Sharp Insight
By Dan Harvey
Radiology Today
Vol. 19 No. 4 P. 22

MR-linacs inspire optimism for real-time radiation therapy.

A novel approach to more efficacious radiation therapy—combining a linear accelerator that delivers highly precise radiation therapy with MRI technology, commonly referred to as an MR-linac—has opened minds to what could be the next stage in the evolution of cancer treatment. MRI enables continuous imaging of soft tissue and creates a more sharply focused target for radiation therapy, allowing more precise monitoring of radiation dose and delivery. Still, with any new technology—as well as with any idea considered to be game changing—value needs to be demonstrated. So far, physicians who have hands-on experience with MR-linacs say the real-time view of a cancerous tumor's shifts in response to a patient's basic body functions is proving its value.

"This fused technology will improve on the precision of delivered radiation as MR allows improved delineation of normal tissue from abnormal tissue," says Kien Vuu, MD, an interventional radiologist/interventional oncologist and assistant clinical professor at UCLA with more than 10 years' experience in image-guided interventions. "This is particularly important in areas such as prostate and brain. This would allow decreased radiation doses to nonpathologic tissue and more effective targeting of pathologic tissue."

Michael Chuong, MD, a radiation oncologist at Miami Cancer Institute, describes the visual element of this new approach. "The difference is that when we use MRI, compared with CT, we are allowed more detail in certain parts of the body," Chuong says. "MR-linac has taken the blinders off during radiation therapy. Now, we can see the tumor and nearby normal tissues in great detail, and, most importantly, we can adapt the treatment accordingly to improve treatment accuracy."

Moving Target
Chuong was a strong advocate for the installment of an MR-linac at the Miami Cancer Institute, one of the first in the southeastern region of the United States. As of early 2018, the MR-linac has been commercialized by two vendors: ViewRay, Inc, whose system is FDA approved, and Elekta, whose system is pending FDA approval. Elekta reports that orders were placed in 2017, and deliveries will be made in 2018.

Chuong specializes in the treatment of liver and abdominal tumors. "Due to a patient's respiration, the liver moves significantly during treatment and makes it difficult to accurately target the tumor without overtreating normal tissue. Previously, we knew it was moving, but now we are able to see," he says, adding that the Miami Cancer Institute installed the ViewRay MRIdian Linac.

Such movement can be now taken into account during treatment. "When you add MR imaging technology into the picture, we can actually have a real-time, constant image of the liver as it is moving, in relation to body function and movement," Chuong says. "In turn, this enables us to turn the radiation beam on when the liver tumor is in a certain position and turn it off when the liver tumor moves out of that position. This leads to a more accurate treatment of the tumor and minimizes the irradiation of normal tissues next to the tumor, ultimately reducing the side effects."

Chuong's observations help underscore the following major significant benefits of combined MR/RT:

  • RT enhanced with MR guidance substantially improves the specific localization of radiation dose delivery, particularly for tumors influenced by respiratory motion, helping to spare surrounding healthy tissue; and
  • more accurate targeting may allow for higher radiation dose to be safely delivered to tumors adjacent to dose-limiting normal tissues, improving tumor control and even prolonging patient survival.

Promising Data
At the ASTRO annual meeting in September, the Elekta MR-linac Consortium, which includes clinics, researchers, and medical physicists, reported encouraging study results. Researchers at the Sunnybrook Health Sciences Centre's Odette Cancer Centre in Toronto revealed early results of an evaluation study involving treatment of glioblastoma multiforme. The research involved 20 patients at the treatment planning stage with intervals that included 10, 20, and 30 days following RT treatment.

With the combined MR/RT approach, the researchers assessed critical treatment elements: gross tumor volume (GTV) and planning target volume (PTV). The intent was to assess the feasibility of the type of treatment planning adaptation that was behind development of the MR/RT concept. At the time of the meeting, the researchers were only able to report data related to the study's first three patients. Data revealed, even within that small number, that closer consideration, if not optimism, was justified, given the following:

  • two of the three patients showed decreases in GTV of 14% and 20% at day 20; and
  • a substantial decrease in GTV (51% and 42% one month following completion of treatment) was clearly evident.

The researchers reported that the imaging set indicating 20% GTV shrinkage at day 20 led to an adapted plan. The changed plan resulted in a new PTV that was evidentially smaller—31%—than the original plan. This led to reductions in maximum dose to brainstem and optic chiasm of 37% and 39%, respectively. These results indicate that MR-linac technology has the potential to significantly reduce PTV as well as dose to at-risk areas. However, while the dosimetric benefit was notable, the researchers concede that this was only a first step toward more research that may lead to equipment and treatment processes that can carry the concept into widespread clinical implementation.

