Gaining MOMENTUM in Optimizing the Clinical Use of Cutting-Edge, Personalized Cancer Treatments
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Radiation therapy is a well-established and effective treatment for cancer. Over the last six decades, the clinical outcomes of radiation therapy have steadily improved due, in large part, to technological innovation driven by clinical needs. The regulatory approval of these new systems is based on limited clinical data that are sufficient to determine that they are at least as safe and effective as the systems currently in use. However, just being “as good” is not the ambition of either the industry or their clinical partners. Continued collaboration is essential for the systematic development of guidelines and evidence that allow these innovations to be optimized in specific patient populations and cancer types.
In 2018, the first radiation therapy device to combine a cutting-edge linear accelerator (linac) with a high-field magnetic resonance (MR) imaging system was approved by regulators in the United States and the EU. It is hard to over-estimate what an enormous engineering achievement this represents, as without its clever design, a linac could not function in the presence of an MR’s large magnetic field, and an MR could not image patients in the presence of the electrical currents of a linac. This revolutionary system – developed in partnership with the global MR-Linac Consortium – was both a technological tour-de-force and a testament to the power of interdisciplinary global collaboration to address today’s most pressing health challenges. With this MR-Linac, clinicians can now see tumors in real time as radiation is delivered, allowing adaptation of the dose to enhance delivery to the tumor while sparing nearby healthy organs and tissues. Increased precision allows a higher dose to be delivered to the tumor – potentially increasing efficacy – or the same dose to the tumor- potentially reducing side-effects that occur when surrounding healthy tissue is damaged. It also supports the use of radiation therapy for hard-to-treat cancers in which this treatment approach was not previously feasible.
From its inception, the MR-Linac Consortium’s guiding principle has been to work out how to use the MR-Linac to maximize the benefits that it can provide to patients. This also involves the dissemination of these best practices to early users and the collection of real-world evidence to demonstrate these benefits to multiple stakeholders. To achieve these goals, the MR-Linac Consortium has launched the MOMENTUM study, which is designed to collect this robust body of real-world MR-Linac clinical data and insights. MOMENTUM is also serving as a platform upon which members of the MR-Linac Consortium can build and rigorously test experimental approaches that will guide the use of high-field MR guided radiotherapy (MRgRT) to achieve optimum cancer patient outcomes.
Promising initial results from 702 patients who have participated in the MOMENTUM study have just been published in International Journal of Radiation Oncology, Biology, Physics.1 Data show that the high-field MRgRT system was used to treat tumors in 39 anatomical sites, with prostate (40%), oligometastatic lymph node (17%), brain (12%), and rectal (10%) cancers the most common indications. Results for 415 patients for whom toxicity data were available at three months follow-up are highly encouraging, with only 4% experiencing grade 3 acute toxicity due to radiation therapy, and no radiation-related grade 4 or 5 acute toxicity reported. Another key finding was that an adapt-to-shape treatment strategy was used in more than half of all radiation fractions delivered. Although this approach is more demanding, it was used in a wide variety of cancer types, likely reflecting clinicians’ belief that adaptive radiation therapy (ART) is solving a general problem in radiation oncology.
Going forward, this initial cohort will continue to be followed for at least two years post-treatment to estimate the late toxicity experience and treatment outcomes. Additional MOMENTUM analyses will focus on developing hypotheses about how high-field MRgRT might improve patient cure rates or quality of life relative to alternative radiation therapy paradigms. Eventually, we envision that MOMENTUM will serve as a platform for formal hypothesis-testing clinical trials that will generate knowledge with the highest level of certainty.
In contrast to history of radiation therapy, in which the real-world evaluation of the safety and efficacy of new radiotherapy devices often occurs many years after their introduction, MOMENTUM enables the systematic collection of safety, efficacy and patient-reported outcomes data concurrent with the clinical implementation of high-field MRgRT. This collaborative approach has the potential to identify indications and patient sub-populations most likely to benefit from this novel approach to radiation therapy and generates information on feasibility and safety in a variety of clinical scenarios just as the community is first applying it. This real-time registry-based assessment of a new technology provides valuable information for all the relevant stakeholders, including vendors, providers, payers, and patients.
Perhaps most importantly, systematic data collection may support “big data” methodologies. For example, a large, curated repository can be used to be used to enhance the device itself by serving as a training data set for machine learning-based workflow algorithms. Alternatively, the data collected can be used to identify patient-, indication- or clinical site-specific factors that predict tumor response to therapy or adverse reactions in adjacent normal tissues that can lead to treatment side effects. Such analyses may not be feasible or may take years to conduct when each individual medical institution collects data in an inconsistent and non-standardized way.
Global, prospective, multi-institutional registries are a powerful tool for facilitating the rapid optimization of novel medical devices and pharmaceutical therapies that have the potential to improve outcomes for patients with cancer. The initial publication from the MOMENTUM study demonstrates the safety and feasibility of Elekta’s high-field MR-Linac but also the value of implementing this type of registry for a new paradigm in radiotherapy. The potential to leverage big data analytical methods on a growing body of real-world safety, efficacy and patient-reported outcomes combined with patient health and demographic data opens the door to using vast amounts of anonymized information to develop highly personalized treatment regimens that offer each patient the best chance at a positive outcome. Expanded use of systematic, collaborative registries should allow the medical device, pharmaceutical and oncology communities to gain additional momentum on the road toward personalized cancer care.
1. de Mol van Otterloo SR, Christodouleas JP, Blezer ELA et al. on behalf of the MR-Linac Consortium. Patterns of care, tolerability and safety of the first cohort of patients treated on a novel high-field MR-Linac within the MOMENTUM Study: Initial results from a prospective multi-institutional registry. Int J Rad Oncol, Biol, Phys. 2021; doi: 10.1016/j.ijrobp.2021.07.003