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Background: Treatments for multiple myeloma (MM) have evolved over time and improved MM survival. While racial differences in MM treatment and prognosis between non‐Hispanic African American (NHAA) and non‐Hispanic White (NHW) patients are well‐established, it is unclear whether they have persisted after the introduction of novel agents. Methods: Using the Surveillance, Epidemiology, and End Results‐Medicare linked database, our study investigated racial difference in the receipt of treatment within 1 year following diagnosis and assessed survival outcomes among Medicare beneficiaries (≥66 years) diagnosed with MM from 2007 to 2017. We applied multivariable Cox proportional hazards models to estimate the association between race and survival and presented hazard ratios (HRs). Results: Of 2094 NHAA and 11,983 NHW older patients with MM, 59.5% and 64.8% received treatment during the first year, respectively. Discrepancy in the proportion of patients receiving treatment between the two groups increased from 2.9% in 2007 to 2009 to 6.9% in 2014–2017. After controlling for relevant factors, patients who received treatment within the first year had lower mortality than those who did not (HR = 0.90, 95% confidence interval [CI]: 0.86–0.94). NHAA patients had a lower probability to receive treatments during the first year than NHW patients (HR = 0.91, 95% CI: 0.85–0.97) but had lower mortality (HR = 0.94, 95% CI: 0.88–1.00). The lower mortality was only observed among patients who received no treatment (HR = 0.84, 95% CI: 0.77–0.93); NHAA and NHW patients who received treatment had similar survival (p = 0.63). Conclusions: The increasing racial disparity in treatment utilization over time is concerning. Efforts are needed to eliminate the barriers of receiving treatment. [ABSTRACT FROM AUTHOR]

Background: Polycythemia vera (PV) and essential thrombocythemia (ET) are linked to increased risk of cardiovascular morbidity and mortality. In addition to the reduction in of arterial thrombotic events, statins may prevent venous thrombosis including among patients with cancer. As previous registry‐ and claims‐based studies revealed that the use of statins may improve the survival of patients with various malignancies we evaluated their impact on outcomes of older adults with PV and ET. Methods: We identified 4010 older adults (aged 66–99 years at diagnosis) with PV (n = 1809) and ET (n = 2201) in a population‐based cohort study using the Surveillance, Epidemiology, and End Results‐Medicare database with median follow‐up of 3.92 (interquartile range: 2.58–5.75) years. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) approaches were utilized to assess potential association between statins and overall survival. Multivariable competing risk models with death as a competing risk were used to evaluate possible relationship between statins and the incidence of thrombosis. Results: 55.8% of the patients used statins within the first year after PV/ET diagnosis, and statin use was associated with a 22% reduction in all‐cause mortality (PSM: hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.63–0.98, p = 0.03; IPTW: HR = 0.79, 95% CI: 0.64–0.97, p = 0.03). Statins also reduced the risk of thrombosis in this patient population (PSM: HR = 0.63, 95% CI: 0.51–0.78, p < 0.01; IPTW: HR = 0.57, 95% CI: 0.49–0.66, p < 0.01) as well as in PV and ET subgroups. Conclusions: These findings suggest that it may be important to incorporate statins into the therapeutic strategy for older adults with PV and ET. [ABSTRACT FROM AUTHOR]

Existing studies regarding the role of DNA methyltransferase inhibitors (DNMTi) and lenalidomide in refractory anemia with ring sideroblasts (RARS) are limited. Using the surveillance, epidemiology, and end results-medicare database, we assembled a population-based cohort of older adults diagnosed with non-del(5q) lower-risk myelodysplastic syndromes during 2007–2015. Of 2167 patients, 30% had RARS. About 16% of RARS and non- ring sideroblasts (RS) patients received DNMTi. RARS patients were more likely to receive lenalidomide (11.1% vs. 7.1%, p < 0.01). Among patients who were transfusion-dependent at treatment initiation, 55.6% of those treated with DNMTi only and 42.5% treated with lenalidomide only achieved red blood cell transfusion independence (RBC-TI) for a median duration of 21 and 12 weeks, respectively. RS status did not impact rate of RBC-TI. RARS patients had a significantly better survival, and the median survival of RARS patients varied by treatment group. In this population-based study of older RARS patients, DNMTi and lenalidomide were clinically active. [ABSTRACT FROM AUTHOR]

