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 Journal Article


Authors: Hibbitts, E.; Chi, Y. Y.; Hawkins, D. S.; Barr, F. G.; Bradley, J. A.; Dasgupta, R.; Meyer, W. H.; Rodeberg, D. A.; Rudzinski, E. R.; Spunt, S. L.; Skapek, S. X.; Wolden, S. L.; Arndt, C. A. S.
Article Title: 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
Abstract: Background: 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. Methods: 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. Results: The 5-year EFS and overall survival (OS) for evaluable patients were 69% and 79%, respectively. Extent of disease (localized versus metastatic) was the first split (EFS 73% vs 30%; OS 84% vs. 42%). FOXO1 status (positive vs negative) was significant in the second split both for localized (EFS 52% vs 78%; OS 65% vs 88%) and metastatic disease (EFS 6% vs 46%; OS 19% vs 58%). Conclusions: After metastatic status, FOXO1 status is the most important prognostic factor in patients with RMS and improves risk stratification of patients with localized RMS. Our findings support incorporation of FOXO1 status in risk stratified clinical trials. © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Keywords: child; event free survival; overall survival; histopathology; bone metastasis; outcome assessment; lymph node metastasis; tumor volume; distant metastasis; childhood cancer; high risk patient; age; risk assessment; lung metastasis; risk stratification; rhabdomyosarcoma; gender; transcription factor fkhr; soft tissue metastasis; clinical trial (topic); intermediate risk patient; bone marrow metastasis; effusion; low risk patient; cancer prognosis; human; priority journal; article; fusion status; survival tree regression
Journal Title: Cancer Medicine
Volume: 8
Issue: 14
ISSN: 2045-7634
Publisher: Wiley Blackwell  
Date Published: 2019-10-01
Start Page: 6437
End Page: 6448
Language: English
DOI: 10.1002/cam4.2504
PUBMED: 31456361
PROVIDER: scopus
PMCID: PMC6797586
DOI/URL:
Notes: Article -- Export Date: 1 November 2019 -- Source: Scopus
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  1. Suzanne L Wolden
    560 Wolden