Temporal Trends in Treatment and Outcomes of Endometrial Carcinoma in the United States, 2005-2020.

Endometrial cancer has continued to see a rising incidence in the US over the years. The main aim of this study was to assess current trends in patients' characteristics and outcomes of treatment for endometrial carcinoma over 16 years. A dataset from the National Cancer Database (NCDB) for patients diagnosed with endometrial carcinoma from 2005 to 2020 was used in this retrospective, case series study. The main outcomes and measures of interest included tumor characteristics, hospitalization, treatments, mortality, and overall survival. Then, 569,817 patients who were diagnosed with endometrial carcinoma were included in this study. The mean (SD) age at diagnosis was 62.7 (11.6) years, but 66,184 patients (11.6%) were younger than 50 years, indicating that more patients are getting diagnosed at younger ages. Of the patients studied, 37,079 (6.3%) were Hispanic, 52,801 (9.3%) were non-Hispanic Black, 432,058 (75.8%) were non-Hispanic White, and 48,879 (8.6%) were other non-Hispanic. Patients in the 4th period from 2017 to 2020 were diagnosed more with stage IV (7.1% vs. 5.2% vs. 5.4% vs. 5.9%; p < 0.001) disease compared with those in the other three periods. More patients with severe comorbidities (Charlson Comorbidity Index score of three) were seen in period 4 compared to the first three periods (3.9% vs. ≤1.9%). Systemic chemotherapy use (14.1% vs. 17.7% vs. 20.4% vs. 21.1%; p < 0.001) and immunotherapy (0.01% vs. 0.01% vs. 0.2% vs. 1.1%; p < 0.001) significantly increased from period 1 to 4. The use of laparotomy decreased significantly from 42.1% in period 2 to 16.7% in period 4, while robotic surgery usage significantly increased from 41.5% in period 2 to 64.3% in period 4. The 30-day and 90-day mortality decreased from 0.6% in period 1 to 0.2% in period 4 and 1.4% in period 1 to 0.6% in period 4, respectively. Over the period studied, we found increased use of immunotherapy, chemotherapy, and minimally invasive surgery for the management of endometrial cancer. Overall, the time interval from cancer diagnosis to final surgery increased by about 6 days. The improvements observed in the outcomes examined can probably be associated with the treatment trends observed.

Cost-Effectiveness of Population-Based Multigene Testing for Breast and Ovarian Cancer Prevention.

Importance: The current method of BRCA testing for breast and ovarian cancer prevention, which is based on family history, often fails to identify many carriers of pathogenic variants. Population-based genetic testing offers a transformative approach in cancer prevention by allowing for proactive identification of any high-risk individuals and enabling early interventions. Objective: To assess the lifetime incremental effectiveness, costs, and cost-effectiveness of population-based multigene testing vs family history-based testing. Design, Setting, and Participants: This economic evaluation used a microsimulation model to assess the cost-effectiveness of multigene testing (BRCA1, BRCA2, and PALB2) for all women aged 30 to 35 years compared with the current standard of care that is family history based. Carriers of pathogenic variants were offered interventions, such as magnetic resonance imaging with or without mammography, chemoprevention, or risk-reducing mastectomy and salpingo-oophorectomy, to reduce cancer risk. A total of 2000 simulations were run on 1 000 000 women, using a lifetime time horizon and payer perspective, and costs were adjusted to 2022 US dollars. This study was conducted from September 1, 2020, to December 15, 2023. Main Outcomes and Measures: The main outcome measure was the incremental cost-effectiveness ratio (ICER), quantified as cost per quality-adjusted life-year (QALY) gained. Secondary outcomes included incremental cost, additional breast and ovarian cancer cases prevented, and excess deaths due to coronary heart disease (CHD). Results: The study assessed 1 000 000 simulated women aged 30 to 35 years in the US. In the base case, population-based multigene testing was more cost-effective compared with family history-based testing, with an ICER of $55 548 per QALY (95% CI, $47 288-$65 850 per QALY). Population-based multigene testing would be able to prevent an additional 1338 cases of breast cancer and 663 cases of ovarian cancer, but it would also result in 69 cases of excess CHD and 10 excess CHD deaths per million women. The probabilistic sensitivity analyses show that the probability that population-based multigene testing is cost-effective was 100%. When the cost of the multigene test exceeded $825, population-based testing was no longer cost-effective (ICER, $100 005 per QALY; 95% CI, $87 601-$11 6323). Conclusions and Relevance: In this economic analysis of population-based multigene testing, population-based testing was a more cost-effective strategy for the prevention of breast cancer and ovarian cancer when compared with the current family history-based testing strategy at the $100 000 per QALY willingness-to-pay threshold. These findings support the need for more comprehensive genetic testing strategies to identify pathogenic variant carriers and enable informed decision-making for personalized risk management.

