Esophageal Cancer Program

Podcast Transcript

Dale Shepard, MD, PhD: Cancer advances at Cleveland Clinic podcast for medical professionals, exploring the latest innovative research in clinical advances in the field of Oncology. Today, I'm happy to be joined by Dr. Siva Raja, surgical director of the Center for Esophageal Diseases and Dr. Suneel Kamath, an Oncologist in the Taussig GI Oncology Group. Suneel was previously a guest discussing disparities in cancer care and young onset colon cancer and those episodes are still available. They're here today to talk about the Cleveland Clinic Esophageal Cancer Program. So welcome Siva. Welcome Suneel.

Suneel Kamath, MD: Thank you.

Siva Raja, MD, PhD: Thank you for having us.

Dale Shepard, MD, PhD: Maybe to start out, Siva tell us a little bit about what you do here at the clinic.

Siva Raja, MD, PhD: Now once again, thanks for having me on the program. And I'm one of the general thoracic surgeons and I specialize in esophageal surgery, both in cancer and benign disease of esophagus. Been on staff for about 10 years after I finished my training here at the Cleveland Clinic.

Dale Shepard, MD, PhD: Very good. Suneel?

Suneel Kamath, MD: Yes, I'm a medical oncologist here. I treat all GI cancers, but definitely one of my focuses on upper GI malignancies, including esophageal cancer.

Dale Shepard, MD, PhD: Excellent. So we're going to talk about the esophageal cancer program here today. Maybe Suneel, give us a little bit of a background just in general, what's involved with the program, and we can talk about some specifics, but give us an overview.

Suneel Kamath, MD: The program really, I think is a multidisciplinary collection of expertise in my view. I think we have world class experts in terms of advanced endoscopists, thoracic surgeons, medical oncologists, and radiation oncology as well. And I think that really allows us to do some very novel and unique things in our program that maybe some other centers may not be able to do.

Dale Shepard, MD, PhD: Siva, there are particular things from a multidisciplinary aspect that you think are particularly good in our program that programs really should focus on including? What are the types of multidisciplinary things we can do here that particularly stand out?

Siva Raja, MD, PhD: So I think that the first thing I would say is, just like everything else in medicine has evolved, there has been significant developments in the last 10 years in the treatment of esophageal cancer. When I trained here over 10 years ago, pretty much we had a couple of tools. You either had surgery or we had chemotherapy, radiation and surgery or some combination of those three things. And no matter what you had, for the most part, you got one of those three things and I don't think it's the case anymore. Now we're able to understand that early stage cancer behaves differently than locally advanced cancer than metastatic cancer. So things that are even pre-cancerous conditions used to get the same operations. Now we're able to treat pre-cancerous conditions in a very organ sparing way so people can keep their esophagus.

Early stage cancers, very early stage cancers are now resected endoscopically without having to have any major surgery. We have that kind of expertise here now. And of course that, given that all of these cancers and pre-cancerous conditions are now managed with less invasive therapies, I don't want to call them less therapies, but less invasive therapies. We're now seeing a significant rise in patients who are undergoing complex surgical procedures, having more advanced cancer, sicker, older. So we've adapted to the demographic of the patients as well as to the nature of the cancer we're treating. So there's been a lot of change in the last 10 years. And I think that a marque element of any esophageal cancer program should be that you have to be able to offer therapies to each of these stages, not just one or the other.

Dale Shepard, MD, PhD: And we had a previous podcast where we talked about endoscopic resections, is that's something that's still relatively uncommon in most centers?

Siva Raja, MD, PhD: It is. So, there are different types of endoscopic therapies. And for small lesions, people have been doing endoscopic therapies for a long time, but for lesions that are intermediate size and in esophageal cancer, the depth of the cancer has a direct impact on the stage, far more than perhaps even the size of the cancer. So having endoscopic sub-mucosal dissection, which is the ability to take out the tumor on block endoscopically with a clean margin, rather than just piecemeal is something that most places don't have the expertise to do. We have several advanced endoscopists that are excellent at that procedure. So I think that is something that we offer that you're not going to find in many places.

Dale Shepard, MD, PhD: Suneel, what are some of the things on the medical oncology side that have changed recently in esophageal cancer?

