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

• Published in: Cancer 2024-07, Vol.130 (13), p.2351-2360
• Main Authors: De Salvo, Gian Luca, Del Bianco, Paola, Minard‐Colin, Veronique, Chisholm, Julia, Jenney, Meriel, Guillen, Gabriela, Devalck, Christine, Van Rijn, Rick, Shipley, Janet, Orbach, Daniel, Kelsey, Anna, Rogers, Timothy, Guerin, Florent, Scarzello, Giovanni, Ferrari, Andrea, Cesen Mazic, Maja, Merks, Johannes H. M., Bisogno, Gianni
• Format: Article
• Language: English
• Subjects: Adolescent; Child; Child, Preschool; Clinical trials; Confidence intervals; Diagnosis; Europe - epidemiology; Female; Forkhead Box Protein O1 - genetics; Forkhead Box Protein O1 - metabolism; FOXO1 protein; FOXO1 protein, human; Histology; Humans; Infant; Male; Medical prognosis; Nomograms; Oncogene Proteins, Fusion - genetics; Original; ORIGINAL ARTICLES; Patients; Pediatrics; Prediction models; Prognosis; proportional hazards models; Regression models; Rhabdomyosarcoma; Rhabdomyosarcoma - mortality; Rhabdomyosarcoma - pathology; Rhabdomyosarcoma - therapy; Risk; Risk Assessment; Risk groups; Sarcoma; Soft tissue sarcoma; Soft tissues; Statistical analysis; Survival; survival analysis; Tumors
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.35258

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. Traditional clinical factors, together with FOXO1 fusion status, in nonmetastatic rhabdomyosarcoma were investigated to develop a predictive model for event‐free survival and provide a rationale for risk stratification in future trials. The most important result was the replacement of histology with fusion status, and this model was used for patient stratification in the new European Pediatric Soft Tissue Sarcoma Study Group Frontline and Relapse Rhabdomyosarcoma trial (ClinicalTrials.gov identifier NCT04625907).