Daniel Orbach

Background In certain rare undifferentiated small round cell sarcomas new specific molecular CIC‐DUX4 /other partner, BCOR‐CCNB3 /other partner, YWHAE fusions, or BCOR‐ITD (internal tandem duplication) were identified. These new “ CIC fused ” (CIC‐fused/ ATXN1::NUTM1 ) and “ BCOR rearranged ” (BCOR fused/ITD/ YWHAE ) soft tissue sarcomas (STS) are not well described. Methods Multi‐institutional European retrospective analysis of young patients (0–24 years) with CIC‐fused and BCOR rearranged STS. Results Overall, out of the 60 patients selected, the fusion status was CIC‐fused ( n = 29), ATXN1::NUTM1 ( n = 2), BCOR::CCNB3 ( n = 18), BCOR‐ITD ( n = 7), and YWHAE ( n = 3), MAML::BCOR STS ( n = 1). The main primaries were abdomen‐pelvic ( n = 23) and limbs ( n = 18). Median age was 14 years (0.9–23.8) and 0.9 (0.1–19.1) for CIC‐fused and BCOR‐rearranged groups, respectively ( n = 29; p < 0.001). IRS stages were I ( n = 3), II ( n = 7), III ( n = 35), and IV ( n = 15). Overall, 42 patients had large tumors (>5 cm) but only six had lymph node involvement. Patients received mainly chemotherapy ( n = 57), local surgery ( n = 50), and/or radiotherapy ( n = 34). After a median follow‐up of 47.1 months (range, 3.4–230), 33 (52%) patients had an event and 23 patients died. Three‐year event‐free survivals were 44.0% (95% CI 28.7–67.5) and 41.2% (95% CI 25.4–67.0) for CIC and BCOR groups ( p = 0.97), respectively. Three‐year overall survivals were 46.3% (95% CI 29.6–72.4) and 67.1% (95% CI 50.4–89.3; p = 0.24), respectively. Conclusions Pediatric patients often present with large tumors and metastatic disease, especially CIC sarcomas. Overall outcome is dismal. New treatment options are needed.