Clinical Trial Shows Safety of Ablative Radiotherapy for Inoperable Pancreas Cancer

Researchers at Miami Cancer Institute, a part of Baptist Health, believe they are one step closer to changing the treatment paradigm for patients with inoperable pancreatic cancer. As one of the highest accruing centers to the first-of-its-kind international phase II SMART trial, the Institute is playing a significant role in demonstrating the benefits of a novel MRI-guided radiation device called MRIdian.

The device enables very high ablative radiation doses ― doses high enough to completely eradicate tumors ― to be precisely delivered in as few as one to five outpatient sessions. The same high-dose regimen delivered on traditional radiation devices using CT scans for targeting has previously been deemed unsafe in prior clinical trials and therefore lower non-ablative radiation dose is currently the standard of care for inoperable pancreas cancer, which improves safety but at the expense of treatment efficacy.

Several retrospective studies published by researchers at Miami Cancer Institute have demonstrated that very high ablative radiation therapy delivered using MRIdian may not only significantly improve overall survival for select inoperable pancreas cancer patients, but also does so with a very low probability of side effects. However, no prospective clinical trials of ablative radiation therapy for pancreas cancer had been previously completed.

Now, initial results of  “A Multi-Institutional Phase II Trial of Ablative 5-Fraction Stereotactic MR-Guided On-Table Adaptive Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer” (SMART) have been published in the International Journal of Radiation Oncology – Biology – Physics, a leading journal in the field of radiation oncology.

The primary objective of the SMART trial was to demonstrate that delivering ablative radiation doses to inoperable pancreas cancer with MRIdian does not cause an unacceptably high rate of severe gastrointestinal (GI) side effects, according to co-principal investigator Michael Chuong, M.D., the lead physician for the MRI-guided radiation program and medical director of Miami Cancer Institute’s Department of Radiation Oncology.

Michael Chuong, M.D., the lead physician for the MRI-guided radiation program and medical director of Miami Cancer Institute’s Department of Radiation Oncology

“We are thrilled that this was a positive trial and that no patient had severe GI toxicity definitely related to radiation therapy,” says Dr. Chuong. “Treatment was exceptionally well-tolerated, despite the exceptionally high dose, which was made possible by the advanced features of MRIdian. It was also encouraging that patients themselves reported that the high-dose radiation therapy did not negatively impact their quality of life.”

More than 64,000 people are expected to be diagnosed with pancreatic cancer each year in the U.S., according to estimates from the American Cancer Society. Pancreatic cancer remains a challenge to treat because symptoms, which can mimic other health problems, rarely occur until tumors are at an advanced stage, at which time treatment options are limited. Most patients are not candidates for potentially curative surgery at the time of diagnosis and are primarily offered chemotherapy and sometimes radiation therapy.

In 2018, Miami Cancer Institute was the second center in the U.S. to treat patients with the MRIdian Linac, the first FDA-approved MR-guided radiation therapy system. Since then, the Institute has become one of the most experienced centers treating inoperable pancreas cancer and other challenging cancers with this advanced device. The Institute also has become a leader in research aimed at defining novel clinical indications and best treatment techniques for MRIdian, influencing practice around the world.

“If a patient is interested in being treated with this technology, then there are benefits to seeking out an established program,” Dr. Chuong advises. “Studies show that outcomes may be significantly better at high-volume centers for a multitude of technical procedures including surgery and radiation therapy. Experience matters.” Lynn Cancer Institute at Boca Raton Regional Hospital, part of Baptist Health, is also now treating cancer patients with the same MR-guided radiation therapy system.

The MRIdian Linac marries two technologies ― a radiation delivery system and an MRI scanner, which more accurately targets the tumor than standard radiation devices that use CT scans with inferior image quality. In addition, a continuous MRI scan is acquired throughout treatment to monitor the tumor position. “If the tumor shifts – due to breathing motion, for example – the treatment is automatically paused until the correct position is achieved,” Dr. Chuong says.

Clinicians are also able to adjust the radiation dose delivery to account for day-to-day changes in the patient’s internal anatomy, further enhancing both safety and efficacy, something traditional radiation therapy is unable to do. These advanced capabilities make it possible to safely increase the dose of radiation to the high level used in the SMART trial and complete treatment in only five days, compared to five to six weeks of standard lower-dose radiation therapy.

Nearly all patients return to work or other normal activities immediately, according to Dr. Chuong. “MRIdian treatment is non-invasive, it requires no anesthesia or needles, it leaves no residual radiation in the body and is quick. Patients are routinely out of the treatment room within 30 to 45 minutes,” he says.

Patients treated with MRIdian are also able to start treatment potentially several weeks sooner than with traditional radiation, which first requires the placement of small metal fiducial markers that serve as surrogates for the tumor position that otherwise would be poorly visualized using CT scans. With MRIdian, the tumor itself can be clearly seen with MRI, thus making fiducial marker placement unnecessary.

The success of the SMART trial has paved the way for the multi-center phase 3 LAP-ABLATE trial (NCT05585554) being led by Dr. Chuong and other internationally recognized pancreas cancer experts. Patients eligible for enrollment include those with locally advanced pancreatic cancer with no evidence of tumor growth after initial chemotherapy who are randomized 2:1 to receive ablative radiation therapy using the MRIdian Linac or no ablative radiation therapy.

Many aspects of the radiation therapy planning and delivery techniques being used in this international trial were developed at Miami Cancer Institute, Dr. Chuong notes. “The primary objective is to evaluate whether the use of ablative MRIdian therapy significantly improves overall survival over chemotherapy alone, which is the current standard of care. If the LAP-ABLATE trial is positive, then it would truly represent a potentially practice-changing study.”