Advances in the Management of Metastatic Bone Disease

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 faor joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a Medical Oncologist, Director of International Programs for the Cancer Institute, and Co-Director of the Sarcoma Program at Cleveland Clinic.

Today I'm happy to be joined by Dr. Jorge Manrique, an Orthopedic Oncologist and Hip Replacement Surgeon and Head of the Sarcoma group at Cleveland Clinic, Florida. He was previously a guest on this podcast to discuss functional drug screening and genomic profiling in advanced sarcoma, and that episode is still available for you to listen to. He's here today to discuss advances in managing metastatic disease in the bone, so welcome back.

Jorge Manrique-Succar, MD: Thank you, Dale. Thanks for having me here.

Dale Shepard, MD, PhD: Absolutely. Tell us a little bit, I gave your title, but what do you do at Cleveland Clinic?

Jorge Manrique-Succar, MD: So, as you mentioned, I do hip and knee replacement surgery and I also do orthopedic oncology. And I coordinate the Sarcoma Group, which puts together in both parties in dealing with sarcoma here in Florida, and then we also partner with main campus on tumor boards to discuss cases, so I try to organize everything so we can treat patients for their sarcomas.

Dale Shepard, MD, PhD: Excellent. And so I think one our programs, one where we work really, really well with you guys down in Florida, so appreciate all the effort.

We're going to talk about advanced disease specifically in the bone, and I guess just there's a lot of different people might be listening in, different backgrounds. Give us a little bit of an idea of how large of a problem is bone metastasis due to cancer.

Jorge Manrique-Succar, MD: So it's becoming more and more problematic as we advance with cancer therapies and we prolong lives, skeletal-related events or metastatic disease to the skeleton, their incidence is higher. So it is a very important topic because skeletal-related events plays a big burden in patients with cancer, with metastatic disease. If they have a fracture or they have an infection of their bone, it can impact severely their well-being and their functionality, so it's becoming a little bit more prevalent.

Dale Shepard, MD, PhD: And so I guess historically we'll talk about maybe how things might be changing or how things need to change, but historically, how have bone metastasis been treated?

Jorge Manrique-Succar, MD: So it's always been trying to prevent fractures, so prophylactically fixing the bones that are affected, but we could also administer radiation or any type of ablation, percutaneous radiofrequency ablation for example. That's been pretty much how we've dealt with this in the past and we're still doing currently.

Dale Shepard, MD, PhD:

When we think about just bone metastasis in general and skeletal disease, this happens with a lot of different cancers. Why does the bone become such a common site for metastatic disease?

Jorge Manrique-Succar, MD: I think this is a great question. So the bone is a very fertile soil. We go back to 1889 with the theory of seed and soil proposed by Dr. Paget. And the bone has a very rich vasculature, which serves as a net to trap these tumor cells, and also has an environment rich in growth factors. So this combination of a very wide vasculature and a rich environment of growth factors create a unique environment for cancer cells to seed and to start growing in the bone, so pretty much that's the reason why skeleton is very prone to receive metastatic disease.

Dale Shepard, MD, PhD: And so you mentioned that it's becoming more prevalent. Maybe we talk a little bit about that. You also talked about trying to avoid problems. What are some of the key things that could be done to avoid problems with skeletal disease?

Jorge Manrique-Succar, MD: I think surveillance, making sure we have a good imaging modality to evaluate any type of symptoms that the patient might be having. Plain X-rays would be the first thing that I would start, but we also have nuclear bone scans and PET scans that can also give us an idea of how the bones are behaving when we have these type of images available. So that's one of the things that I would encourage to be actively looking for any signs or symptoms of pain or dysfunction in the skeleton to be able to address if this is related to any metastatic lesion.

Dale Shepard, MD, PhD: I guess one of the things, just I guess your perspective as an orthopedic surgeon, when we think about things that could be done to minimize skeletal-related events, you use that term, things like bisphosphonates and RANK ligand therapies. These are designed to minimize risk for skeletal-related events, but too often I see people on the medical oncology side that didn't start them soon enough, because we may not have been looking. So do you see that in the orthopedic side as well?

Jorge Manrique-Succar, MD: Historically for us, we recommend these when we talk to the oncologist. And obviously, when we do have bone infection, I think that it's an opportunity to prevent additional lesions from happening. But I think that we are not being aggressive enough in instances to prescribe these medications that are life-changing. They can have a very positive impact on preventing skeletal-related events.

Dale Shepard, MD, PhD: And you mentioned fractures and infections as problems. Talk to us a little bit about, as people already have struggles sometimes with their primary therapies, but then we overlay skeletal disease and complications, what are the primary things that from a morbidity standpoint that you see that's associated with people developing skeletal disease in the first place and then maybe complications?

Jorge Manrique-Succar, MD: And that's all talking about prevention. I think that when we don't prevent this from happening and it happens, and we're intervening in these patients that are actively on chemotherapy and immunosuppressive agents, you open the door for these patients to have a complication. They're at increased risk of infection. For example, say an instance, they have a hip fracture and they need a joint replacement and you do the joint replacement, a setting of an immunocompromised patient and they get an infection, this can delay their treatment for months while we deal with this because you can't obviously provide systemic therapy if you have an active infection, and that could potentially impact their overall survival because of these factors.

So I think that preventing and having an adequate timing that you can modify their systemic therapy and intervening with a window of opportunity, I think that makes a huge difference to prevent those scenarios from happening.

Dale Shepard, MD, PhD: And then I guess along with prevention is that you mentioned prophylactic surgeries to minimize risk for fractures. Have there been changes over time in terms of either how we assess who needs a surgery to minimize the risk of a fracture or the techniques themselves to try to get people sort of back on their feet and maybe to other therapies quicker?

Jorge Manrique-Succar, MD: Yeah. So, historically we've always used the Mirels' criteria to assess the risk of pathologic fracture, and we had seen that we've over treated some patients with these type of interventions. But of course the flip side of it is what we were talking about, having a fracture and complicating things. There has been some research related to the use of computerized tomography, or Cts, to assess the density of the bone to better have a score for fracture. It's not very routinely used, but it's out there. And then in terms of implants, I think that surgery has evolved a little bit more in terms of that we were understanding that early mobilization, once you intervene the patient, you provide them with a surgical procedure, you can get these patients up and moving quicker. And that's pretty much from the joint replacement literature.

We've understood that once we get them up and moving, the recovery is enhanced, they have a little bit more and better recovery because of early mobilization, and you also impact the potential complications. So, having a blood clot, for example, in patients that are prone to have blood clots when they have active cancer, if you mobilize them early and get their muscles to work and have an adequate blood flow, I think that would positively impact by reducing the risk of a blood clot, for example. So those are the things that in terms of the rehabilitation aspect.

And then in terms of the surgical aspect, I think that there's a lot of things that have been evolving from the surgical aspect. We're using a lot of technology. So based on implants for example, we have now more durable implants, carbon fiber implants that not only have the benefit of being radiolucent that will allow us to monitor the bone a little bit better because they don't have any scatter with MRI or CTs or X-rays, but they also have a higher fatigue resistance to these type of conditions. So if you have a patient that's going to load their bone with a delay of bone formation or healing and you have a carbon fiber implant, you can potentially avoid a hardware-related complication because of these implants.

In patients that have multiple myeloma, for example, in their upper extremities, there's these, very similar to angioplasty, are called inflatable devices that you can introduce through very small incisions in the bone and you can inflate them and stabilize those bones and reduce the morbidity with very minimal-invasive techniques to stabilize those fractures or those bones.

And then in terms of the big change in surgical innovation, I think that 3D printing and robotics is making a huge incursion in these type of cases. You can maximize bony apposition because you already have, or you can have a little bit better knowledge because of 3D modeling. And then using robotics, you can optimize component positionings when you don't have bone available because of metastatic disease. So I think all this combination of virtual reality, 3D printing, robotics, navigation, I think it's making a huge change and will be the future in these type of patients.

Dale Shepard, MD, PhD: And I guess when we think about the biggest impact, does the biggest impact tend to be areas where you can do surgery now where you may not have been able to before? Is it maybe minimizing the extent of surgery and things you might've done previously? Patient selection? What are the biggest areas where these new technologies are helpful?

Jorge Manrique-Succar, MD: I think all of the above. I think that before, we could have not been able to visualize adequately where our screw replacement, for example, on a pelvic lesion would be. And now with these technologies, you're able to better visualize this and better position if you have navigation. If you're resecting a tumor, you can have this as an aid to better preserve healthy tissue around, and so on and so forth. So I think that specifically, for example, I've combined the robotic system for joint replacements, modified a little bit because there is a navigation aspect of this technology, and be able to position pins around the acetabulum, and then proceed with the joint replacement with the robotic system that will allow us to help position these components in a better way, and this will optimize the longevity and the functionality of these implants. So I think that all of the above applies to management of metastatic disease currently.

Dale Shepard, MD, PhD: And just one more thing on the implants, because again, a lot of different sort of people listening in and different areas. When we talk about 3D printing and implants, what material are these made out of?

Jorge Manrique-Succar, MD: So they're basically made out of metal. There are new companies coming out that are now printing materials that are similar to bone that they can osteointegrate. So all these things that the possibility of printing these implants that adapt to the defect that you have and not using off-the-shelf allow for maximizing our resection and minimizing the resection of healthy bone.

Dale Shepard, MD, PhD: And I guess at the very beginning we talked about sort of particularly things like sarcoma with multidisciplinary care. If you have someone with skeletal disease, how do you incorporate decision-making and choice of therapies between things like surgery, the radiologist doing an ablation, or the radiation oncologist doing radiation therapy?

Jorge Manrique-Succar, MD: I think it's a combination. It's an ongoing conversation with the medical oncologist, and also depends on the type of tumor that the patient has. So if it's a tumor that's amenable to systemic therapy and we know that they're going to respond well to their systemic therapy and we can hold off in surgery, well, I would not push for surgery. But if it's a tumor with a big segment defect that it's not amenable for surgery, then that's not amenable for any type of non-surgical intervention that I would push for surgery.

But say for example, lesions in the pelvis that are not compromising the structural integrity but are causing pain, you can request or ask your interventional radiology colleagues to go in and do a type of radiofrequency ablation percutaneously to improve pain. So I think that having all these specialists around these patients is absolutely important, and that's part of the coordination that I serve. I mean, once there's a bone lesion, they come to me and I think that I'm responsible for leading the conversations to where we're going to go with this to see if there's any structural compromise that requires me to act or send them to the right person.

Dale Shepard, MD, PhD: You talked about some of the advances and technologies and the changes in graphs and things like that. Where do you think the biggest barriers are right now? What do you think will make that next sort of jump in terms of improvement for patients?

Jorge Manrique-Succar, MD: I think obviously every time we have new technology, it's costly, so I think that we have to be cost-conscious and we have to make sure that we're good stewards of our cost utilization in healthcare. So that's one of the barriers. Also, because it's new and it's not widely available, getting your hands on, or knowing that these products exist is another barrier. And then making sure that people are aware that the orthopedic oncologist can serve a good role or help these skeletal-related events.

There have been instances that there are some orthopedics that don't want to treat these, and it's not because they're not amenable for treatment, it's because they don't feel comfortable doing so, so immediately they get radiation, then they have a fracture and it's because they didn't get those patients to the orthopedic oncologist who has a little bit more of knowledge. And it's all about getting the patient to the right person at the right time.

Dale Shepard, MD, PhD: I think it's just sort of related to that. So within our Cleveland Clinic Florida system, you're there at Weston and there's a couple of other health systems there. How do you guys work to coordinate care within our Cleveland Clinic system in Florida? And then you mentioned about getting people at the right place at the right time. How do you sort of engage with your community partners to make sure that people are getting optimal therapies?

Jorge Manrique-Succar, MD: So I'm very of an open-door policy and everybody from the oncologists that have my number, I'm always available for a phone call. And if there is a patient that needs to get in, I make sure that I get them in, even if there's a need for double booking or whatever it's needed. We do have a colleague, an orthopedic oncologist by training in Martin, that he also serves as a liaison to all the patients over to Weston for more complexity care. So we try to make sure that everybody's aware that we exist and we have that resource available that I'm here and that orthopedic oncology is here at the clinic to help out and serve those patients that are in need.

Dale Shepard, MD, PhD: Very good. Well, certainly, as you mentioned, as we do better at treating patients and they live longer, they're more likely to get skeletal disease, and very important topic. And you've shed some good insights, so thanks for being with us.

Jorge Manrique-Succar, MD: No, thank you and thanks for all the support that you guys provide us here in Florida.

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