Expertise in Treating Advanced Melanoma

The deadliest form of skin cancer is even deadlier when it spreads beyond the skin. When simply cutting out the cancerous skin is not enough, melanoma goes from a dermatology matter to an oncology matter. Dr. Margaret Callahan is a medical oncologist and Dr. Giao Phan is a surgical oncologist. Together they lead UConn Health’s advanced melanoma program, which offers specialized care for when this cancer has spread.

(December 2024, Dr. Margaret Callahan, Dr. Giao Phan, Carolyn Pennington, Chris DeFrancesco)

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Transcript

Chris: Melanoma is the deadliest form of skin cancer, and while the best treatment is prevention, there is still hope, even once it’s spread beyond the skin.

This is the UConn Health Pulse, a podcast to help you get to know UConn Health and its people a little better, and ideally leave you with some health information you’ll find useful.

With Carolyn Pennington, I’m Chris DeFrancesco. When found early enough, the cancer can be cut out of the skin.

Carolyn: But once it’s spread, treatment options are limited. It takes a special level of expertise to treat advanced melanoma. UConn Health recently launched a program to help when treatment requires more than removing the cancerous tissue. And those experts are here with us today. Dr. Margaret Callahan, chief of the Division of Hematology and Oncology, and Dr. Giao Phan, Professor of Surgery. Thank you both for joining us today.

So when it comes to melanoma, we often think about dermatologists. Dr. Phan, you’re a surgical oncologist, Dr. Callahan, you’re a medical oncologist. So we’re talking about melanoma when it goes beyond a dermatology problem. Is that right, Dr. Phan?

Dr. Giao Phan: Yes. And to be honest, most of the time, your dermatologist is the one that’s going to be diagnosing you with melanoma or other skin cancers.

The surgical oncologist comes to play depending on the characteristics of the melanoma. If it’s very early melanoma, often the dermatologists can excise it out themselves. When it becomes a little bit more advanced, and that is dependent on the characteristics of the pathology, there are higher risks of the melanoma going to lymph nodes.

Thus, the dermatologist will refer to us to evaluate whether or not lymph node biopsies or other treatments would be needed based on those initial biopsy characteristics.

Carolyn: So they take the biopsy and then when they look, when the dermatopathologists look at it, they say, “OK, this is definitely more serious and we need to step it up a notch.”

Dr. Phan: Correct. And then a surgical oncologist would then excise the lesion and potentially do a sampling of a lymph node called sentinel lymph node biopsy. And that determines whether or not the melanoma has migrated outside of the original area. And that actually then determines then if patients need additional therapy besides just excision of the melanoma.

Carolyn: So then what happens?

Dr. Margaret Callahan: At that point a medical oncologist might get involved, and there are a couple of different places medical oncologists can be helpful. Medical oncologists such as myself usually prescribe or administer systemic treatments, treatments that help treat the melanoma throughout the body, and those treatments can, um, either reduce the risk of the melanoma recurring in cases that are surgically resectable, or in cases where surgery is not an option because the melanoma is more advanced, systemic treatments are really our go-to therapy.

Carolyn: So that’s like chemotherapy?

Dr. Callahan: Yeah, I’m kind of purposely using the word “systemic” therapy because chemotherapy is not a treatment that works very well for melanoma. And so consequently, we don’t use it very often.

Carolyn: Why is that?

Dr. Callahan: Well, melanoma is resistant to the chemotherapies we’ve developed, but the good news is that that it’s sensitive to some other therapies that have been developed recently and actually seem to work much better with fewer side effects. And those two common types of treatment we use are immunotherapies, or therapies that activate your immune system and get it to fight the cancer, and targeted therapies, these so-called designer drugs or targeted therapies that hit the melanoma specific mutations.

Carolyn: So the patient has fewer side effects with these, the immunotherapy?

Dr. Callahan: Typically, they’re different side effects than what you might associate with chemotherapy. So unlikely that you’re going to feel nauseous or vomiting or lose your hair or have that sort of side effects you might associate with chemotherapy. There of course are risks ’cause this is a cancer treatment, but it’s a different profile of side effects and these tend to be some of the best tolerated cancer therapies we have out there.

