Refinement of risk stratification for childhood rhabdomyosarcoma using FOXO1 fusion status in addition to established clinical outcome predictors: A report from the Children’s Oncology Group

Hibbitts E, Chi YY, Hawkins DS, Barr FG, Bradley JA, Dasgupta R, Meyer WH, Rodeberg DA, Rudzinski ER, Spunt SL, Skapek SX, Wolden SL, Arndt CAS. Refinement of risk stratification for childhood rhabdomyosarcoma using FOXO1 fusion status in addition to established clinical outcome predictors: A report from the Children’s Oncology Group. Cancer Med. 2019 Oct;8(14):6437-6448. doi: 10.1002/cam4.2504. Epub 2019 Aug 27. PMID: 31456361; PMCID: PMC6797586.

Previous studies of the prognostic importance of FOXO1 fusion status in patients with rhabdomyosarcoma (RMS) have had conflicting results. We re‐examined risk stratification by adding FOXO1 status to traditional clinical prognostic factors in children with localized or metastatic RMS. Data from six COG clinical trials (D9602, D9802, D9803, ARST0331, ARTS0431, ARST0531; two studies each for low‐, intermediate‐ and high‐risk patients) accruing previously untreated patients with RMS from 1997 to 2013 yielded 1727 evaluable patients. Survival tree regression for event‐free survival (EFS) was conducted to recursively select prognostic factors for branching and split. Factors included were age, FOXO1, clinical group, histology, nodal status, number of metastatic sites, primary site, sex, tumor size, and presence of metastases in bone/bone marrow, soft tissue, effusions, lung, distant lymph nodes, and other sites. Definition and outcome of the proposed risk groups were compared to existing systems and cross‐validated results.