Hypomethylating agents (HMA) showed overall survival (OS) benefits in patients with higher-risk myelodysplastic syndromes (HR-MDS) in clinical trials. We conducted a retrospective cohort study of Surveillance, Epidemiology, and End Results (SEER)-Medicare data of patients ≥66 years diagnosed with refractory anemia with excess blasts (RAEB), a proxy for HR-MDS, in 01/2001–04/2004 (pre-period) or 01/2006–12/2011 (post-period). Association between post-period diagnosis and OS was examined using propensity scores (PS)-matched samples. Among 1876 RAEB patients, median OS was 9 months and 30.8% received HMAs (3.6% in pre-period; 43.0% in post-period) with no association between post-period diagnosis and OS. In the top PS quartile, post-period diagnosis was associated with a 74% lower risk of death (Hazard ratio [HR] = 0.26, 95%-CI: 0.10–0.69, p = 0.007), while outcomes were worse in the lowest PS quartile (HR = 2.80, 95%-CI: 1.06–7.36, p = 0.037). HMA lead to a 3-month OS benefit for patients most likely to receive HMA but not for unselected RAEB cohort. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a malignant disorder of the bone marrow which is characterized by the clonal expansion and differentiation arrest of myeloid progenitor cells. The age-adjusted incidence of AML is 4.3 per 100,000 annually in the United States (US). Incidence increases with age with a median age at diagnosis of 68 years in the US. The etiology of AML is heterogeneous. In some patients, prior exposure to therapeutic, occupational or environmental DNA-damaging agents is implicated, but most cases of AML remain without a clear etiology. AML is the most common form of acute leukemia in adults and has the shortest survival (5-year survival = 24%). Curative therapies, including intensive chemotherapy and allogeneic stem cell transplantation, are generally applicable to a minority of patients who are younger and fit, while most older individuals exhibit poor prognosis and survival. Differences in patient outcomes are influenced by disease characteristics, access to care including active therapies and supportive care, and other factors. After many years without therapeutic advances, several new therapies have been approved and are expected to impact patient outcomes, especially for older patients and those with refractory disease. [ABSTRACT FROM AUTHOR]

