TAMARA BUSH: Hello. My name is Tamara Bush, a physician liaison at Mayo Clinic. Thank you for viewing our discussion on the topic of melanoma treatment at Mayo Clinic. Identifying the melanoma stage, depth, and severity is critical for selecting the most appropriate treatment combination. Mayo clinic doctors have access to the latest in diagnostic methods and treatment innovations to improve care for patients with melanoma.

Understanding the complexities of melanoma is achievable through an openly collaborative effort by dedicated experts. I am joined by my colleagues-- Dr. Alexander Meves, a dermatologist; Dr. Tina Hieken, a surgical oncologist; and Dr. Svetomir Markovic, a medical oncologist-- who have an integrated clinical practice for patients that have been diagnosed with melanoma. Let's begin our conversation.

Dr. Meves, from your perspective as a dermatologist, would you discuss the melanoma diagnostic methods for patients offered at Mayo Clinic within your practice? In addition, would you talk about your research of genomic profiling of melanoma being done at Mayo Clinic?

ALEXANDER MEVES: Yes. Thank you, Tammy. I wanted to start out by saying that, at Mayo Clinic, we really try very hard to tailor melanoma treatments to each individual patient. And so one key question that we need to address immediately at diagnosis is, how dangerous do we think this cancer is, what is the likelihood of this melanoma metastasizing and creating widespread disease, and how aggressive do we need to be with treatment?

So, in dermatology, we diagnose a lot of melanomas every year, but we know that not all of these melanomas are actually dangerous. In fact, like most of these melanomas we diagnose, they will never lead to problems and are just cured by a local excision. And so the question is, how do we find the ones that need our attention, perhaps need a referral to Dr. Hieken for a lymph node surgery or even treatment with powerful new immunotherapy drugs that are administered by Dr. Markovic?

And the answer to that is that we mostly rely on a very simple concept, the idea of tumor invasion depth. So, in other words, the deeper melanoma has grown into the skin, the higher the risk of having a bad outcome. And so we call the measurement of this invasion depth Breslow thickness, And if Breslow thickness is beyond a certain threshold, we worry about a bad outcome.

So the concept of Breslow thickness was actually developed in the late 1960s. And, you know, we've come a long way since in refining our understanding of cancer at the molecular level and we now have the technology to measure molecular changes in tumor tissue in just routinely collected biopsy tissue. And so, at Mayo Clinic, we developed a test called the Merlin assay that quantifies molecular changes in tumor tissue and can be used to better differentiate between low- and high-risk melanoma than Breslow thickness alone.

And, so in other words, if you have a melanoma that we would call higher risk by the traditional Breslow thickness approach, the Merlin assay may reclassify this lesion as low-risk because it not only takes into account Breslow thickness, but also molecular data that was previously unattainable. And so this ability to better, as we call it, risk-stratify melanoma by a Merlin testing can help patients avoid unnecessary procedures such as sentinel lymph node biopsies.

But for a test like the Merlin assay to be widely accepted by the medical community, it needs to be validated extensively in thousands of patients just like, back in the '60s and '70s, Dr. Breslow had to validate his method. And so we have, therefore, initiated this extensive validation program which is headed by Dr. Hieken.

TAMARA BUSH: Thank you, Dr. Meves. Dr. Hieken, as a surgical oncologist, clinical trials work in tandem with your surgical practice. How do patients with early- and advanced-stage melanoma benefit from the combination of these innovative treatments?

TINA HIEKEN: Thanks so much, Tammy. It's great to join my colleagues here and have an opportunity to talk a little bit about our practice. So, for our practice, we see patients with early-stage disease to late-stage disease. And, really, the secret to our ability to care for these melanoma patients is our team-based approach. So some are practitioners who their patients will meet-- and these are dermatologists, radiation oncologists, medical oncologists, and surgical oncologists like myself-- and then some who work more behind the scenes such as some of our expert radiology colleagues and pathology colleagues, who really helped us provide the best possible care to patients.

So our own group includes a specialty-trained melanoma surgical oncologists, and we have come up with a number of innovations along with our colleagues to try and minimize the side effects of treatment so that, when it's required, we can do things in a minimally invasive way with some innovative techniques to really minimize long-term effects. Most importantly, here, we really have this combination of great facilities and an expert medical staff that allows us to provide the most accurate and precise test results, not just performing testing and doing treatment, but doing both in a really exemplary fashion. And some things that appear to be simple are actually more complex than they appear and really depend on us working hand-in-hand with our colleagues.

