Johanna C. Bendell, MD: Thank you for joining this OncLive^® Peer Exchange^®, “A Global Perspective on Sequencing Treatments in Gastroesophageal Cancers.” Chemotherapy still plays a significant role in the treatment of advanced gastroesophageal cancers. However, recent progress has extended survival and is shifting the landscape toward less toxic regimens. This OncLive^® Peer Exchange^® panel of international experts in gastroesophageal cancers will focus on the current understanding of molecular subtypes, and the availability of newer treatment options is prompting discussions on sequencing.

I am Dr. Johanna Bendell, chief development officer and director of the Drug Development Unit-Nashville at Sarah Cannon Research Institute in Nashville, Tennessee. Participating today on our distinguished panel are Dr. Peter Enzinger, associate professor of medicine and director of the Center for Esophageal and Gastric Cancer at the Dana-Farber Cancer Institute of Harvard Medical School in Boston, Massachusetts. Welcome Peter, you have a really long title. Dr. Yelena Janjigian, chief of the Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center in New York, New York. Thank you so much, from your new busy role, for joining us today. Dr. Kohei Shitara, chief of the Department of Gastrointestinal Oncology at the National Cancer Center Hospital East in Kashiwa, Japan. Welcome. Dr. and Professor Eric Van Cutsem, a professor at the University of Leuven, and Head of Digestive Oncology at the University of Hospitals in Leuven, Belgium. Welcome. Thank you so much for joining us. Let’s begin.

Friends, we’re going to start off with some basics, talking a little bit about global trends in gastroesophageal cancers. I’m so happy we have this group here today to represent the United States, Europe, and Japan in terms of looking at treating gastroesophageal cancer. There’s a lot of discussion about different epidemiologies of gastroesophageal cancers from different parts of the world. Peter, tell us a little bit about the thoughts behind East versus West in gastroesophageal cancer.

Peter C. Enzinger, MD: Sure. I think one of the interesting aspects of gastric cancer in the United States is that it’s a success story, right? Basically, back in the 1920s, 1930s, this was probably the leading cause of cancer death in the United States. With the implementation of refrigeration, improvements in health, sterilization of foods, preservatives, the incidence of gastric cancer has come down dramatically in the United States, so that it’s no longer a top-10 cancer. Now that’s a phenomenal success, and in the United States, we now are changing our minds about preservatives and trying to eat a more natural diet. It’s interesting what that’s going to do with our incidence of gastric cancer.

In comparison, I think in the world, esophageal gastric cancer is the second leading cause of cancer death. That’s primarily due to the high incidence in East Asia where it really is a significant problem and remains a significant problem. In Europe, I think it’s still the sixth leading cause of cancer death. It’s very interesting how different parts of the world have varying incidences. It really has to do, in many ways, with the diet that is eaten and, to a lesser extent, with H. pylori (Helicobacter pylori), but I think there the incidence is relatively similar across the continents. But it is a phenomenon that is remarkable.

Johanna C. Bendell, MD: So, Yelena, New York City, headquarters of the power lunch, right? We were concerned a while ago about an increasing incidence, sort of an association of different risk factors with the lower esophageal cancers. Can you tell us what the thought was behind that, particularly in the Western countries?

Yelena Y. Janjigian, MD: Well, first of all, New Yorkers don’t eat lunch, we’re too busy—go-go-go. I think some of it is environmental, and to Peter’s point, distal gastric cancer is on the decline worldwide. Alarmingly gastroesophageal junction (GEJ) adenocarcinomas are on the rise, particularly in folks without any significant family history or risk factors; reflux and some of the obesity and environmental factors may play a role. In my clinic there is an epidemic of people in their 40s, 50s who exercise and do everything right and still develop this serious problem.

A lot of it, what I tell my patients, is that it’s a combination of the environmental exposures, but also the patient’s vulnerabilities and the germline for dispositions with these tumors, and that’s an important area to explore.

Johanna C. Bendell, MD: Yes, we’re definitely going to touch on that a little bit later. Dr. Shitara, in Japan you screen for gastric cancers. Tell us a little bit about the thoughts of that epidemiology there.

Kohei Shitara, MD: Yes, gastric cancer is slightly decreasing recently in Japan, but there are still 150,000 patients diagnosed with gastric cancer. There are also 50,000 patients dying from gastric cancer even now. So, screening is very important to detect our disease, which is cured by local therapy. But there’s still many patients diagnosed with this disease.

Why it’s important is there’s an epidemiological factor in Japan, very commonly older age, but this has also decreased in younger ages. That may be the one reason of the decreased incidence of gastric cancer in Japan. Another important factor is maybe salty food. In Japan, it’s a traditional food, which may be one cause of the high incidence of gastric cancer in Japan.

Johanna C. Bendell, MD: Let’s talk about the genetics. What are the high-risk groups? What do you test for when you see somebody?

Yelena Y. Janjigian, MD: The historical perspective on hereditary disposition syndromes with gastric cancer are the, sort of the very rare subsets, hereditary diffuse gastric cancer (HDGC), which is a very strict criterion for who qualifies for testing. Generally, it’s patients with a strong family history or patients who are younger than 35. It’s been described with signet ring cell types, subtypes specifically. For those patients, we recommend for their loved ones to be screened, for their families, and carriers of the gene, because there’s such high penetrance of CDH1. For CDH1 germline—mutant patients, prophylactic gastrectomies are recommended.

That subset does not have therapeutic complications yet. Other germline syndromes, such as Lynch Syndrome or hypermutated MSI syndrome is a very important syndrome therapeutically. Actually, data that are being presented at congress from our group and Sissy Stadler show that hypermutated, or MSI, tumors, specifically 16% of them, may have Lynch for disposition syndromes or germline Lynch without any other significant family history. So, now it’s these panels of next-generation sequencing or identifying these patients. It’s important to test them in the germline.

Beyond FAP (familial adenomatous polyposis), and some of the Peutz-Jeghers and other rare syndromes, the gastric and the esophageal genetic predisposition syndromes just haven’t been well described. There’s a lot of effort now, as we’re getting these NGS panels, to also look at germline data; to look at whole exome analysis. Particularly at our institution, we’re very interested in the young population to understand, to answer the question, this existential question, “Why me? Why did I get this cancer?”

Johanna C. Bendell, MD: Kohei, in Japan, do you see a lot of hereditary gastric cancer as well?

Kohei Shitara, MD: Actually no, very few patients. But there are still some patients who have the Lynch Syndrome with gastric cancer and the BRCA mutation; we have some patients. Incidence is less than 5% among the whole of gastric cancer patients, but this is very important.

Yelena Y. Janjigian, MD: The Ashkenazi Jewish population, it was important. Thank you for bringing that up, BRCA alterations.

Transcript Edited for Clarity