Challenges and Opportunities in Pediatric Sarcoma Care

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals, exploring the latest, innovative research in clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma Programs. Today, I'm happy to be joined by Dr. Pete Anderson. Dr. Anderson is a pediatric hematologist and oncologist here at Cleveland Clinic. He's here today talk to us about the challenges and opportunities in sarcoma care. So, welcome, Pete.

Peter Anderson, MD: Oh, thanks, Dale.

Dale Shepard, MD, PhD: So happy to have you here. Can you maybe start out tell us a little bit about your role here at Cleveland Clinic?

Peter Anderson, MD: Like many pediatric oncologists, I'm a utility infielder. We see a wide variety of rare cancers and my subspecialty is sarcomas.

The way I see it is our role is to provide multidisciplinary care. Kind of the conductor of the orchestra, if you will, for children and adolescents, young adults with cancer.

Dale Shepard, MD, PhD: Well, let's start off with that in terms of multidisciplinary care, specifically with sarcoma, how do we make that happen here at Cleveland Clinic?

Peter Anderson, MD: It's funny. That's one of the reasons I'm here is they do it so well. As you know, Dale, we have a 7:00 AM Monday morning conference. But at that conference there's orthopedic surgeons, interventional radiologists, radiation oncologists, medical oncologists, pediatric oncologists, quite a few pathologists. They see actually more cases than the clinicians.

It allows us to not only look at scans and try to decide the best approach to that particular solid tumor or sarcoma, but also what would be the best way to know if the patient's getting better or worse, when to intervene, when not to.

I've been at Mayo Clinic. I've been at the MD Anderson. But this one is probably the best conference in my career. I like to tell our fellows, "You don't get smart talking to yourself." That conference is a perfect example of it because if you're going to do something stupid, they'll tell you, and if you need a new idea, there's enough people in the room to provide that.

Dale Shepard, MD, PhD: I think we're fortunate that we have you on the pediatric side and us on the adult side, and we play off each other's strengths, so it seems to work really well.

One thing you've done really well in the past, and it's been amplified recently, is virtual visits. When we think about how we take care of patients with rare diseases, and COVID kind of forced us into a lot more virtual visits. But this has really been something you've been doing for a while. Maybe tell us a little bit about how you use virtual visits to take care of patients with rare diseases like sarcoma.

Peter Anderson, MD: Actually, it may be one of the most favorite things I do in my job. It's a little bit of detective work. I'll get an email or a phone call just asking a call from a family or caregiver or another physician. And I'll say, "I'd like to do a really good job of helping you out. What I need as a short summary, Cleveland Clinic medical record number", the patients often can upload their scans themselves once they have a medical record number. And then my secretary will schedule a time, and I have carved out Tuesdays and Thursday mornings for this.

But what happens is I have uninterrupted time to put together a summary that has patient contact information, the referring physicians information, about a half a page of history. It's kind of like, do you remember Joe Friday in Dragnet? Just the facts.

And sometimes when they think they're helping you by sending all the medical records it has very little useful information, but the summary I can look at and kind of know where they've been. And that allows me to have a conversation about what I call opportunities to improve health.

And it's an organized approach to sarcomas and other solid tumors where you talk about local control, which drugs to use, how to do you know if it's getting better or worse, imaging or biomarkers, toxicity reduction and preventing side effects, social.

The one I just got off of before this, we ended up with this little baby with Ewing sarcoma needs to go on Make-A-Wish. Now I realize he may be too young to remember his wish, but his siblings will. So how do you go about doing it?

You talk to the social worker, you have your PEDS oncologist sign the form, you decide on a good time when he's on maintenance therapy to go. So you can do things in an un-rushed manner during the virtual visit, where you provide high value information in a non-threatening environment, it's a conversation, and then you follow up with an updated summary so they have something to look at.

So I was doing probably about 150 a year before COVID maybe 200, and now I do even more, but the virtual visits are to provide information and education so that they can then work with their doctors at home to do better. And if they're already in our Cleveland Clinic system it kind of primes them for what they need to do next. Like if they live in Michigan or Pennsylvania, they don't get to come to the R building to have a conversation. We can do that virtually.

Dale Shepard, MD, PhD: And so that's certainly been very, very helpful for patients that are sort of in their course of therapy and you're providing that information.

How have you incorporated the virtual visits for patients that you may be seeing and treating and doing follow-up visits and surveillance scans and things like that? How has that played out?

