By: Dr. Joel Goldwein

Radiation therapy is integral to the management of most cancers, including the three most common cancers globally, breast, prostate and lung cancer. About 50-60 percent of cancer patients receive radiation therapy, making it one of the most common treatment options.

The Elekta MR-linac, a new advance in radiation therapy technology, is bringing this pillar of cancer therapy into the age of personalized, precision medicine. MR-linac is designed to address a decades-long clinical need in radiation therapy: the ability to “see while you treat” in real time and in any plane. MR-linac is the first system that integrates precision radiation therapy delivery with real-time high-field 1.5 Tesla (T) MR imaging.

With high-field 2D MR imaging at a rate of at least five frames per second, tumors can now be precisely located, their movement tracked and treatment delivery adapted in real-time in response to changes in tumor position, shape, biology and the relationship to sensitive organs over time. This is essential for improving efficacy and safety, and developing personalized treatment regimens that can improve patient outcomes.

Addressing a critical unmet need in radiation therapy
Tumors change shape and size and their position relative to surrounding tissue over the course of treatment and during individual treatment sessions. This results in uncertainty about the location of tumor and normal tissue during treatment, and necessitates increased planned treatment volume (PTV) margins in order to ensure complete dosing of the tumor. Larger PTV margins increase the amount of normal tissue that is dosed, which causes more widespread or more severe toxicity that can lead to acute and long-term side effects and reduced quality of treatment outcomes.

The ability to see and monitor radiation dosing in real time could substantially reduce uncertainty about where radiation is being delivered, allowing PTV margin reductions that could better spare healthy tissue. Smaller PTVs may enable delivery of higher doses to the tumor, which could improve efficacy, while minimizing toxicity.

Real-time dose monitoring also allows calculation of the total amount of radiation accumulated in the tumor or surrounding tissue at any point over the course of therapy. Subsequent treatments can then be adjusted to ensure that the actual dose delivered is consistent with the planned dose, which is critical for optimizing outcomes.

MR-linac is expected to have broad utility in the treatment of many cancers, including tumors that are not amenable to current radiation therapy approaches. The following examples demonstrate how MR-linac may improve outcomes, reduce patients’ treatment burden and enable personalized cancer therapy.

Potential for improved outcomes in pancreatic cancer
Effective eradication of pancreatic tumors requires relatively high radiation doses, and the PTV margin is typically large in order to ensure effective dosing of the entire tumor. The high dose coupled with the large PTV exposes the duodenum and other surrounding tissues to high radiation doses, which can lead to toxicity and long-term side effects. In many patients, this toxicity is a barrier to the dose escalation necessary to eradicate the tumor.

Precise tumor tracking with MR-linac can allow clinicians to reduce the PTV margin while remaining confident that the entire tumor is treated effectively, minimizing toxicity and potentially allowing delivery of a higher radiation dose.

Potential for reduced patient treatment burden in prostate cancer
Radiation therapy for prostate cancer is typically delivered over 20-30 fractions, and sometimes even fewer. This high fraction number is largely driven by the desire to protect the rectum, bladder and urethra from the toxic effects of radiation, which requires limiting the total amount of radiation delivered during each treatment session. The reduced PTV that can be achieved with MR-linac could minimize exposure of at-risk organs, allowing higher doses to be delivered during each session and reducing overall treatment time.

It is anticipated that the MR-linac could support regimens comprising five or fewer fractions, which would not only reduce patients’ burden of treatment but could also increase access to radiation therapy by allowing more patients to be seen over a given time period.

Predicting response to therapy
Response to radiation therapy is typically assessed after completion of treatment and is based, among other things, on changes in tumor size. However, tumor shrinkage is sometimes a lagging indicator of response to radiation therapy. Functional MR imaging (fMRI) is an investigational response assessment approach that goes beyond anatomy and detects changes at a cellular level within the tumor. These changes occur before anatomical changes can be detected, potentially allowing treatment to be refined as needed as early as possible.

The use of functional MR monitoring over the course of treatment may help predict which patients are most likely to respond to additional radiation therapy and, potentially, chemotherapy, and which patients may require less. More timely adaptation of the treatment plan based on fMRI data could minimize unnecessary radiation exposure for patients who are not having a response to treatment, and enable personalization of radiation therapy regimens based on the unique biology of each patient’s tumor. Importantly, fMRI may also provide insight into which regions of the tumor are the most biologically active, resulting in refined dosing plans that have the potential for maximizing efficacy and reducing toxicity.

A new paradigm for radiation therapy innovation
While MR-linac is itself an innovative radiation delivery system, the process by which it was developed is also highly innovative. Elekta developed MR-linac in collaboration with the Elekta MR-linac Consortium, which comprises clinicians and scientists from leading cancer centers around the globe. This approach ensured that clinical need – with respect to optimizing both clinical outcomes and clinical workflows – was a key driver throughout the development and evaluation process.

Yet innovating new technology is not necessarily sufficient for improving patient outcomes. Developing the data and guidelines that enable clinicians to identify patients most likely to benefit from MR-linac and use the system effectively is also essential for optimizing patient care. Toward this end, the consortium is taking a systematic approach to evaluating the use of MR-linac for specific cancer indications.

The initial focus is on those indications most likely to benefit from MR-linac, which includes common cancers such as breast, prostate and lung cancers. This collaborative yet systematic approach creates a value proposition for the MR-linac system that comprises both technology and validated clinical insights, and helps to ensure that the full potential of this new technology is realized for patient benefit.

The future is at our doorstep
The MR-linac may be cutting-edge, but it is also a here and now technology. The system received CE mark in June 2018 (under the name Elekta Unity), and is being made available to patients throughout Europe. A 510(k) Premarket Notification has been submitted to the U.S. Food and Drug Administration, and its clearance is pending.

Radiation therapy has been a pillar of cancer care for decades. With MR-linac, this important treatment modality will enter the age of personalized, precision cancer therapy and advance new treatment paradigms. As has been the case with previous technological advances in radiation therapy, MR-linac may support the development of novel combination regimens utilizing other agents that previously couldn’t be delivered with radiation therapy due to potential overlapping or excessive toxicities, and may open the door to wholly new regimens that combine radiation with immunotherapy.

Additionally, the unique high-field imaging capabilities of the MR-linac have the potential to make fMRI a standard component of the personalized therapies that cancer patients need. Ultimately, the combination of the technology with the clinical underpinning that is driving its development has the potential to result in significant outcome improvements that will truly benefit radiotherapy patients.

About the author: Dr. Joel Goldwein is a radiation oncologist and senior vice president, Medical Affairs, Elekta.