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Background Children living in poverty and those of marginalized race or ethnicity experience inferior disease outcomes across many cancers. Whether survival disparities exist in osteosarcoma is poorly defined. We investigated the association between race, ethnicity, and proxied poverty exposures and event-free and overall survival for children with nonmetastatic osteosarcoma receiving care on a cooperative group trial. Methods We conducted a retrospective cohort study of US patients with nonmetastatic, osteosarcoma aged 5-21 years enrolled on the Children's Oncology Group trial AOST0331. Race and ethnicity were categorized to reflect historically marginalized populations, as Hispanic, non-Hispanic Black, non-Hispanic Other, and non-Hispanic White. Poverty was proxied at the household and neighborhood levels. Overall survival and event-free survival functions of time from trial enrollment were estimated using the Kaplan–Meier method. Hypotheses of associations between risks for event-free survival, death, and postrelapse death with race and ethnicity were assessed using log-rank tests. Results Among 758 patients, 25.6% were household-poverty and 28.5% neighborhood-poverty exposed. Of the patients, 21% of children identified as Hispanic, 15.4% non-Hispanic Black, 5.3% non-Hispanic Other, and 54.0% non-Hispanic White. Neither household or neighborhood poverty nor race and ethnicity were statistically significantly associated with risks for event-free survival or death. Postrelapse risk for death differed statistically significantly across race and ethnicity with non-Hispanic Black patients at greatest risk (4-year postrelapse survival 35.7% Hispanic vs 13.0% non-Hispanic Black vs 43.8% non-Hispanic Other vs 38.9% non-Hispanic White; P  = .0046). Conclusions Neither proxied poverty exposures or race and ethnicity were associated with event-free survival or overall survival, suggesting equitable outcomes following frontline osteosarcoma trial-delivered therapy. Non-Hispanic Black children experienced statistically significant inferior postrelapse survival. Investigation of mechanisms underlying postrelapse disparities are paramount. [ABSTRACT FROM AUTHOR]

Background: Autism Spectrum Disorder (ASD) is one of the fastest-growing developmental disorders in the United States. It was hypothesized that variations in the placental chorionic surface vascular network (PCSVN) structure may reflect both the overall effects of genetic and environmentally regulated variations in branching morphogenesis within the conceptus and the fetus' vital organs. This paper provides sound evidences to support the study of ASD risks with PCSVN through a combination of feature-selection and classification algorithms.Methods: Twenty eight arterial and 8 shape-based PCSVN attributes from a high-risk ASD cohort of 89 placentas and a population-based cohort of 201 placentas were examined for ranked relevance using a modified version of the random forest algorithm, called the Boruta method. Principal component analysis (PCA) was applied to isolate principal effects of arterial growth on the fetal surface of the placenta. Linear discriminant analysis (LDA) with a 10-fold cross validation was performed to establish error statistics.Results: The Boruta method selected 15 arterial attributes as relevant, implying the difference in high and low ASD risk can be explained by the arterial features alone. The five principal features obtained through PCA, which accounted for about 88% of the data variability, indicated that PCSVNs associated with placentas of high-risk ASD pregnancies generally had fewer branch points, thicker and less tortuous arteries, better extension to the surface boundary, and smaller branch angles than their population-based counterparts.Conclusion: We developed a set of methods to explain major PCSVN differences between placentas associated with high risk ASD pregnancies and those selected from the general population. The research paradigm presented can be generalized to study connections between PCSVN features and other maternal and fetal outcomes such as gestational diabetes and hypertension. [ABSTRACT FROM AUTHOR]

Purpose: Identification of discrete sub-groups associated with treatment response and resistance in localized Ewing sarcoma (EWS) remains a challenge. The primary objective of the Children's Oncology Group biology study AEWS18B1-Q was to perform molecular characterization of a large cohort of patients with localized Ewing sarcoma treated on prospective trials with modern standard of care therapy., Methods: We analyzed clinical and molecular features from patients with localized EWS enrolled on AEWS0031, AEWS1031, or INT-0154 frontline trials. All patients had available FFPE tissue, frozen tissue, or whole-genome amplified material. Sequencing was performed for identification of canonical fusions, recurrent copy number alterations (CNAs), and alterations in TP53 and STAG2 . Where available, tissue was analyzed for loss of STAG2 protein expression. Molecular features were evaluated for their association with cumulative incidence of relapse in univariate and multivariable analyses., Results: Three hundred and fifty-one cases had sufficient tissue, which in most cases was extracted from two FFPE slides. EWS canonical fusions were identified in 282 cases (80.3%). Pathogenic mutations in TP53 and STAG2 were identified in 5.1% and 7.6% of cases, respectively and 63.1% of cases were found to have recurrent CNAs. In univariate analysis, there was an increased cumulative incidence of relapse in patients with TP53 mutation (5-year cumulative incidence of relapse 43%, CI [17%, 67%] vs. 22%, CI [17%, 27%]; Gray's test P = 0.039), STAG2 mutation (53%, CI [29%, 73%] vs. 21%, CI [16%, 26%]; P < 0.001), and recurrent CNAs (30%, CI [22%, 37%] vs. 16%, CI [9%, 24%]; P = 0.005). In a multivariable analysis, STAG2 mutation was the only molecular biomarker that remained prognostic., Conclusion: This is a prospective validation of the molecular prognostic features of localized EWS receiving standard of care therapy on therapeutic clinical trials. Building on prior work, patients with STAG2 mutations were at high risk of relapse., Context: Key Objective: To determine if molecular features can identify clinically relevant disease sub-groups applicable to frontline clinical trial design among patients with localized Ewing sarcoma. Knowledge Generated: Among 351 patients with localized Ewing sarcoma treated on prospective trials, canonical fusions were identified in 80% of cases. In a multivariable analysis of patients with genomically defined Ewing sarcoma, the presence of STAG2 mutations identified a high-risk population. Relevance (added by Associate Editor).