Trends and Disparities in Curative-Intent Treatment for Early-Stage Non-Small Cell Lung Cancer: A Population-Based Analysis of Surgery and SBRT.

BACKGROUND: Despite the increasing adoption of stereotactic body radiotherapy (SBRT) as a recommended alternative for early-stage non-small cell lung cancer (NSCLC), population-based research on racial/ethnic disparities in curative-intent treatment accounting for SBRT remains limited. This study investigated trends and disparities in receiving curative-intent surgery and/or SBRT in a diverse, retrospective cohort. METHODS: Early-stage NSCLC cases (2005-2017) from the Florida cancer registry were linked to individual-level statewide discharge data containing comorbidities and specific treatment information. Joinpoint regression assessed trends in treatment receipt. Multivariable logistic regression examined associations between race/ethnicity and treatment type. RESULTS: Among 64,999 patients with early-stage NSCLC, 71.6% received curative-intent treatment (surgery and/or SBRT): 73.1%, 72.4%, and 60.3% among Hispanic, White, and Black patients, respectively (P < 0.01). SBRT use increased steeply from 2005 to 2007 and then by 7.9% annually from 2007 to 2017 (P < 0.01); curative-intent surgery remained stable from 2005 to 2014 before declining by 6.2% annually during 2014-2017 (P = 0.04). The Black-White disparity in receipt of curative-intent treatment was significant [ORadj, 0.65; 95% confidence interval (CI), 0.60-0.71]. Patients with Charlson comorbidity index (CCI)≥3 had 36% (ORadj, 0.64; 95% CI, 0.60-0.69) lower odds of receiving curative-intent surgery and no significant difference for SBRT (ORadj, 1.06; 95% CI, 0.93-1.20) compared with CCI = 0. CONCLUSIONS: Racial disparities in receiving curative-intent treatment for early-stage NSCLC persist despite the availability of SBRT, suggesting the full potential of curative-intent treatment for early-stage NSCLC remains unachieved. IMPACT: Addressing disparities in early-stage NSCLC requires addressing differential treatment patterns and enhancing accessibility to treatments like underutilized SBRT, particularly for high-comorbidity populations such as Black patients.

Florida-California Cancer Research, Education and Engagement (CaRE2) Health Equity Center: Structure, Innovations, and Initial Outcomes.

INTRODUCTION: The Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center is a triad partnership committed to increasing institutional capacity for cancer disparity research, the diversity of the cancer workforce, and community empowerment. This article provides an overview of the structure, process innovations, and initial outcomes from the first 4 years of the CaRE2 triad partnership. METHODS: CaRE2 serves diverse populations in Florida and California using a "molecule to the community and back" model. We prioritize research on the complex intersection of biological, environmental, and social determinants health, working together with scientific and health disparities communities, sharing expertise across institutions, bidirectional training, and community outreach. Partnership progress and outcomes were assessed using mixed methods and four Program Steering Committee meetings. RESULTS: Research capacity was increased through development of a Living Repository of 81 cancer model systems from minority patients for novel cancer drug development. CaRE2 funded 15 scientific projects resulting in 38 publications. Workforce diversity entailed supporting 94 cancer trainees (92 URM) and 34 ESIs (32 URM) who coauthored 313 CaRE2-related publications and received 48 grants. Community empowerment was promoted via outreaching to more than 3000 individuals, training 145 community cancer advocates (including 28 Community Scientist Advocates), and publishing 10 community reports. CaRE2 members and trainees together have published 639 articles, received 61 grants, and 57 awards. CONCLUSION: The CaRE2 partnership has achieved its initial aims. Infrastructure for translational cancer research was expanded at one partner institution, and cancer disparities research was expanded at the two cancer centers.

Statins utilization trends and expenditures in the U.S. before and after the implementation of the 2013 ACC/AHA guidelines.

