TP53 Mutation Associated With Worse Survival Among Patients With Chondrosarcomas

Among patients with chondrosarcomas, the most common primary bone tumor in adults, the presence of a TP53 gene mutation is associated with worse overall survival (the time following treatment that a patient is still alive) and metastasis-free survival (the time a patient lives without distant metastases), researchers have found.

A study from a team at The University of Texas MD Anderson Cancer Center of 93 patients with chondrosarcoma published in Clinical Cancer Research found TP53 mutation in 41.9% of patients, with researchers noting that it was “also associated with higher risk of recurrence following curative-intent surgery and worse survival among patients that presented with de novo metastatic disease (cancer which has metastasized prior to initial diagnosis).

While IDH1 and IDH2 mutations were more prevalent at 50.5%, more common with cancers beginning in patients’ extremities and were associated with patients being older at the time of diagnosis, IDH mutation led to no difference in survival, researchers noted.

Study co-author Dr. Anthony P. Conley, an associate professor in the department of sarcoma medical oncology of the division of cancer medicine at The University of Texas MD Anderson Cancer Center in Houston, discussed these findings and their implications for patients with CURE®.

Q: For patients, what do you think the big takeaways from these findings should be?

A: I think there are really two important points about this. What led us to really look at the use of the genetic results was to determine if there were particular clinical signs, symptoms or characteristics that could be tied into a particular group (of patients). And the reason we do this is because this might help us to identify patients in the future, or perhaps help us to better understand which patients might need surveillance at different time points than just the old fashioned (approach of) “Let's get a scan every three months or four months.”

And so, what we found was essentially that patients that had IDH1 or IDH2 mutations typically had a disease that was involving the upper end of their long bone. So, near the shoulder area, or in their hip or pelvis, they are much more likely to have IDH mutations than if their chondrosarcoma occurred at any other site in the body.

The other factor that was important was that they typically were older individuals, there was the tendency that they were more likely to have a different type of chondrosarcoma called dedifferentiated chondrosarcoma.

And then the other big takeaway was how important the TP53 mutation that is. It's a normal gene that controls cell cycle regulation, but in these tumors when it's mutated we think that it probably plays a central role in the disease's development, and it turns out that it can potentially impact survivability and even how long the patient may have before they develop the disease at other places in their body.

Q: And were any of the findings particularly surprising to you?

A: Well, for instance, the part about age was kind of interesting, because a lot of times (patients with) tumors that are defined by a particular type of genetic mutation tend to be younger. And it was a surprise to find that it was actually the older patients that typically are more likely to have IDH1 or IDH2 mutations.

As far as TP53, we know that to TP53 is an important gene that is altered in a lot of different cancers and we know that for many different types of cancers it can play a role in determining outcomes. It was nice to see it actually established, at least within our data set — which is a fairly comparable size, it's of a size that's comparable to other large groups that have been evaluated by other centers.

And to be honest with you, I was thinking that the IDH mutations would be predictive of survival, and they actually weren't. And I say this because it's been a little bit controversial. There have been some studies that suggest yes, it is, (and) other studies that suggest (that) no, it's not. TP53 alone I thought would be important, but I thought the combination of both of those genes would be more likely to affect the person's overall survival. It clearly wasn't necessary, TP53 alone (when) mutated was able to impact survivability.

Q: And with these findings in hand, what sorts of conversations should patients be having with their care team regarding things like genetic testing and awareness of genetic mutations?

A: I think that with all the cancers that are out there, the rule for genetic testing is going to be sort of a unique conversation. I think for patients with chondrosarcomas, the biggest problem that we face is having good medicines that can help treat advanced disease. Surgery is still the best way to cure this disease. But for those folks that develop relapse, if we can't get them back into surgical remission this can be a problem in terms of affecting their survivability.

And so, I look at genetic testing as a way to help us to better define the population of patients affected by chondrosarcoma, and I think it will help us to determine perhaps the best types of therapies. And I think it's ongoing, so it's certainly not an open and closed loop situation. I think this is an area of active investigation and it's only going to get better as drug development improves.

So, as we get closer and closer to targeted therapies across the board in cancer, I think we will see improvements for patients with chondrosarcoma that has some of these alterations, it's just that some of this is still a work in progress. I do think that genetic testing of the tumor is important for chondrosarcoma. I'm not saying that should necessarily represent a standard of care, but I think it's an important aspect of it, and ultimately, it's definitely a topic that should be discussed with their clinician.

This transcript has been edited for length and clarity.

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