Yang, Dongyun

AbstractWe conducted a surveillance epidemiology and end results (SEER)‐based analysis to describe the incidence and characteristics of second primary acute lymphoblastic leukemia (sALL) among adults (≥18 years) with a history of primary malignancies (1M). Standardized incidence ratios (SIRs) of sALL cases were calculated by site and 1M stage. We also evaluated the differences in 5‐year sALL survival by age, site, and extent of 1M, latency of sALL after 1M, and evidence of underlying racial/ethnic disparity. We identified 10,956 patients with de‐novo/primary acute lymphoblastic leukemia (1ALL) and 772 with sALL. Women (49.1% vs. 42.9%), white patients (72.0% vs. 59.5%), older patients (58.8% vs. 25.2%; age ≥65 years), and patients diagnosed between 2003 and 2012 (66.8% vs. 53.9%) had a higher proportion of sALL compared with 1ALL. There was a significantly inferior median 5‐year survival for sALL patients compared to 1ALL (6 vs. 15 months; HR 1.20, 95% CI 1.10–1.31, P < 0.001). The median latency period was 60.0 months; the most common 1M among sALL patients were breast (17.9%) and prostate (17.4%). Patients with any 1M were at increased risk of developing sALL (SIR 1.76, 95% CI 1.58–1.95, P < 0.001). Hematological‐1M sites had significantly higher SIRs (hematological‐SIR 7.35; solid‐SIR 1.33; P < 0.001). We observed a significant increase in sALL incidence after a 1M and a significantly worse 5‐year survival with different demographic characteristics from 1ALL. There is a need to define appropriate screening methods for patients surviving their primary cancer.

29 Background: Better biomarkers are needed in prostate cancer (PCa) to predict disease recurrence and guide optimal therapy. We investigated whether genes associated with a highly tumorigenic, drug resistant, progenitor cancer phenotype impact PCa biology and clinical outcomes in localized disease. Methods: Genes associated with self-renewal, drug resistance, and tumorigenicity were analyzed by qRT-PCR on PCa mRNA from radical prostatectomy (RP) specimens (+/- disease recurrence). Wilcoxon rank sum two-sample test, multivariable recursive partitioning, and bootstrap internal validation measured and confirmed associations with recurrence. Further validation was conducted in external cohorts and in-silico, as well as in vitro and in vivo using siRNA knockdown and lentiviral overexpression to determined the effect of gene expression on PCa proliferation, invasion and tumor growth. Results: Four candidate genes were differentially expressed in PCa recurrence, and of these, low AXIN2 expression was internally validated. Validation in external cohorts demonstrated low AXIN2 expression was associated with more aggressive prostate cancer and was independently associated with biochemical recurrence (BCR) and metastasis-free survival (MFS) after RP. In vitro, low AXIN2 expression was associated with a cancer stem-like cell-surface signature, and siRNA knockdown of AXIN2 resulted in significantly greater invasiveness. Conversely, ectopic overexpression of AXIN2 significantly reduced cell proliferation and tumor growth in mice. Conclusions: Low AXIN2 expression was associated with PCa recurrence after RP in our test population as well as in external validation cohorts. AXIN2 expression levels in PCa cells significantly impacted invasiveness, proliferation and tumor growth. AXIN2 represents a putative biomarker and potential therapeutic target in early prostate cancer.

BACKGROUNDNational Cancer Institute (NCI)/National Comprehensive Cancer Network (NCCN)–designated cancer centers (CCs) offer patients state‐of‐the‐art treatment, but their impact on multiple myeloma (MM) patient outcomes has not been evaluated.METHODSAdult MM patients diagnosed between 1973 and 2011 were identified from the Surveillance, Epidemiology, and End Results database and were stratified by the county of residence at the time of diagnosis and the year of CC designation. The influence of NCI/NCCN CC access, race, and the year of diagnosis on overall survival (OS) was evaluated with a Cox regression model.RESULTSA statistically significant OS improvement was noted in patients diagnosed after 1995 with access to 2 or more NCI CCs overall (P = .002 for 1996‐2002; P < .001 for 2003‐2011) and by race for whites (hazard ratio [HR] for 1996‐2002, 0.85; 95% confidence interval [CI], 0.78‐0.91; HR for 2003‐2011, 0.85; 95% CI, 0.79‐0.91) but not for nonwhites. For NCCN access, improvement was seen in 1996‐2002 (P = .003), in 2003‐2011 (P < .001), and by race for whites (HR, 0.917; 95% CI, 0.88‐0.95) and nonwhites (0.94; 95% CI, 0.89‐0.99), but within nonwhites, this was true only for African Americans (AAs; HR, 0.88; 95% CI, 0.81‐0.97) and not for Asians, Hispanics, or Native Americans.CONCLUSIONSImprovement in OS was seen in MM patients diagnosed after 1995 with access to 1 NCCN CC or 2 or more NCI CCs. NCI access benefited only whites, whereas NCCN access benefited only white and AA patients. No OS benefit was seen for any subgroup with access to only 1 NCI center. Eliminating racial disparities in health care access and utilization is needed to improve outcomes. Cancer 2016;122:618–625. © 2015 American Cancer Society.

SummaryStudies of ethnic disparities in malignancies have revealed variation in clinical outcomes. In multiple myeloma (MM), previous literature has focused only on patients of Caucasian and African‐American (AA) descent. We present a Surveillance Epidemiology and End Results (SEER)‐based outcome analysis of MM patients from a broader range of ethnicities, representing current United States demographics. The SEER 17 Registry data was utilized to analyse adult MM patients diagnosed since 1992 (n = 37 963), as patients of other ethnicities were not well represented prior to that. Overall survival (OS) and myeloma‐specific survival (MSS) were compared across different ethnicities stratified by year of diagnosis, registry identification, age, sex and marital‐status. Hispanics had the youngest median age at diagnosis (65 years) and Whites had the oldest (71 years) (P < 0·001). Increased age at diagnosis was an independent predictor of decreased OS and MSS. Asians had the best median OS (2·7 years) and MSS (4·1 years), while Hispanics had the worst median OS (2·4 years). These trends were more pronounced in patients ≥75 years. Cumulative survival benefit over successive years was largest among Whites (1·3 years) and smallest among Asians (0·5 years). These disparities may be secondary to multifactorial causes that need to be explored and should be considered for optimal triaging of healthcare resources.