Implications of Implementing Children's Oncology Group Risk Stratification to Patients With Rhabdomyosarcoma Treated on European Paediatric Soft Tissue Sarcoma Study Group Clinical Trial

Background: Prognostic factors are crucial in tailoring treatments for patients with rhabdomyosarcoma (RMS). The European paediatric Soft tissue sarcoma Study Group (EpSSG) and the Children's Oncology Group (COG) employ similar prognostic factors, but utilize them differently resulting in diverse stratification systems. This diversity may result in dissimilar treatment approaches for comparable patients and hinder the comparison of clinical trial results. Procedure: We reclassified 1993 patients enrolled in the EpSSG RMS 2005 and MTS 2008 studies based on the risk stratification used in current EpSSG and COG trials, and compared the type and cumulative doses of chemotherapy recommended to the different risk groups. Alkylating agents were compared using the cyclophosphamide equivalent dose formula. Metastatic RMS with high-risk features were excluded because no standard recommended treatment exists. Results: Patients were variably distributed across EpSSG and COG risk stratifications. Notably, 34.2% of EpSSG standard-risk patients fell into three different COG risk groups (very low, low, and intermediate), and 66.8% of the total population, classified as standard, high, and very high risk by EpSSG, would all be considered intermediate risk by COG. Consequently, only 57.3% of the study population would receive comparable intensive chemotherapy under both EpSSG and COG protocols. Disparities emerged, with 16.5% undergoing more intensive and 17.2% receiving less intensive treatment in COG protocols compared to EpSSG studies. Conclusions: Our study shows the complexities of the current RMS risk stratification systems, emphasizing the need for a global consensus. A unified approach would reduce the risk of disparate treatments for similar patients and facilitate more straightforward cross-study comparisons.