Suneel Kamath, MD: Yeah, I think for us, I think a lot of it is, we've learned to intensify therapy for the right people. We're using more combination to chemotherapy at systemic doses than we used to. And I think, the original trial that we use a lot for locally advanced or stage two or three disease was the so-called cross trial. And I think we've since learned over the years of the dosing of the chemotherapy, and that was probably under dose, that's sort of a radio sensitizing dose as opposed to a true systemic dose. And I think we've really modified our practice for those at higher risk, which is most of the patients we see here to use more systemic dose therapy in addition to radiation, to try to treat sort of distant metastatic disease, which is ultimately what people recur with and will die of. And I think that's really made difference. I think immune therapy has also made a big difference. There've been a number of trials, both for metastatic patients and also for patients who've had a curative surgery where immune therapy's making a big difference.

Dale Shepard, MD, PhD:What does the program look like logistically? What does it look like from a patient standpoint? They come to one place and everyone comes to see them? Do you coordinate appointments? How do they make this happen?

Siva Raja, MD, PhD: So I think that one of the things to think about for esophageal cancer is that in terms of the number of patients who have esophageal cancer, just to put things in perspective, over 250,000 people get lung cancer every year, but less than about 15,000 to 18,000 people get esophageal cancer. So in terms of the frequency of this cancer, it's actually relatively uncommon cancer compared to the top three, if you will, for men or women. That being said, a significant number of these patients also present with advanced or stage four disease. So, the people who end up being operable or treatable is actually a significant, but a smaller subset of that. So, what it looks like for a patient is that we try to coordinate care as much as possible, but we don't necessarily have, we have what's called a virtual coordinated consult where they get to see all of the people they need to see at the same time.

But not necessarily, they're not in the same room where people are coming, going in and out. They may have to go to different offices, but they get to come one afternoon or one morning. And then we try to do our best to see everybody they need to see in that one time, so that when they leave, which I think is the most important thing is that, they come in with a lot of doubt and questions. They leave with a lot of their questions answered and far less doubt than they came in with. I think that's our goal and way we try our best to make that happen.

Dale Shepard, MD, PhD: And so that's outstanding because oftentimes patients come in, they're scared. They want to know what to do and they get those answers. But then of course, the next question is when do we start? And so Suneel, one of the big things, certainly at Taussig, we've spent a lot of time and energy on is time to treat and how do we get people to that treatment once we made the decisions as soon as possible. So how are we trying to address that with esophageal cancer?

Suneel Kamath, MD: Yes, that's such a huge thing for esophageal cancer, especially because multidisciplinary care is certainly a great thing, but it definitely adds time, it needs more coordination. The staging, I think also can be challenging for this disease, needing a PET scans and endoscopic ultrasound typically for most patients, that needs a lot of coordination. And I think having a good team, that's really on top of those things, making sure that they're getting done in a timely fashion, I think is a huge part of that because I think that's a big strength of our program is that we have a lot of resources to both track that as a metric and then also resources to work on those and address those issues as they arise.

Dale Shepard, MD, PhD: What kind of research do you find interesting that we're doing here at the clinic?

Siva Raja, MD, PhD: We try to address various aspects of how we treat this. We're not just focusing on how to do this operation better or how to get better chemotherapy, but we're trying to address each element. So, I'll answer that question from a surgical standpoint and perhaps my colleague can answer that from a medical standpoint. One of the first things that we look at is, these are what is considered a low volume, but high complexity operation. Meaning that the number of places in the country that probably do 50 of these in a year, you can count probably in a hand. It's not a lot of places that do it in a lot of volume. We do about a hundred of these a year. And I think that these patients tend to be malnourished, they tend to be older, or they tend to be more debilitated.

So identifying the patient's fitness level ahead of time is something that we've worked on. And I think that we've come up with our own frail to index, to identify these patients who may not do well with surgery, but then also identified patients who will likely have needs after surgery. So we can work on their postoperative needs preoperatively. And of course the concept of prehab, everyone's familiar with rehab, but prehab actually is a big deal. If you can make the person stronger before the operation, they're far less likely to have additional needs after the operation.

So I think on the one side we've worked on identifying patients and identifying their frailty elements. On the operative side, we've done a lot of work to identify patients who benefits from chemotherapy, additional chemotherapy after surgery. If they've already had chemotherapy, do they have benefit? If they haven't had chemotherapy who should get chemotherapy after surgery? Those kinds of things we're currently working on and the results will be coming out soon. And just as a sneak peek, all I can tell you is that it does defy conventional wisdom. So look out for the results on that one.

Dale Shepard, MD, PhD: On my, my, sounds like perhaps another episode coming up.

Suneel Kamath, MD: What a teaser, there you go.

