Treatment of undifferentiated small round cell sarcomas with CIC genetic alterations

In a series of 115 cases of CIC-rearranged small round cell sarcomas, 57 patients had adequate follow-up information.[15] Nine patients presented with metastases, and 53% of patients with localized disease experienced a recurrence commonly involving the lung. Patients treated with neoadjuvant chemotherapy had an inferior survival than patients who were treated with up-front surgical resection. However, this difference in survival might have been related to a larger tumor size at presentation in the former group. The 2-year and 5-year survival rates were 53% and 43%, respectively.

An international retrospective cohort study further highlighted the poor outcomes for patients with CIC-rearranged sarcomas. The 3-year OS rate was 39.6%, which was significantly worse than outcomes for patients with other undifferentiated round cell sarcomas.[13] Likewise, these survival rates are significantly lower than the survival rates observed in patients with Ewing sarcoma. Further study is required to identify optimal treatments for this disease.

In another series of 79 patients with CIC-rearranged round cell sarcomas, outcomes were likewise poor, with a median OS of 18 months.[21] Patients treated with Ewing sarcoma–based chemotherapy regimens had nominally higher response rates compared with patients treated with soft tissue sarcoma–based regimens. However, OS rates were similar between these two groups.

A multi-institution retrospective analysis of patients aged 0 to 24 years identified 29 patients with sarcomas and CIC gene fusions and 25 patients with BCOR-associated sarcomas (18 with BCOR::CCNB3 gene fusions and 7 with BCOR ITD).[14] Using a diverse range of treatments, the 3-year EFS rates were 44.0% (95% CI, 28.7%–67.5%) for patients with CIC gene fusions and 41.2% (95% CI, 25.4%–67.0%) for patients with BCOR alterations (P = .97).