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Multidisciplinary Management of Locally Advanced Gastroesophageal Cancer

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: Thursday, Dec 01, 2016


Transcript:

Johanna Bendell, MD:
When we move into treatment of these cancers, at your institution, what is the process? A patient comes in with a newly diagnosed gastroesophageal cancer. Who needs to see them, and why?

Manish Shah, MD: If we think of locally advanced disease versus advanced or metastatic disease, there is a utility of a multidisciplinary effort for both cases, but particularly for locally advanced disease. Because if it’s a type 1 GE junction cancer or distal esophageal cancer, often you’re thinking of tri-modality therapy involving medical oncology with chemotherapy, radiation oncology, and then surgery. Sometimes you might do chemotherapy and surgery alone. And then for the metastatic patients, it’s also important because there may be palliative approaches that you need to consider, as well. So, I think it’s really quite critical to have a multidisciplinary approach. Also, the other benefit of that is actually having the pathologist there, and the genetic counselor, and nutritionist, and these are all aspects of managing these complex diseases of the foregut that can actually improve patients’ lives and how they tolerate the disease.

Johanna Bendell, MD: Yes. It definitely takes a village in treating these patients. It’s fairly intensive. I personally tell my patients with locally advanced disease, when they’re getting neoadjuvant chemoradiation therapy, that this is going to be a really hard road, but we’re going to get you through the road, we’re going to get you through surgery. But it’s going to be about a year-and-a-half until you’re feeling better.

Manish Shah, MD: Before you feel better, yes.

Johanna Bendell, MD: That’s such an important message to get to the patients, so they know where they’re going. Certainly, across the pond from the US, in the UK and also in Europe, there are different treatment approaches to locally advanced disease. What do you think?

Ian Chau, MD: I wouldn’t say it’s too different. We do take all the evidence together and, again, I really echo what Manish just said. Where you have a multidisciplinary approach is really, really important. In fact, all our newly diagnosed patients have to be discussed by the multidisciplinary team. We’ll have similar members, medical oncologists, radiation oncologists, surgeons, gastroenterologists, dietitians, and specialist nurses, actually, because I think a lot of times we do find that information, as you said, to help the patient. And the nursing support, psychological support, is actually very important. So, in terms of treatment approach, there are different approaches. I think a lot of it is based on randomized controlled trials.

They are done in different geographical regions, and therefore are done different ways. So, we certainly, in the locally advanced, or T2, T3 gastric cancer, we think about perioperative approaches. That’s based on originally the MAGIC trial, which was then supplemented by the French study. So, we give chemotherapy before and after. But perhaps the most important thing, and the newer data that we have generated, is that the improvements in survival, in fact, are coming from better staging investigations. So, we have better CT scanners now. We do do PET scanning at our institution even for gastric cancer. That is debatable. About 15% of the gastric cancers are PET-negative. But we do feel that is an important point. We do pick up peritoneal disease. We do pick up bone metastasis on PET scanning. And then our surgeons do routinely also perform laparoscopy before preoperative chemotherapy. And then the patient is seen in our clinics to assess their suitability for chemotherapy.

Now, for the junctional tumor, and certainly for the lower esophageal cancer, we have taken on the data from CROSS using carboplatin/paclitaxel in conjunction with radiation. The practice is changing. Certainly, there are sites in the UK, and there are many sites in Europe, that would use a preoperative chemoradiation approach. And a lot of centers are getting very good results from this approach. I think certainly in the lower esophageal and OG-junction tumor, a chemoradiation approach is also part of the standard.

Johanna Bendell, MD: Do you do endoscopic ultrasound in staging?

Ian Chau, MD: So, we do endoscopic ultrasound for esophageal and esophagogastric junction adenocarcinoma. We debated a lot, and in the end, we still don’t see a lot of extra benefit of doing endoscopic ultrasound for gastric cancer. We hardly ever see T1 tumors in our routine practice. I can understand if you have a T1 tumor, you then might want to do endoscopic ultrasound to ensure that that really is T1. But, really, in our everyday all-comers in our clinic, I mean that is really not the average patient that comes through our door.

Johanna Bendell, MD: Manish, we saw recent data at ASCO looking at gastric cancers and chemoradiation versus chemotherapy. What was your interpretation of the data and how have you brought it into practice?

