What to Know About Melanoma

Podcast Transcript

Scott Steele: Butts & Guts, a Cleveland Clinic podcast, exploring your digestive and surgical health, from end to end.

Hi again, everybody, and welcome to another episode of Butts & Guts, I'm your host Scott Steele, the Chair of Colorectal Surgery here at the Cleveland Clinic, in beautiful Cleveland, Ohio. As always, we're very pleased to have a wide variety of guests, and none more so than ever with Dr. Brian Gastman, who is the Medical and Surgical Director of the Melanoma and High Risk Skin Cancer program. Brian, welcome to Butts & Guts.

Brian Gastman: Thank you very much. I appreciate this opportunity.

Scott Steele: We always like to start off with each of our guests, give us a little bit about yourself. Where are you from, where'd you train, and how long have you been at the clinic, and how did it come to the point that you're here, at the Cleveland Clinic.

Brian Gastman: Sure, thank you. I'm actually a Midwest kid. I'm from Ann Arbor, Michigan. Not surprisingly, I stayed in Ann Arbor ultimately for undergrad med school. I moved to Pittsburgh where I did actually a head, neck, otolaryngology training, studying how tumors invade the immune system. From there, I went to Wash U, did a head, neck, microsurgery, and cancer fellowship, and then I went back to Pittsburgh to do a full plastic surgery residency. I maintained an interest in tumor immunology, and became interested not just in head neck cancer, but skin cancer. I was able to continue all of that work when I joined the groups of Johns Hopkins and University of Maryland in Baltimore for around five and half to almost six years, and ten years ago, moved to the Cleveland Clinic with a major charge to build the Melanoma and High Risk Skin Cancer program, which we've been doing for the last ten years.

I also still do a lot of head neck surgery, head neck microsurgery, and was honored to be able to lead the last two face transplants here at the Cleveland Clinic. My other interests, at least professionally, include, obviously basic science lab studying tumor immunology where I work a lot with industry for translational outcomes, and I, over the last, I'd say five years, have really moved into the clinical trials realm, and actually doing sort of nontraditional clinical trials for a surgeon, doing a lot of therapeutics directed to patients who are unresectable, mainly with skin cancer or head neck cancer.

Scott Steele: That's fascinating stuff, and for sure we're going to have you back on where we're going to focus in on the face transplants, but today, we're going to talk about something that a lot of our listeners may either know about, think they know about, or know somebody who has had it, if they haven't had it themselves, and that's melanoma. Let's just start with a high level overview. We've heard the term, sounds kind of scary. What is melanoma?

Brian Gastman: It's amazing, if you really know anything about rare cancers, pretty much any cell in our body can convert to cancer. Interestingly, the most common cancer in human is skin cancers, but mainly basal and squamous cell carcinomas, which are much more superficial in our skin, because we are bombarded since we are children with UV radiation from the sun. In fact, UV radiation goes through our clothing, and it's even worse in the sky. In fact, airplane pilots and stewardesses have two times the rate of skin cancer, specifically melanoma.

Deeper within our skin is the cells that cause pigmentation, melanocytes. If you're African American, for example, they're more superficial, and they protect you against skin cancer, but as they go deeper and we become lighter, they become less protective and they themselves can be the origin of cancer. Really from Adam, the first human, till around 2010, if you had metastatic melanoma, it was a death sentence. There was interleukin 2 which had a very high death level from just the therapeutics, and so it was relegated to a very small number of patients, and then all of a sudden, those of us who had been involved in tumor immunology started getting a break through. Around 2010, 2011, the first of many got published looking at a drug which targets, basically a break on the immune system, releasing that break. Of course, it can cause autoimmunity, which is its downside, but at the same time, it turns out makes cancers like melanoma specifically very visible to the immune system.

From there on, it was success after success after success, and in 2018 co-Nobel prize were for those who discovered the two molecules that we now commonly target to treat melanoma. Overall, it used to be a very, very scary cancer, because our parents for example, if they had stage four, they were done for, but today, even stage four cancers were at least at a five year, 50% cure rate. In the local regional diseased patients that have had advanced, complex surgery but with just regional metastases that are resectable, we can give these drugs adjuvantly and get probably at least an 80 percent cure right there, without even talking about other therapies that can be given if those fail.

