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

Emily Hibbitts, Yueh Yun Chi, Douglas S. Hawkins, Frederic G. Barr, Julie A. Bradley, Roshni Dasgupta, William H. Meyer, David A. Rodeberg, Erin R. Rudzinski, Sheri L. Spunt, Stephen X. Skapek, Suzanne L. Wolden, Carola A.S. Arndt

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6437-6448
Number of pages12
JournalCancer medicine
Volume8
Issue number14
DOIs
StatePublished - Oct 1 2019

Keywords

  • fusion status
  • rhabdomyosarcoma
  • risk stratification
  • survival tree regression

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this

    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. (2019). 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 medicine, 8(14), 6437-6448. https://doi.org/10.1002/cam4.2504