Randall Reflects on Breadth of Sarcoma Data and Beyond at MSTS Meeting

R. Lor Randall, MD, FACS

The prevalence of bone metastases at diagnosis of soft tissue sarcomas, recruitment patterns for a trial in perioperative care, a potential therapeutic target in osteosarcoma, and updates on collaborative efforts are just a glimpse of the data presented at the Musculoskeletal Tumor Society (MSTS) 2020 Virtual Annual Meeting. 

The conference, which was presented virtually this year in light of the coronavirus disease 2019 (COVID-19) pandemic, covered a wide variety of topics across sarcomas, bone metastases, connective tissue, and the musculoskeletal system, explained R. Lor Randall, MD, FACS, who is on the executive committee for MSTS. 

"They basically show the breadth of what's going on in the MSTS," he added. “As much as we want to enjoy each other's company, it's nice to see that we're still able, in some way, to move on [all of these research], even in this evolution of COVID-19.”

In an interview with OncLive, Randall, who is also the David Linn Endowed Chair for Orthopaedic Surgery, as well as professor and chair of the Department of Orthopaedic Surgery at the University of California, Davis Health, highlighted the various data presented at the annual MSTS meeting and their implications for the future of sarcoma treatment.

OncLive: How would you categorize the mission of MSTS and its annual meeting?

Randall: It was a very nice meeting; it was condensed, but we had great representation from all of our membership. We chose a few of the top tier abstracts, but then we had a bunch of posters. All things considered, given the evolving nature of how people are communicating in academics and academic medicine, it was a successful meeting, in large part to the leadership team of MSTS.

It's such a specialized meeting that is very near and dear to a lot of people's hearts in this community. MSTS is a group of academic orthopedic oncologists. We do have some affiliate members—some other subspecialties—but it really is the one and only North American orthopedic oncology–focused meeting. It's a dynamic discussion, but everyone is more or less an orthopedic oncologist who manages bone tumors, soft tissue tumors, musculoskeletal tumors, and connective tissue tumors. It has a Venn diagram that overlaps with other societies, such as the Connective Tissue Oncology Society, which is truly multidisciplinary, but the MSTS is pretty much all orthopedic oncologists. 

We also do advocacy in terms of reaching out to legislature around important issues. We feel like we're the stewards for musculoskeletal involvement of other cancers. For example, in breast cancer, prostate cancer, lung cancer, etc.—when they involve the musculoskeletal system in the form of metastatic bone disease, or just the cachexia and sarcopenia associated with these cancers and their treatments—orthopedic oncologists are sort of the stewards of those patients in that regard. 

There has been so much happening in sarcoma in recent years. What were some of the highlights or key themes of research and discussions at this year's meeting? 

In terms of the abstracts that came forward [at the meeting], there were a few that were particularly interesting.

There was a multi-institutional study out of the University of Chicago as well as Case Western Reserve University, looking at soft tissue sarcomas subtypes and their association with metastasis to bone at diagnosis. In bone sarcomas, there is a small percentage of patients who, after lung metastasis, will also develop bone metastases. For soft tissue sarcomas, there's not that many who actually go on to develop bone metastases.

This very nice study by Christopher Collier, MD, showed that about 4% of all patients with soft tissue sarcoma presented with bone metastases at diagnosis. Those comprised pleomorphic sarcomas, liposarcomas, myxofibrosarcomas, synovial sarcomas, angiosarcomas, rhabdomyosarcomas, malignant peripheral nerve sheath tumors, epithelioid sarcomas, and clear cell sarcomas. Therefore, while it's only 4%, that's a real number. 

[These data] brought up the question about whether or not we should be doing such things as technetium-99m bone scans and the workup for these patients. The take-home message for medical oncology colleagues is, if they're managing soft tissue sarcomas, [they need to] realize that maybe around 5%, or 1 in 20 patients may have a bone metastasis. 

I'm not advocating that you should necessarily get a total body bone scan, or some sort of systemic staging for every patient beyond the lungs. But [if a patient has an] ache or pain, you want to drill down on it to see if it could be a bony involvement with their soft tissue sarcomas.

What other data did you find promising at this year's meeting?

Another paper to highlight involved recruitment patterns in the large, international, randomized, control trial of perioperative care in patients with cancer. The lead author here was Aaron Gazendam, MD, and the senior author is Michelle Ghert, MD, FRCSC, and they drilled down on looking at how patients were recruited to the large PARITY study, which is looking at 1 versus 5 days of perioperative antibiotics and these massive endoprosthesis when you take out a bone sarcoma.

[As background,] we take out a bone sarcoma, we implant it with a big megaprosthesis, and then we randomize patients to 1 day versus 5 days of antibiotics. It's a hot question, because there's just a large number of patients who get infected. A total knee, hip, or shoulder can get infected, but these megaprosthesis are at an increased risk. This is because of the amount of heavy metal put in, but then also because of the fact that these patients are immunocompromised, often from systemic therapy, etc. 

This was a nice, multicenter trial out of McMaster University. Dr Ghert and everyone did an incredible job—a huge Herculean effort. They basically were able to look at different referral patterns and realized that you get a core group of people early on to build the momentum behind this. Then, you bridle their enthusiasm, and then that leads to more and more people getting involved. They really were able to get countries from around the world to do it. 

There became this sense of competition to enroll patients on the study. For surgeons, that's a nice thing to see, because usually surgeons are so busy that many of us don't have time to enroll a patient. However, they saw so many of their colleagues doing it that they wanted to get in on the action, so to speak, and get their patients enrolled, which was terrific.

There was a nice study by Eric R. Henderson, MD, et al about the update on combining MSTS with American College of Radiology [ACR] Bone Tumor Radiology Reporting and data systems. This is just a way to look at large data sets around the radiology used to manage patients with bone sarcomas. It just speaks again to the idea that the MSTS, along with ACR, is actually looking at ways to systematically stage patients in controlled ways.

Then, there was also the study by Benjamin J. Miller, MD, MS, looking at the MSTS Tumor Registry. He basically shared his experience across the institutions that participated in developing the MSTS Tumor Registry, which will be very helpful to us and is now going to be rolled out to developing a registry at multiple centers, all thanks to their tenacity.

Could you expand a bit more on the MSTS Tumor Registry?

The initial registry comprised the University of Iowa, Dartmouth University, Johns Hopkins University, Northern Health Care Management, Ohio State University, Cleveland Clinic, and Stanford University. They were able to categorically put in all their diagnoses across the centers derived out of electronic health records, to be able to populate the database. This is also [in collaboration with] the American Academy of Orthopedic Surgeons. This was sort of a pilot study to do this, and they're just going to start rolling out the database to everyone.

Also, Jichuan Wang, MD, with the senior author Bang Hoang, MD, put together a really nice abstract looking at the interaction of Skp2 with P27, and enhancing the progression and tumor-initiating properties of osteosarcoma. This was just a very nice, preclinical model of being able to demonstrate that the role of cell cycle regulation is really critical in many tumors, but this blockade of P27 degradation by Skp2 significantly delayed osteosarcoma tumorigenesis, and prolonged survival. Being able to elucidate that molecular pathway may lead to therapeutic targets in the future.

These are very interesting data. What are the implications for each of them?

The first paper was a clinically relevant paper, looking at bone metastases. We discovered that there is a small percentage of patients who may actually have bony involvement. That is a very hands-on, good piece of clinical information for medical and surgical oncologists to know when they're managing sarcomas. 

When we look at the other studies, we talked a little bit about patterns of behavior of surgeons and how they are willing to get involved with clinical trials, which, in the past, has been like herding cats because we're so busy. We have so many patients to take care of to do that extra legwork. The McMaster University group out of Ontario, Canada, have highlighted the importance of being able to do these kinds of clinical trials.

The same could be said for the ACR collaboration with MSTS that is going on; we are reaching out to other partners, other shareholders, in the diagnostic workup for patients with sarcoma, to work with other disciplines.

Lastly, the MSTS Tumor Registry speaks to a monumental amount of work by a select group of orthopedic oncologists, and this gives us a registry that will allow us to allow us to publish really meaningful data and hopefully improve patient care.

How did this year's meeting operate in a world that now includes COVID-19?

All things considered, the meeting was a success. Who knows where we'll be next year; we hope to be all in the same proximity in a physical world, but that may not happen. This is certainly a nice model for how we can manage ourselves and make sure that we're advancing the field; it is our responsibility to our patients to educate our colleagues even in this COVID-19 era. 

I'm just grateful for the leadership and membership in MSTS. It's been a really challenging year, and our outgoing president Joel Mayerson, MD, has done an incredible job. Carol D. Morris, MD, MS, FAAOS, is our new incoming president. She's been a fantastic support for him, and I'm really looking forward to her presidency. However, the whole executive committee and the membership are to be lauded for maintaining real academic rigor