Background: Despite the approval of azacitidine in 2004 and the approval of decitabine in 2006 in the United States for chronic myelomonocytic leukemia (CMML), the overall survival (OS) benefit with hypomethylating agent (HMA) therapy is unclear.Methods: Older adults (age ≥ 66 years) who had been diagnosed with CMML from 2001 to 2011 were selected from the Surveillance, Epidemiology, and End Results-Medicare database, and propensity score matching was used to match patients who had been diagnosed after HMA approval (2007-2011) and had received HMA treatment with patients diagnosed before HMA approval (2001-2003). Cox proportional hazards models with the matched sample were used to assess the change in OS. A second matched cohort of patients who did not receive HMA after approval and patients diagnosed before HMA approval was used to evaluate survival change attributable to other potential differences between the 2 time periods, such as improved supportive care.Results: Among 1378 older adults diagnosed with CMML, the median OS was 13 months, and 18.8% received HMAs. In the primary matched analysis, with 225 HMA users diagnosed in 2007-2011 and 395 patients diagnosed in 2001-2003, the median OS times were 17 and 11 months, respectively (hazard ratio, 0.72; 95% confidence interval [CI], 0.58-0.91; P = .005). In a secondary analysis, the risk of death did not differ between 395 propensity score-matched HMA nonusers diagnosed in 2007-2011 and 484 patients diagnosed in 2001-2003 (hazard ratio, 1.09; 95% CI, 0.91-1.32; P = .34).Conclusions: Despite limited evidence, HMAs are commonly used to treat older CMML patients. The use of HMAs was associated with a 28% reduction in the risk of death in adjusted analyses. Improvements in supportive care do not appear to account for temporal improvements in OS. Cancer 2017;123:3754-3762. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Although newer treatments for myelodysplastic syndromes (MDS), particularly hypomethylating agents (HMAs), are expensive, it is unclear whether MDS-related costs of care are associated with overall survival. This study evaluated the relation between MDS-related costs and survival among Medicare beneficiaries with MDS.Methods: Eligible patients were identified from the Surveillance, Epidemiology, and End Results-Medicare database with codes for MDS from International Classification of Diseases for Oncology, 3rd edition. The patients were diagnosed between January 1, 2005 and December 31, 2011, were 66 years old or older, and were followed through death or the end of study (December 31, 2012). Medicare payments were used to estimate costs. Cumulative costs in a propensity score-matched group of cancer-free Medicare beneficiaries were subtracted from costs in the MDS cohort in each registry to estimate MDS-related costs. Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived from multivariate Cox proportional hazards models adjusted for patient and disease characteristics.Results: There were 8580 eligible patients, and 1,267 (14.7%) received HMAs. The overall 2-year survival rate was 48.7%, and the 2-year registry-specific MDS-related cost per patient ranged from $40,793 to $78,156 across 16 registries. The 2-year MDS-related cost was not associated with survival in the overall study population (first tertile, reference; second tertile, HR, 0.96; 95% CI, 0.89-1.04; P = .29; third tertile, HR, 0.98; 95% CI, 0.91-1.06; P = .64) or in subgroups of patients who did or did not receive HMAs.Conclusions: Medicare expenditures for elderly patients with MDS varied across registries but were not associated with survival. A lack of an association between costs and outcomes warrants additional research because it may help to identify potential areas for cost-saving interventions without compromising patient outcomes. Cancer 2016;122:1598-607. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background and Aim Doxorubicin-eluting bead transarterial chemoembolization ( DEB-TACE) is a novel locoregional treatment for unresectable hepatocellular carcinoma ( HCC). However, to date, the benefits of DEB-TACE versus conventional transarterial chemoembolization ( TACE) remain unclear. This meta-analysis was conducted to evaluate the efficacy and safety of the two treatments for patients with unresectable HCC. Methods We searched for relevant articles by means of computerized bibliographic search and complementary manual search. Objective tumor response, overall survival, and adverse events were then calculated and analyzed. Results A total of seven clinical studies with 700 participants were included in the current meta-analysis. Significantly better objective tumor response was found for DEB-TACE than for conventional TACE ( OR = 1.92, 95% CI [1.34, 2.77]; P = 0.0004), with relative risk difference of 0.15 [0.07, 0.24] ( P = 0.0003). One-year and 2-year survival rates were statistically significantly higher for DEB-TACE compared with conventional TACE (Peto OR, 95% CI: 0.64 [0.46, 0.89], P = 0.007; 0.61 [0.47, 0.80], P = 0.0003, respectively). Peto ORs of 6-month and 3-year survival were 0.72 [0.46, 1.14] ( P = 0.16) and 0.77 [0.55, 1.06] ( P = 0.11), respectively, showing no difference statistically. However, we could still find a tendency favoring DEB-TACE. Adverse side effects were similar in both groups, with postembolization syndrome occurring most commonly. Conclusions This meta-analysis shows that DEB-TACE provides significantly better tumor response compared with conventional TACE. One-year and 2-year survival are better with DEB-TACE. In addition, DEB-TACE is as safe as conventional TACE. Therefore, DEB-TACE is a better choice for HCC patients for whom curative treatments like liver transplantation and liver resection are not suitable. [ABSTRACT FROM AUTHOR]

