Exploring MRI-Guided Adaptive Radiation to Treat Inoperable Pancreatic Cancer

Michael Chuong, MD

The use of MRI-guided radiation instead of the standard CT-guided technique is being evaluated in a single-arm prospective study led by Michael Chuong, MD, radiation oncologist and medical director of proton therapy and MR-guided therapy at Miami Cancer Institute.¹

The study aims to determine the feasibility and tolerability of single-fraction stereotactic ablative body radiation therapy (SABR) to treat primary or metastatic carcinoma of the lung, liver, adrenal gland, abdominal/pelvic lymph node, pancreas, and kidney.

In July 2021, the first patient was enrolled. At the time of the first patient enrollment, Chuong stated: “Published experience suggests that delivery of single-fraction SABR using MRIdian should be at least isotoxic and is effective as compared to multi-fraction SABR, as supported by its on-table adaptive planning capabilities and continuous soft-tissue tracking with automatic beam gating. We believe the study will demonstrate the feasibility to safely and effectively deliver SABR in only one fraction across these indications that will not only shorten overall treatment time but also reduce cost and improve increase patient convenience."

In an interview with Targeted Oncology™, Chuong provided further explanation of the validity of the MRI-guided radiation technique for use in patients with pancreatic cancer, how it compares with CT-guided radiation, and how a shift toward MRI-guided radiation may impact patients with pancreatic cancer in the future.

TARGETED ONCOLOGY™: From the perspective of radiation oncology, what are the key unmet needs for the treatment of inoperable pancreatic cancer.

CHUONG: Patients who have inoperable pancreas cancer have a pretty poor prognosis, and that hasn't changed very much in the last several years, if not several decades. This is in part because treatment tends to be effective for some amount of time. But long-term disease control remains quite poor and not achievable for most patients. This includes within the pancreas itself, as well as in other areas where tumor spread could happen. So, radiation therapy, we know is an integral part of care for inoperable pancreas cancer because it improves tumor control, as opposed to just chemotherapy alone. What some publications have suggested, including some from our own institution is that if we can give a significantly higher dose of radiation to the pancreas tumor, this could lead to significantly improved long-term tumor control within the pancreas tumor itself. This strategy could potentially lead to prolonged overall survival for patients, representing the first major advance and prognosis for these patients in a number of years.

Can you explain the precise form of radiation you are currently using and what has been shown with this technique historically?

Radiation therapy has been delivered on state of the art radiation machines for many years, and this can be done in a number of different regimens, so as short as 5 days and as long as 5 to 6 week once a day. What is novel about the MRI-guided radiation therapy approach is as opposed to using CT scans, which traditional radiation delivery machines use to image patients for positioning purposes, the MRI, offers a unique and novel imaging that is dramatically improved. It’s not just the quality of the imaging, as MRI has significant inherent soft tissue visualization advantages over CT. But also importantly, there is no other type of image guided radiation therapy other than MRI-guided radiation that offers continuous imaging throughout the patient's treatment. AtMiami Cancer Institute, we have the V-ray meridian linac, and we were the second in the United States to start treating with this as one of the pioneers in the country for image-guided radiation starting back in 2018.

So, both CT and MRI scans are able to be used prior to treatment starting to position the patient but only MRI. Guided radiation can continuously image throughout the treatment to ensure that the treatment accuracy is maintained. For tumors that move for example, those in the pancreas as well as other tumors in the chest and the abdomen and even in the pelvis, being able to visualize these changes even on a millimeter basis can make a tremendous difference in terms of targeting accuracy. It can also make a difference in terms of ensuring that dose to nearby normal organs is avoided. So, for example, as patients breathe, pancreas tumors will move mostly up and down. Our MRI linac, the meridian linac, can detect this and actually will track the tumor, the entire duration of treatment. We can basically tell it to only turn the treatment on when the tumors in an exact position and turn the treatment off if the patient breathes or moves outside of that position. This is something that dramatically reduces the area that we need. To treat in terms of the volume of the tissue that receives a high dose outside of the tumor. This allows us to deliver a significantly higher dose to the tumor as opposed to standard radiation techniques and also reduce those to nearby tissues reducing the risk of major side effects.

Can you describe the characteristics of the patients that you will consider for this type of radiation? How do you think this technique can improve outcomes for these patients?

MRI-guided radiation therapy, which is typically delivered in 5 days here, although to an ablative dose is something that we've seen have tremendous impact in terms of what seems to be improving long-term local control, as opposed to lower doses of radiation. Even those that can be delivered in 5 days on a different machine; we're seeing potentially dramatic improvement in longevity of the ability to keep tumors from essentially regrowing or coming back in the treated area within the pancreas using ablative MRI-guided radiation therapy. What's exciting is that this seems to potentially not only have an impact on local tumor control, but also potentially on long-term patient survival. So, in our recent analysis, we demonstrated that patients who received a blade of MRI-guided radiation therapy here, after typically some amount of chemotherapy, had a median survival of nearly 2 years, which is significantly higher than the historical unexpected outcomes from standard-dose radiation, which is typically about 1 year or a little bit more than 1 year. What's also exciting is that we achieve these results with most patients having no significant adverse effects. In fact, several our patients had no reported adverse effects at all, which is tremendous. So, this is an exciting time for pancreas cancer patients as novel treatments such as a blade of MRI-guided radiation now are emerging. We clearly need additional studies to better understand what the long-term outcomes and results are from this type of treatment. But our experience here at Miami Cancer Institute is one of a growing number of studies that are emerging, essentially demonstrating very similar results leading to enthusiasm that, in fact, this is a viable and promising approach moving forward for patients for whom surgery is not an option.

What else would you like to highlight regarding MRI-guided radiation therapy in pancreatic cancer?

I think the other sort of important ideas that highlight Are you know, this is this is a very exciting sort of, you know, this is a very exciting type of treatment and that the efficacy outcomes seem to be tremendous, but at the same time, really the quality-of-life impacts and really impacts on day-to-day life for these patients during and after treatment are very quite minimal. So, this is a completely noninvasive treatment. There is not one intravenous or one needle that the patients get at any point during treatment. There’s also no anesthesia required for this. So, patients, even those who are a bit older, and we've treated a number of patients who are in their 80s, and even 90s have tolerated treatment exceptionally well. In fact, we're submitting an abstract for outcomes in our older pancreas cancer patients who have gone through this ablative radiation therapy procedure. Nearly all patients have done exceptionally well through this because it is so well tolerated and really doesn't require any, invasive procedure whatsoever.

_Reference:

_{Miami Cancer Institute enrolls first patients in single-fraction stereotactic MRI-guided adaptive radiation therapy for inoperable primary or metastatic cancer trial. News Release. July 7, 2021. Accessed October 6, 2021. https://prn.to/2YpPpXb}