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Additional Advances in Soft Tissue Sarcoma With Brian Rubin, MD, PhD

Last year, Brian Rubin, MD, PhD, Chair of Pathology and Laboratory Medicine and the Chief of Diagnostics at the Cleveland Clinic, served as co-chair for i3 Health's continuing medical education (CME)–/nursing continuing professional development (NCPD)–approved virtual tumor board: Multidisciplinary Management of Advanced Soft Tissue Sarcoma, alongside Kathleen Polson, Nurse Practitioner at Dana-Farber Cancer Institute, and Shreyaskumar R. Patel, MD, Center Medical Director of the Sarcoma Center at MD Anderson Cancer Center.

In this interview, Dr. Rubin sat down with Oncology Data Advisor to discuss updates in the treatment and management of soft tissue sarcoma, what to look forward for the future of treating sarcomas, and his passion for this field.

Oncology Data Advisor: Thank you again for being with us today, Dr. Rubin. We really appreciate it. Would you like to begin with introducing yourself and what you do?

Brian Rubin, MD, PhD: Sure. I'm Brian Rubin, I'm the Chair of Pathology and Laboratory Medicine here at the Cleveland Clinic. I'm also the Chief of Diagnostics, which means I oversee both pathology and laboratory medicine as well as imaging group radiology. Traditionally, I'm a Bone and Soft Tissue Pathologist, so I am very active, and I actually sign out cases every week. I look at a variety of different bone soft tissue lesions. Then I have a research laboratory as well where we study the genetics primarily of sarcomas, and I'm very interested in investigating genetics and developing therapies.

Oncology Data Advisor: Incredible. Thank you again for talking with us today about this activity you participated in. So, first question I wanted to ask you is if you could give us a brief overview of what soft tissue sarcoma is?

Dr. Rubin: I think when you try to explain soft tissue sarcoma, it's also important to explain what it isn't. The most common cancers are ones that arise in organs, like lung cancer, colon cancer, liver cancer, kidney cancer. They arise in organs. Soft tissue tumors are in all the different connective tissues that connect the body together. Those are tumors that arise typically in the extremities or in the wall of the body, chest wall, the back, and they are tumors that arise from bone, from cartilage, from muscle, from nerves, from fat—so it's all that connective tissue, and they tend to be a rare group and people don't hear about them too much.

Oncology Data Advisor: Since they're such a rare group, why do you think it's vital for clinicians to understand and participate in educational opportunities like this with the most up-to-date strategies for sarcoma management?

Dr. Rubin: I mean, medicine has gotten so detailed and really specialized, so people tend to develop expertise in the things that you see all the time. People are very good at breast cancer and lung cancer and whatnot—they see many, many cases. I mean, unfortunately those cancers are quite common, but when it comes to rare cancers, it's really impossible to keep up for the average oncologist. A lot of the work is done in subspecialty areas at big academic medical centers. However, everybody tends to see these things at a very low rate, so it's important to provide these updates because we can distill the information as experts teach what really needs to be taught so that people are at least familiar with some of these things. Oftentimes they're just going to do some initial evaluation, some minimal treatment, and then pass them along to a multidisciplinary center that specializes in the care of some of these rare things, but everybody needs to recognize them and be familiar with them, and I think that this CME activity really provides a good knowledge base for which everybody can learn a lot in an hour from the experts.

Oncology Data Advisor: I did want to make a point that this activity included three perspectives: the oncology perspective, the nurse perspective, and then your perspective as the pathologist. Why do you think it's important for clinicians to understand all three of these perspectives when learning about sarcoma management?

Dr. Rubin: These are complicated diseases, so when patients are going to get therapy, we work in teams. At the Cleveland Clinic and all the big academic medical centers, and probably most of the private practice groups these days as well, everybody tends to work in multidisciplinary teams. So, each patient each week is discussed. If you're going to be treating a patient, we discuss the therapy, and you need to hear from everybody because the pathologist, of course, is sort of the cornerstone for diagnosis. You've got to get that diagnosis. It is what determines all of the downstream therapy. That's why the pathologist is important; however, even in pathology, I may need to work with a surgeon to understand, for instance, where a tumor is arising, how big it is, what the age of the patient is, and discuss a lot even to come up with a diagnosis.

Bone tumors, in particular, require a lot of radiological input, but in terms of the therapy, the nurses are really familiar, for instance, with all of the different side effects of therapy. They really can give their input about maybe the best therapy for a patient. Maybe a patient who's very advanced in age wouldn't want as toxic of a therapy as somebody who was a bit younger who could tolerate maybe a more effective therapy, but one that's slightly a little bit more toxic. In this particular activity, we didn't have surgeons, radiation oncologists, or radiologists come in, but we could have brought those in and discussed as well, just for practical reasons. You can't have six people doing a presentation in an hour, but all of those guys are important, and we need the input of everybody. We'd like to say the treatment of sarcoma is a team sport. It truly is, and everybody's input is really required to come up with the optimal plan for each patient. Every patient's going to get something slightly different.

