UCLA Health has received a $2 million grant from ViewRay Systems, Inc. to support groundbreaking clinical trials in MRI-guided radiotherapy, a cutting-edge approach that combines real-time imaging with precision radiation delivery. The funding will accelerate research aimed at improving the accuracy of cancer treatment, enhancing tumor targeting while reducing harm to surrounding healthy tissue. This innovative technique holds promise for minimizing side effects and improving outcomes for patients undergoing radiation therapy.
Here Dr. Amar Kishan, professor and executive vice chair of radiation oncology at the David Geffen School of Medicine at UCLA and co-director of the Cancer Molecular Imaging, Nanotechnology, and Theranostics Program at the UCLA Health Jonsson Comprehensive Cancer Center, shares insights into how this technology works, the breakthroughs it’s enabling in cancer care, and what’s next for MRI-guided radiotherapy.
First, can you explain what MRI-guided radiotherapy is and how it differs from traditional radiotherapy methods?
Dr. Kishan: MRI-guided radiotherapy is an advanced form of external beam radiotherapy that involves the utilization of magnetic resonance imaging (MRI) to guide radiation delivery. Traditionally, radiation delivery platforms have relied on X-ray-based imaging (either X-rays themselves, or computed tomography [CT] scans) to help guide radiation. MRI offers superior soft tissue imaging and contrast, and in general provides more reliable imaging in areas of the body such as the abdomen, pelvis, and central nervous system particularly. Previously, it was not possible to use MRI-based imaging to guide radiation due to potential interference between a magnetic field and the radiation delivery platform. This technical limitation has been solved with the advent of specialty linear accelerators that have integrated MRI-based imaging (MRI-LINACs).
What advantages does MRI guidance provide in radiation treatment compared to other imaging techniques?
Dr. Kishan: MRI guidance combines a 0.35T MRI with a modern linear accelerator, allowing the delivery of intensity-modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT). These are advanced radiation delivery techniques that use multiple beams to deliver doses precisely to pre-specified targets. The on-board MRI is helpful to target the radiation initially—as discussed above, there is improved soft tissue contrast with an MRI than a CT—but perhaps the biggest advantages are the abilities to (a) track targets in real-time and (b) perform adaptive radiotherapy.
For tracking, the device uses the on-board MRI to obtain images at a rate of four to eight frames per second. This generates a movie that can track the target in “real-time,” with the ability to perform a “beam hold” or stop the radiation if the target moves out of position. Called gating, this degree of fine motion management offers unprecedented precision.
Adaptive radiotherapy is a novel form of radiation therapy where a new radiation therapy plan can be generated based on daily variations in anatomy. Traditionally, the workflow of radiation involves a mapping scan (called a simulation) that is done a week or more before radiation actually starts. The radiation plan that is ultimately delivered is based off of patient anatomy at the time of the planning scan. With adaptive radiotherapy, the radiation plan is manually altered by a team of radiation oncologists, medical physicists, and dosimetrists who are working in real-time as the patient is in position, waiting for radiation to begin. This level of precision is thought to allow an increase in dose to the intended target, and a decrease in dose outside the intended target.
What type of results have you had so far with this type of radiotherapy?
Dr. Kishan: We have prided ourselves on cementing UCLA as a global leader in MRI-guided radiotherapy by establishing a robust clinical and research program. Our team has led multiple important studies in the field. A prominent example is the MIRAGE trial, which demonstrated a dramatic reduction in side effects of prostate cancer SBRT with MRI-guided radiotherapy versus CT-guided radiotherapy. Another example is the results of the SCIMITAR trial, which showed the benefit of MRI-guided radiotherapy in the context of post-prostatectomy radiation. UCLA was also a leader for the SMART trial, which evaluated adaptive, dose-escalated SBRT for pancreatic cancer. Our team of radiation oncologists and medical physicists has performed a number of other studies evaluating the benefits of MRI-guided radiotherapy as well, even dating back to 2014, when UCLA first installed the predecessor device to the modern MRI-LINAC, which was the third such device in the world.
What types of cancers or patient populations are you focusing on in these trials?
Dr. Kishan: We currently have a wide variety of trials, both ongoing and forthcoming, that are exploring this technology. These trials primarily focus on prostate cancer, gastrointestinal malignancies (colorectal and pancreatic cancers), gynecological cancers, and sarcomas.
Examples of active studies:
- HEATWAVE: A trial of “triple precision” therapy for intermediate risk prostate cancer
- MASAMUNE: A trial of adaptive radiotherapy in the setting of post-prostatectomy SBRT
- HERA: A trial of adaptive radiotherapy for post-operative treatment of gynecological malignancies
- NOM-Rectal: A trial of short-course radiotherapy, without surgery, for rectal cancer
- MARS: A trial of short-course radiotherapy for abdominopelvic sarcomas
- MANTICORE: A planned randomized trial evaluating adaptive radiotherapy for prostate cancer
- VORTEX: A planned randomized trial evaluating neurovascular-sparing radiotherapy for prostate cancer
Are there specific challenges in radiation oncology that this technology is particularly suited to address?
Dr. Kishan: A fundamental challenge in radiation oncology is that the efficacy and safety of external beam radiation relies on our ability to visualize the target and the normal organs around it. Just as a surgeon would never operate without visualizing the target, so too would a radiation oncologist avoid delivering radiation without having confidence in localizing the target. As mentioned above, combining the MRI’s enhanced spatial contrast with the ability to track targets in real time and adjust treatment as needed is expected to improve the precision of radiation delivery, which may also impact treatment outcomes and post-treatment quality of life. Indeed, we have already shown that the aggressive margin reduction afforded by being able to perform real-time target tracking reduces side effects in the context of prostate SBRT. We plan on demonstrating the benefits of not only tracking, but also adaptive therapy, in our larger suite of ongoing and forthcoming clinical trials.
