In this installment of our Global Oncology series, Guest Editor Chandrakanth Are, MBBS, MBA, FRCS, FACS, spoke with Kelly M. McMasters, MD, PhD, who, for the past 27 years, has directed a basic and translational science lab studying adenovirus-mediated cancer gene therapy and melanoma biomarkers. He is principal investigator of the Sunbelt Melanoma Trial, a study involving more than 3,500 patients from 79 institutions across North America. He has been President of the Society of Surgical Oncology, the Society of Surgical Chairs, the Southern Surgical Association, the Western Surgical Association, and the Southeastern Surgical Association, and is the current Treasurer of the American Surgical Association.
Kelly M. McMasters, MD, PhD
Please tell us a bit about your personal background.
I am Chair of Surgery at the University of Louisville and a surgical oncologist. I grew up in South New Jersey, in the part of New Jersey for which the state is named the Garden State. My grandparents had a small farm I spent a lot of time on, which stimulated my interest in pursuing my current hobby of farming.
I met my wife, Beth, when I came to train in surgery. She’s now a medical malpractice defense attorney who’s much more accomplished in her field than I am in mine. We had three children, three boys, and we’ve lived in Louisville for my entire career. I’ve been fortunate to be able to stay at the University of Louisville for the whole time.
Our youngest son, Owen, died of leukemia after a long battle with the disease, which certainly has taught me a lot about oncology and patients with cancer. It’s something I have written and spoken about, because it’s easy to spend your whole career as the doctor, but once you’re on the other side of that patient’s door, when you’re the family member, things change. It was certainly an eye-opening experience, and I believe it has helped me take a little bit better care of my patients with cancer.
Can you tell us about your professional background and training pathways?
I went to Colgate University as an undergraduate and then went to Rutgers Medical School in New Brunswick. I wasn’t the best first- or second-year medical student; I really didn’t think memorizing a lot of stuff was all that exciting, so I crammed for tests and spent most of my time volunteering in a research laboratory with Dr. Gordon MacDonald and the late William Moyle, who taught me a lot.
I spent a lot of time learning research. In college, I had gotten the research bug when I was working in a lab studying the Harderian gland of hamsters. If you even know what that is, I give you credit. It is a pigmented lacrimal gland located posterior to the eye with function that is poorly understood, and I was fascinated by it.
When I got to the clinical years of medical school, however, I became engaged and captivated by the opportunities for patient care and research and decided to do the MD/PhD program. I was preparing to apply for residency programs in internal medicine because they told me that surgeons didn’t do research. However, when I did my surgery rotation, I was also bitten by the surgery bug and knew I needed to pursue a career in surgery.
At the time, since I grew up in a little town in New Jersey and was a little intimidated by the big East Coast cities, I applied everywhere else around the country. My mentors suggested I visit the University of Louisville, where Drs. Hiram Polk and David Richardson worked, who were giants in the field of surgery. After meeting them and others, I decided this is exactly the kind of place I wanted to be, and it turned out to be one of the best decisions I ever made. Unfortunately, Dr. Richardson died of COVID early in the pandemic, but Dr. Polk still works almost every day, even though he’s been retired for a long time.
After residency, I went to MD Anderson for a surgical oncology fellowship, working with Drs. Charles Balch, Raphael Pollock, Doug Evans, Merrick Ross, and others. In addition to the clinical challenges of advanced surgical oncology, it was like a playground of intellectual curiosity. I loved every minute of it.
I was fortunate enough to get recruited back to the University of Louisville in 1996 for my first and only job. I became Chair of the Department in 2005 and have had a lot of great opportunities here throughout my career.
Oncology and Immunotherapy
Was there a particular incident or inflection point that triggered your decision to pursue a career in oncology?
As a surgery resident, I continued to do some research, this time in the field of surgical infection and host immunity, but not oncology. At one point, I thought about becoming a vascular or transplant surgeon or even a trauma surgeon. But I settled on surgical oncology, because I loved the challenge of taking out tumors large and small and the fact that patients were so appreciative. It is especially rewarding if we cure the patient of cancer. If things don’t go well, though, patients and their families are still appreciative. And when the cancer recurs, patients always return to the surgeon for advice, and these patients remain with you.
Most patients who need to be followed will ask, “How long am I going to continue to follow you?” I tell them, “Until I die,” because in this great field you create a lifelong relationship with your patients. And perhaps maybe not the most rewarding, but certainly a very important part of the job is easing patients over to the other side when we know that further therapy is going to be futile.
I find all of this to be incredibly rewarding, as well as the research opportunities that go along with it. And over the course of my career in my clinical work and research in melanoma, we’ve seen a miracle occur: the miracle of translational science.
Melanoma has progressed from a period when surgery was the preferred option at every stage of disease to a time where we can cure patients with disseminated stage IV melanoma. I know we don’t like to use the term cure, but we are now achieving durable, complete responses with immunotherapy. Many of our patients with advanced disease are alive and well for many years and will die of something other than melanoma.
