The International Soft-Tissue Sarcoma Database Consortium (INSTRuCT) consists of a collaboration between the Children’s Oncology Group (COG) Soft Tissue Sarcoma Committee, the European pediatric Soft-Tissue Sarcoma Study Group (EpSSG), and the Cooperative Weichteilsarkom Studiengruppe (CWS). As part of the larger initiative of INSTRuCT to provide consensus expert opinions for clinical treatment of pediatric soft tissue sarcoma, we sought to provide updated, evidenced-based consensus guidelines for local treatment of parameningeal rhabdomyosarcoma using both existing literature as well as recommendations from the relevant cooperative group clinical trials. Overall, parameningeal rhabdomyosarcoma represents a distinctly challenging disease to treat given its location near many critical structures in the head and neck, frequently advanced local presentation, and predilection for local failure. Definitive chemoradiation remains the standard treatment approach for parameningeal rhabdomyosarcoma, with surgery often limited to biopsy or salvage therapy for recurrent disease. In this consensus paper, we specifically discuss consensus guidelines and evidence for definitive local management with radiotherapy, with a focus on imaging for radiotherapy planning, dose and timing of radiation, approach for nodal irradiation, various radiation techniques including proton therapy, and the limited role of surgical resection.

Background It is unclear how intensity-modulated radiation therapy (IMRT) impacts long-term risk of second malignant neoplasms (SMNs) in childhood cancer patients. Procedure Patients aged 10 years, many solid SMNs after IMRT in childhood cancer survivors develop in the high dose region. These data serve as a foundation for comparison with other modalities of radiation treatment (e.g., proton therapy).

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.

Background The International Soft Tissue Sarcoma Consortium (INSTRuCT) was founded as an international collaboration between different pediatric soft tissue sarcoma cooperative groups (COG, EpSSG, CWS). Besides other tasks, a major goal of the INSTRuCT is to develop consensus expert opinions for best clinical treatment. This consensus paper for patients with rhabdomyosarcoma of the female genital tract (FGU-RMS) provides treatment recommendations for local treatment, long term follow up and fertility preservation. Methods Review of the current literature was combined with recommendations of the treatment protocols of the appropriate clinical trials. Additionally, opinions of international FGU-RMS experts were incorporated into recommendations. Results The prognosis of FGU-RMS is favorable with an excellent response to chemotherapy. Initial complete surgical resection is not indicated, but diagnosis should be established properly. In patients with tumors localized at the vagina or cervix demonstrating incomplete response after induction chemotherapy, local radiotherapy (brachytherapy) should be carried out. In patients with persistent tumors at the corpus uteri, hysterectomy should be performed. Fertility preservation should be considered in all patients. Conclusion For the first time, an international consensus for the treatment of FGU-RMS patients could be achieved, which will help to harmonize the treatment in different study groups.