One dose versus two doses of COVID-19 vaccine for the prevention of breakthrough infections among people previously infected with SARS-Cov-2.

Studies have suggested the effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 reinfection among those previously infected. However, it is not yet clear if one dose of the vaccine is enough to prevent breakthrough infections compared to two doses. Using data from Optum deidentified COVID-19 Electronic Health Record (EHR) data set, we assessed breakthrough infection risks in individuals previously infected, comparing those with one vaccine dose to those with two doses. Propensity scores were applied to mitigate confounding factors. Follow-up spanned 6 months, beginning 2 weeks postvaccination. Among 213 845 individuals, those receiving one vaccine dose had a significantly higher breakthrough infection risk than the two-dose group (HR 1.69, 95% CI 1.54-1.85). This pattern was observed across genders, racial/ethnic groups, age categories, and vaccine types. This study reveals a substantial disparity in the risk of breakthrough infections between individuals receiving one versus two doses of the COVID-19 vaccine, suggesting that a single dose may not provide adequate protection against reinfection.

Hepatocellular Carcinoma Surveillance among Individuals with Cirrhosis: Trends by Payer, Etiology, and Calendar Year, from a Statewide, Multi-Payer Dataset, 2010-2018.

BACKGROUND: Hepatocellular carcinoma (HCC) surveillance is underutilized, with <25% of individuals with cirrhosis receiving surveillance exams as recommended. The epidemiology of cirrhosis and HCC in the United States has also shifted in recent years, but little is known about recent trends in surveillance utilization. We characterized patterns of HCC surveillance by payer, cirrhosis etiology, and calendar year in insured individuals with cirrhosis. METHODS: We conducted a retrospective cohort study of individuals with cirrhosis using claims data from Medicare, Medicaid, and private insurance plans in North Carolina. We included individuals ≥ 18 years with a first occurrence of an ICD-9/10 code for cirrhosis between January 1, 2010, and June 30, 2018. The outcome was HCC surveillance by abdominal ultrasound, CT, or MRI. We estimated 1- and 2-year cumulative incidences for HCC surveillance and assessed longitudinal adherence to surveillance by computing the proportion of time covered (PTC). RESULTS: Among 46,052 individuals, 71% were enrolled through Medicare, 15% through Medicaid, and 14% through private insurance. The overall 1-year cumulative incidence of HCC surveillance was 49% and the 2-year cumulative incidence was 55%. For those with an initial screen in the first 6 months of their cirrhosis diagnosis, the median 2-year PTC was 67% (Q1, 38%; Q3, 100%). CONCLUSIONS: HCC surveillance initiation after cirrhosis diagnosis remains low, though it has improved slightly over time, particularly among individuals with Medicaid. IMPACT: This study provides insight into recent trends in HCC surveillance and highlights areas to target for future interventions, particularly among patients with nonviral etiologies.

Incomplete HPV Vaccination among Individuals Aged 27-45 Years in the United States: A Mixed-Effect Analysis of Individual and Contextual Factors.

Background: In the United States, the human papillomavirus (HPV) vaccine is approved for use in individuals up to age 45. Individuals 15 years and older require three doses of the vaccine to complete the recommended dosing series. Incomplete HPV vaccination rates (i.e., one or two doses) among those over age 26, however, remain high. This study examined the independent effects of individual- and neighborhood-level factors on incomplete HPV vaccination rates in the United States (U.S.) among those aged 27-45 years. Methods: This retrospective cohort study used administrative data from Optum's de-identified Clinformatics® Data Mart Database to identify individuals aged 27-45 years who received one or more doses of HPV vaccine between July 2019 and June 2022. Multilevel multivariable logistic regression models were applied to the data on 7662 individuals identified as being fully or partially vaccinated against HPV, nested within 3839 neighborhoods across the U.S. Results: Approximately half of the patients in this study (52.93%) were not completely vaccinated against HPV. After adjusting for all other covariates in the final model, being older than 30 years old decreased the odds of not completing the HPV vaccine series. Participants living in South-region neighborhoods of the U.S. had enhanced odds of not completing the vaccine series compared with those residing in Northeast-region neighborhoods (aOR 1.21; 95% CrI 1.03-1.42). There was significant clustering of incomplete HPV vaccination rates at the neighborhood level. Conclusions: This study revealed that individual- and neighborhood-level factors were associated with the risk of not completing the HPV vaccine series among individuals aged 27-45 years in the U.S. Interventions to improve HPV vaccination series completion rates for this age group should take into consideration both individual and contextual factors.

Incidence of human papillomavirus-related cancers among males and females aged 15-34 years in the United States.

Postmarket surveillance of the incidence of human papillomavirus (HPV)-related cancers is essential to monitor the effectiveness of HPV vaccines. We directly compared HPV-related cancer incidences during the pre- and postvaccine era to assess the effects of HPV vaccination among vaccine-eligible age groups in the United States using data from the US Cancer Statistics database. The 5-year average annual incidence rates for HPV-related cancers decreased in 2015-2019 compared with 2002-2006 among females aged 15-24 years and 25-34 years. Overall, a decrease in young males was not observed, whereas males aged 25-34 years experienced a slight decline in oropharyngeal squamous cell carcinoma between 2005-2009 and 2015-2019. Incidence rates for HPV-related cancers statistically significantly decreased in the vaccine era compared with the prevaccine era among females aged 15-34 years, suggesting the potential early effects of the introduction of HPV vaccination in the United States.

Patterns of first-line targeted therapy utilization and adherence among older adults diagnosed with metastatic renal cell carcinoma.

BACKGROUND: Despite the rapid approval of targeted therapies for metastatic renal cell carcinoma (mRCC) evidence on real world treatment patterns remains limited. This study evaluated patterns of first-line targeted therapy utilization and adherence in older adults, a population with a high burden of RCC. METHODS: 2093 patients aged ≥66 years with a primary diagnosis of mRCC were identified from United States (US)-based cancer registry and administrative claims data (2007-2015). We included only patients with de novo disease. We assessed the initiation of first-line targeted therapy within four months of diagnosis and persistence and adherence to targeted therapy, using the proportion of days covered (PDC). Multivariable logistic regression yielded adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to describe characteristics associated with targeted therapy versus no targeted therapy initiation and for high (≥80% PDC) versus low adherence. RESULTS: 28.8% of patients received first-line targeted therapy within four months of diagnosis, with the proportion of patients receiving targeted therapy increasing over time. Older age (one-year increment OR:0.95 95%CI 0.93, 0.97), high comorbidity burden (OR:0.65 95%CI0.46, 0.93) and clear cell histology (OR:1.54 95%CI 1.19, 2.00) were associated with targeted therapy initiation. 48.2% of patients exhibited a high PDC to oral targeted therapy at 120 days, which was attenuated with inclusion of patients who died during the time period (34.2% PDC ≥80%). CONCLUSION: Increasing age, high comorbidity burden and non-clear cell histology were associated with decreased targeted therapy initiation among patients with de novo mRCC. Our findings suggest adherence to oral therapies was low; future research exploring the mechanisms and impact of low adherence in this older patient population is warranted.

Polypharmacy and medication use by cancer history in a nationally representative group of adults in the USA, 2003-2014.

PURPOSE: This study examines polypharmacy and prescription drug use patterns in cancer survivors, a growing population at risk for cancer sequelae and side effects from treatment, which can arise months or even years following diagnosis. Survivors may experience greater medication burden than the general population, increasing concerns for polypharmacy and subsequent risks of drug interactions and non-adherence. METHODS: Using the National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2014, we examined the association between a cancer history and presence of polypharmacy (5+ medications). We estimated prevalence ratios and prevalence differences for polypharmacy comparing those with and without a cancer history using binomial regression models and propensity score (PS) weighting to account for baseline differences between groups. RESULTS: We identified 32,238 adults aged 20 years or older; 1899 had cancer (excluding non-melanoma skin) at least 1 year before the survey. Overall, polypharmacy prevalence was 13% and 35% in those with and without a cancer history, respectively. After PS weighting, the polypharmacy prevalence was 1.26 times higher among those with versus without a cancer history (weighted prevalence ratio, 1.26; 95% CI, 1.18, 1.35). In sub-group analyses, the weighted prevalence ratio was largest for those 20-39 years old at survey (2.78; 95% CI, 1.71, 4.53), and the weighted prevalence difference was largest for those 40-64 years old at survey (9.35%; 95% CI, 5.70%, 13.01%). CONCLUSIONS/IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors of all ages take more medications than those without cancer history and may benefit from discussions with providers about age-tailored medication use management.