Then the other side of it is, a lot of melanoma is being caught earlier, and earlier, and earlier. For example, whereas the numbers in let's say the late 70s were about 35, 40 thousand cases in the United States with about 25 percent death rate, today there's about a hundred thousand melanomas a year, and the death rate's around seven percent. I would love to tell you it's just purely because we're curing stage four melanomas, but really it's mainly because we're picking them up much earlier, where surgery can simply cure the patients. The term melanoma I think 10, 15 years from now will still be a bad term, it's cancer, there's nothing you can say about that, but it's becoming less and less amongst the more deadly ones, and thus it will be a little less scary of a diagnosis. I can tell you as a practitioner there's a big lag. It's good to be scared and have respect for the disease you're dealing with, but sometimes the fear outweighs the reality, and I think again that has to do with the historical nature of melanoma.

Scott Steele: That's a lot to unpack there. Wow. Incredible. What an incredible journey you just took us on just in that brief overview. Let's take a way step back and just start off first, so, a lot of the listeners we have to this particular podcast are patients, family members, and what are the symptoms that a patient may have? A lot of us have moles, and you may look at a mole and think, "Is this melanoma? It looks dark, maybe that's what he was talking about." What are the symptoms that people can develop that they may alert, or how do they do that? Then, along with that, where do we look? Do we look anywhere? How do we look? How do we do a full body exam to make sure we don't have a melanoma? Walk us through those two things.

Brian Gastman: First of all, there is the classic A, B, C, D, E of melanoma, which is A is asymmetry, B is the border of the lesion, which usually, we think of moles. C is the color. Is it heterogeneous, meaning, is it all one color or are there some brown and black in it? D is diameter, six millimeters or larger. E is either evolution or elevation, meaning is it growing and changing? For me, those that are growing and changing lesions of the skin are the ones that concern us the most. Now, I told you earlier, there is much more common skin cancers, and those really are much easier to sort of know that those are not melanoma. A lot of things on the skin, it's pretty clear what they are and what they aren't. In fact, only about 30 percent of melanomas actually arise in a preexisting mole, so a lot of people just see something growing that may or may not be dark. Usually it is dark, but sometimes it's not. Sometimes it's not dark because it starts bleeding, and it effaces all of it's typical features.

For the most part, most people are just not symptomatic. In fact, the most common location of melanoma is on the trunk. Half the trunk is your back. Most of us have never seen the moles on our back. A lot of times, you're coming in for something else, and your family practitioner or your dermatologist says, "Hey, what's that?" That's not uncommon also. It's incidentally found. The good news is, usually the incidental ones are usually the early ones. Usually the ones that start bothering you are the worse ones. The vast majority of patients that will go to a surgeon will have had a biopsy, it says it's melanoma of variable depth, but be completely asymptomatic. The vast, vast majority of those you will not palpate any lymphadenopathy. In fact, a lot of studies have been done, that if you would scan those patients, like with CT scans, you'll rarely find anything, even if there's already disease in the lymph nodes, it's so microscopic, you can't feel it, you can't image it.

From a symptomatology standpoint, the main thing that people can do, unless you have a personal or family history of skin cancers or melanoma, is to do the best you can do. To do a full body scan on your own is tough, unless you're good at it, but most of our patients who get good at it, do have whole body mirrors, have significant others, family members that will help them, but, this is Butts & Guts, and I will tell you, what I tell my patients is head to toe, and everywhere the sun doesn't shine, because melanoma can also be in parts of the skin that people don't realize there's skin, and it can also be even mucosal. Once you start dealing with melanoma, you start to worry about even rectal, vaginal, tongue, sinal nasal melanoma. Those are pretty rare, don't get me wrong, but once you start building a personal history, especially if you've had more than one, you start worrying about those things, and a good dermatologist, or someone who does a really good skin exam, will not forget about those areas.