Dr. Phan: I have many times tell my patients who are often older, in their 80s or more, that there are actually no age-related side effects, that they can actually tolerate very well. And so I think that’s actually one thing that’s very unusual compared to chemotherapy.

Chris: Immunotherapy seems like a fascinating approach to dealing with cancer. It’s not brand new, but can you explain a little bit about just kind of how that works?

Dr. Callahan: Sure. So the broad concept of immunotherapy is, it’s getting your immune system to fight the cancer. But there are a number of different approaches to that. Sometimes we divide those approaches into two different buckets.

Dr. Phan’s really an expert on cellular therapies or therapies that use immune cells from your own body to fight the cancer. And my experience lays more in medicines or drugs that change how your immune system behaves in your body. One example of a class of drugs like that are the checkpoint-blocking antibodies that are probably the most commonly used immunotherapies out there today. Those work by allowing your immune system to get more activated, and then we hope when your immune system is more activated, it’s going to fight the cancer and eradicate those cancer cells.

Carolyn: So, Dr. Phan, when you use the immuno cells, do you actually extract the cells from the person for their own use again, or, how does it work?

Dr. Phan: Yes. Yes. I should say that when I first started using these, they were part of clinical trials, which have been going on for a few decades, actually, where people extract tumor deposits somewhere, grow the lymphocytes or the white blood cells in the tumor to billions, and then re-infuse them back to help fight off the cancer. So kind of like a transplant, but it’s just using anti-tumor cells.

Now, as of this year, it is now FDA-approved, and actually for the appropriate patient, it can be used for someone who has advanced disease. And here I should qualify that advanced disease means having tumors at multiple sites that are not responding to the standard, similar drugs that Dr. Callahan mentioned.

Carolyn: And is that good for any age patient, any advanced stage?

Dr. Phan: This type of treatment, currently as it has been developed, is more for patients who are very robust, because it is very tough on them. And so, unfortunately, it is less likely to be received by patients who, let’s say, are in their 90s. In general it is more difficult, but this is relatively new, and I suspect over the next few years things may change. I think many people are looking to see how to modify these to make it simpler and so that more patients will be able to get that.

Chris: So it sounds like treating advanced melanoma is a very, very specific, specialized type of thing. What kinds of approaches are available at UConn Health at this moment?

Dr. Callahan: We have a fairly wide repertoire of FDA-approved therapies that we use. The immunotherapies I talked about before, there are three FDA-approved immune checkpoint-blocking antibodies, or combinations thereof, as well as three combination targeted inhibitor treatments. We’re also using intralesional treatments with an immunotherapy called T-VEC, which is kind of a unique approach to treat the tumor at the site that the tumor’s growing. And we are in the process of getting a few clinical trials open and UConn’s also launching a, or has launched a, bone marrow transplant program and we’re hoping that cellular therapies are going to be part of our repertoire in the future.

Chris: All right. We’ll get back to the research part of it in just a second. I did have another question along the lines of the therapies. So if you were to look at it from a simple layperson’s point of view, like on the spectrum of where a patient is in melanoma — so there’s the very beginning where you don’t have it yet and there’s the prevention and then there’s like you a little further along you have it or you have a lesion that’s suspicious and you get a biopsy, further along the spectrum, you actually have a melanoma and you get it excised– at some point, they’re not going to be able to be helped by those things we just talked about. And only people like you can help them, right? Can you give us a sense of kind of who the best candidates are, and at what phase in the development of the disease is it where they would be seeing you?

Dr. Phan: Sure. So, starting off, again, it would be the melanoma based on the characteristics of the pathology. I would say the majority of patients would benefit from seeing a surgical oncologist as the pathology does show characteristics that give them a percentage of having lymph node involvement. So a sentinel lymph node biopsy is considered standard for many patients with melanoma. And so often I think that is a good starting point. Fortunately, most of my patients will have a negative sentinel lymph node biopsy, meaning that their tumor has not progressed to anything anywhere else.