We still have a lot of work to do, but the results we see today in melanoma were inconceivable a decade ago. To be a witness and maybe even a small part of this has truly been inspiring and humbling.
I tell people this story because this is such a common thing: President Carter was diagnosed with melanoma, metastatic disease to the liver and brain in 2015, at a time when the median survival for stage IV melanoma was 7 or 8 months—but with brain metastases, a couple months, maybe, if he’s lucky. However, he received a PD-1 inhibitor on a clinical trial and had a durable complete response. Until recently, he was still doing Habitat for Humanity; he is now 98 years old. He experienced firsthand the miracle of modern immunotherapy for melanoma, and we are working on the challenges of using it in other solid tumors.
People heard this story and thought it was a miracle for Jimmy Carter, but we see this miracle happen day in and day out—not for everyone but for a substantial number of patients, and it has been absolutely paradigm-shifting. Immunotherapy truly has changed the world of melanoma; we can cure people who were incurable before.
Could you please elaborate on your research interests?
I came to the University of Louisville in 1996 for my first job, and Dr. Polk sent me my first patient, a lady with subungual melanoma of her great toe. I did a toe amputation, and the first sentinel lymph node biopsy in the state of Kentucky. She had a positive lymph node, underwent a completion lymph node dissection, and received high dose interferon alfa-2b, which she tolerated poorly. And then 2 years later, she died of metastatic melanoma. That was my first patient.
However, I didn’t have very many patients early on. I had a blank computer screen in my office and time on my hands. But 1996 was a time of change in the world of melanoma. I never planned to do melanoma research, by the way, or clinically to focus on melanoma. I was the typical surgical oncology fellow who wanted to do pancreas and liver, hepatopancreatobiliary and upper GI surgery, which I did throughout most of my career.
Now, I’m focused mostly on melanoma and some breast cancer and sarcoma. So, if you find yourself staring at a window of opportunity, you must recognize it and take advantage of it before the window closes. I was fortunate that a lot of things converged. In 1996, the ECOG E1684 trial was the first study to show that high-dose interferon improved overall survival for patients with melanoma. Consequently, we had the first adjuvant therapy for melanoma that was approved by the U.S. Food and Drug Administration.
In 1996, the Intergroup Melanoma Surgical Trial published a study suggesting lymph node dissection might improve survival for some patients with micrometastatic melanoma. In 1996, sentinel lymph node biopsy for melanoma was still new. However, there were publications showing that if you found expression of melanoma-specific messenger RNA (mRNA) within the lymph node, it corresponded to a higher risk of recurrence; this indicated that submicroscopic disease detected by molecular staging may identify patients who had a greater risk of recurrence and might benefit from more aggressive treatment.
That’s where the Sunbelt Melanoma Trial was born. We put together this study with input from a lot of people. I would advise anybody reading this piece that when you write your first clinical trial, you might think about having a two-arm trial that’s simple. This was not. It wound up being seven arms and very complex. Nevertheless, we received industry funding, but it was an investigator-initiated trial; 79 centers across North America participated in this study, and we enrolled over 3,500 patients, of whom many were randomly assigned to treatment.
The eventual analysis showed that adjuvant high-dose interferon in patients with a single positive sentinel lymph node didn’t improve survival. It also showed that polymerase chain
reaction staging to detect melanoma-specific mRNA, although promising at the beginning, when subjected to the rigors of a randomized trial, was not prognostically significant, which was subsequently shown also in the MSLT-1 study.
That led to a lot of publications, a lot of opportunities, and a lot of data. Immediately on the heels of that, breast cancer sentinel lymph node biopsy was a brand-new thing as well, and it didn’t seem to work as well for breast cancer as it did for melanoma. I remember the early days in fellowship when it was not standard practice; it was not accepted that it could replace axillary lymph node dissection.
It’s important to note, then when I started, we had no research personnel, no computers, and no research statisticians. I had never run or participated in a clinical trial. It was a vast learning curve with colleagues from around the country who were engaged in developing and running these trials.
We started the University of Louisville Breast Cancer Sentinel Lymph Node Study, and this had a couple hundred surgeons and enrolled more than 4,000 patients. It was a simple study with a simple endpoint, which didn’t need long-term follow-up. Surgeons at the time wanted to perform sentinel lymph node biopsy and learn how to do it properly. But they were worried about doing it outside of a clinical trial or an independent review board–approved study, so this provided an opportunity.
Over my career, I spent time doing cancer gene therapy research with adenoviruses, which I have to say, we never translated into a clinical trial. Adenoviral vector gene therapy became less well received after some initial patient deaths in clinical trials. But now, I’m excited about immunotherapy. Within the surgery department here, a few years ago, I started a division of immunotherapy, and they’re doing tremendous work. And I get to participate, learn, and provide a lot of patient samples and data to help that research.
