Managing Sarcoma

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals exploring the latest, innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepherd, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma programs. Today, I'm happy to be joined by Dr. Nate Mesko. Nate is Director of Orthopaedic Oncology here at Cleveland Clinic. He's talking to me today about how we are managing sarcoma and cancers involving bone. Welcome, Nate. Maybe as a start, you can tell me a little bit about what you do here at the Clinic.

Nathan Mesko, MD: Good morning, Dale. Thanks for the invitation to join. As you mentioned, the Center Director for Musculoskeletal Oncology, which encompasses essentially bone tumors, but benign, and malignant sarcoma and non sarcoma varieties throughout the skeleton. And partnering with you, I also work on kind of guiding and building our sarcoma program here at the clinic, and implementing new changes, and building the multidisciplinary teams, and searching out clinical trials, and being creative in terms of how we address a difficult problem.

Dale Shepard, MD, PhD: The big topics to cover today would be time to treat, and multidisciplinary care, and a little bit about what you're doing with registries. We had a previous podcast where we talked to Dr. Bolwell about time to treat, and we talked about it in a kind of a global way. Maybe you could tell us a little bit about time to treat in sarcoma, and what kind of things we're doing and what we've seen.

Nathan Mesko, MD: I think the easiest way is to create a background prefects in terms of what sarcoma is and the epidemiology. That's an incredibly rare disease in and of itself for less than 1% of adults and 15% of kids. I think just the overall wherewithal throughout the community with physicians, with patients of this type of a cancer, many people have never heard about it. You can imagine that delays in diagnosis and misdiagnoses ... if you don't have a pathology team that has a comfortable training to be able to look at something that's so rarely seen, can be problematic.

We have a variety of ways that we get patients both direct referrals from our own physicians, but also a lot of patients self-referrals, and probably most commonly referrals from the outside. From a perspective of a physician, we need to treat both the physical and the mental capacity and health of a patient. One of those things that drives both of those is access. Getting a patient in quickly, getting them seen with tests ordered in a efficient, smooth line manner or streamlined manner, and then coming up with a treatment plan in a way that decreases the delays in treatment that patients can see and perceive is incredibly important.

At the clinic, our time to treatments generally are from quarter to quarter. We're seeing are somewhere in the less than three week range, which is better than the national median. Some quarters where even a less than two weeks, depending on people that are seen and we diagnose right off the bat. We meet for the first time. We perform the work up in the diagnosis. Sometimes we can get patients treated in less than a week or starting their treatment, which is incredibly important.

I think it's important also to know, well, how are we doing that? Besides the appointment itself, I think there are some ways that we have tried to shrink that. Getting a quicker diagnosis, doing on the spot or point of care, or fine needle aspirations instead of having to wait for five to seven days for sometimes these soft tissue diagnoses to come back even longer for bone potentially. We can do things potentially even live in the clinic to at least get a family of cancers, a spindle cell malignant genealogy that we can then take to an insurance company that same day and get CT scans, MRIs, and whatever tests are needed so there's no delays on the insurance end.

We are changing the paradigm of how we treat soft tissue sarcomas. And along with a few other institutions in the country, we're challenging, I think, the tradition of needing to do a long course radiation for these soft tissue sarcomas. Radiation we know is incredibly important, but the tradition would say ... especially if you do it before surgery, that you need to do five weeks of radiation, and then wait for anywhere from three to six weeks after radiation completes to do the surgery, which can equate to three months of delays from the time that the person sees you to the time that they perceive their cancer's actually being removed. That obviously can weigh mentally on a patient.

Doing something called hypofractionated radiation where we take that five weeks and we actually cram it into five days ... same biological equivalent. This has been studied in Europe. And then we take the tumor out instead of waiting three to six weeks after radiation completes. We take the tumor out in anywhere from same day that the radiation is completed to within 72 hours. As you can imagine, me being able to tell a patient that I can get your cancer out of your body within seven to 10 days, as opposed to having to wait for up to three months, can be very powerful. Though the literature would suggest that we're not seeing any compromise from previous precedents set with this technique for cancer recurrence or with wound healing issues, which we know radiation can be attributed to. That's another powerful thing.

