Introduction
Magnetic resonance (MR) image guided radiation therapy (IGRT) represents a treatment modality that offers potential solutions to the well-recognized challenges of radiation delivery. Compared with computed tomography (CT)-based strategies, MR imaging (MRI) for treatment guidance offers superior soft tissue definition that is potentially advantageous in numerous disease sites.
1- Noel C.E.
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Comparison of onboard low-field magnetic resonance imaging versus onboard computed tomography for anatomy visualization in radiotherapy.
From a patient-safety perspective, daily image guidance with MR also avoids undesirable radiation exposure inherent to the use of CT imaging guidance such as cone beam CT (CBCT). Moreover, cine MRI can be safely employed throughout a patient's entire treatment fraction and course to monitor and manage intrafraction motion. MR-IGRT enables daily imaging of sufficient quality to permit daily plan adjustments in response to interfraction changes in anatomy.
2- Acharya S.
- Fischer-Valuck B.W.
- Kashani R.
- et al.
Online magnetic resonance image guided adaptive radiation therapy: First clinical applications.
This approach is valid even in disease sites that are typically poorly visualized with conventional x-ray imaging, such as soft tissues within the abdomen and pelvis.
1- Noel C.E.
- Parikh P.J.
- Spencer C.R.
- et al.
Comparison of onboard low-field magnetic resonance imaging versus onboard computed tomography for anatomy visualization in radiotherapy.
This daily plan adjustment, termed online adaptive radiation therapy (ART), has been found in dosimetric studies to potentially improve the therapeutic ratio of radiation therapy (RT) by enhanced sparing of organs-at-risk (OARs) and safe-dose escalation in disease sites where high-dose therapy has been limited.
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Using generalized equivalent uniform dose atlases to combine and analyze prospective dosimetric and radiation pneumonitis data from 2 non-small cell lung cancer dose escalation protocols.
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Simulated online adaptive magnetic resonance-guided stereotactic body radiation therapy for the treatment of oligometastatic disease of the abdomen and central thorax: Characterization of potential advantages.
Thus, MR-IGRT has the potential to improve the accuracy, precision, and safety of RT delivery.
Historically, MR-IGRT has been unavailable due to the challenges of protecting a radiation delivery device from the influence of a magnetic field and maintaining imaging quality in the presence of a treatment device. At our institution, the world's first commercially available device for MR-IGRT was clinically developed and implemented in routine clinical practice (MRIdian System; ViewRay Inc., Oakwood Village, OH). In the more than 2 years after the first patient treatment in January 2014, more than 300 patients have been treated in disease sites such as head and neck, breast, thorax, abdomen, and pelvis. In this study, we review our institutional experience with patients who were treated on the world's first MR-IGRT system. More specifically, we aim to describe our initial clinical experience and the integration of this new technology within a high-volume clinical practice, highlight the technical capabilities of the system, and describe the selection of patients who benefited most from MR-IGRT.
Discussion
The world's first commercially available MR-IGRT system has been successfully used at our institution since 2014. The system features capabilities including onboard low-field MRI, gating based on real-time sagittal cine MR, and a built-in TPS that is capable of both conventional and online ART. This study sought to describe our initial clinical experience with integrating MR-IGRT in a high-volume RT center, characterize the disease sites that were treated with MR-IGRT, and highlight the technical capabilities of the system.
Over the past 3 years, approximately 3,500 patients per year were treated with external beam RT at our facility, including approximately 290 patients treated with proton RT and 316 patients treated with MR-IGRT between January 2014 and June 2016. Since implementing both proton RT and MR-IGRT, the overall volume of patients treated at our facility has steadily increased, thus allowing us to select a highly specific subgroup of patients who would likely benefit from MR-IGRT without a decrease in other treatment modalities in our department. Additionally, the incorporation of the MR-IGRT service into a high-volume clinic has allowed integration of current staff, simulation, and dosimetry without changes to other workflows. The group of initial patients and cases for MR-IGRT was selected based on the improved soft tissue visualization for setup, reduction of treatment margins, and/or increased ability to control for any observed changes during treatment.
