Soft Tissue Sarcoma: Factors Impacting Initial Approach

Transcript:William D. Tap, MD: Let’s lead into that. If we put histology aside… We look at these as different diseases, and that histological diagnosis is important. But when you take patients that walk in your office, what do you actually look for to get some prognostic idea? What is the patient going to go through? How do you gauge really what the patient is going to face over the next few years?

Mark Agulnik, MD: That’s a great question. So, when they’re sitting in front of you, certainly, you need to understand what you anticipate is going to happen to them. Because, how do you guide their treatments if you really don’t know what’s going to happen? If you’re going to choose appropriate therapy, you have to have an outlook. And so, I think when they walk in, certainly you’re looking at whether it localized or it is metastatic. If it’s localized, you’re looking to involve the multidisciplinary team and get others on board. If it is metastatic disease, you are looking at how many metastatic focuses, where are the metastatic lesions, who might you also need from a multidisciplinary care standpoint?

Then, you’re also looking at the size of the tumor, the location of the tumor, and the age of the patient. The histology, even though we say take that out of it, does alter prognosis. And all of this tied together will certainly help you formulate your plan for the patient—performance status of the patient and comorbidities. Because every treatment that we’ll end up talking about today, and even treatments that we don’t talk about, all carry a side-effect profile, and you need to match the side-effect profile to the patient with what you anticipate the outcome will be.

William D. Tap, MD: It’s very dynamic. I think that’s an important aspect of this; that not only is every patient different, every disease is different. But, like we’ll talk about, we don’t have tremendous straightforward treatment paradigms. So, a lot of understanding as to what are goals of care, what are the patient wishes, and the type of disease, they all are going to come into play for this. George, is there anything new coming out? Is there anything with genetic profiling, genomic profiling? How are we applying that into such a heterogeneous disease?

George D. Demetri, MD: I think this is very much an evolution right now. Dana-Farber and Memorial Sloan Kettering have been profiling huge numbers of patients coming into our units. And the American Association of Cancer Research has us sharing those data with five other cancer centers across the world to try to understand where molecular profiling really makes a difference in the care of patients. That’s certainly true in soft tissue sarcomas. We’ve seen dramatic changes in diagnosis when, for example, you pick up an EWS translocation in some small round-cell tumor that might have been called a lymphoma or something like that when it’s an Ewing sarcoma. So, I think molecular markers in the field of sarcomas have always been important, and they’re just getting more important as we move forward. Certainly, that’s true for some of the TSC (tuberous sclerosis complex) 1, TSC2 mutations that are showing up in many different kinds of cancers, as well as other peculiar ones. I think it’s a really interesting question about what is necessary in the work up of each and every soft tissue sarcoma patient.

If you’ve got the eyes or got an extraordinarily experienced soft tissue sarcoma pathologist like Cristina Antonescu at Memorial Sloan Kettering Cancer Center, Chris Fletcher at our place, and many of the other expert pathologists that are at MD Anderson or elsewhere, I think that’s one thing. Most community pathologists, though, simply don’t see these enough to have a great deal of confidence in this, even if it’s a sarcoma, let alone a sarcoma subtype. Although the community pathologists are quite good at referring these cases to the expert centers for a pathology review.

Shreyaskumar Patel, MD: I think, as the therapeutic models are going toward histology-specific or subset-specific therapy, and as we’ll come back to during the treatment part of the discussion, it becomes ever so more important to try to label the diagnosis or give the tumor the right name. And so, from a diagnostic standpoint, roughly a quarter of the patients will have translocations, for example. A synovial sarcoma, or a dedifferentiated liposarcoma, or an alveolar rhabdomyosarcoma, each one of these do have molecular markers. From a diagnostic standpoint, the pathologists probably should run those tests at the time of initial diagnosis so that it’s established in the patient’s pathology report. The separate question, as George was alluding to in terms of its therapeutic implications, is an evolving story. I think we’re not anywhere close to where we would want to be. But from a diagnostic standpoint, there are several of these histologies where there are proven markers that would be helpful to have them right up front at the time of diagnosis.

George D. Demetri, MD: Let me just add to that because this is one of the fields where the location of the tumor is unusually important. And this was a lesson we learned from our pathologists: that if you’ve got a well-differentiated liposarcoma on the arm, optimally managed with surgery, relatively small, it should be cured. So, they don’t even call it a well-differentiated liposarcoma because that will tarnish that patient’s ability to use health insurance or life insurance, and they don’t want to do that because it’s curable. Put the same tumor in the retroperitoneum and we know that the chance of recurrence is significantly higher because you don’t get the same benefit from margins. That is where it’s called a totally different thing, a well-differentiated liposarcoma. I think that kind of confuses a lot of people in the community, but it’s a really rational thing to do on behalf of the experts.

William D. Tap, MD: And I think location is important for another reason, too, because most of these tumors are actually going to disseminate hematogenously, and their primary location actually dictates where these tumors will spread. By far, if we have tumors in the extremity, they’ll spread to the lung. But you may have the same tumor in the retroperitoneum, and they behave differently. So, these are all important characteristics that we see.

Transcript Edited for Clarity