Importance: Statins are drugs of choice in treating hyperlipidemia and preventing or reducing cardiovascular diseases. Purpose: Explore statins utilization and expenditure trends in the United States before and after the publication of the 2013 ACC/AHA guidelines. Method: A retrospective, cross-sectional study of US noninstitutionalized civilians was conducted using MEPS data from 2008 to 2019. Adults who were ≥ 40 years old and who reported taking statins were included in the study. Primary outcomes: Statins use patterns, total cost, and out-of-pocket spending in the general adults who reported taking statins medications. Expenditures were expressed in 2019 US dollars. Results: In this study, 409,804 individuals were eligible to be included (mean age [SE], 59 [0.1] years; 54% female). Of those participants, 22% reported taking statin therapy, and 11% of them filled only one statin prescription. The number of individuals in the general population who reported taking any statin climbed from 31 million (12%) in 2008-2009 to 92 million (35%) in 2018-2019, representing a 197% increase. After 2013, the number of individuals who used statins increased by 149%, from 37 million in 2012-2013 to 92 million users in 2018-2019. The annual number of statins prescriptions increased from 461 million to 818 million (77%; p = 0.000) between 2008 and 2019. Atorvastatin was the most prescribed medication in the statins class (36%), followed by simvastatin (34%). The moderate-intensity statins were the most used by the participants (60%). The total statins cost in 2013 was $8 billion and increased to $10 billion in 2019 (25%; p = 0.000). The total OOP expenditure trend sloped from $4.0 billion in the 2008-2009 cycle to $3.1 billion in 2018-2019. The average OOP paid by Asians was higher than that of other races at $141. Conclusion: The proportion of individuals who used statins significantly increased following the adoption of the 2013 ACC/AHA guidelines. The findings, however, demonstrated suboptimal prescribing trends of high-intensity statins, which need to be addressed by the stakeholders to maximize medication outcomes. Statins expenditures, especially the co-payments, significantly decreased. The results have shown that revised or new regulations have a substantial impact on the healthcare industry.

The Potential Effects of Implementing an Antibiotic Stewardship Program by Integrating It with Medication Therapy Service in a Low-Income Serving Clinic - A Single-Center Experience.

Background: Bacterial antimicrobial resistance (AMR) is a leading cause of mortality worldwide. Although AMR is common in low-income communities, there is limited evidence of the effect of antibiotic stewardship programs in low-income communities in the United States. Objectives: Our goal is to assess the effects of implementing pharmacist-led ASP by integrating it with medication therapy management service (MTM) in a low-income serving clinic. We evaluated the following 1) antibiotic prescriptions per 1000 patients, 2) the frequency of clinic (office) visits 30-day post-index clinic visits for recurring infections. Methods: To achieve our goal, we conducted a pre-post, quasi-experimental intervention study using an interrupted time-series analysis to assess the following: 1) antibiotic prescriptions per 1000 patients and the 2) frequency of office visits (including telehealth) within 30-day post-index clinic visits associated with recurrent infection. Results: Our findings revealed that the long-term effect of our antibiotic stewardship program intervention was associated with 63.69% reduction in antibiotic prescriptions per 1000 patients (change in slope = -0.173, [95% CI: (-0.30, -0.05)], P < 0.007) and a reduction in the frequency of office visits within 30-day post-index clinic visits by 67.27% (change in slope = -2.043, [95% CI: (-3.84, -0.24)], P < 0.028). Conclusion: Implementing antibiotic stewardship programs is feasible for clinics serving low-income populations. It was associated with a reduction in antibiotic prescriptions and preventable clinic (office) visits within 30 days due to infection recurrence.

Exploratory Analysis of Survival and Mortality Rates among Older Lung Cancer Patients Utilizing Different Treatment Modalities.

Objective: To explore the impact of different lung cancer treatment modalities on survival time and mortality rates in older patients. Methods: The Surveillance Epidemiology and End Results (SEER) database was used to identify lung cancer patients aged ≥50 years old in the United States. Descriptive statistics and trend charts from 2000 to 2016 were generated. Regression analysis was performed among lung cancer patients to explore the association between survival time and treatment utilization (chemotherapy, radiation, and surgery). A regression model was also applied to explore the association between treatment modalities and odds of dying. Results: A total of 826,217 patients were diagnosed with lung cancer between 2000-2016. The number of lung cancer cases increased by 7%, and the average annual frequency was 48,529 cases per year. Survival, mortality, and treatment utilization varied over the years based on demographic, clinical characteristics, and social status. Five-year survival rate was less than 10% among the study population, and 84% of included lung cancer patients died. Chemotherapy was more commonly used (62%), followed by radiation (35%) and surgical interventions (22%). Chemotherapy and surgery showed a survival advantage. The odds of dying were two times higher among patients treated with surgery than those who were not (OR: 2.62, 95%Cl: 2.58-2.67). Conclusion: This study highlighted the importance of considering treatment modalities and individual patient characteristics, which may impact survival times and mortality rates among older lung cancer patients.

The association between etiology of hepatocellular carcinoma and race-ethnicity in Florida.

