Team Sport Mentality Required in Treatment of Gastrointestinal Cancers

As molecular discoveries in gastrointestinal (GI) cancers show promise for segmenting care into more precisely defined subtypes, management of patients with the disease is becoming more of a multidisciplinary approach, according to John L. Marshall.

That’s why Marshall, chief of the Division of Hematology/Oncology at Georgetown University Hospital, has designed the first-ever Physicians’ Education Resource (PER) conference on GI malignancies to reflect the collaborative nature of treating patients with these cancers.

The 1st Annual School of Gastrointestinal Oncology, a meeting of oncologists and other oncology professionals in New York City, featured several general sessions and three tracks for medical oncology, surgery and radiation, and multidisciplinary management. Marshall co-chaired the meeting with Michael A. Choti, professor and chair of the Department of Surgery at UT Southwestern Medical Center in Dallas.

“GI cancer is a multidisciplinary team sport,” said Marshall, who also is director of the Otto J. Ruesch Center for the Cure of Gastrointestinal Cancers. “We all work together, and we need each other to optimize outcomes for patients. We created a curriculum that both hits the major research elements everybody has to know across all the subspecialties, but then also allows for smaller-group learning around the very specific subspecialties.”

What major trends do you see emerging now and within the next five years?

In an interview with CURE before the conference, Marshall discussed the changes underway in the field of GI malignancies.During the last decade or so, there has been significant progress in medical therapies for GI cancers, so we’ve moved the bar in that way for metastatic disease. I think the progress that we’ll make going forward is using molecular profiling to identify new targets; new pathways that will move the field even more rapidly. That’s why we’re emphasizing the impact of molecular testing and molecular profiling.

We know that immunotherapy is touching every cancer and GI cancer is no exception.

But what's really happening is a lot of progress in what I’ll call local regional therapy, whether it’s surgery for metastatic disease, radioembolization, or novel techniques in radiation. As patients are living longer—using colon cancer as the model—we’re recognizing that a lot of patients benefit from more efficient local regional approaches to managing metastatic disease.

As scans have gotten better, and surgeons and radiation oncologists and interventional radiologists have gotten better, we have additional tools—surgical-based tools and local tools— to treat the cancer.

Are there new molecular targets on the near horizon in colorectal cancer?

We know HER2 is not common but it happens at a regular enough interval that HER2-directed therapies have some value, and there are clinical trials to support that. But, frankly, when you go beyond that, there are many lower-level expressions [of potential targets].

Instead of going into any specific marker, I think it’s more important to think about broad profiling and understanding how to optimize our treatment. We need markers that bring value to what we’re doing.

Your question comes from more of a drug discovery/new therapy angle. I think it’s going to be equally important for us to use molecular testing to decide whom not to give treatment to and to use alternative kinds of therapies that aren’t necessarily on a pathway.

At this point, the molecular tests with clinical utility seem to involve KRAS/NRAS, BRAF, and microsatellite instability (MSI) or mismatch repair (MMR). Are there any others that can be translated into practice now?

That is not the way I would say it. These are the only ones that are being used. We’re not sure whichever ones might be useful. So right now standard tests are indeed the ones you listed, but the whole point of what we’re trying to do is move the bar.

How are we going to do that? One strategy is to pick this off as individual targets. The other strategy is to do it as more of a broad profile, and at least my bias is that the broad profile will help.

What do you think the molecular profiling landscape might look like five years from now?

We’re at this critical juncture where we believe it’s going to be helpful, but we have to prove its value to patients. There are several efforts going forward to try and do that. My guess is that, given the costs of molecular profiling getting lower and lower, that we will be doing broad profiling on every patient with every cancer and that it will be worth it.

Even if we only find a few rare things, there is an overall value to cancer care in cost, and patient outcomes will improve as a result. That’s my hypothesis. It’s my hope that that’s where that will be five years from now.

Will the ability to categorize colon cancer into molecular subtypes result in viewing the malignancy as many different tumor types of subtypes?

It’s already been published that there are probably at least four subtypes in colon. That’s a first stake in the ground as we go forward. I think we’ll learn to refine that and then use those molecular subtypes or classifications to help us sort patients and sort therapies. So, yes, absolutely, I think that’s where this is going.

How far along that path are we now?

Nobody is doing it in clinical practice, let’s put it that way. We’re not at a point where we are sending off molecular testing, categorizing patients according to these subcategories, and then making different therapy decisions based on those broad categories.

We’re still using the individual markers to make those decisions. So it’s not a standard, something I would recommend to every oncologist, and we’re not doing that routinely at our academic centers either.

What do you think is the potential for immunotherapy in GI malignancies?

Immunotherapy is reaching every field, every tumor type, and GI is no exception. We have defined a relatively small subgroup of patients with colon cancer through the MSI genetic abnormality that predicts for an improved response to checkpoint inhibitors.

But that’s a relatively small number. In gastric cancer, for example, in an unenriched patient population, we’ve seen response rates in the 20 percent to 30 percent range with single-agent checkpoints. It’s very promising, and I would expect we would see relatively quick approvals and acceptance of using checkpoint inhibitors in those subgroups.

It’s exciting. If there’s going to be a lot of resources put into it, my guess is that in the end, we will again have a subset of patients who benefit, hopefully larger than the subset that we have now.

And it may be used in combinations with other immunomodulatory drugs including vaccines and other checkpoint inhibitors but also maybe in combination with chemotherapy and other traditional approaches. Again, very dramatic positive success in GI cancers in certain subgroups, and our challenge going forward is extending that to others.

Is there anything particularly promising on its way for pancreatic cancer?

Because we’ve had some success in the chemotherapy world, there’s been some renewed energy. There are interesting approaches, including stem cell approaches, stromal approaches, and other immunotherapies, as well. The frustration there is that we still haven’t made significant strides beyond the more recent chemotherapy improvements. More attention is being spent, there are some early leads on small clinical trials, and I hope that those things are supported as more studies are done.

In the area of liver cancer, is there excitement about radiotherapy techniques making an impact in early disease? They’re certainly being utilized but that’s been fairly true for a while. I think I have yet to really see something emerge as a major game changer other than what we had over the last several years. I think as the techniques have improved and the experience of the physicians has improved and patient selection has gotten better, I think that’s where we’re seeing our improved outcomes.