Abstract: During 2004–2006, two hypomethylating agents (HMAs) were approved for the treatment of myelodysplastic syndromes (MDS) in the United States. We assessed the impact of HMAs on the cost of care and survival of MDS patients, by constructing a cohort of patients who were diagnosed during 2001–2007 (n =6556, age ≥66.5 years) and comparable non-cancer controls. We assessed MDS patients’ and controls’ Medicare expenditures to derive MDS-related cost. We evaluated the two-year survival of patients as a group and by major subtypes. Taking into account the survival probabilities of MDS, the expected MDS-related 5-year cost was $63,223 (95% confidence interval: $59,868–66,432 in 2009 dollars), higher than the reported comparable cost for any of the 18 most prevalent cancers in the United States. Compared with MDS patients diagnosed in the earlier period (January 2001–June 2004) who received no HMAs, patients diagnosed later (July 2004–December 2007) who received HMAs had a significantly higher 24-month cost ($97,977 vs. $42,628 in 2009 dollars) and an improved 24-month survival (especially among patients with refractory anemia or refractory anemia with excess blasts). The magnitude of the cost of care underscores a need for comparative cost-effectiveness studies to reduce the clinical and economic burden of MDS. [Copyright &y& Elsevier]

Abstract: Comorbid conditions have rarely been systematically studied among patients with myelodysplastic syndromes (MDS). We conducted a large population-based study to assess the role of comorbidity in the survival of newly diagnosed MDS patients. This study included 1708 MDS patients (age≥66 years) diagnosed in the US during 2001–2002, with follow-up through the end of 2004. Hazard ratios (HRs) were estimated using multivariate Cox proportional hazard models. The median survival time was approximately 18 months. Fifty one percent of MDS patients had comorbid conditions. Patients with comorbid conditions had significantly greater risk of death than those without comorbidities. The HR was 1.19 (95% confidence interval (CI): 1.05–1.36) and 1.77 (95% CI: 1.50–2.08) for those with a Charlson index of 1–2 and ≥ 3, respectively. The risk of death increases with Charlson index. MDS patients who have congestive heart failure or chronic obstructive pulmonary disease had significantly shorter survival than patients without those conditions, whereas diabetes did not appear to have an impact on survival. This study confirms comorbidity as a significant and independent determinant of MDS survival, and the findings underscore the importance to take comorbid conditions into account when assessing the prognosis of MDS. [Copyright &y& Elsevier]

The classical myeloproliferative neoplasms (MPNs), specifically chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), represent clonal myeloid disorders whose pathogenesis is driven by well-defined molecular abnormalities. In this comprehensive review, we summarize the epidemiological literature and present our own analysis of the most recent the Surveillance, Epidemiology, and End Results (SEER) program data through 2016. Older age and male gender are known risk factors for MPNs, but the potential etiological role of other variables is less established. The incidences of CML, PV, and ET are relatively similar at 1.0–2.0 per 100,000 person-years in the United States, while PMF is rarer with an incidence of 0.3 per 100,000 person-years. The availability of tyrosine kinase inhibitor therapy has dramatically improved CML patient outcomes and yield a life expectancy similar to the general population. Patients with PV or ET have better survival than PMF patients. [ABSTRACT FROM AUTHOR]

The c-Myc protein has been implicated in playing a pivotal role in regulating the expression of a large number of genes involved in many aspects of cellular function. Consistent with this view, embryos lacking the c-myc gene exhibit severe developmental defects and die before midgestation. Here, we show that Sox2Cre-mediated deletion of the conditional c-mycflox allele specifically in the epiblast (hence trophoectoderm and primitive endoderm structures are wild type) rescues the majority of developmental abnormalities previously characterized in c-myc knockout embryos, indicating that they are secondary defects and arise as a result of placental insufficiency. Epiblast-restricted c-Myc-null embryos appear morphologically normal and do not exhibit any obvious proliferation defects. Nonetheless, these embryos are severely anemic and die before E12. c-Myc-deficient embryos exhibit fetal liver hypoplasia, apoptosis of erythrocyte precursors and functionally defective definitive hematopoietic stem/progenitor cells. Specific deletion of c-mycflox in hemogenic or hepatocytic lineages validate the hematopoietic-specific requirement of c-Myc in the embryo proper and provide in vivo evidence to support a synergism between hematopoietic and liver development. Our results reveal for the first time that physiological levels of c-Myc are essential for cell survival and demonstrate that, in contrast to most other embryonic lineages, erythroblasts and hematopoietic stem/progenitor cells are particularly dependent on c-Myc function. [ABSTRACT FROM AUTHOR]

