Pediatric Cancer By Race, Ethnicity and Region in the United States.

BACKGROUND: In a 2018 descriptive study, cancer incidence in children (age 0-19) in diagnosis years 2003 to 2014 was reported as being highest in New Hampshire and in the Northeast region. METHODS: Using the Cancer in North America (CiNA) analytic file, we tested the hypotheses that incidence rates in the Northeast were higher than those in other regions of the United States either overall or by race/ethnicity group, and that rates in New Hampshire were higher than the Northeast region as a whole. RESULTS: In 2003 to 2014, pediatric cancer incidence was significantly higher in the Northeast than other regions of the United States overall and among non-Hispanic Whites and Blacks, but not among Hispanics and other racial minorities. However, there was no significant variability in incidence in the states within the Northeast overall or by race/ethnicity subgroup. Overall, statistically significantly higher incidence was seen in the Northeast for lymphomas [RR, 1.15; 99% confidence interval (CI), 1.10-1.19], central nervous system neoplasms (RR, 1.12; 99% CI, 1.07-1.16), and neuroblastoma (RR, 1.13; 99% CI, 1.05-1.21). CONCLUSIONS: Pediatric cancer incidence is statistically significantly higher in the Northeast than in the rest of the United States, but within the Northeast, states have comparable incidence. Differences in cancer subtypes by ethnicity merit further investigation. IMPACT: Our analyses clarify and extend previous reports by statistically confirming the hypothesis that the Northeast has the highest pediatric cancer rates in the country, by providing similar comparisons stratified by race/ethnicity, and by assessing variability within the Northeast.

Kidney Cancer Risk Associated with Historic Groundwater Trichloroethylene Contamination.

Trichloroethylene (TCE) is a well-documented kidney carcinogen based on a substantial body of evidence including mechanistic and animal studies, as well as reports from occupational settings. However, the cancer risks for those in residential exposures such as TCE contamination in groundwater are much less clear. The objective of this study was to perform a detailed spatio-temporal analysis of estimated residential TCE exposure in New Hampshire, US. We identified kidney cancer cases (n = 292) and age-, gender-matched controls (n = 448) from the Dartmouth-Hitchcock Health System and queried a commercial financial database for address histories. We used publically available data on TCE levels in groundwater measured at contaminated sites in New Hampshire and then modeled the spatial dispersion and temporal decay. We overlaid geospatial residential locations of cases and controls with yearly maps of estimated TCE levels to estimate median exposures over the 5, 10, and 15-year epochs before diagnosis. The 50th-75th percentile of estimated residential exposure over a 15-year period was associated with increased kidney cancer risk (adjusted Odds Ratio (OR) 1.78 95% CI 1.05-3.03), compared to <50th percentile. This finding supports the need for groundwater monitoring of TCE contaminated sites to identify potential public health risks.

Statins and Left Ventricular Ejection Fraction Following Doxorubicin Treatment.

BACKGROUND: Statins taken for cardiovascular indications by patients with breast cancer and lymphoma during doxorubicin treatment may attenuate left ventricular ejection fraction (LVEF) decline, but the effect of statins on LVEF among patients with no cardiovascular indications is unknown. METHODS: A double-blind, placebo-controlled, 24-month randomized trial of 40 mg of atorvastatin per day administered to patients with breast cancer and lymphoma receiving doxorubicin was conducted within the National Cancer Institute Community Oncology Research Program across 31 sites in the United States. At pretreatment and then 6 and 24 months after initiating doxorubicin, we assessed left ventricular (LV) volumes, strain, mass, and LVEF through cardiac magnetic resonance imaging, along with cognitive function and serum markers of inflammation. The primary outcome was the difference in 24-month LVEF between placebo and treatment groups, adjusted for pretreatment LVEF. RESULTS: A total of 279 participants were enrolled in the trial. Participants had a mean (±SD) age of 49±12 years; 92% were women; and 83% were White. The mean (±SD) LVEF values were 61.7±5.5% before treatment and 57.4±6.8% at 24 months in the placebo group and 62.6±6.4% before treatment and 57.7±5.6% at 24 months in the atorvastatin group. On the basis of a multiple imputed data set for missing data and adjusted for each individual's pretreatment LVEF, 24-month declines in LVEF averaged 3.3±0.6 percentage points and 3.2±0.7 percentage points, for those randomly assigned to placebo versus statins, respectively (P=0.93). Across both treatment arms, similar percentages of individuals experienced changes of more than 10 percentage points in LVEF, LV strain, LV mass, cognition, and inflammation biomarkers, including among those with greater than 90% drug compliance. CONCLUSIONS: In patients with breast cancer and lymphoma with no existing indication for statin therapy, prospective statin administration did not affect LVEF declines 2 years after doxorubicin. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01988571.).

Simplified assay for VWF cleaving protease (ADAMTS13) activity and inhibitor in plasma.

The absence of VWF cleaving protease activity (VWFcp, ADAMTS13) has recently been identified as a central component in the pathogenesis of TTP. Several assays for the measurement of ADAMTS13 activity have been described, but most are cumbersome and employ techniques not easily adapted to routine laboratories. Thus, ADAMTS13 assays are available at only a few reference or research laboratories. Prompt identification of absent or impaired ADAMTS13 activity could prove invaluable to clinical decision-making regarding diagnosis and treatment of suspected TTP patients. We describe an assay for ADAMTS13 that uses a commercial source of VWF substrate and obviates dialysis for sample and substrate preparation. Patient and normal plasma are prepared by desalting over Micro-Spin columns, and barium is added to activate the cleaving protease. Humate-P(R) is prepared over a desalting column and reconstituted in urea prior to use as the exogenous VWF substrate. Desalted plasma is mixed with prepared substrate, and digestion is carried out at 37 degrees C. Maximum sensitivity to very low levels of enzyme activity is achieved by using undiluted plasma and allowing digestion to proceed for 14 hr. The extent of VWF multimer cleavage is then demonstrated by Western blot. We used this assay to analyze VWF cleaving protease activity in plasma samples from 30 patients treated at our institution for TTP. Plasma from patients lacking ADAMTS13 was incubated with PNP and then analyzed by the same methods to determine the presence of an inhibitor. Our results indicate that the assay is suitable for providing timely information regarding ADAMTS13 activity for the diagnosis and treatment of patients with suspected TTP.