The underreporting of phase III chemo-therapeutic clinical trial data of older patients with cancer: A systematic review.

PURPOSE: Inspired by the American Society of Clinical Oncology's recommendations to strengthen the evidence base for older adults with cancer, the purpose of this systematic review is to identify the reporting of treatment efficacy and adverse events specific to older adults with cancer in Phase III chemo-therapeutic clinical trials. This review also investigates the frequency with which these data points were reported in the literature to identify gaps in reporting and opportunities to expand the knowledge base on clinical outcomes for older adults with cancer. METHODS: Chemo-therapeutic clinical trial data published from July 1, 2016 to June 30, 2017 was reviewed. Manuscripts (n = 929) were identified based on keyword searches of EMBASE and PubMed. After removal of duplicates (n = 116) and articles that did not meet this study's inclusion criteria (n = 654), 159 articles were identified for review. RESULTS: Reviewed papers were published in 36 different scientific journals and included twenty-five different cancer types. Of the 159 articles, 117 (73.6%) reported age-specific medians and 75 (47.2%) included stratifications of data by age. Treatment efficacy was reported in 96.2% of the articles with 39.9% reporting effectiveness of treatment by age. Reporting of adverse events was included in 84.9% of the articles with only 8.9% reporting these events stratified by age. CONCLUSION: Results suggest inadequate reporting of treatment efficacy and adverse events as well as basic descriptive statistics about the age distribution of study subjects. Conscious efforts are needed to address these deficiencies at every level of planning and conducting clinical trials as wells as reporting outcomes stratified by age. Ultimately, standardized reporting could lead to improved treatment decisions and outcomes for older adults with cancer.

Association between Concomitant Use of Hydrochlorothiazide and Adverse Chemotherapy-Related Events among Older Women with Breast Cancer Treated with Cyclophosphamide.

BACKGROUND: The pharmacy reference database, Micromedex, lists concomitant hydrochlorothiazide and cyclophosphamide use as a potential, major drug-drug interaction (DDI), although only one small, single-center study supports this claim. Our objective was to estimate associations between this potential DDI and two adverse chemotherapy-related events, neutropenia-related hospitalizations and treatment regimen discontinuation, among a cohort of women with breast cancer initiating adjuvant chemotherapy containing cyclophosphamide. METHODS: Using linked Surveillance, Epidemiology, and End Results Program (SEER)-Medicare data, we included women 66 years and older with breast cancer diagnosis between 2007 and 2011, who initiated a regimen containing cyclophosphamide. Risk ratios (RR) and 95% confidence intervals for adverse outcomes comparing women exposed versus unexposed to the potential DDI were assessed using modified multivariable Poisson regression adjusting for potential confounders. RESULTS: In total, 27% of women receiving cyclophosphamide treatment were exposed to concomitant hydrochlorothiazide, of which 11% experienced a neutropenia-related hospitalization and 21% discontinued their chemotherapy regimen prior to completion. Adjusted risks of both adverse events were similar between those exposed and unexposed to the potential DDI [neutropenia-related hospitalization: adjusted RR (aRR) = 0.92 (0.70-1.21); treatment discontinuation: aRR = 1.00 (0.96-1.05)]. CONCLUSIONS: Our results do not support an association between concomitant hydrochlorothiazide use and two clinically relevant adverse chemotherapy-related events. IMPACT: Our results support reassessing and potentially lowering severity of this potential interaction in drug reference databases.

Trends in Cigarette Smoking Prevalence Among Refinery and Petrochemical Plant Workers, 1950 to 1999.

