Treatment of undifferentiated round cell sarcomas with BCOR genetic alterations

When treated with Ewing sarcoma–like therapies, 75% of patients show significant treatment-associated pathological responses. In one series of 36 cases, the 3-year and 5-year survival rates were 93% and 72%, respectively.[2][Level of evidence C1] In another series of 26 patients, the 5-year overall survival (OS) rate was 76.5%, and survival was better for patients who received induction therapy using an Ewing sarcoma–type regimen.[12][Level of evidence C1] Most of the tumors in these series arose in the bone. A retrospective survey of European cancer centers identified 148 patients with undifferentiated small round cell sarcomas who did not have an Ewing sarcoma–related fusion gene.[13] Of the 148 patients, 88 (60%) had CIC-rearranged sarcomas (median age, 32 years; range 7–78 years), 33 (22%) had BCOR::CCNB3-rearranged sarcomas (median age, 17 years; range 5–91 years), and 27 (18%) had unclassified undifferentiated small round cell sarcomas (median age, 37 years; range 4–70 years). Of the 148 patients, 101 (68.2%) presented with localized disease and 47 (31.8%) had metastasis at diagnosis. Male prevalence, younger age, bone primary site, and low rate of synchronous metastases were observed in BCOR::CCNB3-rearranged cases. The local treatment was surgery for 67 patients (45%) and surgery and radiation therapy for 52 patients (35%). Chemotherapy was given to 122 patients (82%). At a median follow-up of 42.7 months, the 3-year OS rate was 92.2% for patients with BCOR::CCNB3-rearranged sarcomas, 39.6% for patients with CIC-rearranged sarcomas, and 78.7% (P < .0001) for patients with unclassified undifferentiated small round cell sarcomas.

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 event-free survival (EFS) rates were 44.0% (95% confidence interval [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).