The onboard low-field MRI offers improved visualization for selected RT targets and other critical structures compared with other onboard imaging modalities, including CBCT.
1- Noel C.E.
- Parikh P.J.
- Spencer C.R.
- et al.
Comparison of onboard low-field magnetic resonance imaging versus onboard computed tomography for anatomy visualization in radiotherapy.
The geometric accuracy and soft tissue definition of MRI can provide accurate and reproducible daily localization, leading to potential reduction in treatment margins, and can eliminate the need for fiducial markers. For example, >95% of female patients at our institution who are candidates for accelerated partial breast irradiation but unable to undergo high-dose rate brachytherapy (eg, procedural contraindications) are treated with MR-IGRT using treatment margins that are decreased compared with accelerated partial breast irradiation on a conventional linac (
Fig 4b).
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Magnetic resonance image guided radiation therapy for external beam accelerated partial-breast irradiation: Evaluation of delivered dose and intrafractional cavity motion.
We previously reported that the mean lumpectomy cavity displacement during treatment on the cine MR in the anterior-posterior and superior-inferior directions was 0.6 ± 0.4 mm and 0.6 ± 0.33 mm, respectively.
8- Acharya S.
- Fischer-Valuck B.W.
- Mazur T.R.
- et al.
Magnetic resonance image guided radiation therapy for external beam accelerated partial-breast irradiation: Evaluation of delivered dose and intrafractional cavity motion.
Therefore, for these patients, we defined our clinical GTV as the surgical cavity plus a 1-cm margin (excluding chest wall and pectoral muscles and 5 mm from skin), and no additional margin was added for the PTV. This is a median treatment volume reduction of approximately 52% compared with using a 1-cm PTV margin, which may result in improved cosmesis.
8- Acharya S.
- Fischer-Valuck B.W.
- Mazur T.R.
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Magnetic resonance image guided radiation therapy for external beam accelerated partial-breast irradiation: Evaluation of delivered dose and intrafractional cavity motion.
Intra- and interfraction tumor and OAR motion and potential margin reductions are also currently under investigation in the treatment of gastric mucosa-associated lymphoid tissue lymphoma and potentially bladder cancer. We also no longer require fiducial markers to be placed prior to treatment of adrenal metastases and prostate cancer with the MR-IGRT system given the excellent daily imaging used for patient set-up. With a median follow-up of more than 1.5 years, the local control of patients who were treated for oligometastatic adrenal tumors is 90%. Additionally, unlike other onboard imaging techniques such as CBCT, the MRI system does not deliver any additional radiation dose to the patient. Song et al. measured the average dose of 2 widely used onboard CBCT systems and found that the average dose ranged from 0.1 to 3.5 cGy and 1.1 to 8.3 cGy, which would not be included in the dose calculated by the TPS and can degrade the delivered plan quality by blurring the intended isodose lines.
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A dose comparison study between XVI and OBI CBCT systems.
In addition to the improved setup accuracy and reduction in unplanned radiation exposure with daily MR setup imaging, online ART also improves the therapeutic precision of RT. Previously, the standard method of addressing interfraction target positioning variation was to use image guidance for daily patient repositioning on the basis of rigid anatomical registration using the planning image and the image acquired just before treatment, with subsequent delivery of the original plan. To a limited extent, MR-IGRT alone may manage large interfractional anatomic shifts and setup errors, but it cannot sufficiently account for known organ deformation, rotation, and independent motion between organs, such as within the abdomen.
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Dosimetric feasibility of magnetic resonance imaging-guided tri-cobalt 60 preoperative intensity modulated radiation therapy for soft tissue sarcomas of the extremity.
Instead, online ART that uses high-quality 0.35 T volumetric MR images acquired at the start of each fraction with the MR-IGRT system can fully account for interfraction volumetric changes in both target volumes and OARs using reoptimization of treatment plans based on the observed daily anatomy.