Manish Shah, MD: This gets to what was said about the differences in practice. In the United States, a standard approach is, after surgery, to do chemotherapy with radiation. But in the same era, the MAGIC study showed the benefit of perioperative therapy. And so there was a very nice study that looked at chemotherapy neoadjuvant followed by surgery, and then there was a randomization to more chemotherapy as per the MAGIC paradigm or chemoradiation. In this study, they actually showed no difference in the outcome between the two arms, so it suggested that continuing chemotherapy in that setting is probably still a standard approach, and combining the approaches—doing chemotherapy neoadjuvantly, surgery, and chemoradiation, sort of a meld of the MAGIC and Intergroup116—that probably doesn’t actually have benefit. I think that from what was learned from a drug development standpoint is that we need to maybe look at other targets. Dr. Janjigian has a very nice study in the adjuvant setting with a TKI in high-risk patients. So, something like that might be very helpful to move the field forward.

Johanna Bendell, MD: Now, really interesting with this study, and a lot of controversy that ensued, was about the surgery the patients had compared to how we do surgery. I don’t want to bust on the United States, but this is where a lot of the discussion has happened. A lot of how you do in terms of local control of your treatment depends on what surgery you had. And so, Yelena, this is a big discussion point.

Yelena Janjigian, MD: It’s a big discussion, and we can talk about and discuss for a long time which chemotherapy to give, what backbone, etc. But the truth is, and this was very important data actually presented at this Congress, is that patients do best if they are operated on by an experienced surgeon in a high-volume center with multidisciplinary team approach. The hazard ratio for death reduction is 70% almost. So, in a fit, otherwise well, patient, the mortality in a low-volume center was as low as 7% post op within a 30-day mortality. And we’re not even talking about cancer recurrence. We’re just talking about post-op complications and such. So, when approaching a patient who is motivated, and is well, and going for surgery, complete resection with negative tumor margins and adequate lymph node sampling—which is, at minimum, 15 to 30 lymph nodes—is crucial. And the discussion with the team whether or not it makes sense to do preoperative chemotherapy and then surgery, chemoradiation, and surgery. As Ian alluded to, disease management teams are key. And most patients are discussed and imaging is reviewed. I would agree that laparoscopy is crucial to appropriately stage these patients in the majority of these patients. The visible tumors and imaging that clearly states gastric cancer, probably EUS, is not additive.

Johanna Bendell, MD: And just some of the nomenclature, you need at minimum, and this would be very minimum, a D1 resection, but D2 is probably where we’d want to go. So, I think if you get the patient to surgery, count the nodes on the pathology report, and if you have a chance to get that patient to the right surgeon, it sounds like the most appropriate thing to do.

Manish Shah, MD: Modified D2. The original D2 had a splenectomy, which we don’t necessarily do. But, you’re absolutely right, having an extended nodal dissection past the N1 nodes.

Transcript Edited for Clarity
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Transcript:

Johanna Bendell, MD:
When we move into treatment of these cancers, at your institution, what is the process? A patient comes in with a newly diagnosed gastroesophageal cancer. Who needs to see them, and why?

Manish Shah, MD: If we think of locally advanced disease versus advanced or metastatic disease, there is a utility of a multidisciplinary effort for both cases, but particularly for locally advanced disease. Because if it’s a type 1 GE junction cancer or distal esophageal cancer, often you’re thinking of tri-modality therapy involving medical oncology with chemotherapy, radiation oncology, and then surgery. Sometimes you might do chemotherapy and surgery alone. And then for the metastatic patients, it’s also important because there may be palliative approaches that you need to consider, as well. So, I think it’s really quite critical to have a multidisciplinary approach. Also, the other benefit of that is actually having the pathologist there, and the genetic counselor, and nutritionist, and these are all aspects of managing these complex diseases of the foregut that can actually improve patients’ lives and how they tolerate the disease.

Johanna Bendell, MD: Yes. It definitely takes a village in treating these patients. It’s fairly intensive. I personally tell my patients with locally advanced disease, when they’re getting neoadjuvant chemoradiation therapy, that this is going to be a really hard road, but we’re going to get you through the road, we’re going to get you through surgery. But it’s going to be about a year-and-a-half until you’re feeling better.

Manish Shah, MD: Before you feel better, yes.

Johanna Bendell, MD: That’s such an important message to get to the patients, so they know where they’re going. Certainly, across the pond from the US, in the UK and also in Europe, there are different treatment approaches to locally advanced disease. What do you think?

Ian Chau, MD: I wouldn’t say it’s too different. We do take all the evidence together and, again, I really echo what Manish just said. Where you have a multidisciplinary approach is really, really important. In fact, all our newly diagnosed patients have to be discussed by the multidisciplinary team. We’ll have similar members, medical oncologists, radiation oncologists, surgeons, gastroenterologists, dietitians, and specialist nurses, actually, because I think a lot of times we do find that information, as you said, to help the patient. And the nursing support, psychological support, is actually very important. So, in terms of treatment approach, there are different approaches. I think a lot of it is based on randomized controlled trials.