Scott Steele: Now, we like to play a game on here called Truth or Myth Number one: Truth or Myth? Melanoma can only be caused by prolonged sun exposure.

Brian Gastman: Myth, and how do we know that? Because we see melanoma on the bottom of people's feet, we see them, as I mentioned, in mucosal areas. We see them in the eye, even. It is possible that there is some UV radiation that goes through tissues and can just hit the right cell that happened to have some preexisting issues and converted, but as far as we can tell, sun exposure is absolutely related to it, but is not always required to cause the melanoma, but we do assume that the most common melanomas, the ones on the face and the trunk and the arms and the legs, are probably related to sun, and so a lot of parents like take their kids to their beaches and let them enjoy, those are the times when you really could possibly be giving your child a future problem many decades later.

Scott Steele: Second Truth or Myth. It's best to avoid tanning beds as these can cause melanoma to form.

Brian Gastman: I would say, truth. I would say, because the overwhelming majority of melanoma experts would say tanning booths are associated with melanoma and bad and should be banned. There are bans all over the United States in different states and around the world. The data is strong, but it's hard to make pure conclusions, but I would say, from just being part of the overall academic world of melanoma, truth.

Scott Steele: Final truth or myth. Only Caucasians or light colored skin people can get melanoma.

Brian Gastman: That's definitely false. Although it is true that the more fair skinned, blue eye, freckled, red hair, those types of patients are at higher risk, and interestingly, a lot of us, I have freckles, although I'm not a red head, freckles many times can come out in the sun and do add a certain level of protection. They're not melanocytes. They are just pigmented spots in your skin, but many redheads actually have a mutation in them, and that's why they themselves actually are worse off, but African Americans for sure can get melanoma. It's much rarer, but it's much more common for them to get it in what's called acral melanoma types, which are usually on the palms and the bottom of your feet or in your nail bed. That's the most common location in African Americans. However, overall, still more Caucasians get it, and thus they have more of it in those areas even, but it's basically a small percentage of Caucasians times a larger number of Caucasians as a larger total than a higher percentage of African Americans times the small number of them that get it.

We do see some in Asians. It's not that common. Middle east, shockingly it's very rare. Obviously those with darker skin are relatively protected, so their rates are lower, but you can definitely get melanoma regardless of your skin type.

Scott Steele: You talked about this a little bit in the overview. Let's jump into the treatments for melanoma, and walk me through, I got a run of the mill, it's pretty early, what do we do with those? A little bit more advanced, what do we do with those? Lymph node positive, what do we do with those? Then, metastatic melanoma, what do we do with those?

Brian Gastman: Sure. Melanoma, as I tell all my patients, is for the most part cured. As I told you, seven percent death rate. The vast majority of those cures are done through surgery. Whether it's a wide, local excision only, to get rid of the microscopic tentacles that form, and we're very good at curing the primary lesion, whether there's mets beyond it or not. Cure rates, if you just look at the primary lesion are probably above 99 percent, if you follow standard guidelines. For instance, the National Cancer Comprehensive Network's guidelines, you follow those, those are, again, the primary lesion cure rates.

As melanoma gets thicker, we start worrying about it metastasizing to local regional lymph nodes. It can skip the nodes. It can, from the tumor to the node stop and form intransitive mets, or it can take a long time to go from the primary to the node, and that's why sometimes the node will be negative when we biopsy it, and then later they get nodal recurrences. That being said, the vast majority of them, if they metastasize, you'll know right away and with a sentinel lymph node biopsy you can determine that. Sentinel lymph node biopsies are very simple. They're basically, you inject around the tumor area, in the superficial dermis with material. Usually the basis is radioactive material, that will quickly go through lymphatics and conglomerate or concentrate in regional lymph nodes. If it's on the back of your hand, it will be in your axilla within minutes, and then you can take them to the operating room where we have a fancy Geiger counter, we call it a gamma probe, and you can tell right away where you should make your incision.

