Diagnostic Testing Procedure for Soft Tissue Sarcoma

Transcript:

Jonathan Trent, MD, PhD: Welcome to this OncLive® NewsNetwork webinar. Today’s discussion will be focused on “New Treatment Options for Rare Diseases and Soft Tissue Sarcoma.”

I am your host, Dr Jonathan Trent, a professor of medicine, the associate director of clinical research, and the director of the sarcoma program at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine in Miami, Florida.

Today, I am joined by my colleague, Dr Neeta Somaiah, an associate professor and the director of sarcoma clinical research in the Department of Sarcoma Medical Oncology at MD Anderson Cancer Center in Houston, Texas.

During the next 45 minutes, we are going to navigate through some of the questions surrounding how we treat patients with gastrointestinal stromal tumors and other soft tissue sarcomas. We’ll consider how we are using available agents, how they can be sequenced throughout the disease continuum, and how the latest data will help us in making these decisions in our clinics.

Neeta, I’d like to start discussing the work-up of soft tissue sarcoma. It’s really the foundation upon which our treatment arises. We can’t really know how to treat a patient unless we know what type of sarcoma there is. And the recent World Health Organization report showed that there are now 175 different sarcomas. Tell me in your practice, how do you start your work-up?

Neeta Somaiah, MD: Definitely, that’s where the expert sarcoma pathologist comes in. I think every sarcoma patient’s pathology should be read by an expert pathologist because more and more, with these different subtypes that are coming out, the treatment should be tailored, though previously, they were all treated the same. The treatment actually differs quite a bit between the subtypes, so it’s very important for the pathologist to first make a histopathologic diagnosis and then run molecular testing when required, both immunohistochemistry, FISH [fluorescence in situ hybridization], and RT-PCR [reverse transcription polymerase chain reaction]—these are required to further subclassify the subtype. Because that is critical in our decision in treatment management of the patient going forward. I think in our practice, when patients come in, the pathology is requested if it wasn’t done at MD Anderson, and the pathologists there review the pathology so that we can confirm the diagnosis. Because in quite a few cases, actually, they do sometimes change the diagnosis completely when it wasn’t a sarcoma, and call it a sarcoma; but the subtype classification changes quite a bit.

Jonathan Trent, MD, PhD: Yes, I think that’s a really good point. I can think of several examples in my practice where a patient was diagnosed, for instance, with a GI [gastrointestinal] stromal tumor, and then we reviewed the pathology and found in fact they had a dedifferentiated liposarcoma.

Neeta Somaiah, MD: Correct.

Jonathan Trent, MD, PhD: Or other types of differences.

Neeta Somaiah, MD: Totally different treatment.

Jonathan Trent, MD, PhD: Yes, it’s critical.

Neeta Somaiah, MD: Yes.

Jonathan Trent, MD, PhD: Let me just ask a little more about how you fit molecular testing into your practice when you start thinking about not just diagnostics but therapy. Are there specific soft tissue sarcoma subtypes for which you really need testing to be done before you start treatment?

Neeta Somaiah, MD: Right. There are quite a few. Of course, the most common is GIST [gastrointestinal stromal tumor], which is a soft tissue sarcoma. For that subtype, some of our pathologists will reflexively send for a targeted KIT and PDGFR [platelet-derived growth factor receptor] sequencing for the most common mutations. And that does help in treatment decision making because, if I am going to start a patient on treatment, then I need to know their molecular mutation subtype for GIST. So GIST is one of those subtypes that we do order.

There are also other subtypes that, if I’m suspecting a certain mutation that might help me in treatment, if there is, say, a uterine unclassified sarcoma, now I know it’s rare, but NTRK fusions are more common in that subtype. So for those patients, we will send off either the baseline NTRK by immunohistochemistry as a screening, or we might do the whole panel to look for these translocations. There are other subtypes, too, but for translocation testing, say detecting a synovial sarcoma or a myxoid/round cell liposarcoma, that usually is done by the pathologists already. We’re lucky that we’re in a center where they will do that for us. But there are quite a few times where we will specifically request for additional testing if it’s not done. For de-diff [dedifferentiated] liposarcoma, they usually do FISH for MDM2 amplification, but if it’s not done then we send it off, especially if we’re thinking of certain newer drugs that we want to treat on clinical trials.

Jonathan Trent, MD, PhD: And CDK4 [cyclin-dependent kinase 4].

Neeta Somaiah, MD: Exactly, and CDK4 amplification, because we can use those drugs. Yes, there are quite a few subtypes that we will reflexively treat, then order additional testing after if we are looking for additional treatments, once they have gone through their frontline therapies.

Jonathan Trent, MD, PhD: I agree with you. I think it’s a very exciting time, and I think in many ways sarcoma is really leading the field in the importance of molecular testing. For instance, regarding your point about GIST: It used to be that GIST was 1 disease, but now it’s KIT-mutated GIST, PDGFR-mutated GIST, RAF-mutated GIST, SDH-deficient GIST. There are so many different subtypes, and it was surprising to me the recent publication by Jorge Florindez, MD, et al, that only 30% of metastatic GIST patients are getting mutation testing on their tumors in the United States. I think it’s clearly an opportunity for us to provide education on the necessity of mutation testing in patients with GIST, for optimal patient management.

Neeta Somaiah, MD: That was actually surprising. I knew it was low, but I didn’t know it was that low. And the majority of those patients actually did receive treatment, so they went on to start therapy but only 20%, close to 30% of them actually had mutation testing done. But I think what’s good, and we’ll discuss further, is that with the newer drugs available, hopefully it will become more evident why mutation testing is critical up front.

Transcript Edited for Clarity