They are done in different geographical regions, and therefore are done different ways. So, we certainly, in the locally advanced, or T2, T3 gastric cancer, we think about perioperative approaches. That’s based on originally the MAGIC trial, which was then supplemented by the French study. So, we give chemotherapy before and after. But perhaps the most important thing, and the newer data that we have generated, is that the improvements in survival, in fact, are coming from better staging investigations. So, we have better CT scanners now. We do do PET scanning at our institution even for gastric cancer. That is debatable. About 15% of the gastric cancers are PET-negative. But we do feel that is an important point. We do pick up peritoneal disease. We do pick up bone metastasis on PET scanning. And then our surgeons do routinely also perform laparoscopy before preoperative chemotherapy. And then the patient is seen in our clinics to assess their suitability for chemotherapy.

Now, for the junctional tumor, and certainly for the lower esophageal cancer, we have taken on the data from CROSS using carboplatin/paclitaxel in conjunction with radiation. The practice is changing. Certainly, there are sites in the UK, and there are many sites in Europe, that would use a preoperative chemoradiation approach. And a lot of centers are getting very good results from this approach. I think certainly in the lower esophageal and OG-junction tumor, a chemoradiation approach is also part of the standard.

Johanna Bendell, MD: Do you do endoscopic ultrasound in staging?

Ian Chau, MD: So, we do endoscopic ultrasound for esophageal and esophagogastric junction adenocarcinoma. We debated a lot, and in the end, we still don’t see a lot of extra benefit of doing endoscopic ultrasound for gastric cancer. We hardly ever see T1 tumors in our routine practice. I can understand if you have a T1 tumor, you then might want to do endoscopic ultrasound to ensure that that really is T1. But, really, in our everyday all-comers in our clinic, I mean that is really not the average patient that comes through our door.

Johanna Bendell, MD: Manish, we saw recent data at ASCO looking at gastric cancers and chemoradiation versus chemotherapy. What was your interpretation of the data and how have you brought it into practice?

Manish Shah, MD: This gets to what was said about the differences in practice. In the United States, a standard approach is, after surgery, to do chemotherapy with radiation. But in the same era, the MAGIC study showed the benefit of perioperative therapy. And so there was a very nice study that looked at chemotherapy neoadjuvant followed by surgery, and then there was a randomization to more chemotherapy as per the MAGIC paradigm or chemoradiation. In this study, they actually showed no difference in the outcome between the two arms, so it suggested that continuing chemotherapy in that setting is probably still a standard approach, and combining the approaches—doing chemotherapy neoadjuvantly, surgery, and chemoradiation, sort of a meld of the MAGIC and Intergroup116—that probably doesn’t actually have benefit. I think that from what was learned from a drug development standpoint is that we need to maybe look at other targets. Dr. Janjigian has a very nice study in the adjuvant setting with a TKI in high-risk patients. So, something like that might be very helpful to move the field forward.

Johanna Bendell, MD: Now, really interesting with this study, and a lot of controversy that ensued, was about the surgery the patients had compared to how we do surgery. I don’t want to bust on the United States, but this is where a lot of the discussion has happened. A lot of how you do in terms of local control of your treatment depends on what surgery you had. And so, Yelena, this is a big discussion point.

Yelena Janjigian, MD: It’s a big discussion, and we can talk about and discuss for a long time which chemotherapy to give, what backbone, etc. But the truth is, and this was very important data actually presented at this Congress, is that patients do best if they are operated on by an experienced surgeon in a high-volume center with multidisciplinary team approach. The hazard ratio for death reduction is 70% almost. So, in a fit, otherwise well, patient, the mortality in a low-volume center was as low as 7% post op within a 30-day mortality. And we’re not even talking about cancer recurrence. We’re just talking about post-op complications and such. So, when approaching a patient who is motivated, and is well, and going for surgery, complete resection with negative tumor margins and adequate lymph node sampling—which is, at minimum, 15 to 30 lymph nodes—is crucial. And the discussion with the team whether or not it makes sense to do preoperative chemotherapy and then surgery, chemoradiation, and surgery. As Ian alluded to, disease management teams are key. And most patients are discussed and imaging is reviewed. I would agree that laparoscopy is crucial to appropriately stage these patients in the majority of these patients. The visible tumors and imaging that clearly states gastric cancer, probably EUS, is not additive.

Johanna Bendell, MD: And just some of the nomenclature, you need at minimum, and this would be very minimum, a D1 resection, but D2 is probably where we’d want to go. So, I think if you get the patient to surgery, count the nodes on the pathology report, and if you have a chance to get that patient to the right surgeon, it sounds like the most appropriate thing to do.

Manish Shah, MD: Modified D2. The original D2 had a splenectomy, which we don’t necessarily do. But, you’re absolutely right, having an extended nodal dissection past the N1 nodes.

Transcript Edited for Clarity
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