Reappraisal of prognostic factors used in the European Pediatric Soft Tissue Sarcoma Study Group RMS 2005 study for localized rhabdomyosarcoma to optimize risk stratification and generate a prognostic nomogram

Abstract

Nomograms; Pediatrics; Rhabdomyosarcoma

Nomogramas; Pediatría; Rabdomiosarcoma

Nomogrames; Pediatria; Rabdomiosarcoma

Background The objective of this study was to investigate the role of clinical factors together with FOXO1 fusion status in patients with nonmetastatic rhabdomyosarcoma (RMS) to develop a predictive model for event-free survival and provide a rationale for risk stratification in future trials. Methods The authors used data from patients enrolled in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 study (EpSSG RMS 2005; EudraCT number 2005-000217-35). The following baseline variables were considered for the multivariable model: age at diagnosis, sex, histology, primary tumor site, Intergroup Rhabdomyosarcoma Studies group, tumor size, nodal status, and FOXO1 fusion status. Main effects and significant second-order interactions of candidate predictors were included in a multiple Cox proportional hazards regression model. A nomogram was generated for predicting 5-year event-free survival (EFS) probabilities. Results The EFS and overall survival rates at 5 years were 70.9% (95% confidence interval, 68.6%–73.1%) and 81.0% (95% confidence interval, 78.9%–82.8%), respectively. The multivariable model retained five prognostic factors, including age at diagnosis interacting with tumor size, tumor primary site, Intergroup Rhabdomyosarcoma Studies clinical group, and FOXO1 fusion status. Based on each patient's total score in the nomogram, patients were stratified into four groups. The 5-year EFS rates were 94.1%, 78.4%, 65.2%, and 52.1% in the low-risk, intermediate-risk, high-risk, and very-high-risk groups, respectively, and the corresponding 5-year overall survival rates were 97.2%, 91.5%, 74.3%, and 60.8%, respectively. Conclusions The results presented here provide the rationale to modify the EpSSG stratification, with the most significant change represented by the replacement of histology with fusion status. This classification was adopted in the new international trial launched by the EpSSG.

This project was conducted thanks to the support of the KickCancer Foundation and the King Baudouin Foundation. The overall organization of the EpSSG RMS 2005 study was supported by the Fondazione Città della Speranza (Padua, Italy). In France, it was supported by Association Léon Berard Enfant Cancéreux (Grant 2005). In the United Kingdom, the study was supported by Cancer Research UK. Julia Chisholm is supported by the Giant Pledge through the Royal Marsden Cancer Charity, and this independent research is supported by the National Institute for Health Research Biomedical Research Center at the Royal Marsden National Health Service Foundation Trust and the Institute of Cancer Research, London. The views expressed are those of the authors and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care. Open access funding provided by BIBLIOSAN.