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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

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. ME...

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Autores principales: Hibbitts, Emily, Chi, Yueh‐Yun, Hawkins, Douglas S., Barr, Frederic G., Bradley, Julie A., Dasgupta, Roshni, Meyer, William H., Rodeberg, David A., Rudzinski, Erin R., Spunt, Sheri L., Skapek, Stephen X., Wolden, Suzanne L., Arndt, Carola A. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797586/
https://www.ncbi.nlm.nih.gov/pubmed/31456361
http://dx.doi.org/10.1002/cam4.2504
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author Hibbitts, Emily
Chi, Yueh‐Yun
Hawkins, Douglas S.
Barr, Frederic G.
Bradley, Julie A.
Dasgupta, Roshni
Meyer, William H.
Rodeberg, David A.
Rudzinski, Erin R.
Spunt, Sheri L.
Skapek, Stephen X.
Wolden, Suzanne L.
Arndt, Carola A. S.
author_facet Hibbitts, Emily
Chi, Yueh‐Yun
Hawkins, Douglas S.
Barr, Frederic G.
Bradley, Julie A.
Dasgupta, Roshni
Meyer, William H.
Rodeberg, David A.
Rudzinski, Erin R.
Spunt, Sheri L.
Skapek, Stephen X.
Wolden, Suzanne L.
Arndt, Carola A. S.
author_sort Hibbitts, Emily
collection PubMed
description 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.
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spelling pubmed-67975862019-10-21 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, Emily Chi, Yueh‐Yun Hawkins, Douglas S. Barr, Frederic G. Bradley, Julie A. Dasgupta, Roshni Meyer, William H. Rodeberg, David A. Rudzinski, Erin R. Spunt, Sheri L. Skapek, Stephen X. Wolden, Suzanne L. Arndt, Carola A. S. Cancer Med Cancer Prevention 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. John Wiley and Sons Inc. 2019-08-27 /pmc/articles/PMC6797586/ /pubmed/31456361 http://dx.doi.org/10.1002/cam4.2504 Text en © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Prevention
Hibbitts, Emily
Chi, Yueh‐Yun
Hawkins, Douglas S.
Barr, Frederic G.
Bradley, Julie A.
Dasgupta, Roshni
Meyer, William H.
Rodeberg, David A.
Rudzinski, Erin R.
Spunt, Sheri L.
Skapek, Stephen X.
Wolden, Suzanne L.
Arndt, Carola A. S.
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Cancer Prevention
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797586/
https://www.ncbi.nlm.nih.gov/pubmed/31456361
http://dx.doi.org/10.1002/cam4.2504
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