We have additional vital dyes that helps us identify them. Once we find the node and it's removed, and then the node is checked, if there is cancer in there, and again, the chances of that varies, as how thick the tumor gets. If it's a really thick tumor, it can be 50, 60 percent chance that there is microscopic disease, but even in those cases, the majority of them will be microscopic. I can't palpate it, I can't image it, I can only know that it's in there because of pathology.

Then, at that point, we will image the rest of the body. About 93 percent of patients with microscopic disease in the lymph nodes will be clean on imaging, so it's still rather rare that at that point they have anything beyond that microscopic disease, so we're catching it rather early. In those patients, which will jump from a stage one or two, which is not in the nodes, to some form of stage three, which is in the nodes, those patients can then be offered FDA approved drugs, and the drugs are the same drugs that we offer to stage four or unresectable disease, which mainly are immunotherapies, which are mostly focusing on blocking the blocks in the immune system. I mentioned earlier, think of that as like turning the volume up on your immune system, and it caused havoc. It turns out, if you think back to the 80s, we used to have equalizers in our radios. There's a lot of nuances in the immune system, and we're trying to figure that out, and some of those have been figured out to the point where we don't overwhelm the patient with autoimmunity, but we do cause better antitumor immunity.

They started out in stage four, they were so effective, they asked, will it work in stage three, and the answer was yes. The addition to that is that 45 percent of all melanomas of the skin have a mutation, a driver mutation, that can be targeted by a pill. Without going into too much detail, it's actually two pills now, that can also give you an excellent response, and what's really great about those is if you're riddled with melanoma, the responses are quick. They call it the Lazarus effect. People in the ICU, on a ventilator, trached, they get the pill and within a week, they're driving themselves home. The problem is, like any targeted mutation, tumors can re-mutate, and then they become resistant. The immunotherapy is great because it's an external therapy to the tumor. It's the immune system that's being revved up, killing the tumor. When you get a complete response, it's durable. I mean, these patients are being cured.

For example, our best immunotherapy for stage four or unresectable disease is at five years now, 50 percent, and these look like they're going to be a hundred percent cured. That 50 percent is likely cured. The other 50 percent are starting to already get other novel therapies, and maybe the actual death rate is actually less than that 50 percent. It's a very exciting time, but in earlier disease, in stage three, we do not have anything FDA approved. I will say, it worked in stage four, through an FDA approved clinical trial. Now it's FDA approved. These drugs worked in stage three through FDA approved clinical trials, phase three, randomized, control, et cetera. It's now FDA approved, and now there are multiple clinical trials going on for high risk stage 2B and stage 2C melanoma, we have one of those trials here at the Cleveland Clinic. I happen to be a co-PI on this international trial, so these therapies are being brought earlier and earlier in the disease process, but they've not yet made it to standard care yet.

Scott Steele: Absolutely exciting times. I'm a patient, I just got told, "Hey, your mole looks like melanoma," or your scared of that, and now I got to come to your office. Can you walk us through somebody would expect during that visit with you or one of your colleague at Cleveland Clinic's Melanoma and High Risk Skin Cancer program?

Brian Gastman: Sure. I will qualify that that I always tell my patients I'm a melanoma killer not a finder. I don't like being responsible for identifying them, because I'm not the one who does great head to toe and everywhere the sun doesn't shine examinations. That includes things like dermoscopy, other things that dermatologists and other practitioners of skin evaluation do. Assuming they came in with some diagnosis, the first thing I'd do is I'd tell them this, that melanoma is highly curable today. 93 percent of people, all comers, are going to be cured, and the majority of them are going to be cured with a simple outpatient surgery that I'll be able to provide for you. We at the cancer center here are very focused on time to treat. We published, I think the first article ever, using the National Cancer Database, looking at their time to treat data, we did it in the melanoma program at the Cleveland Clinic.