Some big research questions fascinate me. For instance, we see patients who have a positive sentinel lymph node. When you look at the histology and immunohistochemistry, you see a little speck of melanoma hiding in plain sight within the one organ most uniquely designed to detect and eradicate it, surrounded by millions and millions of lymphocytes and antigen-presenting cells in the lymph node. And how’s that possible? Why don’t they know it’s there? This fundamental question is something we’ve been working on, and it’s been very rewarding.
Society of Surgical Oncology
You had the honor of serving as President of the Society of Surgical Oncology (SSO). Can you tell us briefly about the organization?
The SSO is the home organization for surgical oncologists who trained in surgical oncology fellowships. It’s where we were brought up. Those like myself are intensely loyal to the organization and have taken part in committees and leadership roles throughout our careers. I feel strongly this is a professional organization that does a lot to promote careers, science, interaction, and collaboration opportunities for young people. Serving as its president was certainly a tremendous highlight of my career.
The SSO has grown into a global society. I still participate in a lot of activities and learn a tremendous amount from the educational offerings. And the SSO Annual Meeting is a great place to interact with people. If you want to be involved in the global conversation of how best to take care of patients in your area of specialty, this is where a lot of that interaction takes place, and it sets the stage for asking questions, answering questions, and finding a better way to take care of patients.
Could you share one highlight from your term as President?
I certainly wouldn’t take credit for anything, but we did engage in strategic planning during my presidency, which set the stage for redesigning the meeting and helping to engage membership. We thought long and hard about how to make this a better organization for the future to meet the needs not only of the old people like me, but young members who we want to engage throughout their career and let them help to design how it’s going to look and what it’s going to be in the future. And globally, we want to look at how to engage our partners in other countries and other continents. I was a small part of those conversations and continue to serve on the executive council through my role as the editor of the journal.
Annals of Surgical Oncology
Can you say a few words about the journal Annals of Surgical Oncology and the powerful impact it has had on cancer surgery?
It’ll be 5 years this year that I took over from Charles Balch, my mentor, as Editor-in-Chief of the Annals of Surgical Oncology, and it has been a highlight of my career to have the opportunity to do this. It has given me a lot of opportunities to think about trying to do new things and add new features to the journal, which is the premier publication in surgical oncology.
Over the past 5 years, we’ve added many editorial series and review articles like the Landmark series. I thought it was a good idea to have a way to summarize, review, and comment on the key evidence in every solid tumor type that informs our clinical decisions. We’ve also started podcasts, social media, videos, visual abstracts, video abstracts, and a -Twitter feed with close to 13,000 followers. We’re going to interview actual heroes and legends in surgical oncology and have a video format to talk to them, so they can share their perspective as well as their advice and mentorship.
Sharing Lessons Learned
Is there anything else you would like to share with the readers of The ASCO Post?
Those of us in oncology need to remember that we’re not treating cancer, we’re treating patients with cancer. In the current time of electronic medical records and the pressure to increase clinical productivity, it’s easy to forget that basic concept. If you are spending your time typing on a computer instead of talking to your patients, you are doing a disservice to both your patients and yourself.
This was part of the topic of my SSO presidential address; I talked about the fundamental difference between cancer treatment and patient care and the focus on the early institution of palliative care when appropriate. We need to recognize when care is futile, because all of us are guilty of continuing fifth-line chemotherapy when we know it is not going to work. We’re doctors and don’t want to give up. But as a society of oncologists, we need to come to a better understanding of the continuum of care and when we need to have those difficult conversations with our patients with cancer. Patients who receive early palliative care have a better quality of life at the end, and, in fact, several studies have showed that many of them have a longer life, so we need to be better at that around the world.
Chandrakanth Are, MBBS, MBA, FRCS, FACS
Dr. Are is the Jerald L. & Carolynn J. Varner Professor of Surgical Oncology & Global Health; Associate Dean for Graduate Medical Education; and Vice Chair of Education Department of Surgery, University of Nebraska Medical Center, Omaha.
Another piece of advice is to diversify your professional life like you diversify your retirement portfolio. Find a way that you’re going to be excited about waking up and coming to work every morning as well as find other areas of your professional life that you will find stimulating and rewarding. Whether it’s in research or teaching or advocacy or community service or global service or administration, it’s healthy to embrace change throughout your career.
And finally, for those in academics, it’s just as easy to spend your career trying to ask and answer important questions as it is to try to ask and answer trivial questions. Often the most important questions may be simple or obvious ones, but no one has really addressed them in the correct way. The curiosity that drives us to be in academics and do research is something you need to try to rekindle now and again. I think it’s good to regroup and refocus now and again and think about what clinical questions need to be answered. And if you spend a little time thinking about those things, you may come up with a lot of good ideas. It’s frustrating and difficult, but that’s what makes research rewarding. Keep at it, and don’t be discouraged when your papers and grants get rejected. I’ve often said that more success in research is born of stubbornness and pure pig-headed persistence than of brilliance.
DISCLOSURE: Dr. McMasters reported no conflicts of interest.