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The Prognostic Value of Molecular Testing

Insights From: Neeta Somaiah, MD, MD Anderson Cancer Center; Jonathan Trent, MD, PhD, Sylvester Comprehensive Cancer Center
Published: Friday, Apr 03, 2020



Transcript:

Jonathan Trent, MD, PhD: The other thing I was thinking about are these different mutations in GIST [gastrointestinal stromal tumor] but also mutations in other types of sarcoma. Do you think there is any prognostic value or any rationale for doing those types of molecular testing to predict outcomes of patients?

Neeta Somaiah, MD: Of course, even in GIST itself, I think it’s more predictive of response. I think there is prognostic value for GIST mutations, but there is a little bit of controversy. People do think that if you have a KIT or exon 11 mutation, but again, even KIT exon 11 comes in different varieties. So depending on the type, some could have a prognostic significance in the sense that it’s thought to probably be more likely to recur, as opposed to say the PDGFR [platelet-derived growth factor receptor] or not having a mutation.

But for other sarcoma subtypes, I think there are data for desmoid tumors where the CTNNB1 mutation and certain mutations can have a worse prognosis. So there’s a little bit of prognostication that we get by getting mutation testing done in other subtypes. But I think it also more so helps us in figuring out the subtype better and predicting whether one treatment might work or not. And I think as we’re going in to more clinical trials that are subtype specific, these nuances about what mutations are important; like we knew about translocations such as Ewing sarcoma, the most common translocation, and then this new 6 ducts translocation emerged, which is not a Ewing sarcoma, but has a worse prognosis. So there are definitely prognostic implications for certain translocations in the other subtypes as well that we use to determine whether it’s going to be a bad actor or a good actor, or figure out how to predict how this patient is going to do on certain therapies.

Jonathan Trent, MD, PhD: Yes, and the BCOR gene.

Neeta Somaiah, MD: Yes, the BCOR as well.

Jonathan Trent, MD, PhD: The BCOR also seems to prognosticate that patients may do a little bit better.

Neeta Somaiah, MD: Yes.

Jonathan Trent, MD, PhD: I think that the presence of some of these molecular signatures may help us to figure out which subsets of patients we need to be more aggressive with, in terms of chemotherapy, and which subset of patients we need to be developing new agents for.

Neeta Somaiah, MD: Correct.

Jonathan Trent, MD, PhD: And I think that, regarding all of the molecular data we’re gathering today, in the next few years we’re going to be able to be more prognostic and predictive.

Neeta Somaiah, MD: I totally agree, and I think as you just mentioned before, that they’re now classified. We keep coming up with more subtypes of sarcoma because that’s true, once you understand the molecules better, they’re able to classify them better, and we’re able to understand why one performs differently than the others and they don’t all fall into 1 bucket.

Transcript Edited for Clarity
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Transcript:

Jonathan Trent, MD, PhD: The other thing I was thinking about are these different mutations in GIST [gastrointestinal stromal tumor] but also mutations in other types of sarcoma. Do you think there is any prognostic value or any rationale for doing those types of molecular testing to predict outcomes of patients?

Neeta Somaiah, MD: Of course, even in GIST itself, I think it’s more predictive of response. I think there is prognostic value for GIST mutations, but there is a little bit of controversy. People do think that if you have a KIT or exon 11 mutation, but again, even KIT exon 11 comes in different varieties. So depending on the type, some could have a prognostic significance in the sense that it’s thought to probably be more likely to recur, as opposed to say the PDGFR [platelet-derived growth factor receptor] or not having a mutation.

But for other sarcoma subtypes, I think there are data for desmoid tumors where the CTNNB1 mutation and certain mutations can have a worse prognosis. So there’s a little bit of prognostication that we get by getting mutation testing done in other subtypes. But I think it also more so helps us in figuring out the subtype better and predicting whether one treatment might work or not. And I think as we’re going in to more clinical trials that are subtype specific, these nuances about what mutations are important; like we knew about translocations such as Ewing sarcoma, the most common translocation, and then this new 6 ducts translocation emerged, which is not a Ewing sarcoma, but has a worse prognosis. So there are definitely prognostic implications for certain translocations in the other subtypes as well that we use to determine whether it’s going to be a bad actor or a good actor, or figure out how to predict how this patient is going to do on certain therapies.

Jonathan Trent, MD, PhD: Yes, and the BCOR gene.

Neeta Somaiah, MD: Yes, the BCOR as well.

Jonathan Trent, MD, PhD: The BCOR also seems to prognosticate that patients may do a little bit better.

Neeta Somaiah, MD: Yes.

Jonathan Trent, MD, PhD: I think that the presence of some of these molecular signatures may help us to figure out which subsets of patients we need to be more aggressive with, in terms of chemotherapy, and which subset of patients we need to be developing new agents for.

Neeta Somaiah, MD: Correct.

Jonathan Trent, MD, PhD: And I think that, regarding all of the molecular data we’re gathering today, in the next few years we’re going to be able to be more prognostic and predictive.

Neeta Somaiah, MD: I totally agree, and I think as you just mentioned before, that they’re now classified. We keep coming up with more subtypes of sarcoma because that’s true, once you understand the molecules better, they’re able to classify them better, and we’re able to understand why one performs differently than the others and they don’t all fall into 1 bucket.

Transcript Edited for Clarity
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