What we showed is, in especially early melanoma, it does matter when you have your tumor resected, and you want to do it in the first 30 days from diagnosis. We try to get people in as fast as humanly possible. The things that slow us down are, number one, a lot of times the pathology is done outside of the Cleveland Clinic, and we have had our experts change the diagnosis. Thicker or thinner or not even melanoma, but usually for us, I tell patients you're looking at, because I usually do clinic Wednesday and Thursday. Our major melanoma OR day is Tuesday, so I said, you're going to have surgery six, five days from now, or 13, 12 days from now, and most people will accept that. The surgery is going to again, be a combination of wide local excision of the primary, which we do a great job of, plus or minus a sentinel lymph node biopsy. That's going to cover the vast majority of patients, and certainly the ones you're describing.

Now, there are other elements, especially a place like the Cleveland Clinic where we have a lot of academic things going on. If this is your second melanoma, your brother had a melanoma, we have a genetics program, which is run by Dr. Pauline Funchain, who really is my partner, and she's the co-director with me of the melanoma program, her strong interest is in familial genetics, which has been understudied, and we're making amazing headways in that. She is becoming a world leader in that area.

There are other things we do as well. For patients that are stage three, let's say we do the wide excision and cell node biopsy, we find out there's disease in the node, we are using circling tumor DNA to see if we can identify their recurrences before symptomatology or imaging would tell us. We are about to start a DOD funded trial for patients who mainly for stage 1B, which is again, early, all the way up to stage three, with a vaccine. The vaccine's really cool because it targets proteins within melanoma, but and this is where I added to it, it's a partnership with myself and Craig Slingluff, a surgeon at UVA, who's a internationally known vaccine specialist and surgeon in melanoma, but it turns out those mutations that I told you about that are 45 percent of melanomas, they're like 90 percent of all moles. If we can get rid of moles, we can reduce the burden of surveillance and risk to patients, specifically people that have already had one melanoma.

Our goal is to have something for the earliest stages all the way up. For example, I have another project, which the Melanoma Research Alliance funded us and Stanford, where we're using artificial intelligence to look at moles to see if we can use pictures from your iPhone to say, "Hey, that mole should be biopsied, that one shouldn't be."

Scott Steele: That's fantastic stuff, and as always, it is great to hear what's on the horizon in melanoma and other skin cancer, as well as the clinical trials that are going on. As we wind up here, we all like to get to know you a little bit better, so we do some quick hitters, so first of all, what's your favorite sport?

Brian Gastman: Football.

Scott Steele: What's your favorite food?

Brian Gastman: Oh, I'm really simple. I like a bagel and eggs. I mean, something like that. An omelet. It's crazy, but it's true.

Scott Steele: Your last non-medical book that you've read?

Brian Gastman: Oh, I read a lot of science fiction and I'm blanking on the name. Well, I know the name of the book series. It starts off with the Atlantis Gene, and I'm trying to remember the other two books, but it's a triplet. It's really good.

Scott Steele: Then finally, what is something that you like about living here in Cleveland?

Brian Gastman: There's a lot I like about living here in Cleveland. Believe it or not, when the weather is good, which is a good chunk of the time, living here, it's really good. I love the lake. My wife's from the east coast, my parents are in Michigan. I think the centrality of it, and honestly, most of my life is at home or in the Cleveland Clinic, my car ride is 15, 17 minutes each way, so the fact that the Cleveland Clinic is here. Not to sound like an overly enthusiastic cheerleader, but it's true.

Scott Steele: That's fantastic. We're so glad to have you here. To learn more about melanoma and Cleveland Clinic's Melanoma and High Risk Skin Cancer Program, download a free treatment guide at ClevelandClinic.org/melanoma. That's ClevelandClinic.org/melanoma, M-E-L-A-N-O-M-A. To make an appointment with Cleveland Clinic's Cancer Center, please call our Cancer Answer line at 866-223-8100. That's 866-223-8100. Please always remember, that in times like these, it's important for you and your family to continue to receive appropriate medical care and rest assured here at the Cleveland Clinic we're taking all the necessary precautions to sterilize our facilities and protect our patients.  Brian, thanks again for joining us here on Butts & Guts.

Brian Gastman: Thank you very much.

Scott Steele: That wraps things up here at Cleveland Clinic. Until next time, thanks for listening to Butts & Guts.