To date, two MR-Linac devices are commercially available, Unity Elekta (Elekta, Stockholm, Sweden) and MRIdian Viewray (Viewray Inc., Cleveland, OH, USA) [30,31].

Unity Elekta conjugates a 1.5 T magnetic resonance system with a 7 MV linear accelerator and it allows daily-adapted radiotherapy by means of two different workflows: the adapt-to-position (ATP) procedure is based on a daily update of the iso-center position, with no need for re-contouring, while in the adapt-to-shape (ATS) workflow, the daily treatment plan is re-calculated on the re-contoured volumes of the real-time anatomy of the patient (Figure 1).

The MRIdian Viewray combines a 0.35 T split magnetic resonance scanner with a circular ring-gantry in which all 6 MV Linac components are shielded to avoid magnetic field interferences. This hybrid machine enables also different types of plan adaptation ranging from simple re-optimization to a full online-adaptive workflow with re-contouring and dose re-optimization. Moreover, it allows real-time soft tissue tracking and gating.

For both devices, given the relatively longer treatment time per session, the simulation process is a crucial factor in order to perform an accurate and refined treatment delivery. Based on available literature, most experiences reported a similar protocol in terms of bladder filling and rectal emptying ([32,33,34,35,36,37,38]—see Table 1). For both the CT scan (performed for dose calculation purposes) and the MRI scan, patients were educated to have a half-full bladder in order to take into account residual volume changes during the plan adaptation phase (Figure 2).

A T2-weighted gradient-echo sequence is acquired for a better visualization of the prostate gland. After the re-optimization of the plan, a further cine MR, usually acquired on sagittal and coronal planes, is performed to check organ motion during the beam-on time (Figure 3).

The Viewray system, in addition to T2-weighted imaging, currently has a True Fast Imaging with steady-state-free precession (TRUFI) sequence. The system enables simple couch shifts, as well as more elaborated online plan adaptation strategies [40].

Currently available evidence reports MR-guided SBRT as a safe and feasible treatment option. Alongi et al. [36] reported excellent preliminary results in terms of PROMs in a cohort of 25 patients who received 35 Gy in 5 fractions, with no evidence of acute G ≥ 3 adverse events. Interestingly, the favorable results in terms of quality of life (QoL) outcomes after a median treatment time of 56 min (range, 34–86) per fraction, indicate the tolerability of MR-guided SBRT for prostate cancer and show that the longer treatment time per session has only a minimal impact on QoL. In agreement with these findings, also the study by Bruynzeel et al. [32], performed using a 0.35 T MR-Linac, reported early promising results in a phase II study enrolling 104 patients, with only 5.9% of grade 3 genitourinary toxicity according to RTOG criteria. Similarly, on QoL evaluation, no relevant differences were detected at any time point of the study, with the exception of role functioning. These data were recently updated with a final PROMs analysis after one year of follow-up, which confirmed the absence of G ≥ 3 adverse events. Furthermore, at 12 months after the end of treatment, QoL returned to baseline conditions, with only 2% of patients reporting persistent bowel symptoms [33].

A further recent paper has been published by Uguerler et al. [38] reporting in a series of 50 patients with a median follow-up of 10 months with no evidence of G3 acute or late toxicity. Although observing a 36% rate of G2 GU adverse events, when available, late GI and GU toxicity rates were respectively 2% and 6%.

In this scenario, the use of rectal spacers for mitigating prostate motion represents a helpful tool to maximize the safety and accuracy of extremely hypofractionated treatments for prostate cancer [41,42]. To date, the use of this device has been safely reported by Alongi et al. in a series of 20 patients who received MR-guided prostate SBRT using rectal hydrogel spacer. Interestingly, the authors recorded a significant advantage in terms of rectal sparing and target coverage, in comparison with a cohort of patients who did not receive the administration of the rectal spacer. In addition, despite the invasive procedure, no adverse impact on QoL was observed using PROMs assessment [43].

The same sample of patients was also analyzed in a subsequent study with the aim of evaluating a potential positive effect in terms of intra-fraction motion mitigation. The authors recorded a statistically significant effect of the rectal hydrogel spacer on rotational antero-posterior displacements compared to patients without spacers. Although these data are preliminary, they suggest a potential effect of prostate fixation due to the squeezing effect towards the pubic bone, but mature evidences is still needed to support a potential clinical impact of these dosimetric advantages [44,45,46].

Consistent with this, the study by Nicosia et al. [39] also highlights the beneficial impact of a superior anatomy visualization provided by MR-guided radiotherapy. In a dosimetric comparison between 40 patients receiving prostate SBRT using MR-Linac or a Volumetric Modulated Arc Therapy (VMAT) technique with or without fiducials, the authors recorded a significantly lower rate of constraints violation in the MR-Linac cohort compared to Volumetric Modulated Arc Therapy - Image Guided Radiation Therapy (VMAT-IGRT) patients treated without fiducials. Thus, the authors suggest that in VMAT-IGRT, only the implementation of fiducials can lead to a comparable quality in terms of real dose-distribution, which consequently highlights the advantages of MR-Linacs as a fiducial-free technique for extreme prostate hypofractionation.