MR-LINAC Provides Greater Precision With Adaptive Radiation Across Cancers

The Agility multileaf collimator (MLC) mounted in Elekta linear accelerators features some unique design characteristics, such as large leaf thickness, eccentric curvature at the leaf tip, and defocused leaf sides.

MR-LINAC (magnetic resonance-guided linear accelerator) is a new technology that provides greater precision of radiation treatment via adaptive treatment planning. In an interview with Targeted Therapies in Oncology, Paul B. Renz, DO, a radiation oncologist at Allegheny General Hospital, Allegheny Health Network (AHN), in Pittsburgh, Pennsylvania, discussed the ideal uses of MR-LINAC in pancreatic, prostate, liver, head and neck, and rectal cancers.

“MR-LINAC can be used across a broad range of cancers and is not limited to any one [cancer type], although it shines [when used] with stereotactic body radiation therapy [SBRT],” Renz explained.

Other innovations associated with this new technology include novel MR contrast agents to identify and target smaller tumors early on and biology adaptive radiation, which can provide insight into how exactly a patient’s tumor is responding. Renz noted that this makes it easier for radiation and chemotherapy treatments to be customized.

Renz also discussed advances in adaptive treatment planning solutions that incorporate CT scans and artificial intelligence. These advancements allow for more personalized cancer care, adapting to each patient’s changing anatomy on a daily basis and adding a new dimension to individualized cancer treatment.

Targeted Therapies in Oncology: How does MR-LINAC compare with conventional radiation therapy regarding survival rates and long-term remission?

Paul B. Renz, DO: A patient’s anatomy may change throughout the course of the treatment. They may gain or lose weight; their tumor may move or change its motion based on their respirations. [In addition,] the filling of the stomach or differences in the bowel position change day by day. On a regular LINAC, these changes are not accounted for, and instead, we try to mimic the plan [that is established] at their initial planning session.

We [still] do that same initial planning session, but MR-LINAC enables us to conduct a fresh, detailed image set each day of the patient’s treatment. This allows us to then customize the radiation in a process called adaptive treatment planning, where we can reshape and move the radiation based on the patient’s daily anatomy. Thus, if the stomach position changes, or they are breathing differently, or if a tumor grows or shrinks in size during the treatment, we can account for all those changes and then customize the radiation [dose location].

As that translates into outcomes, we are gaining more and more data. It is very new technology, so our [survival] outcome data are still being accrued. There are some early studies showing a great benefit in toxicity rates. Randomized trials in both prostate and pancreatic [cancers] have shown a decrease in toxicity rates throughout the course of the treatment due to the accuracy of treatment delivery.¹

Are there specific types or stages of cancer where MR-LINAC is most effective, or is it beneficial across a broad range of cases?

We talked about prostate and pancreas being 2 cancer types that shine for MR-LINAC because they have very sensitive organs in proximity. The prostate has the rectum, which is sensitive [and] within millimeters, and then the pancreas has the stomach and the duodenum within millimeters, which are also very sensitive. The goal is to give the tumor as much of a dose as we can while avoiding those sensitive organs. So there are a lot of different cancers that have different reasons why MR-LINAC might [provide] benefit.

Some of the downside with MR-LINAC is that it is a longer-[term] treatment and can elicit feelings of claustrophobia similar to an MRI. A patient also cannot have metal in the body or pacemakers.

Can you explain how the real-time imaging during treatment changes the approach to radiation dosing and targeting?

That is a great question. With conventional radiation, different machines from various companies do this similarly, with some minor differences. In general, a conventional linear accelerator uses a cone beam CT, which is a basic version of a CT scan taken while the patient is positioned on the table. This gives us an overview of basic anatomy, such as the kidneys and bones, helping us align the patient based on the reference plan. Once everything is set, the clinician and radiation therapists verify it, and then the treatment begins. The treatment usually takes about 5 to 10 minutes, but in that time, a patient might cough, move, or twitch. With conventional equipment, we can only monitor these movements through a camera, and some treatments account for this by allowing more margin for error. However, with high-precision treatments, small movements can affect the outcome.

What is different with MR-LINAC–guided radiation is that we can monitor the patient’s movements in real time during treatment. We can watch a movie of the patient’s body and tumor while delivering the treatment. For example, as the patient breathes, their MRI scan moves, and we can adjust the radiation accordingly if any movement is detected. This allows us to pause the beam if needed, adjust the delivery, and ensure the treatment is as precise as possible. We also monitor breathing patterns and internal organ motion to manage changes, such as if a patient’s stomach shifts or their breathing becomes heavier, so we can keep everything on target.

What are some of the most exciting advancements in MR-LINAC technology you’ve seen or anticipate?

There are a lot of interesting clinical trials being developed through the international consortium, and then a number of different projects are being done at our institution. One example is my partner and mentor, Alexander V. Kirichenko, MD, PhD, [clinical director of the gastrointestinal and SBRT programs at the AHN Cancer Institute,] who is an expert in [treating patients with] liver tumors. He has been pioneering novel MR contrast agents that help us see tumors better in order to deliver radiation more accurately.²

Patients were referred to him for a single tumor, and when he enrolled them in the clinical trial, evaluating the novel MR contrast agent, he found 1 or 2 more [tumors] and was able to treat all of them at the same time and clear all their disease early on. The alternative would have been repeat CT scans 3 months later, then 6 months later, and eventually those tumors would have showed up, and we would have thought they were new. With this novel MR contrast agent, he was able to identify them earlier and treat them earlier. Dr Kirichenko is working on the second phase of the trial now.