We're doing a lot of brachytherapy, which is at the same time we removed the tumor, we see a patient, we diagnose them, we get them in the operating room right away. And instead of having to do long course radiation, we actually lay little brachy catheters ... it's like little coffee straws on the wound, and can complete the entire radiation course in about five days. Then we do delayed reconstruction with our plastic surgeons on some of these wounds where we'll bring them back to the operating room, remove the catheters, and put a muscle flap or close over top of the wound. That coordination of care, that multidisciplinary care, is incredibly important.

Something that is not necessarily a change in the treatment ... timing. But certainly is definitely better for patients when it comes to at least living locally. We're trying to move more toward outpatient chemotherapy regimens as best as we can. Our pediatric sarcoma group is really pushing this, and having a patient sleep in their own bed is certainly an incredibly important thing. That's not for everybody. But in the right patient population, the right patient selection, that can also be yet another powerful tool in the armamentarium of kind of challenging the old tradition paradigm.

Dale Shepard, MD, PhD: I guess when we think about multidisciplinary care, the thing that comes to mind with a lot of tumors is sort of just the traditional oncology surgery, radiation oncology. But sarcoma takes on a new dimension in terms of what that means from multidisciplinary care. Maybe share with us a little bit about the breadth of specialties that are involved with this multidisciplinary care that we've had to get established here.

Nathan Mesko, MD: Yeah. If you take sarcoma and you compare it to ... let's say a little bit more streamlined of a diagnosis like breast cancer or colorectal cancer, where there's really a one surgeon group. You may get a plastic surgeon involved with reconstruction. But from a cancer perspective, cancer involves really one primary location. It's a pretty streamlined process. It's easy to have a multidisciplinary clinic, and you can have all providers there that are "experts" in the same room in a pretty easy manner.

Sarcoma, because it's bone and skeletal muscle or connective tissue, can occur literally anywhere in the body from intracranial all the way to the tip of your toe. It can occur in the abdomen retroperitoneum, and it can involve at least 11 different subspecialties of people seeing sarcomas from a surgical perspective. We know about orthopedic oncology and surgical oncology, but spine surgeons, and plastic surgeons, and urologists, and pediatric surgeons. And you go down the list.

When you have that much breadth covered and that many disciplines involved, some providers are going to see a higher volume than others. That's where that concept of multidisciplinary care becomes very important, so that we know that the standards are upheld for treatment. That every case is reviewed at what we call a multidisciplinary tumor board, where we have every discipline represented: the chemotherapy team, the radiation team, the pathology team, the radiology team that can help us look the films and make the diagnosis that way. And the surgeon teams, the pediatric teams, et cetera.

And then taking it the next step after we have a plan formulated, and a recipe created, and that plan is implemented when we get into the operating room oftentimes in these complex cases that involve the spine, or the pelvis, or the abdomen that involves multiple organs ... perhaps the inferior vena cava, or the liver, et cetera, we can have multiple surgeon disciplines. I think probably the most extreme example is I was involved in a case that lasted over two days. A planned two day case. About 35 hours of operating time with eight surgical disciplines to get a negative margin resection, and rebuild the anatomy that had been removed in order to remove a tumor. That only happens when communication and a team approaches the top priority.

Dale Shepard, MD, PhD: So, certainly volume of patients seen plays an important role in these tumors. Maybe you can touch on that a little bit in terms of ... these are rare tumors. A lot of providers may not see them often. Tell me a little bit about volume and management.

Nathan Mesko, MD: This has been parsed out actually with sarcoma in multiple locations or multiple specialties. It's been parsed out head-neck. It's been parsed out intraperitoneal. It's been parsed out in extremity. It's been parsed out in chest-wall. That certain thresholds are needed. In those thresholds one can argue what the appropriate threshold is, but the main message is that institutions that are seeing things over, and over, and over again in a repetitive manner are able to hone in and their diagnostic skills. They're able to streamline the process of getting patients access. And they're able to take on difficult surgical challenges, or difficult radiation plans, or things that require perhaps more than just a baseline understanding, or a once in a while treatments approach in order to make it successful.

One example in the United States, we obviously are privatized and we do not have a centralized system. But I think a good example is in the United Kingdom. The NHS, National Health Services, only fund five bone sarcoma hospitals in the entire country. And the minimum amount of bone sarcomas that's required to treat in the NHS to be funded is 50. With soft tissue sarcomas, there's 10 hospitals that are funded, and the minimal amount of treat is 100 soft tissue sarcomas. It's a concept of centralization where things are driven to hospitals of excellence in a manner that repetition builds mastery.

