Expert Discusses Local Control in Ewing Sarcoma

Patients with Ewing sarcoma in their pelvic area typically have poorer local control and overall survival (OS), says Dimosthenis Andreou, M.D.

Local recurrence is associated with very poor prognosis in patients with Ewing sarcoma. Thus, researchers in the field are working on identifying potential factors associated with local recurrence in patients undergoing multimodal treatment.

A retrospective analysis evaluated the data from 1,207 patients with previously untreated Ewing sarcoma who were registered in the Euro-EWING99 trial (NCT00020566) between 1998 and 2009. The results of this analysis were presented at the 2016 Annual CTOS Meeting. The primary outcome was local recurrence-free survival, which was defined as the interval between diagnostic biopsy and local recurrence. A secondary outcome was OS.

“We found several things in this meta-analysis that were rather good,” said Andreou. “We confirmed some of the known prognostic factors.”

What were the key findings from this analysis?

In an interview with CURE, Andreou, an orthopedic oncologist at the University Hospital Münster, discusses the significant findings of this retrospective analysis and what he hopes people in the field of oncology took away from this year’s CTOS meeting.This was a retrospective analysis of the data that was not one of the primary or secondary objectives of the trial. We found several things in this meta-analysis that were rather good. We confirmed some of the known prognostic factors. Patients with pelvic Ewing sarcoma have poorer local control and poorer OS, and the same is the case for patients with primary metastases with large tumors.

Interestingly, what we also saw was not so well known up until now. We saw modifications of treatment; we had a lot of patients who didn’t proceed to finish the protocol as planned, either due to toxicity or because patients were simply fed up with the treatment and did not want to be in the hospital on and off for a year. These patients had a worse local control and worse OS probability, and we also saw some surgical factors that had some influence. For instance, patients presenting with a pathological fracture of the bone had poorer OS, but not the worst local control. That would suggest that the pathological fracture is a marker for an aggressive disease.

What are the next steps following these results?

Patients with bone Ewing sarcoma usually have a large soft tissue component. And the question is, after neoadjuvant treatment, is the soft tissue component still there? Moreover, the patients who still had soft tissue infiltration of the tumor, after neoadjuvant chemotherapy, had significantly worse prognosis, both in terms of local control and in terms of OS compared with patients who did not have that soft tissue component anymore. Well, one of the most interesting findings that I haven’t mentioned yet is that in pelvic Ewing sarcomas, in our data at least, in cases where the complete involved bone was resected rather than operated through the involved bone, those patients had significantly better overall and local recurrence-free survival. This is a finding that actually contradicts current practice, as you would typically try to maintain as much of the bone as possible.

What we would like to do is examine the data from other prospective Ewing trials with the same questions, to see if we can validate these findings. That’s one step that’s planned. Another step concerns the modality of local treatment. Again, in patients with localized tumors of the pelvis, we saw that the patients who received surgery alone had significantly worse overall and local recurrence-free survival compared with patients who received combined treatment with surgery and radiotherapy, as well as worse survival compared with patients who received radiotherapy alone.

What challenges do you face in this space?

What would you like to see in this treatment landscape in the next five to 10 years?

Interestingly, there were no significant differences, especially in terms of OS, between patients who received the combined treatment and patients who received radiotherapy alone. What we know now is that radiotherapy is a bit worse in terms of both local control and OS for patients with Ewing sarcoma. We would like to see if we could validate these findings in other patients with bone Ewing sarcomas.Well, there are no trials that involve a prospective randomized setting examining surgical questions. That’s always the problem; the trials don’t really look at local treatment options. It’s something that we don’t have, and it’s very difficult to have a randomized trial for local control options in Ewing sarcoma, so that’s something that perhaps in the future, given the results we’re now presenting, could be changed.That’s a good question. So, on the one side, I’m an orthopedic oncologist, so I’m actually a surgeon, and I’m mostly concerned about new local treatment options, and I’m mostly excited for new reconstructive methods. There are some centers that are working with individually made, custom-made implants for each patient. We have to admit that we don’t usually need them, but there are always special cases where we’re not able to reconstruct what we want to reconstruct with available treatment options. So the question would be whether these custom-made implants can provide better results for these patients. That’s the surgical side.

For the oncological side, we’re interested in getting a better prognosis for patients. We’re interested in the immune trials, which are currently ongoing in several sarcoma subtypes. We’re also interested in studies that examine the value of intensified treatment, and whether this provides better results for patients.