FRONTLINE AND RELAPSED RHABDOMYOSARCOMA: FAR-RMS

• Applicant: Professorin Dr. Monika Sparber-Sauer
• Subject Area: Pediatric and Adolescent Medicine
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 510548233

Rhabdomyosarcoma (RMS) is the most common sarcoma, with 59% of cases occurring in children. Although relatively rare, RMS is the most common pediatric soft tissue sarcoma and is newly diagnosed in approximately 80 children and adolescents per year in Germany. The majority of patients receive preoperative chemotherapy. However, despite its sensitivity to chemotherapy, treatment including surgery and/or radiotherapy is required to prevent relapse in the long term. In patients with metastatic disease, remission can be achieved with intensive chemotherapy and local therapy in 75% of cases, but the vast majority relapse, resulting in a 3-year event-free survival (EFS) of only 27%. Because it is a rare disease, the greatest challenges in treating patients are in the "very high risk" (VHR), "high risk" (HR), and relapsed RMS groups. In these patient groups, progress with currently available agents has been insufficient and new approaches are needed. FaR-RMS is an overarching study for children, adolescents, and young adults with newly diagnosed and also relapsed rhabdomyosarcoma (RMS). This study is taking place in many European countries. It includes multi-arm and multi-stage questions with three main objectives to improve prognosis by: 1. introducing new drug regimens at the most advanced disease stages: very high risk (VHR), high risk (HR), and relapse. 2. increasing the duration of maintenance therapy 3. improvement of local tumor control with radiotherapy in patients at VHR, HR and standard risk (SR), and for the treatment of metastases. In addition, the study will investigate the new risk classification by using PAX-FOXO1 fusion gene status instead of the previous histological subtyping. The German participation in FaR-RMS will be integrated into the Cooperative Soft Tissue Sarcoma Study Group (CWS) network, including joint national research projects with the Hopp Children's Cancer Center Heidelberg. These are an essential part of the collaboration, but not the subject of this application. In order to be able to put these national research projects into a clinical context, Germany's participation in the European FaR-RMS study is indispensable. It sets the prerequisite for a uniform therapy in the future. Only in this way can molecular research projects in Europe be meaningfully compared with clinical data. A consolidation of the clinical data with the registry data of the CWS is planned. Since RMS is a rare disease with a large intratumoral heterogeneity, a collaboration on a European level in the context of joint biological projects/data analyses is planned.

• DFG Programme: Clinical Trials
• Co-Investigators: Professor Dr. Martin Ebinger; Professor Dr. Axel Franz