Dale Shepard, MD, PhD: So, certainly something we do within our sarcoma program is we have people seen by a number of specialists, but some of their care can be done here on main campus where we may have a particular expertise. But something like the chemo might be done out in the community. When you think about patients, what are your thoughts? Everybody needs to come see a multidisciplinary group? Are there certain patients that are at higher risk for problems if they don't? What guidance would you provide for people about when to send someone to see us?

Nathan Mesko, MD: Well, I think if you are staring at a pathology report or looking at a radiology report on an MRI or CT scan that that suggests a sarcoma process, and this is something that you have to go look up and then say, "Remind me of what that is." I.e. an example of you don't see it very often. I think the easiest and the absolute best thing to do is to pick up the phone, and get a referral in, and let somebody else handle with the headaches. As a provider, you shouldn't have to deal with that anxiety and you shouldn't have to deal with all of the follow-up that occurs with something that you're just not familiar with.

From a standpoint of when we bring patients and patients are referred to us, I would say not every single patient must be seen in a multidisciplinary clinic setting. A common example would be somebody who comes to our office with a chondrosarcomata of the bone picket, maybe the femur bone. We know that that is not a cancer that responds to chemotherapy, and we know that that's not a cancer that radiation is a standard of care. If we can get the appropriate diagnosis based on pictures and plus or minus a biopsy, and we can stage the patient and say, "You know what? This is a localized process." I think that's a good example of the orthopedic oncologist saying, "I will pick up the primary cancer care and surveillance of this patient. And if things change, now I will involve the multidisciplinary team."

But there are just so many diagnoses that either the anatomy involved crosses multiple surgical territories, if you will. Or there's a kind of a gray zone for whether or not chemotherapy is necessary, or is radiation really going to ... it's been described, but it's not standard. Would this be a reason to give radiation? Those are all reasons that a multidisciplinary team can be helpful, because each person brings their area of expertise and knowledge of the literature.

Dale Shepard, MD, PhD: If people are listening and they may want to sort of think about putting together a multidisciplinary group, what kind of guidance might you provide? What's the most important parts?

Nathan Mesko, MD: I think right off the bat it's going to be very hard to recruit people that way in such a rare discipline where there's very few people in the world that are trained specifically in it to your institution to make it so that you can do it on your own. I think there are ... if we've learned anything from this COVID-19 pandemic, is that there is power with virtual ways that we can manage parts of our medical practices. We have cancer centers such as ours, and some large cancer centers all over the country, and in Ohio have multidisciplinary tumor boards where we have virtual capabilities.

I think you may have a surgeon that has confidence in removing something, or you may have a pathologist that trained at a large sarcoma institution and has confidence in calling something, but you need each piece of that puzzle. And using a partnering institution, an affiliated institution for a lot of those discussions to build your confidence to help you with your diagnostic skills and to let you know, "You know what? This is probably something that ... Let us handle the anxiety, and the complications, and the things that come with the complexity of this particular case." I think that's a good way to start involving some kind of an affiliate that has that background, and then kind of using that as a springboard to build your own practice over the course of the next few years.

Dale Shepard, MD, PhD: You've mentioned perhaps a silver lining from COVID, and that is a virtual visits. So, hopeful that maybe we can provide specialty care to remote areas that didn't have access to it in the past. Have you noticed a big part of that in your practice? Of course, you ultimately have to see people to treat them. But has that made a big difference?

Nathan Mesko, MD: I think in two populations. One is the surveillance population, I think. Especially if I have a patient get advanced imaging because they're due for it. Let's say they're two years out from their cancer surgery. It's very easy to look at a picture to go through it with them on the screen. I don't necessarily rely on my physical exam at that time, because I already have advanced imaging. A physical exam is not going to add any benefit. I think that's a wonderful way to say, "You do not necessarily need to come into my office. I can talk through things on a screen with you," and patients still have that personal interaction.

I think the second population are those patients that drive from a long distance. Where I'm looking for a second opinion, I have some pictures, or I have a tissue that's been taken from a mass. Our ability to look and triage things in the cancer world is actually pretty easy. Oftentimes, my partners in sports medicine orthopedics relies so heavily on their physical exam, and it's very difficult to make a diagnosis without touching a patient. In the world of cancer, if I have some pictures ... and definitely if I have a biopsy, and I can just sit, and listen, and talk.