Siva Raja, MD, PhD: Foreshadowing. Correct. And the last element actually is that these are operations that can be life altering. You know, we've gotten very good at getting people through that. You know, people rarely die from those operations and in a place like here, but these are life altering operations where your anatomy has been rerouted to some degree. And it's not only important to figure out how often we're curing people of cancer, but also important to figure out how people are doing after they've gone through this, a pretty rigorous treatment with chemotherapy, radiation, and surgery. So we're actually working on a lot of quality metrics. We're working on our own Cleveland Clinic esophageal questionnaire to identify various domains that directly affect people with esophageal diseases, cancer and otherwise, so that we can then not only track how people are doing from an oncologic standpoint, but also on a personal standpoint, symptom standpoint, how they're doing.

So there's a lot of work being done on a patient level and getting patient level data to figure out how can we be better? Or if we identify a certain element as being a problem for people, are the most commonly reported problem, how could we make their life better on that? So, those are a lot of projects that we're working on from a surgical standpoint, maybe Suneel can comment on some work on perhaps immunotherapy and things like that.

Suneel Kamath, MD: Yeah, definitely. I think that immune therapy certainly has been kind of a big advance, first in metastatic setting. But I think probably it may have even greater of an impact really for those with stage two or three resectable disease. And so, we have some data for the adjuvant setting now, and we're really excited. We'll be bringing us a trial here through the ECOG Cooperative Group, where we'll be looking at combination immune therapy as a neoadjuvant and adjuvant therapy. And I think that really could make a big difference cause unfortunately despite curative intent intervention with the number of these patients, we know that a lot of them are going to recur. And I think, the earlier we can treat people with more aggressive therapy. I think that greater the impact we can have.

Dale Shepard, MD, PhD: And the trial, is this looking at pre-op or postop or both? Is that the structure we're looking at?

Suneel Kamath, MD: Yeah, it's very interesting actually, it is both pre-op and postop. The pre-op, everyone will get both. The randomization, it actually has two randomizations in it, which I think is really interesting. Some will get only PD one, some will get PD one plus a CTLA four inhibitor, it's nivolumab and ipilimumab. And then some similarly in the post-op setting will also get single agent nivolumab or nivolumab plus ipilimumab. So, I think rather interesting to analyze after the fact, but I think it's a really great design to answer a couple of different questions at the same time.

Dale Shepard, MD, PhD: And then how do our palliative medicine colleagues play into management of patients and symptoms and things afterward, because, as you mentioned, these are complex operations and patients come in sick and there's quite a rehab despite your prehab, there's still a rehab period. So, do we involve palliative medicine in an organized way in this as well?

Suneel Kamath, MD: We definitely do. You know, I think the surgery certainly is life altering, but chemo-radiation is definitely no walk in the park either. And I've definitely found early involvement of palliative medicine is so important for managing the toxicities of our treatments themselves. They're very harsh on people to deal with, but if we can support them through that, I can certainly make that experience more manageable. So definitely I think having palliative medicine involved, I would also say having nutrition involved early has been really helpful as people have very limited ability to eat or swallow during this time. Helping patients to navigate that in terms of which foods are going to taste good for them during that time, which foods are actually going to pass down through their esophagus during that time, these things seem simple, but they actually do make a massive difference. You know, if we address them adequately.

Dale Shepard, MD, PhD: Siva, you mentioned something about not necessarily just working on surgical techniques, but I'm going to ask you a surgical question. And that's the role of lymph node resection. Are you doing some work in that area?

Siva Raja, MD, PhD: Yeah. You know, I think that there are several elements to an operation. I mean, at some level, this operation has been around for many, many decades, but how we do this operation has evolved. And it went from very, very, very large incisions to really small holes with minimally invasive techniques use of surgical robotics. All of those things have made the return to recovery return to function much better, but we're also looking to figure out about the oncologic effectiveness of an operation in terms of lymph node resection and things like that. And an esophageal cancer, we've written a lot about it and it, I think my predecessor also had a significant interest in it, Tom Rice, and that we are looking to see just because you've had chemotherapy and radiation, many people believe that's already maximum therapy.