The projected benefits of online ART are many and include margin reduction and an increase in the therapeutic window of RT via reduced OAR dose and the possibility for PTV dose escalation.
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A dosimetric pilot study that was performed with the current MR-IGRT system demonstrated that simulated online ART MR-IGRT SBRT would eliminate 100% of unintended OAR constraint violations that occurred in 61% of unadapted fractions and permit simultaneous dose escalation.
4- Henke L.
- Kashani R.
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Simulated online adaptive magnetic resonance-guided stereotactic body radiation therapy for the treatment of oligometastatic disease of the abdomen and central thorax: Characterization of potential advantages.
ART does require a time investment from the physician and daily physics support for online quality assurance of the adaptive plan prior to delivery. However, as we have previously reported, this is feasible within an acceptable clinical time frame (median, 26 minutes) for recontouring, reoptimization, and quality assurance.
2- Acharya S.
- Fischer-Valuck B.W.
- Kashani R.
- et al.
Online magnetic resonance image guided adaptive radiation therapy: First clinical applications.
Efforts are also underway to train advanced therapy personnel to assist in the contouring tasks that account for the majority of the time required for adaptation. Presently, we are evaluating the clinical feasibility of online adaptive MR-guided SBRT for oligometastatic and unresectable primary malignancies of the abdomen and central thorax (Trial NCT02264886) and for dose escalation for inoperable pancreatic cancer with full dose concurrent chemotherapy (Trial NCT02283372). These trials use a fraction-by-fraction isotoxicity approach with planning prioritization of hard constraints for OARs to minimize toxicity and maximize the safe deliverable dose to the target. We have established that there were no instances of grade 3 or greater toxicities in our patients who were treated in a phase 1 study of online adaptive SBRT for abdominal and central thoracic malignancies despite the use of prescriptions for biological equivalent doses >100.
Our current MR-IGRT system also permits sagittal planar cine MR gating. The management of intrafraction motion during RT is a long-standing concern, particularly within the thorax and abdomen where respiratory motion and intrafraction physiologic motions challenge technology. Prior attempts to track target and OAR motion, such as the use of 4-dimensional CT planning, internal target volume construction, and fiducial markers are insufficient. Within the abdomen, internal target volume instability has been shown to range from 46% to 127% for tumors as small as 1 cm in diameter.
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A study by Ge et al. revealed that 4-dimensional CT inadequately represents the daily motion of abdominal tumors, with a discrepancy noted between planning CT and daily fluoroscopic video imaging in 90% of cases.
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Planning 4-dimensional computed tomography (4DCT) cannot adequately represent daily intrafractional motion of abdominal tumors.
Similarly, for patients who receive thoracic SBRT, in which treatment precision is paramount, daily intrafraction motion was found to exceed the mean target position by >2 mm for 41% of patients and by >5mm for 7% of patients.
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Intrafraction variation of mean tumor position during image-guided hypofractionated stereotactic body radiotherapy for lung cancer.
Even with fiducial use and daily adjustment of gating windows, studies have shown decreased gating accuracy over the course of a single treatment session for nearly half of the delivered fractions in the abdomen.
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In the absence of real-time tumor imaging, all surrogates for motion require some additional planning margin to account for these uncertainties, which that reduce therapeutic precision. However, with cine MR gating in real time, the GTV itself is the gating target, enabling potential reduction of PTV expansions and eliminating the inherent uncertainties of motion surrogates. Although there is some overall system latency in cine imaging processing, our institution has developed a policy of a 3 mm gating structure that is expanded from the GTV, which is smaller than the typical PTV expansion of 5 mm, to minimize the concern of organ motion beyond the gating target during that processing lag window. For patients with early stage non-small cell lung cancer, we selected treatment with MR-IGRT and cine gating for tumors that remain excessively mobile (>1 cm) after maximal abdominal compression (eg, tumors near the diaphragm). We have found that MR gating for such mobile tumors is also more time efficient compared with other gating systems, and the tumor can be directly visualized throughout treatment.
