New Subtypes of GI Cancer Beginning to Surface

John L. Marshall, MD

John L. Marshall, MD

The differentiation between squamous and adenocarcinomas in gastrointestinal (GI) cancer could revolutionize the disease's treatment paradigm, according to John Marshall, MD.

In an interview withTargeted Oncology, John L. Marshall, MD, chief, Division Of Hematology/Oncology, Georgetown University Hospital Associate Director, clinical research, Lombardi Comprehensive Cancer Center at Georgetown University Hospital, discusses the new research into GI molecular subtyping, targeted therapies for the malignancy, and identifying new patients.

TARGETED ONCOLOGY:What are some of the advances in GI cancer that you find exciting?

Marshall:

We're making progress in GI cancers, but let's break it down a little bit. In pancreas cancer, the biggest news there is a clear shift in adjuvant therapy. So for a long, long time, we've been giving gemcitabine chemotherapy, and there were other studies that showed 5FU chemotherapy would work. Finally we did a combination study combining gemcitabine with capecitabine, and it was positive, and not to really anyone's surprise, but it finally took the study to do it. So there was an immediate transition on a dime from a former standard of care to a new standard of care. The suggestion that maybe we should build on this even further, the concept of maintenance therapy and other approaches in the adjuvant setting, which I think will move things forward.

There's still this debate about the role of radiation. I think you're hard-pressed to find solid evidence that says post-operative radiation is beneficial. it's important to emphasize the quality and the negative margin status of surgery is important. A positive margin in patients with pancreas surgery is basically not helpful, so you need to get those patients there. So there's a lot of focus on defining locally advanced, resectable, borderline, and there were some good discussions on just how gray this all is. Again, I stress multi-disciplinary teams in the management of pancreas cancer.

A second area, gastric and gastro-esophageal (GE)cancer, I think we've presented some recent data that was good, and others have shown that they're different cancers. So we've been thinking of squamous cell and adeno-cancers of the esophagus as kind of the same, but they're clearly different. We presented a paper around molecular profiling in these groups, and they have different profiles. The same is true in gastric cancer. We've been thinking of east versus west, but there was some very nice work done by Dr. Bass out of Boston that shows that there are at least four molecular subtypes of gastric cancer, and they do track with location, but that's not perfect. The lion's share of the data says squamous are different than adenos, GE junctions are more like gastric, and within that group there are probably four molecular subtypes. Within those subtypes, we're seeing therapeutic choices. So there are groups where checkpoint immunotherapy is going to help, groups where chemotherapy is going to help, but by dividing that out, we're going to get smarter. So those are the biggest changes we're seeing in GI cancer right now.

TARGETED ONCOLOGY:How can we target therapies to target these specific subtypes, and what implications will that have on survival?

Marshall:

The importance of the separation is that we'll get away from this "one size fits all" approach. We already know that there are certain genetic testing. We're doing HER2 testing, we're starting to do more MSI testing, but as we get to a deeper dive and put these cancers into different categories, we will get smarter.

There was an important follow-up on our knowledge of molecular testing, and if that does change our practice. I think the answer is probably not so much, but we know that's where we're going. So to that end, we will see a shift and we'll see more personalized medicine being done and it'll improve outcome.

TARGETED ONCOLOGY:What is the difference between squamous and adenocarcinoma?

Marshall:

We know they're caused by different risk factors, different populations get them, and so we've been bundling them together because they happen to be in the same location. Our studies are muddied by the fact that we have these two kinds of cancer, and now that we're going to separate those out more, I think what we'll see is improvement on both sides. The positives that we find in one won't cloud the other disease.

TARGETED ONCOLOGY:How do you think patients should be treated differently?

Marshall:

Squamous cell cancers tend to be higher up in the esophagus, tend to be more responsive to chemo and radiation in terms of complete response, and so I think we tend to treat those more like head and neck cancers, where combined modality therapy is the standard. Adenocarcinomas of the esophagus tend to be lower down, a little less responsive to chemo radiation, although still the gold standard treatment, and should be bundled more like gastric cancers. That to me is the primary distinction.

TARGETED ONCOLOGY:How do you get the best results for pancreatic cancer?

Marshall:

GI cancers in general need to be managed by multi-disciplinary teams. You need specialized surgery. This is not something you can do once per year. You need to be doing it all day, every day. Gastroenterology needs to be capable of doing endoscopic ultrasound, biopsies, and stenting. So it's high-end gastroenterology. Radiation oncology needs to be relatively specialized as the data increase there. Radiology, you need the kinds of people who are used to making the distinctions around locally advanced, borderline or resectable pancreas cancer. Of course, we as oncologists are part of the team, but beyond that you need nutrition. You need social work, palliative care, and interventional radiology.

Right there I think I've listed nine different subspecialties that are almost always involved in almost all pancreas cancer patients. So it's that kind of multi-disciplinary team that needs to be involved in the care of that patient, that develops the treatment strategy together on how we're going to go forward. I think it's only then that we get the best results.

TARGETED ONCOLOGY:Are there any kinds of barrier right now in treating pancreatic cancer?

Marshall:

Pancreas cancer is a very difficult disease. We're seeing a lot of it — around 40,000 new cases in the United States alone this year. The majority of these patients have metastatic disease, or at least unresectable at the time. Many of these people are quite sick, and their time course can be quite short. Median survival is around one year for this disease. So it's bad, and it requires a lot of intervention early on. I think those people who have access to those teams do better than those who do not. When you only have such a short window, I think the biggest barrier is getting all that team mobilized for that patient the quick way. To get that patient feeling as well as they can, to get that treatment initiated as soon as possible.