Adjuvant/Neoadjuvant Therapy for Pancreatic Cancer

Transcript:

John L. Marshall, MD: Let’s shift a little bit to the role of adjuvant therapy. For us in GI cancer, maybe the most important news is in adjuvant therapy in pancreas cancer. To get us started, Kabir, why don’t you get us going on just the fundamentals. What’s happening on the surgical side? This is not an easy operation. Any major evolution there going forward?

Kabir Mody, MD: I think that our surgery colleagues have made a lot of headway in terms of the types of operations they’re able to do. It’s not necessarily a simple Whipple. They can do pretty major vascular reconstructions.

John L. Marshall, MD: So, more and more people are going to surgery than were before?

Kabir Mody, MD: Right, exactly. They realize the value of doing it in a high-volume center. That’s important. They’ve made strides in laparoscopic surgeries, robotics included, and then also in terms of the imaging that goes along with their surgical planning. I think they're doing a great job. But, ultimately, I think they’ve also made strides in accepting that chemotherapy is part of that paradigm, and it’s really a multidisciplinary approach to even resectable disease.

John L. Marshall, MD: That is a big culture shift that I think some centers are moving forward faster than others. Some where the surgery folks are saying, “I’ve got my window now, I don’t want to lose it.” But, as our chemotherapies have gotten more and more effective, we do see some acceptance. So, I think that’s variable around the country as to what your institutional standard is about surgery right away, versus chemotherapy approach. Toni, how do you guys decide who is an operable candidate in your shop?

Tanios S. Bekaii-Saab, MD: This is a multidisciplinary discussion that has to involve at least the surgeon, the medical oncologist, and the radiation oncologist, at least in the neoadjuvant setting. We’ve moved frankly, all our treatment to what we call a “total neoadjuvant approach” to try to give the whole treatment prior.

John L. Marshall, MD: That takes away that discussion, right? You’re going to start chemotherapy and then see where it lands?

Tanios S. Bekaii-Saab, MD: That does affect some level of discussion. For example, whether radiation would be necessary, especially in the patients with clearly resectable disease or not. For the borderline resectable it’s a 50/50; depending again on the surgical preferences. Then for locally advanced, which a very small proportion of patients actually end up in surgery—10% to 15%—in highly selected groups, probably less than that. But, for those patients, you probably should consider radiation. That may be the only group, so it does affect how you plan around the radiation more than anything else.

John L. Marshall, MD: We’re clearly doing this in rectal cancer, right? Everybody with some data is moving all of their postoperative treatment into preoperatively, to surgery. Is this the argument, just to do this in pancreas cancer, and get it in and get it done? Eileen?

Eileen M. O’Reilly, MD: Yes, I think the biology is very compelling for a neoadjuvant strategy; getting more treatment, and more modalities of treatment into more patients, addressing early micrometastatic disease, and facilitating the chance for an R0 oncologic outcome. John, you asked about this year’s ASCO and you’re right, we have two exciting presentations; one that supports this notion of neoadjuvant therapy, and the other that endorses an improvement in outcome in the adjuvant space.

John L. Marshall, MD: In the more traditional surgery first approach.

Eileen M. O’Reilly, MD: Yes. So, we still have an open question, and ultimately, it’s going to be patient selection, in terms of trying to see which approach is best for a given individual.

John L. Marshall, MD: You think we’re doing a better job of diagnosing these patients, and this is why we’re seeing more locally advanced pancreas? Is everybody getting a CT scan every time they go to the airport? George, do you see a shifting paradigm in pancreas cancer as to why we’re seeing some better outcomes here?

George P. Kim, MD: It’s a lot of the management, the surgery, and the decision for more active chemotherapy. I think we are having impact, and more and more we are using preoperative, and we’re going to see some good results in that area.

John L. Marshall, MD: Kind of granular; what’s the imaging that you guys do in making a baseline imaging strategy; is it just CT, is it MRI, is it EUS?

George P. Kim, MD: It has to be a CT dedicated to looking at the pancreas, so triple slices through the pancreas, getting a good look at it. Then also, you can do MRIs; we do a lot of that at Mayo. PET scan is not that helpful.

John L. Marshall, MD: EUS?

George P. Kim, MD: EUS for defining resectability.

John L. Marshall, MD: And getting tissue maybe?

George P. Kim, MD: Getting tissue, absolutely. But for resectability, kind of, sort of.

John L. Marshall, MD: Anybody else have thoughts or changes on that?

Tanios S. Bekaii-Saab, MD: I think it’s preferable to have an angiogram with your CT, which helps a lot with defining the vasculature.

John L. Marshall, MD: Well, they can model that, right?

Tanios S. Bekaii-Saab, MD: Yes, but the CT angiogram would be preferable. We have actually established a program with a PET-MRI for all of our patients, and we follow both the metabolic. Although the PET scan, and I do agree, should not be widely used, we’re using it primarily in the research, but also with clinical information.

John L. Marshall, MD: Do I need all that imaging if I’m giving chemotherapy first?

Tanios S. Bekaii-Saab, MD: Well, I’ll explain why we’re doing it, and that’s why I wouldn’t advocate for it outside certain confines. In our practice, the surgical preference is, to see both a strong metabolic, if indeed there was activity from the get-go, and biochemical responses in addition to other changes, to proceed with surgery. It’s part of our selection, so our surgeons are very progressive about not doing surgery for those patients where they think, even if close to clearly resectable, but have not yet biochemically responded and metabolically responded. They may be more reluctant to proceed with surgery. We do switch regimens to ensure that, and we have data that hopefully will be published soon, that suggested the strategy that tends to work quite significantly for patients. Primarily, because once you have the right patient going through resection, and because we know about our failure rates remain quite high for these patients. Once you select patients better and better, the outcome is likely much better.

John L. Marshall, MD: Eileen, do you have a comment?

Eileen M. O’Reilly, MD: Yes, I was going to say that’s research, Toni, and I think that’s great, that’s the future. But, just for our colleagues in the community, CT, angiogram, using water as the negative oral contrast agent for the gut, and reconstruction to the pancreas.

Transcript Edited for Clarity