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

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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)
JournalCancer medicine
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Rhabdomyosarcoma
Disease-Free Survival
Survival
Clinical Trials
Histology
Lymph Nodes
Bone Marrow
Neoplasm Metastasis
Bone and Bones
Lung
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

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.

In: Cancer medicine, 01.01.2019.

Research output: Contribution to journalArticle

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. In: Cancer medicine. 2019.
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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.",
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author = "Emily Hibbitts and Chi, {Yueh Yun} and Hawkins, {Douglas S.} and Barr, {Frederic G.} and Bradley, {Julie A.} and Roshni Dasgupta and Meyer, {William H.} and Rodeberg, {David A.} and Rudzinski, {Erin R.} and Spunt, {Sheri L.} and Skapek, {Stephen X.} and Wolden, {Suzanne L.} and Arndt, {Carola A.S.}",
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T1 - Refinement of risk stratification for childhood rhabdomyosarcoma using FOXO1 fusion status in addition to established clinical outcome predictors

T2 - A report from the Children's Oncology Group

AU - Hibbitts, Emily

AU - Chi, Yueh Yun

AU - Hawkins, Douglas S.

AU - Barr, Frederic G.

AU - Bradley, Julie A.

AU - Dasgupta, Roshni

AU - Meyer, William H.

AU - Rodeberg, David A.

AU - Rudzinski, Erin R.

AU - Spunt, Sheri L.

AU - Skapek, Stephen X.

AU - Wolden, Suzanne L.

AU - Arndt, Carola A.S.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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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KW - rhabdomyosarcoma

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KW - survival tree regression

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