BACKGROUND AND AIM: The incidence of hepatocellular carcinoma (HCC) has risen considerably in the US since 1980. The main causes include metabolic disorders (NAFLD, diabetes, obesity, metabolic syndrome), alcohol-related disease (ALD) and hepatitis C and B virus infections (HCV, HBV). Etiology-specific HCC incidence rates by detailed race-ethnicity are needed to improve HCC control and prevention efforts. METHODS: All HCC cases diagnosed in Florida during 2014-2015 were linked to statewide hospital discharge data to determine etiology. Age-specific and age-adjusted rates were used to assess the intersection between etiology and detailed racial-ethnicities, including White, African American, Afro-Caribbean, Asian, Cuban, Puerto Rican and Continental Hispanic (Mexican, South and Central American). RESULTS: Of 3666 HCC cases, 2594 matched with discharge data. HCV was the leading cause of HCC among men and women (50% and 43% respectively), followed by metabolic disorders (25% and 37%) and ALD (16% and 9%). Puerto Rican and African American men had the highest HCV-HCC rates, 7.9 and 6.3 per 100 000 respectively. Age-specific rates for HCV-HCC peaked among baby boomers (those born in 1945-1965). Metabolic-HCC rates were highest among populations above age 70 and among Continental Hispanics. Afro-Caribbean men had high rates of HBV-HCC, whereas Puerto Rican men had high ALD-HCC. CONCLUSIONS: HCC etiology is associated with specific race/ethnicity. While HCV-related HCC rates are projected to decrease soon, HCC will continue to affect Hispanics disproportionately, based on higher rates of metabolic-HCC (and ALD-HCC) among Continental Hispanics, who demographically represent 80% of all US Hispanics. Multifaceted approaches for HCC control and prevention are needed.

Risk of Cancer Death Among White, Black, and Hispanic Populations in South Florida.

BACKGROUND: The cancer burden in South Florida, with a population of more than 6 million with a heavily Hispanic and large Afro-Caribbean population, has not been quantified. METHODS: We analyzed 2012-2016 cancer mortality data from South Florida for white, Hispanic, and black populations with disaggregation for Cuban, Puerto Rican, South American, African American, and Afro-Caribbean groups. We calculated cancer site-specific and all-sites combined age-adjusted mortality rates, and we used negative binomial regression to determine mortality rate ratios to compare South Florida's cancer mortality rates with those of the rest of the nation. RESULTS: We analyzed 53,837 cancer deaths. Per 100,000 population, cancer mortality rates in South Florida were similar among white (173 per 100,000) and black (176 per 100,000) men and among white and black women (133 for both), and they were lowest among Hispanic men (151 per 100,000) and women (93 per 100,000). However, compared with their counterparts nationally, Hispanic residents in South Florida had higher cancer mortality rates, largely driven by Cuban residents, and mortality rates among white and black residents, especially male residents, were substantially lower. Liver cancer rates were high among white and Puerto Rican "baby boomers"; lung cancer mortality was low among all groups except Cuban men; cervical cancer was high among white, black, and Puerto Rican women. CONCLUSION: Cancer patterns are not monochromatic in all US regions; South Florida is distinctive. Meeting the needs of an aging diverse population presents challenges for all major metropolitan areas. Expanding surveillance, increasing minority participation in clinical trials, and investing in culturally specific community-based health promotion must continue.

Liver cancer: A leading cause of cancer death in the United States and the role of the 1945-1965 birth cohort by ethnicity.

Liver cancer is highly fatal and the most rapidly increasing cancer in the US, where chronic hepatitis C (HCV) infection is the leading etiology. HCV is particularly prevalent among the 1945-1965 birth cohort, the so-called "baby boomers". Focusing on this cohort-etiology link, we aim to characterize liver cancer patterns for 15 unique US populations: White, African American, Mexican Immigrant, Mexican American, Cuban and Chinese, among others. METHODS: Individual-level mortality data from 2012-2016 from the health departments of 3 large states - California, Florida, New York - were pooled to compute liver cancer mortality rates for each racial/ethnic group and for 2 birth cohorts of interest: "1945-1965 cohort" and "older cohort". RESULTS: Liver cancer is a major cause of cancer death among all US male groups and the leading cause in Mexican American men. Over 50% of the age-adjusted liver cancer mortality of White, African American, Mexican American, and Puerto Rican males came from the 1945-1965 birth cohort. In contrast, foreign-born male and all female populations had higher liver cancer mortality originating from the older cohort. Internationally, US White male baby boomers had a 49% higher liver cancer mortality rate than their counterparts in Europe (mortality rate ratio 1.49; 95% CI 1.43-1.56). CONCLUSIONS: Populations burdened disproportionately by liver cancer in the 1945-1965 cohort include US-born males who were all present in the US during the 1960s-1990s when significant HCV transmission took place; these individuals will benefit most from HCV screening and treatment. For the others, including all women, Asian subgroups, and especially burgeoning Hispanic immigrant populations, comprehensive liver cancer prevention efforts will require detailed study of the distribution of etiologies. LAY SUMMARY: Liver cancer, a major cause of cancer death among US males, is increasing. The causes of liver cancer are varied, including hepatitis C, hepatitis B, alcohol-related liver disease, and non-alcoholic fatty liver disease. Racial/ethnic groups are impacted differently, but the highest rates are seen among US-born men born between 1945-1965, the so-called "baby boomers", whether White, Black, or Hispanic, likely linked to the known high prevalence of hepatitis C infection among this cohort.

