Background To assess the outcomes of pediatric patients with Undifferentiated Embryonal Sarcoma of the Liver (UESL) and treatment including at least surgery and systemic chemotherapy. Methods This study included patients aged up to 21 years with a pathological diagnosis of UESL prospectively enrolled from 1995 to 2016 in three european trials focusing on the effects of surgical margins, preoperative chemotherapy, use of radiotherapy (RT) and chemotherapy. Results Out of 65 patients with a median age at diagnosis of 8.7 years (0.6-20.8), 15 had T2 tumors, and 1 had lymph node spread, 14 were Intergroup Rhabdomyosarcoma Study (IRS) I, 9 IRSII, 38 IRSIII, and 4 IRSIV. Twenty-eight upfront surgeries resulted in 5 operative spillages and 11 infiltrated surgical margins, whereas 37 delayed surgeries resulted in no spillages (P= 0.0119) and 3 infiltrated margins (P=0.0238). All patients received chemotherapy, including anthracyclines in 47. Radiotherapy was administered in 15 patients. With a median follow-up of 78.6 months, 5 year overall and event free survivals (EFS) were 90.1% (95%CI 79.2-95.5) and 89.1% (95%CI 78.4-94.6), respectively. Two out 4 local relapses had previous infiltrated margins and 2 out of 3 patients with metastatic relapses received reduced doses of alkylating agents. Infiltrated margins (P=0.1607), T2 stage (P=0.3870), use of RT (P= 0.8731), and anthracycline-based chemotherapy (P= 0.1181) were not correlated with EFS. Conclusions Neoadjuvant chemotherapy for pediatric patients with UESL increases the probability of complete surgical resection. The role of anthracyclines and radiotherapy for localized disease remains unclear. The use of alkylating agents is recommended.

BACKGROUND: Irinotecan is a drug active against pediatric sarcomas with a toxicity profile that theoretically allows for its association with more myelotoxic drugs. We examined the feasibility of a dose-density strategy integrating irinotecan in standard chemotherapy regimens for patients with high-risk sarcomas. METHODS: Between November 2013 and January 2020, 23 patients < 21 years old with metastatic (11 children) or recurrent (12 children) sarcomas were treated with 9 IrIVA/IrVAC cycles. All newly-diagnosed patients received IrIVA (ifosfamide 3g/m2 on days 1 and 2, vincristine 1.5 mg/m2 on day 1, actinomycin D 1.5 mg/m2 on day 1, irinotecan 20 mg/m2 for 5 consecutive days starting on day 8). Two relapsed patients received IrIVA and 10 IrVAC (cyclophosphamide 1.5 g/m2 on day 1 instead of ifosfamide). Feasibility was assessed in terms of toxicity and time to complete the treatment. RESULTS: 17 rhabdomyosarcomas, 4 Ewing sarcomas, 2 desmoplastic round cell tumors received a total of 181 cycles (range 2-10). Grade 4 neutropenia occurred in 62.4% of the cycles. 13 patients had febrile neutropenia. Diarrhea occurred in 14 cycles. The median time to complete the treatment was 195 days (range 170-231), 83.4% of cycles were administered on time or with a delay <1 week. With a median follow-up of 2.6 years (range 0.2-5.0), 12 patients are alive, 9 complete remissions, 3 with the disease. Conclusions: A dose density strategy combining irinotecan with standard chemotherapy is feasible. This approach will be investigated in the next trial coordinated by the European pediatric Soft tissue sarcoma Study Group.