February 27, 2024

Multi-institutional study of Wilms tumor facilitates enrollment, optimizes treatment

Multi-institutional study finds that enrollment and outcomes were similar across racial and ethnic groups for children participating in therapeutic trials for Wilms tumor — the most common pediatric kidney cancer worldwide.

Enrollment and outcomes were similar across racial and ethnic groups for children participating in therapeutic trials for Wilms tumor — the most common pediatric kidney cancer worldwide, according to a recent report in the Journal of the American College of Surgeons.

The study analyzed more than 13 years of data collected by the Children’s Oncology Group, a National Cancer Institute-supported clinical trials group that unites experts at more than 200 institutions. The findings also confirmed previously observed variations in Wilms tumor incidence across diverse race groups.

Harold Lovvorn III, MD

“While the racial variations in incidence for Wilms tumor remain poorly explained, it is encouraging that trial enrollment and outcomes — both in the overall study and in different therapeutic groups — remained largely consistent between race groups,” said Harold Lovvorn III, MD, professor of Pediatric Surgery at Monroe Carell Jr. Children’s Hospital at Vanderbilt and the corresponding author of the study.

“This study emphasizes the tremendous benefits of multi-institutional cooperative studies to facilitate enrollment and optimize treatment for a pediatric cancer that has global variations in incidence and survival according to race and ethnicity.”

Wilms tumor, also called nephroblastoma, is a tumor of embryonic origin and accounts for nearly 7% of all childhood cancers. About 650 cases of Wilms tumor are diagnosed in the United States each year, and the five-year survival rate is 93%, according to the National Cancer Institute. Children of Black sub-Saharan African ancestry have a higher incidence of Wilms tumor compared with white children, and children of Asian descent have the lowest incidence worldwide.

Daniel Benedetti, MD

The Children’s Oncology Group Wilms tumor study, called AREN03B2, is an umbrella study that enrolled patients from 2006 to 2019 and stratified patients initially into four different treatment groups with increasing treatment intensity based on disease characteristics and biologic risk factors.

“This study contains the most robust set of North American patients and disease characteristics, including demographic and specific biologic variables that drive risk assignment,” said co-author Daniel Benedetti, MD, assistant professor of Pediatrics in Hematology and Oncology at Monroe Carell.

In total, 5,146 patients with Wilms tumor enrolled in AREN03B2, and 1,434 patients enrolled in the therapeutic trials. Race group distribution was 69.3% white, 15.3% Black, 2.5% Asian and 12.9% multiracial/other/unknown, and 15% of the cohort was of Hispanic ethnicity.

Enrollment by race group differed from U.S. census data as expected, with Black children overrepresented — reflecting higher incidence of Wilms tumor — and Asian/Pacific Islander children underrepresented — reflecting lower incidence.

Overall, the study found no statistically significant differences between race and ethnic groups regarding risk-assigned therapeutic study enrollment, disease stage, histology, biologic factors, or event-free and overall survival, other than the following:

  • Black children were older and had larger tumors at enrollment.
  • Hispanic children had lower rates of an “unfavorable” type of Wilms tumor (diffuse anaplastic) and of a particular genetic change (LOH at 1p).

Enrollment in the four therapeutic trials was consistent between race groups, with no one race group appearing to be predisposed to a higher risk-assigned therapy.

For one of the therapeutic study groups (the most intense therapy for diffuse anaplastic Wilms tumor), Black children had worse event-free and overall survival. This finding was not replicated when patients from the larger umbrella study who had the same treatment but were not enrolled in the therapeutic trial were included in the analysis.

“Even though additional analysis did not confirm this survival gap for Black children with diffuse anaplastic Wilms tumor, we will need to consider this observation and explore potential clinical differences in future studies, particularly considering that Black children were older and had larger tumors at enrollment, which could indicate a potential delay in presentation or diagnosis,” Benedetti said.

The study confirmed previous findings that although Asian/Pacific Islander children have lower incidence of Wilms tumor, they are diagnosed at younger ages and have potentially poorer survival, suggesting that Wilms tumor impacts this racial group differently, the researchers noted.

“Overall, the excellent and largely equivalent survival observed between race and ethnic groups in each of the therapeutic groups highlights the capacity of cooperative trials to promote optimal health equity and reduce historic cancer health disparities,” Lovvorn said.

Future studies should explore whether the burden of late toxic effects of treatment are equally distributed across race and ethnicity, the researchers noted.

Lindsey Renfro, PhD, in the Division of Biostatistics at the University of Southern California is co-first author of the study with Lovvorn. The research was supported in part by St. Baldrick’s Foundation and National Institutes of Health grants to the Children’s Oncology Group (U10CA180886, U10CA180899, U10CA098543, U10CA098413, U24CA114766, U24CA196731).