Observational Study

. 2025 Jul 10;6(3):100466.

doi: 10.1016/j.xhgg.2025.100466. Epub 2025 Jun 9.

The impact of genetic ancestry on survival outcomes in pediatric rhabdomyosarcoma: A report from the Children's Oncology Group

Ekene A Onwuka¹, Christina L Magyar², Bailey A Martin-Giacalone³, Michael E Scheurer⁴, Deborah A Marquez-Do³, Mark Zobeck³, Elizabeth G Atkinson⁵, Erin R Rudzinski⁶, Michael A Arnold⁷, Donald A Barkauskas⁸, David Hall⁹, Javed Khan¹⁰, Jack F Shern¹¹, Paul Scheet¹², Brian Crompton¹³, Corinne M Linardic¹⁴, Douglas S Hawkins⁶, Rajkumar Venkatramani³, Lisa Mirabello¹⁵, Chad D Huff¹², Melissa A Richard¹⁶, Philip J Lupo¹⁷

Affiliations

¹ Department of Pediatric Surgery, Surgical Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
² Graduate Program in Genetics and Genomics, Baylor College of Medicine, Houston, TX 77030, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA; McNair Medical Institute, The Robert and Janice McNair Foundation, Houston, TX 77030, USA; Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
³ Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
⁴ Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta University, Atlanta, GA, USA; Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta, Atlanta, GA, USA.
⁵ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
⁶ Division of Hematology-Oncology, Seattle Children's Hospital, University of Washington, Seattle, WA 98105, USA.
⁷ Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, CO 80045, USA; Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
⁸ Department of Population and Public Health Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90032, USA; QuadW Childhood Sarcoma Biostatistics and Annotation Office, Children's Oncology Group, Monrovia, CA 91016, USA.
⁹ QuadW Childhood Sarcoma Biostatistics and Annotation Office, Children's Oncology Group, Monrovia, CA 91016, USA.
¹⁰ Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹¹ Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
¹² Department of Epidemiology at the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹³ Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02141, USA.
¹⁴ Departments of Pediatrics and Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
¹⁵ Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA.
¹⁶ Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
¹⁷ Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta University, Atlanta, GA, USA; Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta, Atlanta, GA, USA. Electronic address: plupo@emory.edu.

PMID: 40495382
PMCID: PMC12256324
DOI: 10.1016/j.xhgg.2025.100466

Observational Study

The impact of genetic ancestry on survival outcomes in pediatric rhabdomyosarcoma: A report from the Children's Oncology Group

Ekene A Onwuka et al. HGG Adv. 2025.

. 2025 Jul 10;6(3):100466.

doi: 10.1016/j.xhgg.2025.100466. Epub 2025 Jun 9.

Authors

Affiliations

¹ Department of Pediatric Surgery, Surgical Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
² Graduate Program in Genetics and Genomics, Baylor College of Medicine, Houston, TX 77030, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA; McNair Medical Institute, The Robert and Janice McNair Foundation, Houston, TX 77030, USA; Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
³ Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
⁴ Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta University, Atlanta, GA, USA; Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta, Atlanta, GA, USA.
⁵ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
⁶ Division of Hematology-Oncology, Seattle Children's Hospital, University of Washington, Seattle, WA 98105, USA.
⁷ Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, CO 80045, USA; Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
⁸ Department of Population and Public Health Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90032, USA; QuadW Childhood Sarcoma Biostatistics and Annotation Office, Children's Oncology Group, Monrovia, CA 91016, USA.
⁹ QuadW Childhood Sarcoma Biostatistics and Annotation Office, Children's Oncology Group, Monrovia, CA 91016, USA.
¹⁰ Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹¹ Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
¹² Department of Epidemiology at the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹³ Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02141, USA.
¹⁴ Departments of Pediatrics and Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
¹⁵ Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA.
¹⁶ Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
¹⁷ Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta University, Atlanta, GA, USA; Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta, Atlanta, GA, USA. Electronic address: plupo@emory.edu.

PMID: 40495382
PMCID: PMC12256324
DOI: 10.1016/j.xhgg.2025.100466

Abstract

Emerging evidence suggests genetic ancestry may influence childhood cancer outcomes, but its impact on pediatric rhabdomyosarcoma (RMS) is unknown. We explored genetic ancestry's impact on survival among children with RMS. This multi-center observational cohort study is a secondary analysis of previously collected biobanking, genomic, and clinical data. The study included 920 individuals with newly diagnosed RMS under 40 years of age enrolled from 2005 to 2017 under the COG soft tissue sarcoma biobanking protocol D9902. The primary endpoints were (1) event-free survival (EFS), defined as the time from study enrollment to tumor recurrence/progression, secondary malignancy, or death from any cause; and (2) overall survival (OS), defined as the time from study enrollment to death from any cause. Genetic ancestry was estimated using Grafpop software, and Cox regression assessed the association between genetic ancestry and EFS and OS, considering RMS overall, by fusion status, and by histological subtype. Covariates included sex, age at diagnosis, tumor stage, and histology, except during stratified analyses. In embryonal RMS and PAX3/7:FOXO1 fusion-negative RMS, individuals with South Asian or Asian-Pacific Islander ancestry showed worse EFS (hazard ratio [HR] 2.06, 95% confidence interval [CI] 1.07-3.97, p = 0.03 and HR 2.01, 95% CI 1.07-3.76, p = 0.03, respectively) and OS (HR 2.30, 95% CI 1.09-4.84, p = 0.03 and HR 2.33, 95% CI 1.15-4.70, p = 0.020, respectively) compared to those with primarily European genetic ancestry. These findings suggest that genetic ancestry influences survival outcomes within RMS subtypes, and further understanding may improve precision-medicine-based efforts.

Keywords: South Asian/Asian-Pacific Islander; genetic ancestry; health disparities; rhabdomyosarcoma; survival outcomes.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Figures

**Figure 1**
Cox proportional hazards model forest plots (A) Overall and (B) event-free survival. AFR, African; EUR, European; LA, Latin American; SA, South Asian or Asian-Pacific Islander.

**Figure 2**
Kaplan-Meier curves among Children’s Oncology Group participants with RMS grouped by genetic ancestry (A) Embryonal rhabdomyosarcoma overall survival. (B) Embryonal rhabdomyosarcoma event-free survival. (C) Fusion-negative overall survival. (D) Fusion-negative event-free survival. AFR, African; EUR, European; LA, Latin American; SA, South Asian or Asian-Pacific Islander.

**Figure 3**
Kaplan-Meier curves among pediatric cases with rhabdomyosarcoma obtained from SEER database grouped by self-reported race and ethnicity (A) Kaplan-Meier curve grouped by reported race/ethnicity from surveillance, epidemiology, and end results (SEER) data of all RMS cases combined from 1992 to 2020 in patients 0–24 years of age. (B) Kaplan-Meier curve grouped by reported race/ethnicity from SEER data of ERMS cases combined from 1992 to 2020 in patients 0–24 years of age.

See this image and copyright information in PMC

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The impact of genetic ancestry on survival outcomes in pediatric rhabdomyosarcoma: A report from the Children's Oncology Group

Affiliations

The impact of genetic ancestry on survival outcomes in pediatric rhabdomyosarcoma: A report from the Children's Oncology Group

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous