Soft tissue sarcoma is a rare cancer, estimated to be 0.7% of all new cancer cases in 2021. In this excerpt of the transcript from their continuing medical education/nursing continuing professional development (CME/NCPD)-approved activity, Virtual Tumor Board: Optimizing Personalized Care Plans for Patients with Advanced Soft Tissue Sarcoma, Vicki L. Keedy, MD, MSCI, of the Vanderbilt-Ingram Cancer Center, and Brian P. Rubin, MD, PhD, of the Cleveland Clinic, discuss the rarity of this disease and the ways to properly diagnose it in its myriad forms.
Vicki L. Keedy, MD, MSCI: Real briefly, I just want to discuss the reason for this tumor board and the scope of the problem. Sarcomas, although we discuss them as a single entity, are a group that make up more than 100 different rare cancers. These are malignancies of mesenchymal origin, and the incidence is quite rare at 15,000 to 16,000 cases per year. Although sarcomas have historically been thought of as being chemotherapy-resistant, it's not actually the case. But chemotherapy sensitivity is quite variable amongst the different histologies. And so it does impact our treatment options for each individual patient, and we will review how histology does matter in our treatment decisions. And broadly, we categorize these sarcomas into sort of large groups, based on the underlying cell of origin, such as fibroblastic or fibrohistiocytic tumors, lipomatous tumors, et cetera.
And the state of drug development: as I mentioned, historically, sarcomas have been thought of as being relatively chemotherapy-resistant, and that's because we did go through several decades where very limited advancements were made as new chemotherapy classes were discovered. This was partially due to the fact that these diverse groups of tumors were studied as one.
Brian P. Rubin, MD, PhD: If you look at the history of how we diagnosed sarcomas, originally everything was histology-based, and then we had immunohistochemistry way back in the 70s; we started doing karyotype sarcomas, and one of the things that we noticed right away was that sarcomas had relatively normal karyotypes and most of them had 46 chromosomes. However, there were focused alterations, so they were genetically quiet and focused alterations, such as if you look at alveolar soft parts sarcoma with the T(x;17), that's really the only alteration you typically see in an alveolar soft parts sarcoma. What that told us was that that translocation was probably a driver that drove the biology of these sarcomas. And these therapeutic targets were put on the map: they would either target those or target the biology since these were unique.
And again, the (x;17) translocation is unique to alveolar soft sarcoma. We don't see that in other cancers and other sarcomas. So again, kind of confirming that they have their own biology, that they're going to respond to individual inhibitors, and also placing on the screen really those fusions—because at the end of the day, these translocations, they can code gene fuses which occurred—fusion oncoproteins are going to be drug targets.
Typically, if you have a lesion that's a spindle cell lesion involving the gastrointestinal (GI) tract and it's KIT- and DOG1-positive, you're dealing with a gastrointestinal stromal tumor (GIST).
Dr. Keedy: You can consider other GIST tyrosine kinase inhibitors if they fail avapritinib, but response rates are quite low. And then for the wild-type, it is based on what actual abnormality we find. There are some that we still do not have targeted therapies for, but also sometimes these are some of the more indolent subtypes, particularly those with NF1 mutations or succinate dehydrogenase-altered GISTs that are sometimes more indolent and may not necessitate treatment right away.
Dr. Rubin: I always tell every pathologist that I train—and I have fellows that I'm training constantly—anytime you see an epithelioid neoplasm on the hand or foot, think about epithelioid sarcoma, because that's typically where they arise. They have this granuloma disappearance—in other words, central necrosis with the cancer cells surrounding them. And by epithelioid, we mean they're round cells. When we see that appearance, we think of epithelioid sarcoma right away. We do a keratin stain. Now, keratin is non-specific; it'd be positive in any kind of carcinoma, of course. However, it's diffusely positive in epithelioid sarcoma. One of the main mimics of epithelioid sarcoma are rheumatoid nodules, and granulomatous diseases, true granulomas diseases. They won't be keratin-positive, so we can sort of exclude them.
Recently, we realized that all epithelioid sarcomas, or at least the vast majority, have a loss of INI1 in the BRG complex. And so we can actually do an immunohistochemical stain. The cells that are staining are background endothelial cells and lymphocytes and things, but all the other cells are tumor cells, and you can see that they don't have any signal. In other words, they've lost INI1; that's really pathognomonic. Now in this setting with this histology, for the diagnosis of epithelioid sarcoma, you mentioned local recurrence. I mean, I spend a lot of my life looking at the histology, and what the problem with epithelioid sarcoma is, is they're not circumscribed at all. They're one of the more infiltrative neoplasms; they'll crawl along structures like nerves. You can actually see them coating the outsides of nerves, and they'll crawl right up into the axilla and they'll metastasize in the axillary lymph nodes. And so for those surgeons out there who might be viewing this, epithelioid sarcoma is a hard one to operate on because there's a lot more tumor than you think, based on the clinical appearance.
It takes a village to treat a sarcoma. We can't do it alone. I mean, I'm part of the imaging and diagnostic team, basically looking at these things and providing the diagnosis. We all work together to treat these sarcoma patients.
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Surveillance, Epidemiology, and End Results (2021). Cancer stat facts: soft tissue including heart cancer. Available at: https://seer.cancer.gov/statfacts/html/soft.html
About Dr. Keedy, Dr. Rubin, and Ms. Polson
Vicki L. Keedy, MD, MSCI, is an Associate Professor of Medicine in Hematology/Oncology, a Clinical Director in the Sarcoma Program, and a Medical Director at the Clinical Trials Shared Resource at the Vanderbilt-Ingram Cancer Center.
Brian P. Rubin, MD, PhD, is Chairman of the Robert J. Tomsich Pathology and Laboratory Medicine Institute at the Cleveland Clinic. He specializes in the diagnosis of bone and soft tissue diseases, including the diagnosis of sarcomas.
Edits have been made to this excerpt for the sake of clarity and brevity. Any views expressed above are the speakers' own and do not necessarily reflect those of i3 Health. Gain additional perspectives from Dr. Keedy, Dr. Rubin, and Ms. Polson by completing the full complimentary CME/NCPD activity.