The Role of Radiation Therapy for Borderline Resectable Pancreas Cancer

At the 2023 Great Debates and Updates in Gastrointestinal Malignancies meeting, Joseph Herman, MD, discussed the argument against use of radiotherapy in borderline resectable pancreas cancer.

Transcript:

It's a pleasure to be here today. My name is Joe Herman. I am the Director of Clinical Research at Northwell Health Cancer Institute. It's been a pleasure to be part of the Great Debate and Updates, sponsored by HMP and the Oncology Learning Network.

Today, I had the pleasure of debating Dr Lisa Kachnic of the Department of Radiation Oncology at Columbia University, and our overarching topic was to evaluate the role of radiation in patients with borderline resectable pancreatic cancer. And my specific role was advocating on behalf of still incorporating radiation in this setting.

The role of radiation in borderline resectable pancreatic cancer is actually quite controversial. And I think the reason for this is that there are several single-institution studies and even multi-center studies that have evaluated the role of radiation in this setting and have shown a benefit in terms of an R0, or a margin negative, resection, as well as signals that there was also survival benefit.

There's benefits to giving radiation in this setting because it's likely to increase the likelihood of going to surgery. And patients who get to surgery clearly have a better survival than those who do not. I think in essence, there's an understanding that giving radiation is ultimately going to stack the deck to increase that likelihood. However, there have been some conflicting data, and that was a big part of our discussion today. And so, one that's most recent is the ALLIANCE trial that asked a very important question of whether or not patients benefit from a short course of stereotactic or hypofractionated radiation therapy after receiving upfront FOLFIRINOX.

This study's really important because it's really the first study to evaluate the role of hypofractionated radiation in the community or the cooperative setting. And it's also unique in a sense that patients were randomized at diagnosis. So, it does provide us with some real-world data of how these patients do both at academic and also in the community setting. However, I think the other thing that we recognize is that the study was small and it really wasn't developed or powered to ask a radiation question. That's the main crux of my discussion today, which was to just essentially keep the door open as it relates to radiation therapy, because this study did have a lot of caveats that are unique. But also what's really important, and Dr Matt Katz [University of Texas MD Anderson Cancer Center] and I talk about this all the time because as a disclosure, I am an author on the study, is that we're still going to learn a ton from this study that's going to help us understand how to derive and develop next trials.

As a quick summary, this trial did not show a benefit with radiation therapy in this setting, FOLFIRINOX alone before surgery was at least as good as historical controls, and I think it is now a backbone of how we should develop these trials moving forward. Although the ALLIANCE Trial ultimately was negative as it relates to radiation therapy, I think it's important to acknowledge again that there were some imbalances in the radiation arm, specifically higher CA 19-9, more patients were unable to get the full dose of chemotherapy. There's some understanding that probably the fact that less patients made it the surgery also contributed to the negative outcome.

Nevertheless, I think what this highlights is that as we continue to develop new trials, it's important, number one, that all patients are discussed in a multidisciplinary clinic or tumor board to make sure that from the very beginning we're enrolling the right patients on these trials.

Number two is that we're using everything available to us to select patients. What's really exciting is we are coming up with better biomarkers. We're sequencing these patients. We're getting ctDNA. We’re using all of these in modern trials are going to help us derive which patients are likely to benefit from radiation, which is a local therapy and surgery, as well as understand which ones should not get those therapies.

Finally, in the community setting and even in academic settings, there's a lot of heterogeneity in terms of how radiation is delivered and how we define “deliver radiation” and what dose we're actually delivering. And also the technology is evolving such that we have to understand what kind of biases that might induce within these new trials. As part of the GI Steering Committee, and we are currently working together across multiple disciplines to really ensure that the next trials that we develop use not only modern ways to select the patients, but also that we standardize as much as humanly possible, the way that we deliver radiation, so that the results are going to be more comparable now and in the future.

Personally, from my own perspective in taking care of patients, I do believe that we should always offer patients upfront systemic therapy. If they have a great performance status we should be aggressive with multi-agent chemotherapy. For the older patients that might not have great performance status, we probably need to lean on more of a single-agent chemotherapy regimen. And then I think after patients have completed their systemic therapy, if they haven't progressed, if they still are healthy, but frankly they need a break from the systemic therapy, I think that those are great patients to have consolidative radiation therapy to prevent local regional recurrence because local recurrence or progression can cause symptoms. It could cause bile duct obstruction, it could cause duodenal obstruction.

From a quality of life perspective and a quantity of life perspective, I think in those patients, radiation is still indicated. And in my own practice and at our center, those are the patients that we're giving radiation.

Also, we do have a clinical trial open right now, the GRECO-2 study, at our institution and wherever possible, again, assuming they meet the eligibility criteria, we are putting patients on that trial. And that's an international study, and we believe studies like this are going to help derive more information to help us develop future trials.

Source:

Herman, J. “Debate: Is There A Role for Radiation Therapy in Borderline-Resectable Pancreatic Cancer? Yes vs No — Yes.” Presented at the Great Debates and Updates in Gastrointestinal Malignancies; March 30-April 1, 2023; Chicago, IL.