This article is more than 5 years old. Information may no longer be current.

Genetic rearrangement defines separate sarcoma subtype

Add topic to email alerts

Receive an email when new articles are posted on

Please provide your email address to receive an email when new articles are posted on .

Subscribe

Added to email alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

Back to Healio

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Back to Healio

Ravin Ratan

WAILEA, Hawaii — Patients with CIC-DUX4 rearranged primitive small round blue cell sarcoma represented a separate clinical entity distinct from Ewing sarcoma, according to study results presented at the Connective Tissue Oncology Society Annual Meeting.

Ravin Ratan, MD, MEd, assistant professor in the department of sarcoma medical oncology at The University of Texas MD Anderson Cancer Center, and colleagues observed that some patients with tumors considered Ewing sarcoma family tumors did not harbor the characteristic EWSR1-FLI1 translocation.

“There’s been increasing recognition that some of the tumors that are negative for that translocation are defined by others — including BCOR and CIC rearrangements — and that these tumors may behave differently from classical Ewing sarcoma,” Ratan told HemOnc Today. “CIC rearrangements are one of the most commonly seen alternative translocations — although still very rare — and are felt to carry a poor prognosis.”

Ratan and colleagues conducted a retrospective chart review to document the natural history of 14 patients with CIC-rearranged sarcomas treated between 2013 and 2017.

“We decided to look at our data because, frankly, we don’t know the right way to treat these tumors, particularly in the metastatic setting,” Ratan added. “We have usually tried salvage regimens that are employed in Ewing sarcoma, but it’s not clear how successful that is.”

Ten patients (male, n = 5) had demographic data available. Eight patients were white, one was Hispanic and one was black. Most patients (80%) had extraosseous primary sites, and two had osseous primary tumors.

Eight patients had treatment data available. All these patients received VAC/IE — vincristine, doxorubicin and cyclophosphamide alternating with ifosfamide and etoposide — or VDI (vincristine, doxorubicin and ifosfamide) chemotherapy regimens.

One patient who underwent surgery after neoadjuvant chemotherapy achieved complete response. Two other patients achieved partial response, and one patient achieved stable disease.

Of the other patients, one had progressive disease, and three did not have evaluable disease at the time of initial treatment.

Four patients received salvage VIT (vincristine, irinotecan and temozolomide) chemotherapy, and three received gemcitabine and docetaxel. However, researchers noted they did not observe any activity with gemcitabine and docetaxel.

“Metastatic patients past their first line of therapy generally do poorly with salvage regimens,” Ratan said. “However, I didn’t expect the responses in the frontline setting to be so poor. Our sample size is small so comparison is difficult, but in Ewing sarcoma you would expect complete responses in approximately 80% of patients, and we didn’t see anything close to that.”

After a median follow-up of 15.6 months, median OS was 17.8 months.

Two patients remained alive without evidence of disease at the time of the analysis. One of these patients received VDI, surgery and VIT and remained disease free 34 months following treatment completion. The most active regimen appeared to be those that contained doxorubicin and ifosfamide, according to the researchers.

Overall, although patients responded to treatments typical for Ewing sarcoma, these responses were less robust. Only one out of three patients had stable disease on VIT.

However, a small subset of patients achieved long-term survival and may achieve cure.

Based on these data, researchers now seek opportunities for collaboration to better define the natural history of this disease.

“It’s an uncommon and recently recognized entity, and I am hoping to use this meeting to generate connections with colleagues at other centers that will allow us to look at treatment outcomes in a larger group of patients,” Ratan said. “There are a minority of patients who respond quite well to therapy; we need to look at what makes those patients different from those who don’t.” – by Alexandra Todak

Reference:

Ratan R, et al. Poster 055. Presented at: CTOS Annual Meeting; Nov. 8-11, 2017; Maui, Hawaii.

Disclosures: The authors report no relevant financial disclosures.