Retrospective study comparing MR-guided radiation therapy (MRgRT) setup strategies for prostate treatment: repositioning vs. replanning

The goal of radiation therapy is to deliver an accurate prescription dose to the target while minimizing the dose to normal tissue. External beam radiotherapy (EBRT) is a common definitive treatment option for localized prostate cancer [1‐7]. In the last decade, significant technological advances in EBRT have been achieved. Intensity-modulated radiation therapy (IMRT) is a type of conformal radiation therapy and is widely used to treat prostate cancer [1, 7, 8]. However, the complexity of the treatment delivery and inter- and intra-fraction variations are a concern when using IMRT for prostate cancer [9, 10]. Adding margins around the clinical target volume (CTV) can account for these variations to ensure target coverage. Gill et al. reported that when daily cone beam computed tomography (CBCT) was used for soft-tissue alignment of the prostate, a PTV margin of 3 mm allowed sufficient coverage for CTV [11]. On the other hand, in Engels’s study, margins of 6 mm LR and 10 mm AP and CC were used in patients who did not hve markers implanted in them. Margins of 3 mm LR and 5 mm AP and CC were used for patients with implanted markers [12]. However, expanding the irradiated volume consequently increases normal organ toxicity, which is limited by the tolerances of the bladder and rectum [8, 13]. In recent years, advances in image guidance have allowed for better localization of the prostate [14‐20]. Using image guidance together with IMRT delivers the dose to the prostate more precisely with smaller margins to decrease the doses to the rectum and bladder. Image-guided radiation therapy (IGRT) technology has been widely adopted to provide anatomic information with the patient in the treatment position. With image guidance (typically X-ray imaging such as kilovolt (kV), megavolt (MV), and CBCT), the patient positions in the daily images are registered to the planning images based on either bony landmarks or soft tissues [16‐18, 21, 22]. Furthermore, fiducial markers for prostate IGRT have been in use since the 1990s and O’Neill et al. reviewed the evidence for the use of fiducial markers in clinical practice [23]. Image guidance corrects not only for patient position variations but also for changes in the target volume and shapes. Adaptive radiation therapy (ART) has been introduced to compensate for variations in patient treatment during a radiotherapy course [24‐26]. ART techniques can be categorized as offline or online adaptive planning [27]. Offline adaptive planning uses a feedback strategy for current treatment by incorporating the obtained daily treatment images. This adaptive planning reflects patient-specific anatomic variations and provides a reoptimized treatment plan for the remaining treatment fractions. Online adaptive planning is the optimal strategy for each fraction delivery because the treatment plan is reoptimized while the patient is waiting on the treatment table. However, clinical implementation of both offline and online adaptive techniques with a common imaging modality based on X-rays is still in the development phase because it is not sufficient to modify the treatment plan according to anatomic changes on inter- and intra-fraction bases. In 2009, Thongphiew et al. compared three online IGRT techniques (bony-anatomy matching, soft-tissue matching, and online replanning) for prostate IMRT treatment using daily CBCT [18]. They demonstrated that CBCT can feasibly be used for reoptimizing the treatment plan online, which has significant benefits when a high degree of deformation or differential organ position displacement occurs. Clinical implementation of ART for prostate cancer has been greatly promoted by image guidance with onboard CBCT [28‐31]. Onboard CBCT allows the target volume and adjacent anatomies to be localized before treatment of a patient in the treatment position. However, CBCT has insufficient image quality compared to planning computed tomography (CT) to provide an accurate delineation of structures and dose calculation owing to the higher noise and lower contrast [29, 32]. Furthermore, the inconsistency between the CT number to electron density curves of CT and CBCT images can result in a discrepancy in the dose calculations.

Recently, the high soft-tissue contrast and real-time imaging capability of magnetic resonance imaging (MRI) have allowed for more accurate assessment of inter- and intra-fraction variations [33‐36]. MR-guided radiotherapy (MRgRT) systems that integrate MR scanners with radiation delivery machines can potentially facilitate the online ART strategy. ViewRay™ (ViewRay Inc., Cleveland, OH, USA) is the first commercial MRgRT system and has been treating patients since 2014 [37]. Much work has been carried out on prostate treatment with the MRgRT system because it is very useful for identifying the prostate as well as detecting normal tissues [33, 34, 38‐40]. The present study compared adaptive replanning and repositioning corrections based on soft-tissue matching for prostate cancer with the ViewRay system in a retrospective manner.