Another interesting study regarding biology adaptive radiation [is under way], where you are [able to] watch the kinetics and dynamics of the MRI scans as you treat the tumor and then use that as a predictive value.³ This way you can inform the patients whether their tumor is responding, and then customize the radiation and chemotherapy plans accordingly.

Is MR-LINAC therapy more expensive than traditional radiation treatments, and do most insurance providers cover it?

As it stands now, it is no more expensive than the conventional linear accelerator. It uses the same billing codes, and so insurance is covering the treatment. However, they are not covering what is called adaptive planning. There are [currently] no Medicare codes for this as it is a newer concept in radiation oncology.

There are many large institutions lobbying Congress to plan how to accommodate those adaptive planning charges because [the process] is very labor intensive from a staffing standpoint. For each individual treatment, there is a physicist, a physician, and 2 radiation therapists there throughout the treatment course. So they are working on figuring out how to accommodate that and create appropriate billing codes.

When these [codes] exist, they will be covered by insurance, and that will translate into a nominal increase in co-pays and so on, but it should be covered under the patient’s regular insurance through the preapproval processes of selecting those right patients [for this type of treatment].

As it stands right now, [the treatment] costs the same as a regular, conventional linear accelerator treatment, and the hospitals essentially [absorb] the cost, because it is what we need to do.

How do you think the patient experience differs with MR-LINAC vs standard radiation therapy, both physically and psychologically?

The adverse events [AEs] profile in the short term is much lower, and thus, [it is] favorable. However, the patient experience depends on personal preference as it is a more claustrophobic [experience]. The treatment is [conducted in] an MRI tube that is very cold because they must keep the magnet cold. In addition, the patient needs to hold still for 40 to 45 minutes, as opposed to 10 minutes [with other treatments]. Thus, it is not the most comfortable of treatments from [the patient’s] standpoint. However, many patients prefer the 5 claustrophobic, longer treatments to 30 quicker treatments.

It is not for everyone, but I have had patients with claustrophobia undergo treatment with MR-LINAC. We were able to get medications to help, and most patients who said they were claustrophobic were still motivated to do it. We [used] a number of different techniques, such as goggles that help you see outside of the magnet tube to make it look less confined, anxiety medications, or slight sedation.

From a psychological aspect, it is a mental battle to have cancer in general. That is a very underappreciated aspect of oncology. To be put in what looks like a sensory deprivation chamber and sitting there with your thoughts for an hour can be very isolating and could be a mental battle in and of itself.

This is a good question, and I cannot say I have elaborated too much on this. [As a team,] we have talked about doing some projects such as playing relaxing music or conducting guided meditations during the treatment and then evaluating how anxiety, convenience, and comfort affect tumor motion and so on. We have not been able to move forward with this yet, but we are working on training to conduct a guided meditation. Overall, this is a very underdeveloped topic in all of oncology but is something that we are very interested in paying more attention to.

Do you see MR-LINAC becoming the new standard for radiation therapy, or do you anticipate other emerging technologies taking the lead?

As this technology advances over time, I do see it becoming a de facto standard for cancers affecting the prostate, pancreas, or liver. There are other cancer types that are more nuanced, such as head and neck or lung cancer, sarcoma, [that benefit]; however, these are the [most-common] disease sites, and that is why the trials are centered around those.

That said, there are some competing modalities, such as the adaptive treatment plan, which customizes the radiation daily. Instead of providing a singular template radiation plan for however many treatments are needed, it provides custom radiation based on your daily anatomy. The MRI does that now through more advanced imaging; however, as mentioned, the time expenditure of doing an MRI, [accompanied by] the lack of efficiency of the machine, does not lend itself to scaling it for all the individual treatments.

Thus, the companies that market and create our radiation equipment have come up with adaptive treatment planning solutions for more conventional treatments that are CT and artificial intelligence–based adaptive treatment planning. I see this becoming a significant de facto standard for a lot of treatments because it is simply a better way to deliver radiation, being customized daily as opposed to allowing more margin and wiggle room to accommodate daily changes in anatomy.

These competing devices are excellent, and there is a significant role for them; however, the MRI complements this, offering a different level of precision beyond those with real-time motion monitoring that these new machines do not have, by taking some of the adaptive principles and scaling them globally so that we can give all patients more customization.

What is the key takeaway for community oncologists regarding this technology?

The key takeaway is that this technology is available for the right patients. As this becomes more mainstream and the data mature, when evaluating patients, consider whether they should be treated locally with a more conventional treatment, or whether the advantages of MR-LINAC make it a good fit for the patient.

We are always available [for clinicians] to ask questions and to provide information. Although it may be burdensome for certain patients to travel for an [initial] consult and discuss co-pays, local oncologists are welcome to reach out with questions and start triaging those patients ahead of time. Just know that this technology is available, offering precision radiation treatments, and to keep it on their radar for disease sites, primarily pancreas, prostate, and liver.

REFERENCES :

1. Ladbury C, Amini A, Schwer A, Liu A, Williams TM, Lee P. Clinical applications of magnetic resonance-guided radiotherapy: a narrative review. Cancers. 2023;15(11):2916. doi:10.3390/cancers15112916

2. Kirichenko A, Uemura T, Liang Y, et al. Stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) with single photon emission computed tomography (SPECT) functional treatment planning in patients with advanced hepatic cirrhosis. Adv Radiat Oncol. 2023:9(2):101367. doi:10.1016/j.adro.2023.101367

3. Otazo R, Lambin P, Pignol JP, et al. MRI-guided radiation therapy: an emerging paradigm in adaptive radiation oncology. Radiology. 2021;298(2):248-260. doi:10.1148/radiol.2020202747