Nine times out of 10 I can come up with a pretty reasonable plan minus maybe a few details in terms of: this is what we need to do, or you're in good hands, or you've got a great plan there. Or you know what? I'd like to see you. I would like to examine you. I'd like to get another test. But that virtual visit power of kind of the triage process is really important. It can save somebody wasted plane flight, or a long car drive, or I can say, "You know what? Why don't you buy that ticket? Because we've got a good solution for you here that you may not have been offered."

Dale Shepard, MD, PhD: Let's switch gears real quick here. Registries. You've taken a leading role in sort of seeing what we can learn about treatment of sarcomas through registries. Tell us a little bit about what you've been doing, and how you're setting up work with registries here at Cleveland Clinic.

Nathan Mesko, MD: Sure. I think, again, context. Very rare disease. Compare it to breast cancer. We just had a recent retroperitoneal sarcoma randomized control trial looking at the role of radiation. It was 216 patients. My radiation colleague, who also treats breast cancer, made the comment that in the world of breast cancer 216 patients as a case series. In the world of sarcoma, that's a game-changing study. It points to the fact that with such a rare diagnosis, it's really hard to accumulate numbers. Embarrassingly, if you look at least a lot of the surgical literature of how we treat cancers, and cancer outcomes, and how we reconstruct sarcomas specifically, it's all done on really old retrospective case series.

A lot of the institutions that have been historically at the forefront ... Mayo Clinic, or Sloan Kettering, et cetera. We use this, but it's never been really great science because we just can't accumulate numbers. And so the power of a registry with one institution certainly lets you answer your experience, but the power of a registry on a collaborative nature around the country is game changing. Because now I can prospectively collect variables that multiple disciplines agree upon to say: here are things that we need to answer questions. And one of the beauties of a national registry is we can go back and ask the same questions that we've always thought were gospel, but never really based on anything more than retrospective case series and say: let's either validate this. Or let's change the way we think about this, because we have new information that's come to light that's not just specific to one institution. It's generalizable because we have all the entire population around the country pouring into this.

With that said, our institution along with five others ... So, Ohio State, University of Iowa, Johns Hopkins University, Dartmouth, and Stanford started a pilot in 2019 collecting data in a national registry. We do this with the collaboration of the large orthopedic governing society, the American Academy of Orthopedic Surgeons, and our orthopedic oncology society, the Musculoskeletal Tumor Society. That was very successful. In 2019, we were able to get funding for that. We've procured further additional funding that we are now inviting basically all comers, all institutions that we have 35 institutions currently in legal agreement discussions, so that by the end of 2020 there's hope that we could have over 40 institutions pouring into this registry.

Big picture? The next step is include functional outcomes. Right now it's demographics. It's surgical stuff. There's some limited chemotherapy and radiation discussions in terms of dosing and medications given. We'd like to include patient reported outcomes is our next step, which is already built. We'd like to start collecting metastatic-related events, as you well know. About 800,000 new skeletal related events from metastatic carcinoma. It will be diagnosed in the U.S. in 2020. There's 14,000 soft tissue sarcomas and 3,000 bone sarcomas in the U.S. a year, so that's a huge discrepancy. That's an important thing that we should be collecting. And then also partnering with organizations like ASTRO and like ASCO. The main governing bodies for medical and radiation oncology is going to be incredibly important to take this collaborative nature and take it to the next level. How can we tissue bank? How can we do things that actually are game-changing based on the simple concept of collaboration?

Dale Shepard, MD, PhD: Well, Nate, you've provided us some great insight today.

Nathan Mesko, MD: I love talking about the concept of this rare cancer sarcoma. We have a wonderful team here that you head up, and I'm just happy to be a part of it.

Dale Shepard, MD, PhD: Thank you very much for being with us today.

Nathan Mesko, MD: And thanks to all our listeners.

Dale Shepard, MD, PhD: This concludes this episode of Cancer Advances. You will find additional podcast episodes on our website, clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google Play, Spotify, SoundCloud, or wherever you listen to podcasts. And don't forget you can access real-time updates from Cleveland Clinic's Cancer Center experts on our Consult QD website at consultqd.clevelandclinic.org/cancer. Thank you for listening. Please join us again soon.