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Classification of Gastric and Gastroesophageal Junction Cancers

Panelists: Johanna C. Bendell, MD, Sarah Cannon Research Institute; Yelena Y. Janjigian, MD, Memorial Sloan Kettering Cancer Center; Manish Shah, MD, Weill Cornell Medical College; Ian Chau, MD, Royal Marsden Hospital
Published: Friday, Nov 04, 2016


Transcript:

Johanna Bendell, MD:
Hello, and thank you for joining us today for this OncLive Peer Exchange® panel discussion on the topic of “Treating Advanced Gastroesophageal Cancers.” Gastroesophageal (GE) cancers remain difficult to treat, with most patients diagnosed in the later stages and only about half of those diagnosed with resectable tumors. In this OncLive Peer Exchange®, a panel of experts in gastrointestinal oncology will provide practical information on classification and treatment of advanced gastroesophageal cancers. In addition, we’ll explore the latest data on emerging therapies and where they will potentially fit into clinical practice.

I’m Dr. Johanna Bendell, and I am the director of the Gastrointestinal Oncology Research Program and associate director of the Drug Development Unit at the Sarah Cannon Research Institute in Nashville, Tennessee. Participating today on our distinguished panel are Dr. Ian Chau, who’s a consultant medical oncologist of the Gastrointestinal and Lymphoma Units at the Royal Marsden Hospital in London and Surrey; Dr. Yelena Janjigian, assistant attending physician of the Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center in New York; and Dr. Manish Shah, director of the Gastrointestinal Oncology Program of the Division of Hematology and Oncology at the Weill Cornell Medical College in New York. Thank you all for joining us, and let’s begin.

What an exciting time! We’re here at ESMO 2016, and we’re seeing more and more data and research and new treatment options for patients with gastroesophageal cancers. So, I think it behooves all of us to go back and think a little bit more about what these cancers are, what are the differences in treatment, how are they classified, and what’s the language around them. I’m going to start with Ian. We hear about esophageal, we hear about gastroesophageal junction cancers, we hear about gastric cancers. Are there differences between them? What can you tell us about the epidemiology of these cancers?

Ian Chau, MD: Really, for gastric cancer, the incidence actually has been falling ever since the beginning of the 20th century. And in most parts of the world, that particular disease is diminishing. But, yet, in Far East Asia, China, Japan, Korea, it remains a very common disease. But, in fact, it is actually, nowadays, the third most common cause of cancer death. But if you’re adding the esophageal cancer, as well, that actually will push it up to the second most common cause of cancer death.

Now, for the esophagus, there are two different cell types: the squamous cell cancer, as well as the adenocarcinoma. A squamous cell cancer is very common in many parts of the developing world and is less so in the western world. As for adenocarcinoma, which is mainly in the lower esophagus, there’s actually a rise in the western world. There are many different reasons for this that have been proposed. A lot of it is because of the reflux disease, and that might be related to obesity, which is becoming more and more common in the western world. So, I think those are some of the reasons why adenocarcinoma of the lower esophagus and gastroesophageal junction is rising.

Johanna Bendell, MD: What do you think about Asia versus the United States? There have been a lot of discussions about people in Asia having potentially a better prognosis for their gastroesophageal cancers.

Ian Chau, MD: Yes, I think there are many different reasons for it. Part of it is because it is a very common disease in Asia. There is much more public awareness of it, so they do undergo endoscopy—whether you think it is a screening program. In fact, in Korea, they will actually start having endoscopy after the age 40 out of their own wish. It’s not like a national screening program; they automatically go to the hospital because that is reimbursed. So, they do find those tumors much earlier, and they do develop them when they’re younger. Whereas in the western world, it is less common; it is not cost-effective to do a screening program in that situation. And it happens in older age groups with more comorbidities. So, I think it’s multifactorial. It’s not necessarily just the biology of the disease, but actually the whole person with the comorbidities, age, and everything that actually will dictate the prognosis of our patients.

Johanna Bendell, MD: And we’ll see some of the data, where there were different results for patients from Asia versus the rest of the world. So, it will be an interesting concept to talk about soon. Manish, all of these trials are happening. People are asking for Siewert classifications, Lauren classifications. How is a medical oncologist to keep this all straight, and what does it actually mean?

Manish Shah, MD: For Siewert classification, I think as we’re learning more about the potential differences of esophagus and gastric cancer and how they’re treated, particularly if it’s a localized disease, the gastroesophageal junction tumors that exist, they’ve been subclassified into type I, type II, and type III GE junction tumors as per the Siewert classification. For metastatic patients, we don’t really think that that matters so much. But for patients with localized disease, as we’ll talk about later, tumors that are Siewert type I and often type II tend to be treated with more of an esophageal paradigm, which may include chemotherapy and radiation, whereas Siewert type III tumors are really the gastric cardiac tumors, and these tumors tend to be treated more in a gastric paradigm.

So, I think from a Siewert standpoint, it does make a difference with regard to where the location is, and there may be biologic differences, as well, with regard to the genomic analyses that have been done. With regard to diffuse and intestinal types, that’s also an evolving area. Intestinal type gastric cancers are much more prevalent in the epidemic areas in Far East Asia or also in South America. The biology is a transformation from dysplasia to metaplasia to cancer, and it takes years and chronic inflammation. Diffuse gastric cancer is a little bit different; it actually has relatively uniform epidemiology across the globe. About 1 per 100,000 people get diffuse gastric cancer, and the biological drivers of that may be different, like an e-cadherin mutation and things like that.

