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Current Treatment Landscape of Soft Tissue Sarcoma

Insights From: Neeta Somaiah, MD, MD Anderson Cancer Center; Jonathan Trent, MD, PhD, Sylvester Comprehensive Cancer Center
Published: Wednesday, Mar 25, 2020



Transcript:

Neeta Somaiah, MD: We can go on and talk about where we are right now with the treatment or management of soft tissue sarcomas and GISTs [gastrointestinal stromal tumors]. We’ll start with soft tissue sarcomas and basically discuss your approach to the usual high-grade pleomorphic sarcoma that comes through the door; the standard chemotherapies you use; whether you think chemotherapy is beneficial, and for which subtypes it is beneficial; and what are the limitations of chemotherapy.

Jonathan Trent, MD, PhD: Those are all really good questions, and I think that there are a lot of different answers. And a lot of what we do in clinic, anytime we’re discussing chemotherapy with patients, we reach a decision about whether to use chemotherapy through shared decision making with the patient. The patient has to be engaged because any type of treatment, whether it’s chemotherapy or targeted therapy, is going to have adverse effects, which could interfere with quality of life.

In general terms, when I see a patient with metastatic or inoperable soft tissue sarcoma, let’s say an unclassified pleomorphic sarcoma, if they’re young and otherwise healthy, with no substantial comorbidities, my general regimen is doxorubicin plus ifosfamide. We use 75 mg/m2 for doxorubicin, and we give 10 grams/m2 usually for ifosfamide. The reason we do that is because that’s the regimen that has the highest success rate in terms of progression-free survival and response rate. And there is some hint that it may provide an overall survival advantage. There’s certainly a trend to that for the patients with inoperable soft tissue sarcoma.

Neeta Somaiah, MD: Right. I think that’s the same, as you said, you have to take into account all the patient factors, and the disease factors, and decide. And combination chemotherapy is really what we recommend if the patient is otherwise healthy. Because if you get that great response, you don’t know, there are those patients with locally advanced or slightly inoperable disease whom you can actually convert into operable disease. And then subtype becomes important in deciding if there’s synovial sarcoma, or a myxoid/round cell liposarcoma, or even a leiomyosarcoma or UPS [undifferentiated pleomorphic sarcoma], these subtypes do have a higher response than some of the rarer subtypes that we still need to learn more about.

Jonathan Trent, MD, PhD: I think your point about the patients with oligometastasis or patients with locally advanced disease, if we can shrink the tumor enough, they may be eligible for surgery, or they may be eligible for radiation therapy or ablative procedures to render them disease free. And those are probably the subset of patients who get long-term benefits.

For the patients with GIST, I think it’s a little bit different than the patients with sarcoma. For patients with GIST, in my practice, when they’re inoperable or metastatic, we always do mutation testing 100% of the time just to understand what the mutation is for all the reasons we discussed previously. And then we choose the therapy based on the mutation subtype that the patient may have. And then we assess response, usually by CT [computed tomography] scan. We usually do a CT scan on the abdomen and pelvis, and perform chest x-rays, blood tests, initially every 2 or 3 months, and follow the patient over time as long as they’re benefitting. If they have a robust response, we might stretch that out a little bit.

And then we monitor the patient for progression. If they develop progression and it’s limited, for instance if there’s a solitary lesion in the liver that’s progressive, then we might treat that with a localized approach, either radiation or hepatic arterial embolization, and resection. If the patient has widespread progression, multiple lesions and different organs, then we really, at that point, need to switch systemic therapy, and look for clinical trials; there are lots of exciting clinical trials right now.

Neeta Somaiah, MD: You’re right. All the retrospective, even though it’s retrospective data with surgery, they have shown that patients with limited progression or with patients who are even responding or doing well, but they have residual disease, could derive benefit from being rendered NED [no evidence of disease] by surgery. So GIST is very different from the other subtypes and almost a whole different disease by itself.

Transcript Edited for Clarity
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Transcript:

Neeta Somaiah, MD: We can go on and talk about where we are right now with the treatment or management of soft tissue sarcomas and GISTs [gastrointestinal stromal tumors]. We’ll start with soft tissue sarcomas and basically discuss your approach to the usual high-grade pleomorphic sarcoma that comes through the door; the standard chemotherapies you use; whether you think chemotherapy is beneficial, and for which subtypes it is beneficial; and what are the limitations of chemotherapy.

Jonathan Trent, MD, PhD: Those are all really good questions, and I think that there are a lot of different answers. And a lot of what we do in clinic, anytime we’re discussing chemotherapy with patients, we reach a decision about whether to use chemotherapy through shared decision making with the patient. The patient has to be engaged because any type of treatment, whether it’s chemotherapy or targeted therapy, is going to have adverse effects, which could interfere with quality of life.

In general terms, when I see a patient with metastatic or inoperable soft tissue sarcoma, let’s say an unclassified pleomorphic sarcoma, if they’re young and otherwise healthy, with no substantial comorbidities, my general regimen is doxorubicin plus ifosfamide. We use 75 mg/m2 for doxorubicin, and we give 10 grams/m2 usually for ifosfamide. The reason we do that is because that’s the regimen that has the highest success rate in terms of progression-free survival and response rate. And there is some hint that it may provide an overall survival advantage. There’s certainly a trend to that for the patients with inoperable soft tissue sarcoma.

Neeta Somaiah, MD: Right. I think that’s the same, as you said, you have to take into account all the patient factors, and the disease factors, and decide. And combination chemotherapy is really what we recommend if the patient is otherwise healthy. Because if you get that great response, you don’t know, there are those patients with locally advanced or slightly inoperable disease whom you can actually convert into operable disease. And then subtype becomes important in deciding if there’s synovial sarcoma, or a myxoid/round cell liposarcoma, or even a leiomyosarcoma or UPS [undifferentiated pleomorphic sarcoma], these subtypes do have a higher response than some of the rarer subtypes that we still need to learn more about.

Jonathan Trent, MD, PhD: I think your point about the patients with oligometastasis or patients with locally advanced disease, if we can shrink the tumor enough, they may be eligible for surgery, or they may be eligible for radiation therapy or ablative procedures to render them disease free. And those are probably the subset of patients who get long-term benefits.

For the patients with GIST, I think it’s a little bit different than the patients with sarcoma. For patients with GIST, in my practice, when they’re inoperable or metastatic, we always do mutation testing 100% of the time just to understand what the mutation is for all the reasons we discussed previously. And then we choose the therapy based on the mutation subtype that the patient may have. And then we assess response, usually by CT [computed tomography] scan. We usually do a CT scan on the abdomen and pelvis, and perform chest x-rays, blood tests, initially every 2 or 3 months, and follow the patient over time as long as they’re benefitting. If they have a robust response, we might stretch that out a little bit.

And then we monitor the patient for progression. If they develop progression and it’s limited, for instance if there’s a solitary lesion in the liver that’s progressive, then we might treat that with a localized approach, either radiation or hepatic arterial embolization, and resection. If the patient has widespread progression, multiple lesions and different organs, then we really, at that point, need to switch systemic therapy, and look for clinical trials; there are lots of exciting clinical trials right now.

Neeta Somaiah, MD: You’re right. All the retrospective, even though it’s retrospective data with surgery, they have shown that patients with limited progression or with patients who are even responding or doing well, but they have residual disease, could derive benefit from being rendered NED [no evidence of disease] by surgery. So GIST is very different from the other subtypes and almost a whole different disease by itself.

Transcript Edited for Clarity
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