This study explored different MRgRT techniques to compensate for inter-fraction errors during prostate treatment. The Soft plan, which repositions the patient by using the target volume, may be sufficient for correcting anatomic variations. For OARs with the Soft plan, the dose to the bladder was relatively low, while the dose to the rectum was relatively consistent during treatment. The Adaptive plan, which is a replanning technique, may be suitable for correcting anatomic variations, and the doses to the OARs remained relatively consistent during treatment. The Adaptive plan performed very similarly to the initial plan and compensated for inter-fraction uncertainty. The large variations in the mean values and standard deviation indicate that substantial fluctuations in target coverage can occur weekly with IGRT techniques based on patient repositioning. Only the replanning technique (i.e., Adaptive plan) maintained a consistent quality during the treatment period in terms of target coverage. However, the Adaptive plan did not achieve the better results in terms of sparing the bladder during the treatment course. In this study, the enrolled patients were not controlled for bladder and rectum filling because they had been treated with gated radiotherapy using the ViewRay system. Thus, the bladder and rectum were filled with various volumes during the treatment course. Figure 5 shows the averaged volume variation for all patients during the treatment course. The changes in the bladder volume were significant with large standard deviations. Significant variations in the bladder volume affect both the bladder dose volume and positions of adjacent organs [44‐46]. The Adaptive plan did achieve the better results for rectum sparing because the variation in the rectum volume was not significant. Figure 6 compares the example plans. In this case, the Soft plan had better OAR sparing than the Adaptive plan while missing target coverage. Thongphiew et al. used daily CBCT and also reported that the adaptive technique does not achieve the better OAR sparing for all fractions [18]. They discussed the limitations of CBCT. Compared to CT, CBCT images make it more difficult to distinguish the boundaries of soft-tissue organs (e.g., the prostate, bladder, and rectum) because of more noise and poorer soft-tissue contrast. In this study, however, a 0.35 T MRI was used with high soft-tissue contrast and real-time imaging capability to exactly define the soft-tissue organ variations. Even low-field-strength MRI gives improved anatomic visualization compared with CT and CBCT [47]. The MRI allowed for the most accurate delineation of soft tissues and observation of organs changing. Thus, we adopted PTV margins of 3 mm and 5 mm in all directions for the prostate and seminal vesicles, respectively. McPartlin et al. reported that the CTV-to-PTV margin can be safely reduced to less than 3 mm in MRI-guided prostate adaptive radiotherapy because of high soft-tissue contrast and real-time imaging capability [48]. On the other hand, the plan quality was not better than that of a treatment-based linear accelerator (linac) because of the large penumbra of the ⁶⁰Co source and a large width of the multileaf collimator (MLC). The patient positioning techniques were also limited because only translational corrections were available. An MR-linac with 6 MV beam is available in a clinic, and this system provides a better plan quality than a system equipped with ⁶⁰Co beams because of small penumbra and a small width of MLC [49, 50]. In addition, adaptive planning will increase the time between the imaging and the beam delivery. The intra-fractional motion and deformation also increase with time [51]. These could be handled by using the gating delivery technique in treatment delivery. Furthermore, the Adaptive plan is not the actual dose delivered and the actual delivered dose should be assessed in parallel after treatment.

In this study, the MRgRT technique using adaptive planning was compared to the technique based on patient repositioning for 19 prostate cancer patient with the MRI. Patient repositioning based on the target volume (Soft plan) can relatively retain the target coverage for patients and the OARs remain at a clinically tolerance level during the treatment course. Although the Adaptive plan did not clinically improve for the dose delivered to OARs, it kept the dose delivered to the target volume constant. However, the Adaptive plan is beneficial when organ positions and volumes change considerably during treatment.