Race and Ethnic Group Enrollment and Outcomes for Wilms Tumor: Analysis of the Current Era Children's Oncology Group Study, AREN03B2

Abstract

Background: To review race and ethnic group enrollment and outcomes for Wilms tumor (WT) across all 4 risk-assigned therapeutic trials from the current era Children's Oncology Group Renal Tumor Biology and Risk Stratification Protocol, AREN03B2.

Study design: For patients with WT enrolled in AREN03B2 (2006 to 2019), disease and biologic features, therapeutic study-specific enrollment, and event-free (EFS) and overall (OS) 4-year survival were compared between institutionally reported race and ethnic groups.

Results: Among 5,146 patients with WT, no statistically significant differences were detected between race and ethnic groups regarding subsequent risk-assigned therapeutic study enrollment, disease stage, histology, biologic factors, or overall EFS or OS, except the following variables: Black children were older and had larger tumors at enrollment, whereas Hispanic children had lower rates of diffuse anaplasia WT and loss of heterozygosity at 1p. The only significant difference in EFS or OS between race and ethnic groups was observed among the few children treated for diffuse anaplasia WT with regimen UH-1 and -2 on high-risk protocol, AREN0321. On this therapeutic arm only, Black children showed worse EFS (hazard ratio = 3.18) and OS (hazard ratio = 3.42). However, this finding was not replicated for patients treated with regimen UH-1 and -2 under AREN03B2 but not on AREN0321.

Conclusions: Race and ethnic group enrollment appeared constant across AREN03B2 risk-assigned therapeutic trials. EFS and OS on these therapeutic trials when analyzed together were comparable regarding race and ethnicity. Black children may have experienced worse stage-specific survival when treated with regimen UH-1 and -2 on AREN0321, but this survival gap was not confirmed when analyzing additional high-risk AREN03B2 patients.

Figure 1.

Kaplan-Meier survival plots when combining AREN03B2 therapeutic trials according to race and ethnicity. (A, B) Event-free survival (EFS) at 4 years according to race (A) and ethnicity (B). No statistically significant difference in EFS emerged between race and ethnic groups, although Asian/Pacific Islander (green) appeared lowest (EFS Probability: 73.3%; CI 58.2% - 92.4%). (C, D) Overall survival (OS) at 4 years according to race (C) and ethnicity (D). No statistically significant difference in OS emerged between race and ethnic groups, although Asian/Pacific Islander (green) appeared lowest (OS Probability: 88.6%; CI 7.2% - 100%).

Figure 2.

Kaplan-Meier survival plots of Wilms tumor (WT) patients enrolled on therapeutic trial, AREN0532. No statistically significant differences in 4-year event-free survival (EFS) or overall survival (OS) were detected between race groups for any treatment approach after WT resection, whether observation (ie surgery only; A, B), 2 drug (ie vincristine and actinomycin-D for 18 weeks; C, D), or 3 drug (ie vincristine, actinomycin-D, and doxorubicin for 24 weeks; E, F) with or without any radiation. For the highest risk treatment arm of AREN0532 (E, F), Asian/Pacific Islander race (green) showed the lowest 4-year EFS (64.6%; CI 43.9% - 95.1%) and OS (86.2%; CI 70% - 100%). This race was not included in lower-risk strata analyses due to suppression of low enrollment numbers.

Figure 3.

Kaplan-Meier survival plots of Wilms tumor (WT) patients enrolled on therapeutic trial, AREN0533. No statistically significant difference in 4-year event-free survival (EFS) or overall survival (OS) was revealed between race groups for patients treated with (A, B) 3 drugs (ie vincristine, actinomycin-D, and doxorubicin for 24 weeks) or (C, D) Regimen M (ie vincristine, actinomycin-D, doxorubicin, cyclophosphamide, and etoposide with radiation [XRT]).

Figure 4.

Kaplan-Meier survival plots of Wilms tumor (WT) patients having bilateral, or a genetic syndrome predisposing to bilateral masses and treated on therapeutic study, AREN0534, designed to spare nephrons and preserve renal function. (A, B) 4-year event-free survival (EFS) and overall survival (OS) were not statistically different between race groups. Asian/Pacific Islander here again showed lower EFS (EFS probability: 66.7%; 30% - 100%) and OS (OS probability: 66.7%; 30% - 100%, albeit neither was statistically significant in this therapeutic trial.

Figure 5.

Kaplan-Meier survival plots of diffuse anaplasia Wilms tumor (DAWT) patients enrolled on high-risk protocol, AREN0321. Treatment intensity escalated significantly from Stage I (ie vincristine, actinomycin-D, and doxorubicin for 24 weeks) to Regimen UH1/2 for Stages II-IV (ie vincristine, actinomycin-D, doxorubicin, cyclophosphamide, carboplatin, etoposide, irinotecan, and radiation [XRT], depending on unique variables). 4-year event-free survival (EFS) and overall survival (OS) were not significantly different across race groups for DAWT patients having Stage I disease (A, B). However, 4-year EFS and OS plummeted for Black children with Stage II-IV DAWT and treated on Regimen UH1/2 (C, D).

Figure 6.

Stage-specific survival analysis for diffuse anaplasia Wilms tumor (DAWT) patients treated on Regimen UH1/2 of AREN0321. (A, B) Event-free survival (EFS) and overall survival (OS) at 4 years was significantly lower for Black patients having Stage II-III DAWT. (C, D) For DAWT patients having Stage IV disease, 4-year EFS and OS appeared similarly worse for Black patients compared with Whites, although absolute statistical significance was not achieved due to lower numbers in both race groups, as well as more uniformly worse survival for Black and White patients.