Undifferentiated Embryonal Sarcoma of the Liver in Children Versus Adults: A National Cancer Database Analysis.

This study evaluates the clinicopathological characteristics and outcomes of children vs. adults with undifferentiated embryonal sarcoma of the liver (UESL). A retrospective analysis of 82 children (<18 years) and 41 adults (≥18 years) with UESL registered in the National Cancer Database between 2004-2015 was conducted. No between-group differences were observed regarding tumor size, metastasis, surgical treatment, margin status, and radiation. Children received chemotherapy more often than adults (92.7% vs. 65.9%; p < 0.001). Children demonstrated superior overall survival vs. adults (log-rank, p < 0.001) with 5-year rates of 84.4% vs. 48.2%, respectively. In multivariable Cox regression for all patients, adults demonstrated an increased risk of mortality compared to children (p < 0.001), while metastasis was associated with an increased (p = 0.02) and surgical treatment with a decreased (p = 0.001) risk of mortality. In multivariable Cox regression for surgically-treated patients, adulthood (p = 0.004) and margin-positive resection (p = 0.03) were independently associated with an increased risk of mortality. Multimodal treatment including complete surgical resection and chemotherapy results in long-term survival in most children with UESL. However, adults with UESL have poorer long-term survival that may reflect differences in disease biology and an opportunity to further refine currently available treatment schemas.

Race disparities in genetic alterations within Wilms tumor specimens.

BACKGROUND: Wilms tumor (WT) affects Black children disproportionately. Genetic aberrations within WT specimens that contribute to this disparity have not been reported. METHODS: The Therapeutically Applied Research to Generate Effective Treatments (TARGET) database was queried for WT patient and genomic features. Clinical and genetic variables were compared by race. RESULTS: Within the discovery set (enriched for adverse events; N = 94 White, 19 Black, 14 Other/unreported patients), Black children were more likely to present with advanced stage disease (p = 0.019). Within the validation set (primarily a random sampling of NWTS-5; N = 360 White, 92 Black, 72 Other/Unreported), Black children appeared older at diagnosis (p = 0.050), had decreased median follow-up time (p<0.0005) and were over-represented (17.4%) relative to the concurrent U.S. Census (12.8%). Among the 37 target genes sequenced, ACTB (p = 0.030) and DICER1 (p = 0.026) mutations were more common in Black patient specimens, whereas DGCR8 (p = 0.041) mutations were more common in White patient specimens. White patient specimens were more likely to contain one or multiple targeted mutations (p = 0.026). CONCLUSION: Within the TARGET database, Black children were over-represented and harbored WT specimens containing more frequent ACTB and DICER1 mutations. In contrast, WT from White children contained overall more mutations in targeted genes and specifically in DGCR8. LEVEL OF EVIDENCE: III.

Molecular and epidemiologic characterization of Wilms tumor from Baghdad, Iraq.

BACKGROUND: Wilms tumor (WT) is the most common childhood kidney cancer worldwide, yet its incidence and clinical behavior vary according to race and access to adequate healthcare resources. To guide and streamline therapy in the war-torn and resource-constrained city of Baghdad, Iraq, we conducted a first-ever molecular analysis of 20 WT specimens to characterize the biological features of this lethal disease within this challenged population. METHODS: Next-generation sequencing of ten target genes associated with WT development and treatment resistance (WT1, CTNNB1, WTX, IGF2, CITED1, SIX2, p53, N-MYC, CRABP2, and TOP2A) was completed. Immunohistochemistry was performed for 6 marker proteins of WT (WT1, CTNNB1, NCAM, CITED1, SIX2, and p53). Patient outcomes were compiled. RESULTS: Mutations were detected in previously described WT "hot spots" (e.g., WT1 and CTNNB1) as well as novel loci that may be unique to the Iraqi population. Immunohistochemistry showed expression domains most typical of blastemal-predominant WT. Remarkably, despite the challenges facing families and care providers, only one child, with combined WT1 and CTNNB1 mutations, was confirmed dead from disease. Median clinical follow-up was 40.5 months (range 6-78 months). CONCLUSIONS: These data suggest that WT biology within a population of Iraqi children manifests features both similar to and unique from disease variants in other regions of the world. These observations will help to risk stratify WT patients living in this difficult environment to more or less intensive therapies and to focus treatment on cell-specific targets.