"There are ongoing trials that we will see, and those trials are important, because what we've witnessed so far appears to be only the tip of a large iceberg," Chuong says. "Future studies will provide us with much more specific information about what specific patients and what specific forms of cancer will most benefit."

Collaborative Approach
For many involved in the cancer battle, the step to combine MRI and radiation therapy technologies seemed an obvious area for exploration. Kevin Brown, Elekta's vice president of research and innovation, provides a backstory to this narrative. "The idea was there, but the obvious step was how to combine these two technologies," Brown says. "The technologies once seemed incompatible."

Despite that challenge, the idea wasn't pushed aside. Collaboration, not competition, was chosen as the path forward.

"In the face of that challenge, an ongoing discussion was held among Elekta, Philips, Siemens, and ViewRay. All were intent on making this happen," Brown recalls. "Discussions led to initial conceptual designs, bolstered by the generated enthusiasm, support, and grants. Of course, the designs weren't meant to treat patients. Rather, we were all hoping to demonstrate that technologies that once seemed disparate could effectively function together."

In early June 2017, the Michigan-based Henry Ford Cancer Institute acquired ViewRay's MRIdian Linac. It enabled real-time tumor visualization and a more precise tool for tailoring treatment to a patient. Furthermore, this treatment can be adapted even as it is delivered.

To best understand this, consider how the first moving pictures were made: collecting static images, placing the images together, and flipping through the acquired images to generate an illusion of movement. MR-linacs remove the illusion from the equation and reveal, in real time, the movement of the lungs, the diaphragm, the head and neck, and, most importantly, the subtle but highly critical shifting of a cancerous tumor as affected by routine bodily functions. Some clinicians have even presented this "movie" to their patients.

That theme was highlighted by a panel discussion, "MRI-Guided Adaptation: From Anatomy to Biology," held at the 2017 ASTRO conference, which reviewed recent data insights about image-monitored RT, response to adapted treatment, selection of tumor sites, and the algorithms and equipment necessary to further treatment-plan adaptation. There is much about MR/RT technology to digest and absorb, but, according to the panel, it appears that the following are established:

  • localization of tumors is enhanced;
  • early clinical trial results indicate improved survival rates, particularly related to pancreatic cancer treatment;
  • areas of the body where tumor location is affected by normal bodily functions, eg, breathing, pose a decreased challenge for clinicians;
  • combined MR/RT can potentially increase the efficacy of adapted treatment for gastrointestinal, musculoskeletal, colorectal, esophageal, and pancreatic cancers;
  • imaging visibility challenges are potentially reduced in regions including the head, neck, and spine as well as in neurological structures, eg, optic-related anatomy; and
  • new product introductions—Elekta's MR-linac and ViewRay's MRIdian Linac—offer more precise oncologic treatment.

"Real-time adaptation better specifies the shape and location of a patient's specific and individual tumor," Brown says. "We're witnessing something very exciting."

Next Steps
But excitement doesn't readily translate into arrival. Speak to anyone deeply involved with this technology, and they acknowledge that this is only an early stage—even if clinical trials reveal positive results. Chuong observes, "Historically, we have been agnostics about what happens within a patient's body, especially during radiation treatment." Agnosticism recognizes that you know there's something you don't know. That's what provokes questions and subsequent answers.

"But we [haven't had] the available technology to answer those questions," Chuong continues. "It appears that we now do. This could be a large paradigm shift in how we approach radiation therapy, for at least some tumors."

Brown is equally optimistic, if a bit less cautionary. "Efficacy of the combined technology is becoming self-evident," he says. "We are close to the point where we don't have to convince anyone." But, he adds, "We've moved into a phase where we're now imaging. And the images received are excellent."

Chuong offers an example of how treatment can be positively impacted. "For moving tumors such as those in the chest and abdomen, an MR-linac will automatically turn the radiation beam off when the tumor moves out of treatment range, and then it will turn back on when the tumor comes back into the appropriate location, all based on real-time MR imaging throughout treatment. To see all of this was never possible before with CT-based imaging."

What he is describing is how a piece of technology becomes a clearly focused, intuitive member of a treatment team. Its potential seems to point to further exploration.

"The fusion compatibility of MR/RT adds to the exciting armamentarium of new cancer treatments including immune cell cancer therapy and new immune checkpoint modulators," Vuu says.

— Dan Harvey is a freelance writer based in Wilmington, Delaware.