Oncology Data Advisor: Changing pace a little bit, I wanted to ask you if there have been any developments in the management of sarcoma since recording, particularly in biomarkers and pathology, that you would like to speak on?

Dr. Rubin: It is interesting. I've been in this field for about 25 years now, and it's not like there are a lot of sudden developments, where one day you're doing something one way and all of a sudden, the next day you're doing it differently. The next-day things tend to kind of move on a continuum. I would say in our practice here, we're getting very interested in immunotherapy with sarcomas. It's kind of a new area. You hear mainly about immunotherapy for melanoma, bladder cancer, and lung cancer, to some degree in the more common cancers, but we're also using immunotherapy in sarcoma, and we think there's a very small subset of patients who might benefit.

The biomarkers that we're looking at are things like TMB—that's total mutational burden or tumor mutational burden—which is basically the number of mutations that a tumor might have. We're looking at biomarkers like programmed cell death ligand 1 (PD-L1). Nobody has really a very concrete answer on that. There haven't been a lot of recommendations so far, but the National Comprehensive Cancer Network (NCCN), for instance, has allowed people to look at TMB and PD-L1 expression as a mechanism of putting people onto immunotherapy. So, I think that's a new trend that I've seen emerge recently.

Of course, the classification of sarcoma is always undergoing a lot of scrutiny and reinvention. We're using genetics a lot these days to try to understand different categories of tumors which are actually turning out to have many different subtypes that are genetically-based. I would say that that's an evolving classification. We're trying to understand if that classification matters from a treatment standpoint, but I would say that's always a hot topic, and genetics and sarcoma is just exploding.

Oncology Data Advisor: Off the top of your head, do you know of any clinical trials that are currently going on with evolving treatment options like immunotherapy in sarcoma and genetics? Do you know of any clinical trials we could keep our eye on?

Dr. Rubin: I'm not sure what trials are open in immunotherapy, to be honest, but one thing I'm very interested in are TEAD inhibitors. This is my focus of research, so I'm always very focused on my own stuff. However, I think TEAD inhibitors are going to be really, really interesting. I work on a rare cancer called epithelioid hemangioendothelioma—we call it EHE for short. It's a kind of an angiosarcoma, if you will. It's like a subtype of angiosarcoma, and we've discovered through the genetics that a protein called TAZ is fused to another protein called CAMTA1, and they require binding to a protein called TEAD. Now, this is not just exclusive to the treatment of EHE, but is going to be a general theme throughout cancer. For instance, mesothelioma patients are also included in clinical trials, but there are three clinical trials now looking at TEAD inhibitors, and I'm pretty optimistic that one of the trials is going to show some efficacy and move on. They're all phase 1 right now, about to move on to a phase 2 and 3, but I think TEAD inhibitors are an emerging area that will be hopefully very successful in the treatment of sarcoma, but then also in the treatment of more common cancers.

Oncology Data Advisor: Before we end, I wanted to ask if there were any other thoughts you had that you would like to share with listeners concerning sarcomas or just any information you would like to share?

Dr. Rubin: I like to just share my general enthusiasm for the field. I think we've made so much progress. I mean, when I first started working on sarcomas, I was a resident and a fellow. In 1998 as part of a postdoctoral research project, we discovered that KIT was mutated in a tumor called gastrointestinal stromal tumor. Fortunately for the patients, there was a KIT inhibitor that was moving forward through clinical trials, and we were able to start testing that. We actually got an FDA approval within two years and it really transformed that disease from something that was uniformly lethal in six months to a disease that now patients survive, in some cases, for decades. It really moved the needle there, and I think that we're going to start—we've seen this to some degree with some of the other cancers—but we're going to start to really see some very dramatic ability to treat sarcomas one after another. We've known about the genetics and sort of the biology for a while, but the oncology is really catching up fast, and a lot of good inhibitors are being developed.

I would just say, if you're a patient, if you're a family member, if you're a person who treats sarcoma, there are a lot of really interesting treatments coming through the pipeline, and I think that the next decade—especially with the influx of artificial intelligence in terms of diagnosis and perhaps having some insights into therapy—that it's going to be a tremendous time where we're going to see a lot more progress and really be able to more effectively help our patients.

Oncology Data Advisor: Thank you for your passion on this topic. It's really refreshing and encouraging to see someone so enthusiastic about this. So, thank you so much for your work, Dr. Rubin, and thank you for your time today.

Dr. Rubin: Okay, nice talking to you.

About Dr. Rubin

Brian Rubin, MD, PhD, is the Chair of Pathology and Laboratory Medicine and the Chief of Diagnostics at the Cleveland Clinic. Dr. Rubin's passion, specialty, and research revolve around the pathology and diagnosis of sarcomas, particularly within bone and soft tissue. He is an active speaker and leader in the field of sarcomas and remains involved in trials for this field as well.

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor. 


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