Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Oct;8(14):6437-6448.
doi: 10.1002/cam4.2504. Epub 2019 Aug 27.

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  1 , Yueh-Yun Chi  1 , Douglas S Hawkins  2 , Frederic G Barr  3 , Julie A Bradley  4 , Roshni Dasgupta  5 , William H Meyer  6 , David A Rodeberg  7 , Erin R Rudzinski  8 , Sheri L Spunt  9 , Stephen X Skapek  10 , Suzanne L Wolden  11 , Carola A S Arndt  12
Affiliations

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 et al. Cancer Med. 2019 Oct.

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.

Keywords: fusion status; rhabdomyosarcoma; risk stratification; survival tree regression.

PubMed Disclaimer

Conflict of interest statement

None: Dasgupta, Chi, Meyer, Rudzinski, Hibbitts, Rodeberg, Skapek, Spunt. Positive disclosures: Arndt ‐‐ stock ownership Pfizer and Merck; Bradley‐‐ honoraria and travel funding from Ion Beam applications; Hawkins‐‐ travel funding from Bayer, BMS, loxo oncology, Celgene; Barr‐‐ stock ownership by self or immediate family member in Abbott Labs, General Electric, Danaher corp, Abbvie inc, Baxter international, Celgene, Colgate Palmolive, Edwards lifesciences, Eli Lilly, Johnson and Johnson; Wolden—travel expenses from IBA and consulting role in Y‐mAbs.

Figures

Figure 1
Figure 1
Event‐free survival (EFS) tree of analytic cohort with terminal leaves labeled by risk groups. EFS, event‐free survival; Fusion, FOXO1 fusion status
Figure 2
Figure 2
EFS curves by risk group as defined by (A) D‐series criteria; (B) ARST‐series criteria; (C) proposed stratification
See this image and copyright information in PMC

References

    1. Ognjanovic S, Linabery AM, Charbonneau B, Ross JA. Trends in childhood rhabdomyosarcoma incidence and survival in the United States, 1975–2005. Cancer. 2009;115(18):4218‐4226. 10.1002/cncr.24465 - DOI - PMC - PubMed
    1. Meza JL, Anderson J, Pappo AS, Meyer WH. Analysis of prognostic factors in patients with nonmetastatic rhabdomyosarcoma treated on intergroup rhabdomyosarcoma studies III and IV: the Children's Oncology Group. J Clin Oncol. 2006;24(24):3844‐3851. 10.1200/JCO.2005.05.3801 - DOI - PubMed
    1. Oberlin O, Rey A, Lyden E, et al. Prognostic factors in metastatic rhabdomyosarcomas: results of a pooled analysis from United States and European Cooperative Groups. J Clin Oncol. 2008;26(14):2384‐2389. 10.1200/JCO.2007.14.7207 - DOI - PMC - PubMed
    1. Parham DM, Barr FG. Classification of rhabdomyosarcoma and its molecular basis. Adv Anat Pathol. 2013;20(6):387‐397. 10.1097/PAP.0b013e3182a92d0d - DOI - PMC - PubMed
    1. Williamson D, Missiaglia E, De Reyniès A, et al. Fusion gene‐negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. J Clin Oncol. 2010;28(13):2151‐2158. 10.1200/JCO.2009.26.3814 - DOI - PubMed

Publication types