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: Outcome of children with bladder-prostate rhabdomyosarcoma has improved with multimodal therapies, including surgery and/or radiotherapy for local treatment. Our aim was to report the long-term urological complications after a conservative approach combining conservative surgery and brachytherapy. Patients and methods: Eighty-six patients, free of disease, were retrospectively reviewed. Symptoms related to urinary tract obstruction, incontinence, infection and lithiasis were reported and graded according to CTCAE classification. Only symptomatic patients underwent urodynamic studies. Risk factors for complications were analyzed. Results: There were 76 males and 10 females. The median follow-up was 6.3 years (18 months-24 years). Complications occurred after a median follow up 5 years (0-21). Twenty-two patients had long-term urological complications. Urinary tract obstruction was found in 15 patients, urinary incontinence in 14 patients. Recurrent urinary tract infection and urinary lithiasis were found in 5 patients respectively. Beyond symptom, 3 etiologies were identified: bladder dysfunction in 15 patients, urethral stenosis in 6 and uretero-vesical junction stenosis in 5. Posterior bladder wall dissection used in large prostatic tumors, operation at age less than 2 years and partial prostatectomy were identified as risk factors for these complications. Conclusion: The conservative surgical approach combined with brachytherapy for BPRMS leads to long-term urological complications in 22% of patients free of their disease. Optimizing brachytherapy doses for young children and establishing a clear and long term follow-up protocol, could help to reduce these complications.

Background: Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and European cooperative groups. In order to define the better therapeutic strategy, we analyzed two studies conducted between 2005 and 2016 by the European paediatric Soft tissue sarcoma Study Group (EpSSG) and Children’s Oncology Group (COG). Methods: We retrospectively identified patients with ARMS N1 enrolled in either EpSSG RMS2005 or in COG ARST0531. Chemotherapy in RMS2005 comprised IVADo (ifosfamide, vincristine, dactinomycin, doxorubicin), IVA and maintenance (vinorelbine, cyclophosphamide); in ARST0531 it consisted on either VAC (vincristine, dactinomycin, cyclophosphamide) or VAC alternating with VI (vincristine, irinotecan). Local treatment was similar in both protocols. Results: The analysis of the clinical characteristics of 239 patients showed some differences between study groups: in RMS2005, advanced IRS Group and large tumors predominated. There were no differences in outcomes between the two groups: 5-year event-free survival (EFS), 49% (95%CI=39-59) and 44% (95%CI=30-58), and overall survival (OS), 51% (95%CI=41-61) and 53.6% (95%CI=40-68), in RMS2005 and ARST0531, respectively. In RMS2005, EFS of patients with FOXO1-positive tumors was significantly inferior to those FOXO1-negative (49.3% vs 73%, p=0.034). In contrast, in ARST0531, EFS of patients with FOXO1-positive tumors was 45% compared with 43.8% for those FOXO1-negative. Conclusions: The outcome of patients with ARMS N1 was similar using different schemas of chemotherapy. However, patients with FOXO1 fusion-negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that this subgroup may benefit from the EpSSG strategy which included maintenance chemotherapy.