So why would you keep taking more things than you need to and increase the morbidity? And our own studies have shown that adequate lymph node resection, even after getting chemotherapy and radiation still adds value to survival. And so I think those are some of the things that we're working on and many ways we are trying to redefine what should be an acceptable amount of lymph node section for oncologic adequacy, if you will, in patients who are undergoing what they call trimodality therapy, because it's not common these days to get the early stage cancers for esophagectomy, because they're now treated endoscopically. The pre-cancerous conditions are treated endoscopically. So the vast majority of patients we are operating on are people who've had chemotherapy and radiation. And so this is now the norm, this is the new norm. And so I think our studies are focusing on maintaining oncologic adequacy while trying to get our incisions smaller decrease the morbidity. Our length of stay is now somewhere in eight to nine days. And you know, most people are pretty well recovered within four to six weeks

Dale Shepard, MD, PhD: Now, Suneel, I guess rare disease, you'd mentioned 15,000 cases or so. So rare disease. It always makes questions like screening tough, right? But we know we've mentioned that if you have small lesions, you could do it endoscopically, it's always better to catch a cancer early. Any thoughts that there might ever be effective screening programs for this?

Suneel Kamath, MD: Yeah, I think that's going to be a tough one. You know, I think any intervention from a cost effectiveness standpoint, it's going to be challenging. I do wonder and this is definitely on a speculative scale, but I definitely wonder about these CT DNA based technologies that are being developed. You know, I think they're certainly very expensive, but I would definitely say from an ease of use standpoint, simply getting a blood test and detecting genomic material from a tumor at an early stage, I think is a very attractive technology. One that can be easily rolled out into a primary care setting or any basic lab setting. So, I think there is a chance for that. And I think that could be rolled out on a true pop population scale because it's just a challenging disease.

I mean, the presenting symptoms are not really that different, especially in the early phases from standard acid reflux and we certainly know that's a risk factor for this disease, but the majority of people with acid reflux are not going to get Barretts and they're not going to get esophageal cancer either. So it's just a challenging, if you think about the narrowing of the pool as you go through those two processes, it's very hard to identify who to screen with endoscopy or things along those lines. But definitely I think a blood based test could be done.

Siva Raja, MD, PhD: I think that there's a lot of interest in the field for these blood based test. And in fact, in esophageal cancer, I guess other malignant, solid malignancies, they've coined the term liquid biopsy. And so, I think that a screening test needs to have the following elements. It needs to be cheap, it needs to be easy to use and it needs to be relatively predictive. And I think that these are the elements, right now a test that meets some of them, not all of them and saying it's, but you know, it's a work in progress.

I completely envisioned this in our lifetime that those kinds of things come to play where we are identifying them earlier. And, I think we're going to see the treatment of disease of this disease expand on both sides. You're going to find more early cancers that we can intervene on and improve survival. And then we're going to find, that we have treatments that make inoperable disease, operable, or treatable, in patients who are a stage four disease that are palliative may actually become curable and treatable. So I think that as medicine expands, as a treatment are the armamentarium of the group increases, you're going to find that we're able to treat a larger number of patients, despite their states early, or late.

Dale Shepard, MD, PhD: So tell us a little bit about outcomes and how our outcomes compare to other places?

Siva Raja, MD, PhD: In thoracic surgery, the society of thoracic surgeons, they maintain a database. It's a voluntary database, that we submit all our data because we like to have feedback to figure out, what we're doing well compared to others and maybe what we're not doing so well, so we can catch up. It was intended as a quality based quality database. And what it also allows us, is compare ourselves to how other people are doing and within that database, while admittedly not everyone participates in it, we are one of the lowest moralities in the United States for this operation. And our morbidity is one of the lowest. So I think overall, we are a three star program and there's very few programs in the country that have three stars in every domain that they look at for esophageal cancer. So, I want to take a second to highlight the entire team that makes this happen. It's not just any one person. I tell my patients, when I come out of the operating room and I talk to the family at the end of the day, I tell them that, all right we're halfway there. So, there's a lot more work to be done, and there's a lot more people that are going to help.

Dale Shepard, MD, PhD: Well, there's good encouraging news as we close out. Appreciate your guy's insight on the program. All the hard work you guys do for this disease. Thanks for being with us.

Siva Raja, MD, PhD: Oh, thanks for having us.

Suneel Kamath, MD: Thanks for having us.

Dale Shepard, MD, PhD: To make a direct online referral to our Taussig Cancer Institute, complete our online cancer patient referral form by visiting clevelandclinic.org/cancerpatientreferrals. You'll receive confirmation once the appointment is scheduled. This concludes this episode of cancer advances. You'll find additional podcast episodes on our website, clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google Play, Spotify, Sound Cloud or wherever you listen to podcasts. And don't forget you can access real time updates from Cleveland Clinics Cancer Center experts on our consult QD website. At consultqd.clevelandclinic.org/cancer. Thank you for listening. Please join us again soon.