MRI-Guided Radiation Therapy: A Novel Treatment for Pancreatic Cancer

Complete surgical removal of a pancreatic tumor is not possible for most patients. Chemotherapy and radiation therapy are typically recommended to slow tumor growth, but ultimately are not expected to be curative, writes Michael Chuong, MD.

Pancreatic cancer is responsible for more than 48,000 deaths annually in the United States, making it one of the leading causes of cancer mortality.1 Most pancreatic cancer patients have a short life expectancy because a diagnosis is not usually made until the cancer has progressed to an advanced stage, when symptoms such as jaundice and abdominal pain are more likely. As a result, complete surgical removal of the tumor is not possible for most patients. Chemotherapy and radiation therapy are typically recommended to slow tumor growth, but ultimately are not expected to be curative.2

Over the last decade, the transition from single-agent to multi-agent chemotherapy has achieved a modest improvement in survival for unresectable pancreatic cancer. However, the approach to radiation therapy has not changed significantly over that same time, and the prescribed radiation dose has stayed within a modest range to prioritize patient safety. Recent studies have suggested that delivering much higher doses of radiation could potentially improve both local tumor control and potentially overall survival.3-5 However, the proximity of the stomach and intestines to the pancreas is a limiting factor in significantly escalating the radiation dose for most patients while not causing significant toxicity.

MRI-guided radiation therapy (abbreviated as MRgRT) is a novel treatment approach that is changing the paradigm for how certain tumors, including those of the pancreas, are fundamentally treated.6 Offered only at a limited number of centers worldwide, MRgRT utilizes pre-treatment MRI instead of the more typical CT scans to ensure accurate patient positioning, and uniquely can continuously image the patient’s internal anatomy throughout treatment delivery, allowing for any change to be detected in real time and automatically pausing treatment if the tumor shifts even a few millimeters out of the intended position. Another distinction of MRgRT is the ability to adapt the treatment plan each day based on changes in the patient’s internal anatomy, which ensures accurate tumor targeting and avoidance of nearby critical organs.

As the second institution in the United States to treat cancer patients with the ViewRay MRIdian Linac in 2018, Miami Cancer Institute, part of Baptist Health South Florida, has since become recognized as a global leader for MRgRT, with patients regularly seeking treatment there from across the country and internationally. The MRIdian Linac is routinely used at the Institute to treat the most challenging tumors with a higher dose than could be safely delivered on a standard radiation delivery machine. Treatment on the MRIdian Linac for many tumors can be completed in five or fewer days, is completely noninvasive, and does not require anesthesia, resulting in little to no downtime for patients.

At the European Society for Radiotherapy and Oncology annual conference in Madrid on August 29, I presented long-term outcomes of 50 inoperable pancreatic cancer patients treated with chemotherapy followed by stereotactic ablative body radiation therapy (SABR) on the MRIdian Linac. An ablative prescription dose was used (50 Gy in five fractions) and most patients were treated to elective regions in addition to gross disease. Nearly all fractions required that the treatment plan be adapted before treatment delivery because of interfraction anatomic changes in the stomach and/or small bowel position that would otherwise have resulted in dangerously high dose to these organs using the original plan.

While the historical median survival time for inoperable pancreatic cancer patients is only about 12-15 months after non-ablative radiation therapy, I reported that patients treated on the MRIdian Linac achieved a median survival of 21 months. In addition, while lower radiation dose is associated with 2-year survival of 20%, I reported 2-year survival of 50% with some patients being alive more than 3 years after their initial cancer diagnosis. Significant side effects were rare.

These exciting results support MRgRT as a potential paradigm shift in the management of inoperable pancreatic cancer, offering the possibility of achieving long-term survival while maintaining a high quality of life. I and my fellow investigators at Miami Cancer Institute are leading several novel clinical trials for pancreatic cancer and other challenging cancers using the MRIdian Linac that aim to significantly improve patient outcomes and redefine the standard of care for radiation therapy.

REFERENCES:

1. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin 2021;71:7-33.

2. Hammel P, Huguet F, van Laethem JL, et al. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The lap07 randomized clinical trial. JAMA 2016;315:1844-53.

3. Krishnan S, Chadha AS, Suh Y, et al. Focal radiation therapy dose escalation improves overall survival in locally advanced pancreatic cancer patients receiving induction chemotherapy and consolidative chemoradiation. Int J Radiat Oncol Biol Phys 2016;94:755-65.

4. Rudra S, Jiang N, Rosenberg SA, et al. Using adaptive magnetic resonance image-guided radiation therapy for treatment of inoperable pancreatic cancer. Cancer Med 2019;8:2123-2132.

5. Reyngold M, Parikh P, Crane CH. Ablative radiation therapy for locally advanced pancreatic cancer: Techniques and results. Radiat Oncol 2019;14:95.

6. Hall WA, Paulson ES, van der Heide UA, et al. The transformation of radiation oncology using real-time magnetic resonance guidance: A review. Eur J Cancer 2019;122:42-52.