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. 2021 Mar 15;127(6):946-956.
doi: 10.1002/cncr.33334. Epub 2020 Nov 20.

Survival outcomes of patients with localized FOXO1 fusion-positive rhabdomyosarcoma treated on recent clinical trials: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group

Christine M Heske  1 , Yueh-Yun Chi  2 , Rajkumar Venkatramani  3 , Minjie Li  4 , Michael A Arnold  5   6 , Roshni Dasgupta  7 , Susan M Hiniker  8 , Douglas S Hawkins  9 , Leo Mascarenhas  10
Affiliations

Survival outcomes of patients with localized FOXO1 fusion-positive rhabdomyosarcoma treated on recent clinical trials: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group

Christine M Heske et al. Cancer. .

Abstract

Background: The objective of this analysis was to evaluate the clinical factors influencing survival outcomes in patients with localized (clinical group I-III), FOXO1 fusion-positive rhabdomyosarcoma (RMS).

Methods: Patients with confirmed FOXO1 fusion-positive RMS who were enrolled on 3 completed clinical trials for localized RMS were included in the analytic cohort. Outcomes were analyzed using the Kaplan-Meier method to estimate event-free survival (EFS) and overall survival (OS), and the curves were compared using the log-rank test. A Cox proportional hazards regression model was used to perform multivariate analysis of prognostic factors that were significant in the univariate analysis.

Results: The estimated 4-year EFS and OS of 269 patients with localized, FOXO1 fusion-positive RMS was 53% (95% CI, 47%-59%) and 69% (95% CI, 63%-74%), respectively. Univariate analysis revealed that several known favorable clinical characteristics, including age at diagnosis between 1 and 9 years, complete surgical resection, tumor size ≤5 cm, favorable tumor site, absence of lymph node involvement, confinement to the anatomic site of origin, and PAX7-FOXO1 fusion, were associated with improved outcomes. Multivariate analysis identified older age (≥10 years) and large tumor size (>5 cm) as independent, adverse prognostic factors for EFS within this population, and patients who had both adverse features experienced substantially inferior outcomes.

Conclusions: Patients with localized, FOXO1 fusion-positive RMS can be further risk stratified based on clinical features at diagnosis, and older patients with large primary tumors have the poorest prognosis.

Keywords: FOXO1; PAX3; PAX7; alveolar; localized; prognosis; rhabdomyosarcoma; risk stratification; translocation.

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Conflict of interest statement

Conflict of Interest: The authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.. EFS and OS of entire cohort.
Kaplan-Meier curves representing EFS (blue) and OS (red) for for study population of localized (group I-III) FOXO1 fusion positive rhabdomyosarcoma (RMS) treated on either D9602, D9806, or ARST0531 between 1997 and 2013.
Figure 2.
Figure 2.. Event-free survival (EFS) and overall survival (OS) by age.
Kaplan-Meier curves representing (A) EFS and (B) OS for patients with localized (group I-III) FOXO1 fusion positive rhabdomyosarcoma (RMS) who, at diagnosis, were under 1 year of age (blue), between 1 and 9 years old (red) or 10 years or older (green).
Figure 2.
Figure 2.. Event-free survival (EFS) and overall survival (OS) by age.
Kaplan-Meier curves representing (A) EFS and (B) OS for patients with localized (group I-III) FOXO1 fusion positive rhabdomyosarcoma (RMS) who, at diagnosis, were under 1 year of age (blue), between 1 and 9 years old (red) or 10 years or older (green).
Figure 3.
Figure 3.. Event-free survival (EFS) and overall survival (OS) by tumor size.
Kaplan-Meier curves representing (A) EFS and (B) OS for patients with localized (group I-III) FOXO1 fusion positive rhabdomyosarcoma (RMS) with tumors less than or equal to 5 cm (blue) or greater than 5 cm (red).
Figure 3.
Figure 3.. Event-free survival (EFS) and overall survival (OS) by tumor size.
Kaplan-Meier curves representing (A) EFS and (B) OS for patients with localized (group I-III) FOXO1 fusion positive rhabdomyosarcoma (RMS) with tumors less than or equal to 5 cm (blue) or greater than 5 cm (red).
Figure 4.
Figure 4.. Event-free survival (EFS) and overall survival (OS) by tumor invasiveness.
Kaplan-Meier curves representing (A) EFS and (B) OS for patients with localized (group I-III) FOXO1 fusion positive rhabdomyosarcoma (RMS) with tumors confined to the anatomic site (T1) (blue), or tumors that had extended into the surrounding tissues (T2) (red).
Figure 4.
Figure 4.. Event-free survival (EFS) and overall survival (OS) by tumor invasiveness.
Kaplan-Meier curves representing (A) EFS and (B) OS for patients with localized (group I-III) FOXO1 fusion positive rhabdomyosarcoma (RMS) with tumors confined to the anatomic site (T1) (blue), or tumors that had extended into the surrounding tissues (T2) (red).
Figure 5.
Figure 5.. Event-free survival (EFS) and overall survival (OS) by age and tumor size.
Kaplan-Meier curves representing (A) EFS and (B) OS for patients with localized (group I-III) FOXO1 fusion positive rhabdomyosarcoma (RMS) with age between 1 and 9 years and tumors less than or equal to 5 cm and (blue), age between 1 and 9 years and tumors greater than 5 cm (red), age 10 years or older and tumors less than or equal to 5 cm (green), or age 10 years or older and tumors greater than 5 cm (brown).
Figure 5.
Figure 5.. Event-free survival (EFS) and overall survival (OS) by age and tumor size.
Kaplan-Meier curves representing (A) EFS and (B) OS for patients with localized (group I-III) FOXO1 fusion positive rhabdomyosarcoma (RMS) with age between 1 and 9 years and tumors less than or equal to 5 cm and (blue), age between 1 and 9 years and tumors greater than 5 cm (red), age 10 years or older and tumors less than or equal to 5 cm (green), or age 10 years or older and tumors greater than 5 cm (brown).
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