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Racial and Ethnic Survival Disparities Among Children With High-Risk Neuroblastoma: A Children's Oncology Group
Puja J Umaretiya1,2, Arlene Naranjo3, Fan F Zhang4
1Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas.
Insights
Racial and ethnic survival disparities persist for children with high-risk neuroblastoma in clinical trials. Black and Hispanic children had worse overall survival (OS) despite uniform treatment, indicating a need for further investigation into equity.
Area of Science:
- Pediatric Oncology
- Clinical Trials
- Health Disparities
Background:
- Population-based studies show racial and ethnic survival disparities in high-risk neuroblastoma.
- It remains unknown if these disparities persist within the controlled environment of clinical trials.
Purpose of the Study:
- To investigate racial and ethnic survival disparities among children with high-risk neuroblastoma treated on frontline clinical trials.
- To identify potential factors contributing to survival differences in pediatric cancer patients.
Main Methods:
- Retrospective cohort study of Children's Oncology Group (COG) high-risk neuroblastoma trials (2007-2016).
- Analysis of overall survival (OS) and event-free survival (EFS) using Kaplan-Meier and Cox regression models.
- Race and ethnicity categorized as Hispanic, non-Hispanic Black, non-Hispanic other, and non-Hispanic White.
Main Results:
- Hispanic children had significantly inferior OS on induction/consolidation trials (HR, 1.78; P=.01).
- Non-Hispanic Black and Hispanic children experienced inferior OS on post-consolidation trials (P=.009).
- Hispanic children also had inferior EFS on post-consolidation studies (HR, 1.68; P=.02).
Conclusions:
- Racial and ethnic disparities in OS for high-risk neuroblastoma persist even within COG clinical trials.
- Current data do not fully explain the mechanisms behind these survival differences.
- Further research into treatment toxicities and post-relapse care is crucial to promote health equity.
Importance:
Whether population-based racial and ethnic survival disparities for children with high-risk neuroblastoma persist in the clinical trial setting is unknown.
Objective:
To investigate racial and ethnic survival disparities among children with high-risk neuroblastoma treated on frontline clinical trials.
Design, Setting, And Participants:
This retrospective cohort study used data from Children's Oncology Group (COG) high-risk neuroblastoma trials from January 1, 2007, to December 31, 2016, with a data freeze on June 30, 2021. Children with high-risk neuroblastoma were analyzed in 2 cohorts: induction/consolidation trial participants and post-consolidation trial participants. Statistical analyses were performed from September 2, 2021, to December 30, 2024.
Exposures:
Race and ethnicity were the primary exposures, categorized as Hispanic, non-Hispanic Black, non-Hispanic other (American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander), or non-Hispanic White.
Main Outcomes And Measures:
Primary outcomes included overall survival (OS) and event-free survival (EFS) from time of trial enrollment, estimated by Kaplan-Meier methods. Associations with race and ethnicity were evaluated by log-rank tests and Cox proportional hazards regression models. Secondary outcomes included induction delays, early trial withdrawal, relapse as first event, death as first event, postrelapse OS, and early phase trial enrollment.
Results:
The induction/consolidation cohort (median follow-up, 8.3 years [IQR, 6.1-9.8 years]) included 696 patients (404 males [58.1%]; 79 Hispanic patients [11.4%], 109 non-Hispanic Black patients [15.7%], 27 patients of non-Hispanic other race [3.9%], and 481 non-Hispanic White patients [69.1%]). The post-consolidation cohort (median follow-up, 7.5 years [IQR, 5.8-9.4 years]) included 935 patients (567 males [60.6%]; 87 Hispanic patients [9.3%], 145 non-Hispanic Black patients [15.5%], 41 patients of non-Hispanic other race [4.4%], and 662 non-Hispanic White patients [70.8%]). In multivariable Cox proportional hazards regression models, Hispanic children experienced significantly inferior OS (hazard ratio [HR], 1.78; 95% CI, 1.25-2.53; P = .01) on induction/consolidation studies compared with non-Hispanic White children; EFS did not differ. Non-Hispanic Black (HR, 1.54; 95% CI, 1.13-2.11) and Hispanic children (HR, 1.63; 95% CI, 1.09-2.43) experienced inferior OS on post-consolidation studies compared with non-Hispanic White children (P = .009); Hispanic children in post-consolidation studies experienced inferior EFS (HR, 1.68; 95% CI, 1.14-2.47; P = .02). Death as first event and postrelapse OS also differed by race and ethnicity.
Conclusions And Relevance:
This study suggests that Black and Hispanic children with high-risk neuroblastoma experienced inferior OS despite uniform planned treatment on frontline COG clinical trials. Investigated mechanisms did not completely explain survival disparities. Future evaluation of disparate treatment-related toxicities and postrelapse care as explanatory mechanisms are key next steps to promote equity.
