MRIdian-Guided Radiation Therapy Is Safe and Effective in Patients With Cancer

Ablative radiation therapy guided by MRIdian technology provides individualized tumor imaging and treatment that improves upon traditional imaging and radiation therapy approaches offering patients with cancer a noninvasive, short-course treatment option that does not hinder their quality of life (QOL), according to Michael D. Chuong, MD.

The single-arm, phase 2 SMART trial (NCT03621644) investigated the efficacy and safety of 5-fraction stereotactic magnetic resonance–guided on-table adaptive radiation therapy (SMART) in patients with borderline resectable or locally advanced pancreatic cancer. Acute gastrointestinal toxicities of grade 3 or higher that were possibly related to SMART were observed in 8.8% of patients, and none were definitely related to SMART. Additionally, the 1-year overall survival (OS) rate after SMART was 65.0%.¹

The upcoming LAP-ABLATE trial (NCT05585554) will evaluate induction chemotherapy followed by SMART vs chemotherapy alone in patients with locally advanced pancreatic cancer, with 2-year OS as the primary end point.²

“Magnetic resonance imaging [MRI]–guided radiotherapy offers superior imaging capabilities and certainty that radiation is being delivered to the correct location in certain parts of the body, especially the upper abdomen and the pelvis,” Chuong said in an interview with OncLive^®.

In the interview, Chuong discussed the role of MRI-guided radiation therapy in pancreatic cancer and other solid tumors; the benefits of the MRIdian system; and future directions regarding MRIdian operation training and research investigating this approach in combination with chemotherapy.

Chuong is the vice chair and medical director of Radiation Oncology and leader of the GI radiation service at Baptist Health Miami Cancer Institute in Florida.

OncLive: How has MRI-guided radiation therapy been incorporated into the cancer treatment armamentarium?

Chuong: Radiation therapy has evolved significantly over the past few decades, both regarding how targeted radiation treatments are and how image guidance has evolved. Even if we can deliver pinpoint radiation to a tumor, ensuring that radiation goes exactly where it needs to go and not to organs outside the tumor is important. MRI-guided radiation represents a paradigm shift in how radiation therapy is delivered.

Standard radiation therapy, which is not MRI guided, is delivered typically using computed tomography [CT] scans that are built into the radiation delivery machine or x-rays that are taken while the patient is in the radiation delivery machine. Although those scans or x-rays are good for imaging some tissues, [they are not good for imaging] others. For example, [when] imaging tumors in the upper abdomen, such as pancreas cancers, it is difficult to clearly see with CT scans or x-rays. Improvements in image guidance are needed for tumors in that area of the body.

MRI guidance offers significantly improved soft-tissue imaging of certain areas, especially in the upper abdomen, lower abdomen, and pelvis. Whereas on CT scans, for example, [it may] be difficult to clearly see the tumors, on MRI, [the images are] crystal clear. When understanding exactly where the radiation is going, it becomes easier to understand that the radiation is being delivered to the correct area with MRI guidance.

The second ability of MRI guidance to transform how radiation is delivered is that it can adapt treatment. Standard radiation machines deliver the same radiation dose to the same place in the body day after day or week after week, whatever the prescribed regimen. For example, [in a patient with] pancreas cancer, the stomach and intestines are constantly in motion. Each day the patient comes in for treatment, the stomach and intestines may be in different locations. With standard radiation therapy, either using CT scans or x-rays for image guidance, the same radiation is delivered to the same location, even if the stomach or intestines are closer to the tumor on any given day, and potentially may receive significantly higher doses of radiation.

With MRI guidance, and specifically with the MRIdian system, we can understand changes in the anatomy each day because a new MRI scan is acquired on the treatment machine. Within a few minutes, we can shape and sculpt the radiation dose and beams so the high dose is not delivered to the stomach if it is closer to the tumor, while still ensuring that a high dose of radiation is delivered to the tumor itself. This can decrease the risk of adverse effects [AEs] and can also safely allow us to deliver higher doses of radiation to the tumor itself.

When we combine the capability to have clearer pictures and confidence that the radiation dose is targeted to the right area with the ability to modify the treatment and personalize the radiation delivery each day based on the anatomy we see, the ability to deliver ablative radiation doses, [which are] high doses that could result in surgical tumor control and eradication, become enhanced with MRI guidance. Centers like Miami Cancer Institute and others internationally have been exploiting this technology to offer ablative radiation to patients who do not have good surgical alternatives because their tumors are too large or extensive for surgery. In many cases that we’ve seen firsthand [this approach has] resulted in complete eradication of tumors. We’ve achieved that with minimal, if any, AEs.

What research supports the use of the MRIdian system in radiation oncology?

Miami Cancer Institute is a unique cancer entity because we offer state-of-the-art radiation therapy, from proton therapy, specifically pencil beam proton therapy, to the state of the art in x-ray therapy, including the MRIdian Linac system. We just passed the 5-year anniversary of our MRIdian program, and over those years, we have become experienced in understanding the value of each of these technologies.

MRI-guided radiotherapy has a prominent role for certain indications that outshines other technologies, and it provides potentially curative outcomes for certain unresectable tumors that other technologies are not as well suited for. For example, [many of the patients we have treated with MRIdian have] large, unresectable pancreas cancers and typically have short survival times and limited options. We have published several studies from our institution, and participated in some international, prospective clinical trials, and have been 1 of the leading accruers to the SMART trial, which was the first prospective trial to evaluate ablative MRI-guided radiation therapy delivered in 5 days.

[The findings] from all those studies have stimulated excitement within the pancreas cancer and radiation oncology communities that these patients could have significantly prolonged survival compared with [their outcomes with] standard radiation options. For example, the median [OS] for patients with this disease, either with chemotherapy alone or chemotherapy plus standard, lower-dose, non-ablative radiation is approximately 15 months, and the 2-year [OS rate is] approximately 20%. In the data published from our center and others with this high-dose, escalated, ablative radiation approach with MRIdian, the numbers are substantially higher. The median [OS] is approximately 20 months, and the 2-year [OS rate] is approaching 50%, representing a potential doubling of long-term OS for patients. This is exciting for a disease as difficult to treat as pancreas cancer and exemplifies the ability of this technology to deliver such a high radiation dose that no other radiation platform can deliver, at least safely.

On the heels of those data, we’re excited to be 1 of the lead institutions, [with me as] 1 of the principal investigators for the LAP-ABLATE trial, an international trial comparing chemotherapy alone vs chemotherapy plus 5-day ablative radiation treatment using the MRIdian device. [This trial hopes] to show that the addition of ablative radiation improves long-term OS. This trial is slated to open at Miami Cancer Institute soon, as well as globally across several countries and institutions.

How does the MRIdian system optimally operate in patients with cancer?

The MRIdian device facilitates higher-dose radiation and the delivery of radiation within a shorter period. At many centers, treatment is only offered once a day Monday through Friday for many weeks, if not multiple months. [With] the MRIdian device, the same dose, or substantially higher doses, can be safely delivered in a more compact period, as short as 1 day. We’ve been increasingly treating patients with just 1, 30-minute treatment of high-dose ablative radiation that can potentially eradicate tumors entirely, instead of those patients receiving treatment for days, weeks, or months. [MRIdian] offers convenience to patients; lowers overall costs for health care systems; and in the right hands and with the right experience, can result in wonderful outcomes of tumor control and eradication, [while being] delivered safely.

When we consider treatment with higher doses, it’s not just the technology that makes the difference, it is pairing the technology with expertise to deliver the treatment appropriately. As 1 of the first adopters of this technology in the United States and worldwide, [Miami Cancer Institute has] substantial experience treating [patients with] the most difficult tumors. Patients have recognized that. We’ve had patients be referred from across the world, as far as Thailand and Brazil, as well as domestic patients from other academically renowned institutions that don’t have this technology, who recognize that certain institutions have expertise in treating [patients with] certain tumors.

How are radiation oncologists trained to use the MRIdian system?

Training with this device is an evolution. As of 2018, we were the second institution in the United States to start treating with the MRIdian device. There were only a few centers [with this technology then], and today there are still a relatively small number of MRIdian devices in the United States or worldwide, approximately 50 systems.

As the community has grown, the need for training and standardization has grown as well. The infrastructure for that is being built. Efforts are developing to create robust, advanced training programs.

[Miami Cancer Institute was] 1 of the first [centers] to offer such an advanced training program. We are slated to start this program in fall [2023]. Currently, there is not a worldwide, established training program, as the technology is new. However, Miami Cancer Institute is leading the way for sharing best practices and experience in treating patients with this device for the past 5 years. I hope that will help create better practice standardization across new and current MRIdian systems. There is a plan for the curriculum from our program to be expanded and offered at other centers, so these training opportunities can be more widely taken advantage of by centers that may not be geographically close to Miami.

How does MRIdian-guided radiotherapy affect patient QOL?

The fact that we could potentially change the treatment paradigm for patients with certain cancers who are not surgical candidates and that we might prolong life without causing toxicity is incredible. All this is done without needles, incisions, or anesthesia. This is a completely noninvasive treatment. Patients lie still on the table for approximately 30 minutes, [then] they get up and go home, or go back to work, or go play golf, and they come back the next day to finish their treatments over a few days, typically. All this is achieved without downtime for the patient, which is important for patients who need to work, have children to take care of, [etc.]. The effect on day-to-day activities is minimal, if any.

That is an important consideration. We routinely have patients who travel from across the country and world who can get on a plane, come here for 5 days of treatment or as short as 1 treatment, get on a plane the day after their treatment or potentially the same day, and have no ill effects. It’s incredible. The fact that all this can be done potentially with the outcome of their tumor being eradicated and having potentially no AEs is a paradigm shift in what we can expect regarding the outcomes and AEs of the radiation.

References

1. Parikh PJ, Lee P, Low DA, et al. A multi-institutional phase 2 trial of ablative 5-fraction stereotactic magnetic resonance-guided on-table adaptive radiation therapy for borderline resectable and locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. Published online May 19, 2023. doi:10.1016/j.ijrobp.2023.05.023
2. Locally advanced pancreatic cancer treated with ABLAtivE stereotactic MRI-guided adaptive radiation therapy (LAP-ABLATE). ClinicalTrials.gov. Updated October 19, 2022. Accessed August 7, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05585554