The other group of patients that we sometimes see are patients who show up with a mass or bump or something that they or their primary care physician have diagnosed or noticed. And so we start out with them having a diagnosis of metastatic disease, meaning that melanoma has migrated somewhere else already. Then in that case, we then see the patient and we meet as a team to discuss the patient to see what approaches would be best. Sometimes it may be surgery first, although that is going to be less and less.

Nowadays, we actually would like to see whether or not patients can get some of the systemic drugs in first to help shrink the tumor and to prevent the tumor from going elsewhere first. Then we then reassess and then do the surgery afterwards. So it is definitely a person-by-person situation. Every treatment plan is personalized for that patient depending on what disease stage they are at.

Dr. Callahan: Yeah, Chris, if we were to sort of take that timeline you described before from precancer and prevention to early-stage disease and resection by a dermatologist, the place that Dr. Phan and I get involved is when there’s a real risk that some melanoma cells have broken off and traveled somewhere else in the body. And so there really needs to be an escalation of care and an escalation of the surveillance to make sure that the disease doesn’t advance to organs in the body and become life-threatening. Of course, we want to avoid that at all costs or reduce the risk of the disease advancing.

Chris: UConn recruited you from other high-profile institutions to come and build this program, correct? So talk a little bit about that story. How did this program come to be?

Dr. Phan: Well, I actually saw that there was an opportunity to develop a melanoma program here, and so I joined in the summer of 2023. And then I met with Dr. Callahan and we talked about potential here at UConn.

Carolyn: So did you guys know each other before? No?

Dr. Callahan: Not really. I mean, we met each other before either of us joined the institution, but we were in similar professional circles, but it hadn’t worked together.

Carolyn: Oh, OK.

Dr. Phan: But yes, it’s a small world, the melanoma world, actually, and often we know each other’s work. So it was nice to have a colleague here who has similar mindset how to treat patients, and so it ended up falling together really nicely.

Dr. Callahan: Yeah, I, as you mentioned, was at another institution that had a fairly big melanoma practice and was really, really keen to see what we could build here at UConn. But having Dr. Phan here really was an important part of the puzzle. A medical oncologist and a surgical oncologist together really are a core team, together with dermatology, pathology, radiology, but having somebody who has the level of melanoma expertise and immunotherapy expertise that Dr. Phan has is really unique and it’s really a treat for me. So our interests match very well. And then on a personal note, I’ll say I was a student here at UConn previously. So there was some draw to come back.

Chris: Excellent.

Carolyn: That’s cool. Research, let’s talk about that. Was that a draw for you guys to come to an institution where you could do research?

Dr. Callahan: Yeah, so I think Dr. Phan and I both have been involved in research throughout our careers, whether it’s clinical trials or basic or more translational research. I really have a lot of respect for the different ways people practice oncology, but for me, being involved in the research effort has been just a really important and enriching part of my practice. The idea that we can not only do a really great job treating patients, but keep thinking about ways to make treatments better was really important for me. And in this particular area of Connecticut, UConn really has the academic bent and the investment in research that made it an ideal environment for me to say, “OK, I can see building my practice and my research career here.”

Chris: And in order to get in with you, a lot of your referrals come from other physicians, I would imagine, but folks can schedule directly with you, is that correct?

Dr. Phan: That is correct.

Chris: OK, so we’ll put the information on how to get a hold of you in the notes of the show for people listening.

From UConn Health, Dr. Margaret Callahan, medical oncologist and chief of the Division of Hematology and Oncology, and Dr. Giao Phan, surgical oncologist and professor of surgery, thank you for joining us.

Dr. Phan: Thank you.

Chris: That is our time for today. For Dr. Phan, Dr. Callahan, and Carolyn Pennington, I’m Chris DeFrancesco. Thank you for listening to the UConn Health Pulse. Be sure to subscribe so you can catch us next time, and please share with a friend.