Radiation Could Aid in Increasing Pancreatic Cancer Resections

Better utilization of radiation therapy can allow for more patients with pancreatic cancer to undergo resection, and has the potential to lead to better outcomes, said Amol K. Narang, MD.

Patients with unresectable cancer have been limited to treatment with traditional chemotherapy agents. Over the past few years, however, systemic therapeutic improvements have been made.

For those who have been previously thought to have unresectable disease, chemotherapy combinations may have the potential to downstage tumors to the point that they are resectable, said Narang, who is an assistant professor of radiation oncology and molecular radiation sciences at Sidney Kimmel Comprehensive Cancer Center of Johns Hopkins Medicine. However, ongoing research is exploring other options, such as radiation.

Radiation can be helpful for marginal sterilization, but higher doses will need to be administered, said Narang. In other malignancies, such as lung cancer, high doses of radiation have been shown to be reduce the tumor enough to allow for surgery to become a potential option. If given at the right dose, Narang hypothesized that similar success may be seen in the pancreatic cancer space.

“Local [tumor] growth can not only drive poor quality of life, but also mortality,” said Narang. “Controlling that growth will be a huge benefit of radiation.”

OncLive: What does the current pancreatic cancer treatment paradigm look like?

In an interview with OncLive, Narang discussed recent advances made in the treatment of pancreatic cancer and explained how radiation oncology can be used to provide further clinical benefit to this patient population.Narang: Over the past few years, there have been improvements made in the systemic therapy we give these patients. We are using combinations of various chemotherapy agents that have been around for quite some time. There were 2 landmark studies some years ago that looked at FOLFIRINOX and gemcitabine in patients with metastatic disease. The studies compared that regimen with gemcitabine alone, which was the standard of care. The combination showed significant improvement in patient outcomes. With the proof of concept for these chemotherapy combinations, it geared us towards being more locally aggressive in pancreatic cancer. Previously, there had been a lot of disillusionment in doing this given the high rate of systemic relapse.

We have seen some recent reports on the use of local therapy with radiation and surgery for patients who had previously been thought to have unresectable disease. While these are retrospective studies, there have been interesting findings, specifically in that these chemotherapy combinations can downstage tumors. It can potentially render them to a point where unresectable. The radiographic response after chemotherapy, or, perhaps, the lack thereof, is inconsistent with path findings or what you find in the operating room (OR). Patients with locally advanced disease comprise approximately 30% of the patients with pancreatic cancer. Survival of these patients tends to be on the order of what is historically presented for those who are considered to have the best outcomes: those with resectable disease. Median overall survival (OS) is about 36 months. This has been really encouraging, and it has encouraged several high-volume centers to be more aggressive in pursuing exploration for patients.

Where does radiation fit into this paradigm?

At Johns Hopkins Medicine, we published our experience [in 2018] for patients with locally advanced disease who underwent treatment through our multidisciplinary clinic. What we found was that for these patients, most of them received these more aggressive regimens and undergo exploration. Three-quarters of those patients were able to have their tumor resected. About 90% of the patients who underwent resection underwent a margin-negative resection, which is very encouraging. Median OS has been 36 months for these patients, but perhaps, with longer follow-up, we will see even more impressive results. Again, this is similar to what we see in the patients with the most favorable presentation of disease. In terms of radiation, it can be useful for several different endpoints. In the setting of more aggressive attempts at resection, the radiation can be helpful for margin sterilization, helping the surgeons peel the tumor off the blood vessels; this is the impediment to resection. Now that more patients are being taken to exploration, it assists in achieving a margin-negative resection. The other thing that we are finding is that in this patient population with locally advanced tumors, local recurrence is a common pattern whereas in resectable disease it is a distant pattern of failure. Radiation can be beneficial in that setting as well.

The other issue is that for some of these patients, even with our best chemotherapy, their tumors are never going to come out. What do we do after chemotherapy for those patients? Do we tack on radiation at the backend of chemotherapy? This is an open question because we don't have any randomized data to suggest that. However, there is value in doing that to help prevent the morbidity of local growth of the tumor.

What are some of the ongoing efforts to increase radiation dosage?

Ultimately, we need to give higher doses of radiation. The doses that we give right now are not particularly high because we are limited by the location of the tumor, [which is often] close to vital, sensitive organs such as the bowel and stomach. Strategies that can help increase the dose of the tumors will be beneficial. We are seeing in other diseases, like lung cancer, that high-dose radiation can reduce the tumor in such a way that it is easily resected. Perhaps with the right dose in pancreatic cancer, we can see something similar. One of the ways we are doing this is to see if we can endoscopically inject a material between the pancreas and the bowel that will essentially push the bowel away from the radiation site. This has been a successful approach in prostate cancer, where the neighboring rectum is the dose-limiting organ at risk. In prostate cancer, there has been a large randomized trial, which showed that endoscopically pushing the rectum away from the prostate allows for less complications to the rectum. We are trying to see if we can replicate this. We have a trial at Johns Hopkins Medicine looking at that.

Another thing we are looking at is intraoperative radiation, which is radiation delivered in the OR. We are also looking at more advanced means of radiation, like proton therapy and other new technologies that can help guide treatment. There is a lot on the horizon to be encouraged about.