Right now, we still treat these cancers similarly. In the metastatic and locally advanced settings, they still are similarly treated, but I think, as we will talk about later, some of the target therapies may be better suited for different subtypes of gastric cancer. It’s something to be aware about, but it doesn’t impact practice right now.

Transcript Edited for Clarity
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Transcript:

Johanna Bendell, MD:
Hello, and thank you for joining us today for this OncLive Peer Exchange® panel discussion on the topic of “Treating Advanced Gastroesophageal Cancers.” Gastroesophageal (GE) cancers remain difficult to treat, with most patients diagnosed in the later stages and only about half of those diagnosed with resectable tumors. In this OncLive Peer Exchange®, a panel of experts in gastrointestinal oncology will provide practical information on classification and treatment of advanced gastroesophageal cancers. In addition, we’ll explore the latest data on emerging therapies and where they will potentially fit into clinical practice.

I’m Dr. Johanna Bendell, and I am the director of the Gastrointestinal Oncology Research Program and associate director of the Drug Development Unit at the Sarah Cannon Research Institute in Nashville, Tennessee. Participating today on our distinguished panel are Dr. Ian Chau, who’s a consultant medical oncologist of the Gastrointestinal and Lymphoma Units at the Royal Marsden Hospital in London and Surrey; Dr. Yelena Janjigian, assistant attending physician of the Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center in New York; and Dr. Manish Shah, director of the Gastrointestinal Oncology Program of the Division of Hematology and Oncology at the Weill Cornell Medical College in New York. Thank you all for joining us, and let’s begin.

What an exciting time! We’re here at ESMO 2016, and we’re seeing more and more data and research and new treatment options for patients with gastroesophageal cancers. So, I think it behooves all of us to go back and think a little bit more about what these cancers are, what are the differences in treatment, how are they classified, and what’s the language around them. I’m going to start with Ian. We hear about esophageal, we hear about gastroesophageal junction cancers, we hear about gastric cancers. Are there differences between them? What can you tell us about the epidemiology of these cancers?

Ian Chau, MD: Really, for gastric cancer, the incidence actually has been falling ever since the beginning of the 20th century. And in most parts of the world, that particular disease is diminishing. But, yet, in Far East Asia, China, Japan, Korea, it remains a very common disease. But, in fact, it is actually, nowadays, the third most common cause of cancer death. But if you’re adding the esophageal cancer, as well, that actually will push it up to the second most common cause of cancer death.

Now, for the esophagus, there are two different cell types: the squamous cell cancer, as well as the adenocarcinoma. A squamous cell cancer is very common in many parts of the developing world and is less so in the western world. As for adenocarcinoma, which is mainly in the lower esophagus, there’s actually a rise in the western world. There are many different reasons for this that have been proposed. A lot of it is because of the reflux disease, and that might be related to obesity, which is becoming more and more common in the western world. So, I think those are some of the reasons why adenocarcinoma of the lower esophagus and gastroesophageal junction is rising.

Johanna Bendell, MD: What do you think about Asia versus the United States? There have been a lot of discussions about people in Asia having potentially a better prognosis for their gastroesophageal cancers.

Ian Chau, MD: Yes, I think there are many different reasons for it. Part of it is because it is a very common disease in Asia. There is much more public awareness of it, so they do undergo endoscopy—whether you think it is a screening program. In fact, in Korea, they will actually start having endoscopy after the age 40 out of their own wish. It’s not like a national screening program; they automatically go to the hospital because that is reimbursed. So, they do find those tumors much earlier, and they do develop them when they’re younger. Whereas in the western world, it is less common; it is not cost-effective to do a screening program in that situation. And it happens in older age groups with more comorbidities. So, I think it’s multifactorial. It’s not necessarily just the biology of the disease, but actually the whole person with the comorbidities, age, and everything that actually will dictate the prognosis of our patients.

Johanna Bendell, MD: And we’ll see some of the data, where there were different results for patients from Asia versus the rest of the world. So, it will be an interesting concept to talk about soon. Manish, all of these trials are happening. People are asking for Siewert classifications, Lauren classifications. How is a medical oncologist to keep this all straight, and what does it actually mean?

Manish Shah, MD: For Siewert classification, I think as we’re learning more about the potential differences of esophagus and gastric cancer and how they’re treated, particularly if it’s a localized disease, the gastroesophageal junction tumors that exist, they’ve been subclassified into type I, type II, and type III GE junction tumors as per the Siewert classification. For metastatic patients, we don’t really think that that matters so much. But for patients with localized disease, as we’ll talk about later, tumors that are Siewert type I and often type II tend to be treated with more of an esophageal paradigm, which may include chemotherapy and radiation, whereas Siewert type III tumors are really the gastric cardiac tumors, and these tumors tend to be treated more in a gastric paradigm.

So, I think from a Siewert standpoint, it does make a difference with regard to where the location is, and there may be biologic differences, as well, with regard to the genomic analyses that have been done. With regard to diffuse and intestinal types, that’s also an evolving area. Intestinal type gastric cancers are much more prevalent in the epidemic areas in Far East Asia or also in South America. The biology is a transformation from dysplasia to metaplasia to cancer, and it takes years and chronic inflammation. Diffuse gastric cancer is a little bit different; it actually has relatively uniform epidemiology across the globe. About 1 per 100,000 people get diffuse gastric cancer, and the biological drivers of that may be different, like an e-cadherin mutation and things like that.

Right now, we still treat these cancers similarly. In the metastatic and locally advanced settings, they still are similarly treated, but I think, as we will talk about later, some of the target therapies may be better suited for different subtypes of gastric cancer. It’s something to be aware about, but it doesn’t impact practice right now.

Transcript Edited for Clarity
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