Peter Anderson, MD: Oh, all different ways. One, I really liked is he has desmoplastic small round cell tumor. So he's got a rare kind of sarcoma, but he lives in Florida. So he can get his scans at Cleveland Clinic Weston. They show up on EPIC just like he lived in Cleveland. And it allows me to supervise his care with his medical oncologist. He can stay on study.

So, the world's become a small place because of things like emails, shared medical records, as well as the virtual visits, which I think are much more friendly than email. I don't know how many emails you get a day, Dale, but I get way too many.

Dale Shepard, MD, PhD: Too many. Absolutely.

Peter Anderson, MD: So the virtual visits allow you to have a quality conversation that's better than a phone call and way better than an email.

Dale Shepard, MD, PhD: Great. Now you mentioned that we start our week together at 7:00 AM with a tumor board, and we used to meet in a room and now we're sort of doing this by Zoom, but tell me about virtual tumor boards and the work that's being done and really driven on the PEDS side and a lot of ways for virtual tumor boards for sarcoma.

Peter Anderson, MD: I think for us the epiphany was Stacey Zahler seeing a lot of the desmoids, this very rare, indolent sarcoma like solid tumor and most patients with desmoid have never met anybody else with desmoid it's so rare. So they all belong to this club and they said, "Well why don't we have a desmoid tumor board across the nation?" So the Desmoid Foundation facilitated that and Stacey realized this was a very good or forum for rare diseases where you get people with interest and expertise weighing in.

Matteo Trucco is going to be doing this now for Ewing sarcoma. I can see doing it and the future for other types of sarcomas, particularly as patients will need more individualized therapy. We've got good at the upfront therapy, but then what to do for the relapse or the maintenance or the local control or the special situation. This would be a tremendous resource for these patients.

Dale Shepard, MD, PhD: The virtual tumor boards and the virtual visits really allow us to help patients in areas that might not have a specialist nearby.

Peter Anderson, MD: Oh right, and even for us, I always like learning new things. Like I said, you don't get smart talking to yourself, and this is another way to learn new things.

Dale Shepard, MD, PhD: Very good. Tell me a little bit on a treatment side about work that you were involved with pazopanib and radiation therapy.

Peter Anderson, MD: Oh, yeah. I remember having a conversation. This was 2005 or 2006 when I was at MD Anderson, I talked to their head of radiation therapy and I said, "It seems to me that chemo alone is not enough and radiation alone is often not enough, but together they do better." And I told them about an experience that I had with osteosarcoma where it really made a big difference using both.

So I asked him is there any cancer that does better with radiation alone versus radiation and chemo? Can he think of, he had 40 years of experience. He said, "Nope, not in my long career." When we started seeing patients with bone metastases, Jake Scott, Erin Murphy, and Chirag Shah are very good at SBRT, so the question is, could we make the SBRT not only more effective, but treat other areas of their bodies that are not getting radiation while they're getting simulated, the physicist developing the plan, and then they're getting the radiation.

So pazopanib, which does not have a big effect on blood counts, but also works well with radiation, and also blocks one of the signals we call vascular endothelial growth factor, which tumors try to, in normal tissue, try to heal after their damage. They try to make new blood vessels, the pazopanib blocks that. So it's kind of a way of making the radiation more of a sure thing. So pazopanib approved for sarcomas. So we started using it in many of these patients, and I actually got a large enough series that we could get that presented at the most recent major national meeting for radiation oncology, we call ASTRO.

Dale Shepard, MD, PhD: Very good. One of the things I know we talk about quite often in tumor board is about cytoreduction. And I know one of the areas you're interested in is desmoplastic small round cell tumors. Tell me a little bit about the work you're doing in that.

Peter Anderson, MD: Oh, this is a nightmare for the patient because they present with lots of metastases in their abdomen. And it's like, how do I ever get this under control? And, and these patients have Ewing's family tumor, so desmoplastic small round cell tumor is very similar to Ewing's sarcoma. So it responds to that kind of therapy, but it doesn't go away.

So they need a very patient talented surgeon. When I was at MD Anderson it was Andrea Hayes-Jordan. Here it's Anne-Joyce. But their job is to eventually when the patient reaches a plateau of response, that could be six months, nine months. The most recent one we did had been treated for two and a half years, and finally the surgeon says, "I can remove almost all of this." And our job is to get rid of 95 to 99% of the tumor, do a cytoreductive surgery, if you will, but then have PEDS oncology or medical oncology help get your nutrition back to normal and then you get whole abdominal radiation.

So it's another example of multidisciplinary care where radiation alone wouldn't be enough. Surgery alone wouldn't be enough. Chemo wouldn't be enough. But together you can accomplish a lot. And some of these patients get remissions.