Although MR-IGRT has made significant strides in addressing the historic limitations of RT, this novel technology has limitations of its own. MR-IGRT, particularly adaptive treatment, requires additional clinical time for implementation, training, and treatment delivery. An ongoing phase 1 trial addresses the feasibility of online adaptive SBRT, and the timing data collected will be used for process improvement. Additionally, the use of a low-field MR-imaging unit could be considered a limitation of the current device. However, in our experience, the current, clinically available low-field MR is sufficient for daily imaging localization, cine gating, and online-adaptive planning. Diagnostic-quality imaging may have specialized applications in MR-IGRT, but its primary applications comprise initial staging/diagnosis and simulation; it is not essential for daily use. Other MR-IGRT units under development offer higher magnet strength and improved imaging resolution, but their clinical implementation has been impeded by challenges such as geometric distortion, dose distribution uncertainty, and undesirable patient heating.
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We acknowledge that both the imaging and radiation delivery components of MR-IGRT devices will continue to improve with advancing technology, but we maintain that the current clinically implemented technology is sufficient for broad therapeutic use. Another limitation is the use of
60Co sources. Although the plan quality between
60Co and linac plans has been shown to be comparable,
60Co still has limitations such as less tissue penetration, greater low dose spread, and longer treatment times with source decay.
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Quality of intensity modulated radiation therapy treatment plans using a (6)(0)Co magnetic resonance image guidance radiation therapy system.
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Benchmark IMRT evaluation of a Co-60 MRI-guided radiation therapy system.
These limitations may be addressed by future technologies that use MR-linac systems. In our department, the cobalt radiation delivery system will be replaced with a 6MV linac while leaving the current MRI potion of the system in the treatment vault for use with the linear accelerator.
In addition to the limitations inherent to the MR-IGRT system, many other challenges were faced during the implementation of this technology. The machine was quickly integrated into clinical use and simultaneously available to all clinical services (eg, breast, thorax, gastrointestinal, genitourinary). Therefore, each service had to identify its unique challenges and/or specific patients who would benefit the most from the MR-IGRT technology. As new applications became available (ie, online adaptation, cine gating), each service also needed to determine when, how often, and for whom to use these features. For example, the thorax and gastrointestinal services have had specific challenges in determining when and how often to adapt hypofractionated treatment courses. Daily adaptations for extended treatment courses (ie, >10 fractions) is likely excessive and burdensome on the MR-IGRT workflow, and trials are in development to determine the ideal time point to adapt. Specific margin sizes and gating windows also remain challenges. These are questions that are still being answered today, and a collaboration between multiple institutions that have this technology has been extremely beneficial and informative.
MR-IGRT has been successfully implemented and provides unique advantages in the treatment of a variety of malignancies. Multiple clinical trials are in development to formally evaluate MR-IGRT in the treatment of various disease sites using techniques such as SBRT and adaptive RT. An in silico trial of MR-IGRT with mid-treatment adaptive planning for hypofractionated stereotactic RT in centrally located thoracic tumors is ongoing. Additionally, an analysis of online adaptive SBRT for patients with prostate cancer who use a hydrogel prostate-rectal spacer is currently underway. Other areas of interest include autosegmentation, dose accumulation, motion management, and the financial implications of MR-IGRT. Lastly, a multi-institutional registry is under development, which will allow for sharing of clinical outcomes and treatment techniques.
Article info
Publication history
Published online: June 01, 2017
Accepted:
May 25,
2017
Received in revised form:
May 21,
2017
Received:
March 20,
2017
Footnotes
Conflicts of interest: Benjamin Fischer-Valuck, Lauren Henke, Olga Green, Rojano Kashani, Jeffrey Bradley, Cliff Robinson, Maria Thomas, Imran Zoberi, Jiayi Huang, Jeff Olsen, Parag Parikh, Sasa Mutic, and Jeff Michalski have received either a grant, honorarium, speaker's bureau, or travel expenses reimbursement from ViewRay Inc. outside the scope of this report.
Copyright
© 2017 the Authors. Published by Elsevier Inc. on behalf of the American Society for Radiation Oncology.