Background: The aberrant expression of microRNAs (miRNAs) is associated with a variety of diseases including cancers. In the present study, the miRNA expression profile was examined in astrocytoma, a malignant and prevalent intracranial tumour in adults. Methods: We screened the expression profile of 200 miRNAs in a training sample set consisting of 84 astrocytoma samples and 20 normal adjacent tissue (NAT) samples using the method of stem-loop quantitative RT-PCR. The significantly altered miRNAs were validated in another independent sample set consisting of 40 astrocytoma samples and 40 NAT samples. The correlation of the miRNA levels with survival in astrocytoma samples was estimated by performing Kaplan–Meier survival analysis and univariate/multivariate Cox proportional hazard regression analysis. Results: After a two-phase selection and validation process, seven miRNAs were found to have a significantly different expression profile in astrocytoma samples upon comparison to the NAT samples. Unsupervised clustering analysis further revealed the great potential of the 7-miRNA profile to differentiate between tumours and normal brain tissues. The down-regulation of hsa-miR-137 in astrocytomas was shown to be associated with advanced clinical stages of this disease. Using Kaplan–Meier survival analysis we showed that low expression of hsa-miR-181b or hsa-miR-106a, or high expression of hsa-miR-21 was significantly associated with poor patient survival. Moreover, Cox proportional hazard regression analysis revealed that this prognostic impact was independent of other clinicopathological factors. Conclusions: Our results suggest a great potential for the use of miRNA profiling as a powerful diagnostic and prognostic marker in defining the signature of astrocytomas and in predicting the post-surgical outcome. [Copyright &y& Elsevier]

To elucidate whether the interaction between Anxa2 and Stat3 could promote the progression of hepatocellular carcinoma (HCC) and that high co-expression of Anxa2 and Stat3 could predict poor prognosis in HCC patients. We investigated Anxa2 and Stat3 expression using Western blot analysis in 4 HCC and adjacent nontumor tissues and using immunohistochemistry in 100 patients' paraffin sections. Then we assessed the expression of Stat3, Anxa2 and co-expression of Stat3 and Anxa2 with relevant clinical pathological parameters and their prognostic value in HCC patients. The recurrence and overall survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. The prognostic analysis was carried out with univariate and multivariate Cox regressions models. The incidence of high Stat3 expression in HCC tissues (35%) was significantly higher than that in non-HCC tissues (8%) (P < 0.001). The same result was observed in Anxa2 (P < 0.001). Also, the overexpression of Stat3 or Anxa2 showed a significant relationship with the recurrence of the 100 HCC patients (P = 0.012; P = 0.003). Additionally, tumor size >3 cm in diameter, multiple tumor number, and the presence of microvascular tumor thrombus were also significantly associated with recurrence in 100 patients. Then, all enrolled patients were divided into four groups according to IHC score of Stat3 and Anxa2, and the results indicated a significant difference in recurrence time between the subgroups (P < 0.001). What's more, co-highexpression of Stat3 and Anxa2 was related to the presence of microvascular tumor thrombus (P = 0.003) and poor tumor differentiation (P < 0.001), but not relevant with other clinical features (All P > 0.05). The expression of Stat3, Anxa2, or co-high-expression of the two proteins was associated with HCC recurrence and survival. [ABSTRACT FROM AUTHOR]