So the one I remember the best was, she had a very similar to DSRCT, was EWS ZNF444 fusion. So it's super rare Ewing's fusion. Looked just like desmoplastic. And when she had the surgery, she had to come from another center, but she convinced her medical oncologists by saying, "I just want to become a statistical outlier. I know my chances are low." And sure enough, she's now three years later, without a relapse she's gone through graduate school, got her master's in public health and she's on to do great things.

So it might seem like at the time, how could you do a surgery like this and not relapse, but if you have a sequential type of therapy after that you've got way better chances than you did in the old days, whereas just do the surgery and hope for the best.

Dale Shepard, MD, PhD: So certainly sarcoma's a complex set of diseases, but where do you see the gaps? What do we need to be focusing on?

Peter Anderson, MD: Getting more molecular information nowadays? Because it's possible. That field has gone so fast. It's been amazing. Rabi Hanna was forward thinking enough to realize this. So we now have two geneticists embedded in our clinic and one's a genetic counselor, Britney Griffin, and then Harry Lesmana, and just having those resources so you can not only make the diagnosis, but say, "What is special about this tumor and will it provide us with information we can act on in the future?"

For a while, I was fairly, I'd say pessimistic, that we'd come up with targeted therapies from foundation one or our campus reports. But I think we're approaching the point where we'll be getting more information like the flanking regions next to break points to develop personalized vaccines.

So what's missing now is gumption by people like me, to take the time, do the deep thinking, work with people like Britney, and it's interesting the conversations I've had with FoundationOne and Tempus, they're willing to provide the information and even our own molecular lab and do some of this.

So how do we get ourselves organized? So if and when a company like BioEnTech, and they should have the resources after the COVID vaccine. You would think, let's see they're shipping Pfizer, BioEnTech two-billion doses in 2021. I think they have the resources to do this.

And the real question will be, how will they do that? When will they did do that? And I'm optimistic because ‎Özlem Türeci‎ and Uğur Şahin, who founded BioEnTech came from pediatric oncology backgrounds. So they understand the problem of rare diseases needing very specific treatment.

But I think if you can prove the concept and things like what we treat, it'll be generalizable. So how to stay in the mainstream, but ahead of it so you don't get left behind. Or instead of saying, "Why me?" You should say, "Why not me?" We can do this at Cleveland Clinic.

What's missing is a little bit of gumption, a little bit of being organized, trying to decide what's important. Where would we want to be three, five years from now? And then positioning ourselves to do that.

Dale Shepard, MD, PhD: Very good. You mentioned vaccine therapies and you've done work with vaccine therapies in that in the past, is that continuing as we move forward?

Peter Anderson, MD: I don't have a lab anymore, but it was interesting, part of my efforts in the lab were on adjuvants. And everybody always focuses on what are you immunizing against?

I think as important as what you're immunizing against, the antigen or the protein or the MRNA that codes the protein nowadays, is how it's immunogenic and presented to the T cells.

So, one of the missing pieces says, who responds and who responds well. And immunology has come a very long ways from when I had a lab. I think Tim Chan is going to do great work here figuring these things out, but it's almost as if, you think to yourself, well, our elderly and our immune compromised patients have responded well to the COVID vaccine, why wouldn't they respond well to an MRNA vaccine?

And I think what it tells me is the adjuvant problem of coming up with ways to present antigens to the immune system that work is being solved.

What is not known is what you have to do to get polyclonal immunity. And I think it's going to be a process. You'll want to do what's easy first, but kind of like many projects. It's the in depth details that'll count. Do you make a nest out of MRNA, so you develop polyclonal immunity.

So the way I see what we're doing here, I don't have a current vaccine protocol, but what I would like to see is us having the capability to start with single patient, IND's or join trials very quickly that do, because we have the information on our patients.

Dale Shepard, MD, PhD: Very good. Well, you've provided some great insight today. Any additional comments?

Peter Anderson, MD: Well, a couple. The first is I think none of us can tell what's happening in the future, but if you look at the trend, there'll be good things that have come out of COVID, like some virtual visits is a good example. I think the other is a certain willingness to see centers and industry and patients cooperate in ways we never thought. So stay tuned. I think we'll be in for some good surprises in the next couple years.

Dale Shepard, MD, PhD: Very good. Well, thanks Pete.

Peter Anderson, MD: Well thank you. It's a pleasure to share.

Dale Shepard, MD, PhD: This concludes this episode of Cancer Advances. You will find additional podcast episodes on our website, clevelandclinic.org/Cancer Advances podcast. 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.