each fraction, we can produce a new radiotherapy plan for that day, adjusted for any changes in anatomy," explained Pathmanathan. "With MR-guidance, this can be further adjusted whilst the patient is having the radiotherapy delivered, to take into account intrafractional movement of the prostate and the 'bystander' organs-at-risk."

The next step

Online plan adaptation immediately prior to irradiation has already been demonstrated using both the ViewRay MRIdian cobalt-60 system and the Unity MR-linac. Real-time adaptive radiotherapy, while the treatment beam is on, remains a significantly greater challenge. Pathmanathan sees timing as the greatest hurdle in implementing both adaptive approaches.

"Online and real-time replanning … must be rapid enough to still reflect the anatomy," said Pathmanathan. "The overall time for the patient on the bed needs to be minimized to reduce patient movement and improve comfort." Doing so requires optimization of each step in the treatment workflow, from imaging and contouring to plan optimization, the update of beam parameters and quality assurance.

Using adaptive MRI-guided treatments, prostate patients could benefit from more extreme hypofractionation than is currently achievable with external beams, including, potentially, single fraction treatments. Reduced fractions cut the numbers of clinic visits for patients, increase patient throughput and could improve clinical outcomes.

Adaptive MRI-guided radiotherapy could also improve treatments by targeting tumour sub-volumes that respond poorly to treatment and carry a greater risk of recurrence. Though significant research is still needed, diffusion weighted imaging (DWI) has been flagged by researchers as a promising approach for monitoring tumour response.

A further dramatic shift in approach is the potential elimination of CT scans from clinical workflow. Doing so eliminates geometric uncertainties resulting from the co-registration of MR and CT images and one less scan is required. However, an alternative strategy is needed to map electron density in the patient in order to calculate treatment plans.

Currently, MRCAT from Philips is the only commercial product available, with a reported dosimetric accuracy of 0.5% compared with CT calculated dose distributions. It generates pseudo CT scans from an mDIXON echo sequence, automatically segmenting five types of tissue using a classification algorithm and pelvic bone atlas. Voxels are assigned bulk Hounsfield units according to their classification.

Moving forward, the consortium partners are currently working on pre-clinical prostate studies. The first patients will be treated at consortium sites in early 2018 following a jointly-written protocol, enabling data to be pooled for analysis. As a starting point, patients will receive a conventional fractionation of 60 Gy in 20 fractions to assess feasibility and adverse effects.

"Initial treatment will be with a mixed CT and MR workflow with online replanning prior to each treatment and the use of prostate motion monitoring within each fraction," Pathmanathan told medicalphysicsweb.