A new frontier of image guidance: Organs at risk avoidance with MRI‐guided respiratory‐gated intensity modulated radiotherapy: Technical note and report of a case

Abstract The case of a 50‐year‐old man affected by a rhabdomiosarcoma metastatic lesion in the left flank Is reported. The patient was addressed to 50.4 Gy radiotherapy with concomitant chemotherapy in order to locally control the lesion. A Tri‐60‐Co magnetic resonance hybrid radiotherapy unit was used for treatment delivery and a respiratory gating protocol was applied for the different breathing phases (Free Breathing, Deep Inspiration Breath Hold and Final Expiration Breath Hold). Three intensity modulated radiation therapy (IMRT) plans were calculated and Final Expiration Breath Hold plan was finally selected due to the absence of PTV coverage differences and better organs at risk sparing (i.e. kidneys). This case report suggests that organs at risk avoidance with MRI‐guided respiratory‐gated Radiotherapy is feasible and particularly advantageous whenever sparing the organs at risk is of utmost dosimetric or clinical importance.


| INTRODUCTION
Several sources of geometric uncertainties exist in the radiotherapy process. Tumor motion represents a major source of uncertainty.
Particularly, breathing-induced tumor motion up to 2 cm is common in lung and upper abdomen and even larger excursions can occur. [1][2][3] To ensure an adequate coverage of the tumor with the intended dose, a margin for intra/inter-fraction patient changes (internal margin) and for setup uncertainties (setup margin) is added around the clinical target volume to obtain the planning target volume (PTV).
Strategies to account for this motion while minimizing PTV include breath hold or free-breathing (FB) respiratory tracking and gating techniques. In particular, breath hold technique can be guided by supporting the patient with dedicated systems, such as the active breathing co-ordinator system (Elekta, Stockholm, Sweden). All these methods require a technological link between the detection of tumor position during the breathing cycle and treatment delivery. For this purpose, invasively implanted fiducial markers are available but they are associated with additional risks, costs, and require specific expertise. Fiducial-less solutions based on surrogates of tumor motion, such as the body surface or the diaphragm, have been proposed; variations in the correlation between tumor movements and surrogate signals can lead, however, to uncertainties resulting in a poor treatment outcome. Real-time cine planar magnetic resonance imaging (MRI) offers the unique possibility to directly detect and gate the treatment to a particular condition of the respiratory cycle eliminating the need for surrogate-based systems and imaging dose to either breath hold or FB, depending on patient compliance and organs at risk (OARs) irradiation which may vary during the different conditions of the breathing cycle. 4 Even though a particular tumor may not show significant respiratory induced motion, remarkable changes may occur in the position of the surrounding OARs during the breathing cycle: this particular situation generally occurs when the target lesions are fixed (i.e., infiltrating tumors such as sarcomas) or when spinal or bone metastases (more specifically of the axial skeleton) are treated. In such cases, gating the radiation treatment to the position of an OAR might offer a possibility for a further personalization of the treatment delivery. The MRIdian ® system (ViewRay Inc., Cleveland, OHo, USA) is a hybrid machine that consists of two main components: a 0.35 Tesla MRI scanner and a radiation delivery system, composed either by a set of three Cobalt-60 (tri-Co-60) sources or a 6 MV linear accelerator, in its recently released MRI-Linac version. 5 The MRIdian ® system offers an integrated solution for online adaptive radiotherapy, allowing to modify the dose distribution taking into account the morphological changes occurring among different therapy days. 6,7 In the next future, the online replanning could also be carried out on the basis possibly biological variations highlighted through advanced imaging analysis and diffusion weighted MRI sequences. 8,9 A case where MRI-guidance has been successfully used to reduce normal tissue irradiation by performing the gating on an OAR is described in this report. To the best of our knowledge, this is the first study demonstrating the technical feasibility of this approach.  The average intensity projection has been used for FB planning, while the aforementioned DIBH and FEBH CT scans for the respective respiratory condition. The GTV was expanded by 5 mm in all directions to create a PTV to account for delineation error, internal motion, and setup error.

| CASE DESCRIPTION
Considering the negligible movement observed for the primary lesion during the simulation condition and taking into account the foreseen maintenance chemotherapy that the patient would undergo after the radiochemotherapy treatment, we decided to preserve as much as possible the surrounding organs at risk and in particular the omolateral kidney, in order to reduce the risk of potential renal complications related to the expected further treatments.
Volumetric values for left kidney, GTV, and PTV for FB, DIBH, and FEBH plans are reported in Table 1.
Three intensity modulated radiation therapy (IMRT) plans were calculated (FB, DIBH, and FEBH) and compared one to each other.     The tumor size remained stable for 6 months, after that the mass started to re-growth. No radiation-induced toxicities were observed during-treatment and during the follow-up period.

3.B | Treatment delivery
The sagittal plane chosen for cine-MRI acquisition was manually defined, selecting the slice in which the distance between the two centers of mass (COM) of the PTV and the left kidney was minimal. The adequate target coverage for the single fractions was assured using the dose prediction tool of the MRIdian treatment planning system.

| CONCLUSION
Organs at risk avoidance with MRI-guided respiratory-gated tri-60-Cobalt Intensity Modulated Radiotherapy is feasible and relatively easy to implement. The described procedure appeared to successfully deal with organ motion, as the MRI has the advantage of displaying soft tissues with better contrast and higher anatomical detail as compared to the usual on-board kV or cone beam CT (CBCT) imaging systems that provide only rough visualization of the therapy volumes or their surrogates (such as the diaphragm for respiratory movements).
Besides these technical advantages, the principal rationale of using this approach was the observation of a sound overall dosimetric benefit using a specific breathing condition for planning purposes.
F I G . 3. Two-dimensional magnetic resonance treatment cine views: the kidney (red) and the boundary area (green) are contoured and shown in beam on (left) and beam off (right) conditions.
The use of a gating approach on a movable OAR allowed indeed to maximize organ sparing, ensuring a clinical advantage that appeared not to be reachable in the other considered breathing conditions (FB and DIBH), while maintaining in the same time an optimal target coverage. Further advantages of this technique are represented by the high time resolution (unlike the 4D CBCT, which typically requires at least a single 1 min gantry rotation to acquire) and the possibility to not expose patients to unnecessary radiation.
The approach we used also improved the treatment's dosimetric outcome as we demonstrated that directly tracking the target volume is not always the most suitable planning solution and that the described irradiation technique could therefore be particularly advantageous whenever sparing the organs at risk is of utmost importance, such as in stereotactic treatments and re-irradiation, however, in case of retreatment the calculation of dose accumulation may be hampered by the difference of breathing conditions.