So in terms of clinical trials, the things that the trial that Dr. Meves mentioned, the MERLIN_001 trial is one that we were fortunate to help initiate and, along with seven other US melanoma centers, to validate this approach to looking at a combination of clinical and genomic factors to figure out which of our patients with intermediate thickness melanoma who have no clinical evidence of spread of the melanoma to the lymph nodes really might benefit from surgical staging of their disease in which patients really don't need it and might avoid it. Patients who are having melanoma sentinel lymph node surgery here at Mayo Rochester or in Mayo Florida or Mayo Arizona are all eligible to participate in the study. And some of the things that we'll be looking at along with the validation component are some scientific correlatives and some patient-reported outcomes work.

Kind of at the other end of the spectrum of our practice for patients who have the opposite of that, clinically evident disease that's already gone to the lymph nodes, we're working with other medical oncology colleagues on a study that's open at University of Minnesota and Mayo Florida and Mayo Rochester called NeoACTIVATE. And, in this study, we're really looking at these novel combinations of immunotherapy based on the hypothesis that some immunotherapy given for a short period of time before surgery may actually be more effective in developing a very precise, tumor-specific response for the patient and improving patient outcomes compared to doing a potentially curative operation first and then giving a year of treatment afterward. It also gives us an opportunity to shorten the treatment time for patients and to do some scientific research along with this.

So one of the things that we're looking at is technical, and that's looking at whether or not the lymph node that's originally biopsied to establish the diagnosis might be a great barometer of the disease status of that whole area of lymph nodes and, therefore, might be used in the future to help us further deescalate surgical treatment. And, secondly, we're doing a lot of blood and tissue and microbiome-based assays to help us try and sort out why do some patients have a great response to treatment while other patients who seem to be quite similar don't. Why do some patients have significant toxicities of some of these treatments that are life-saving while others have very, very minor effects or none? And, you know, what's going on, here, so that we might develop really precise therapies and minimize the toxicity of these treatments?

So what's really exemplary and really great for someone like me working here is to work with such intelligent and committed colleagues, both clinicians and scientists and sometimes who wear both hats, really committed to rapid advancement in sort of state-of-the-science work and then bringing that right back to the bedside because we're really all aligned in just trying to improve care for our individual melanoma patients. So thanks for the opportunity to speak today.

TAMARA BUSH: Thank you, Dr. Hieken. Dr. Markovic, as a medical oncologist, you work closely with Melanoma Research Program at Mayo Clinic. Would you talk about the program and how this research translates into clinical care for the patient?

SVETOMIR MARKOVIC: Thank you, Tammy, for the opportunity to speak with me today and for sharing this beautiful venue with us to discuss the melanoma practice. I've had the pleasure of being associated with the melanoma program since its inception 22 years ago, and I'm truly proud and privileged to work with such brilliant colleagues like Dr. Hieken and Dr. Meves.

Over the years, what we've tried to do is to provide the best care of our patients using what has historically been the Mayo model of care. We all work together. We all share our experiences. We build on our experiences to create the best possible treatment option that we can come up with for every unique patient that comes into our care.

We also applied the same collaborative effort with colleagues that do research and not only take care of patients. Many of us are trained both scientists and as physicians, and the application of that scientific knowledge into the care of patients every day is something that we truly find gratifying and the aim of our very exciting teamwork.

There are many examples of this that I would just simply like to share with you, a few that have come to mind. For instance, Dr. Jeff Johnson and Dr. Matthew Block work together. Dr. Johnson is a nuclear medicine expert, someone works behind the scenes in our practice, who has developed a peptide that directly binds to melanoma cells to make a better scanner. If this peptide works to identify cancer cells better, we can add to it therapeutic radioactive substances that will then treat the melanoma from inside.

Dr. Laura Devlin studies as an ophthalmologist. She studies melanoma of the eye.

Dr. Robert McWilliams, a dear friend of mine, studies melanoma of mucosal origins, which is uniquely difficult to treat, and is currently preparing a large national study [INAUDIBLE].

Dr. James Jakub, a surgical oncology colleague, studies in-transit melanoma metastasis, when the melanoma jumps from one lymph channel to the other, spreading throughout the skin. He has devised a method with collaborators across the country to use a device through which he can deliver therapy and treat the tumor quickly.

And, finally, my dear friend Dr. Tobias Peikert, who is a pulmonologist, someone that we don't normally see in our practice, who is devising a method to deliver immunotherapy by inhalation, not just in the vein, to try and reset the immune system's ability to recognize cancer.

There are many other examples, but, in the interest of time, all I would say is that I've felt privileged and honored for the last 22 years to work with such an amazing group of people. And one thing is for sure-- we come to work in order to make our patients better with these four pieces that we face every single day. So, with that, I'll thank you for your time.

TAMARA BUSH: Thank you, Dr. Markovic. We would like to conclude by saying thank you for reviewing our discussion about the integrative practice for the treatment of melanoma at Mayo Clinic.