Non-tenera Contamination and the Economic Impact of SHELL Genetic Testing in the Malaysian Independent Oil Palm Industry.

Oil palm (Elaeis guineensis) is the most productive oil bearing crop worldwide. It has three fruit forms, namely dura (thick-shelled), pisifera (shell-less) and tenera (thin-shelled), which are controlled by the SHELL gene. The fruit forms exhibit monogenic co-dominant inheritance, where tenera is a hybrid obtained by crossing maternal dura and paternal pisifera palms. Commercial palm oil production is based on planting thin-shelled tenera palms, which typically yield 30% more oil than dura palms, while pisifera palms are female-sterile and have little to no palm oil yield. It is clear that tenera hybrids produce more oil than either parent due to single gene heterosis. The unintentional planting of dura or pisifera palms reduces overall yield and impacts land utilization that would otherwise be devoted to more productive tenera palms. Here, we identify three additional novel mutant alleles of the SHELL gene, which encode a type II MADS-box transcription factor, and determine oil yield via control of shell fruit form phenotype in a manner similar to two previously identified mutant SHELL alleles. Assays encompassing all five mutations account for all dura and pisifera palms analyzed. By assaying for these variants in 10,224 mature palms or seedlings, we report the first large scale accurate genotype-based determination of the fruit forms in independent oil palm planting sites and in the nurseries that supply them throughout Malaysia. The measured non-tenera contamination rate (10.9% overall on a weighted average basis) underscores the importance of SHELL genetic testing of seedlings prior to planting in production fields. By eliminating non-tenera contamination, comprehensive SHELL genetic testing can improve sustainability by increasing yield on existing planted lands. In addition, economic modeling demonstrates that SHELL gene testing will confer substantial annual economic gains to the oil palm industry, to Malaysian gross national income and to Malaysian government tax receipts.

Differences in Colorectal Cancer Outcomes by Race and Insurance.

Colorectal cancer (CRC) is the second most common cancer among African American women and the third most common cancer for African American men. The mortality rate from CRC is highest among African Americans compared to any other racial or ethnic group. Much of the disparity in mortality is likely due to diagnosis at later stages of the disease, which could result from unequal access to screening. The purpose of this study is to determine the impact of race and insurance status on CRC outcomes among CRC patients. Data were drawn from the Surveillance, Epidemiology, and End Results database. Logistic regressions models were used to examine the odds of receiving treatment after adjusting for insurance, race, and other variables. Cox proportional hazard models were used to measure the risk of CRC death after adjusting for sociodemographic and tumor characteristics when associating race and insurance with CRC-related death. Blacks were diagnosed at more advanced stages of disease than whites and had an increased risk of death from both colon and rectal cancers. Lacking insurance was associated with an increase in CRC related-deaths. Findings from this study could help profile and target patients with the greatest disparities in CRC health outcomes.

Engineered zinc-finger transcription factors activate OCT4 (POU5F1), SOX2, KLF4, c-MYC (MYC) and miR302/367.

Artificial transcription factors are powerful tools for regulating gene expression. Here we report results with engineered zinc-finger transcription factors (ZF-TFs) targeting four protein-coding genes, OCT4, SOX2, KLF4 and c-MYC, and one noncoding ribonucleic acid (RNA) gene, the microRNA (miRNA) miR302/367 cluster. We designed over 300 ZF-TFs whose targets lie within 1 kb of the transcriptional start sites (TSSs), screened them for increased messenger RNA or miRNA levels in transfected cells, and identified potent ZF-TF activators for each gene. Furthermore, we demonstrate that selected ZF-TFs function with alternative activation domains and in multiple cell lines. For OCT4, we expanded the target range to -2.5 kb and +500 bp relative to the TSS and identified additional active ZF-TFs, including three highly active ZF-TFs targeting distal enhancer, proximal enhancer and downstream from the proximal promoter. Chromatin immunoprecipitation (FLAG-ChIP) results indicate that several inactive ZF-TFs targeting within the same regulatory region bind as well as the most active ZF-TFs, suggesting that efficient binding within one of these regulatory regions may be necessary but not sufficient for activation. These results further our understanding of ZF-TF design principles and corroborate the use of ZF-TFs targeting enhancers and downstream from the TSS for transcriptional activation.