OBJECTIVE: Smoking is a potential confounder in studies of workplace exposures and smoking-related disease, but little data exist to quantitatively adjust for smoking in statistical models. METHODS: We estimated smoking prevalence trends between 1950 and 1999 for 12,299 female and 43,307 male hourly and salaried petrochemical workers using company physical examination data. RESULTS: Nearly half of hourly male and female employees smoked during the study period, compared with 38% of salaried males and 29% of females. Smoking prevalence in the 1950s reached 80% and 66% among female and male hourly workers, respectively, significantly higher than the US general population. CONCLUSIONS: As hourly workers typically comprise higher exposure groups and expected case counts are typically generated from the US general population, biased risk estimates may result from standardized mortality ratio analyses if smoking rate differences are not accounted for.

Polypharmacy and Incident Frailty in a Longitudinal Community-Based Cohort Study.

OBJECTIVES: Polypharmacy may affect frailty, a common and costly condition among older adults. Frailty prevalence is elevated among racial/ethnic minorities and persons living in the US South, and research is needed to inform future pharmacologic interventions in these populations. Our aim was to quantify the prevalence of frailty and polypharmacy, and to estimate the association between polypharmacy and incident frailty. DESIGN: Prospective cohort study. SETTING: A community-based cohort study of adults residing in Johnston County, North Carolina. PARTICIPANTS: White and African American adults aged 50 to 95 years (n=1697). MEASUREMENTS: At each study visit, all prescription and over-the-counter medications were recorded. We calculated annual polypharmacy (5-9 medications) and excessive polypharmacy (≥10 medications) prevalence at the 2006-2010 visit (n = 1697) and operationalized the Fried frailty phenotype to describe prevalent and incident frailty at two consecutive visits (2006-2010 and 2013-2015). We estimated risk ratios (RRs) and 95% confidence intervals (CIs) for the association between polypharmacy and incident frailty using weighted log-binomial regression to account for measured confounding and attrition using inverse probability of treatment and attrition weights, respectively. RESULTS: At the 2006-2010 visit, 678 (41%) and 260 (16%) participants were exposed to polypharmacy and excessive polypharmacy, respectively. Overall, 353 (21%) participants and 180 (21%) participants were frail at the 2006-2010 and 2013-2015 visits, respectively. Frailty was more common among participants identifying as white, women, and having less educational attainment relative to those without these characteristics. Incident frailty at the 2013-2015 visit was 15% (mean follow-up = 5.5 years). Our results suggest that polypharmacy is positively associated with incident frailty (weighted RR = 1.4; 95% CI = .9-2.0), yet estimates are imprecise and should be interpreted with caution. CONCLUSION: Consistent with the current weight of evidence, our results suggest an association between polypharmacy and incident frailty. Prospective studies evaluating deprescribing interventions are needed to clarify whether reducing polypharmacy decreases frailty incidence. J Am Geriatr Soc 67:2482-2489, 2019.

Breast cancer stage variation and survival in association with insurance status and sociodemographic factors in US women 18 to 64 years old.

BACKGROUND: Few population-based studies have examined the association between health insurance status and breast cancer stage at diagnosis and survival. The degree to which sociodemographic characteristics explain this association is also unclear. This study examined associations between insurance status and sociodemographic characteristics and stage at diagnosis and survival. METHODS: Using the Surveillance, Epidemiology, and End Results 18 registries database, we identified 52,048 women aged 18 to 64 years who were diagnosed with breast cancer in 2007 and 2008. Associations between insurance status and sociodemographic variables and stage at diagnosis and survival were examined with logistic and Cox proportional hazards regression models to calculate adjusted odds ratios (ORs), hazard ratios (HRs), and associated confidence intervals (CIs). RESULTS: The odds of a later stage breast cancer diagnosis were increased in women with Medicaid (OR, 2.36; 95% CI, 2.19-2.55) and no insurance (OR, 2.64; 95% CI, 2.29-3.04) versus private insurance, in women who had reported black race (OR, 1.18; 95% CI, 1.09-1.28) versus white race, in women who were unmarried (OR, 1.25; 95% CI, 1.18-1.33) versus married at diagnosis, and in women who were 18 to 39 years old (OR, 1.29; 95% CI, 1.18-1.41) versus 40 to 64 years old at diagnosis. The hazard of breast cancer death was increased in association with Medicaid (HR, 1.40; 95% CI, 1.30-1.51) and no insurance (HR, 1.61; 95% CI, 1.41-1.84) versus private insurance, with reported black race (HR, 1.39; 95% CI, 1.29-1.50) versus reported white race, and with being unmarried (HR, 1.19; 95% CI, 1.12-1.27) versus being married. CONCLUSIONS: Insurance status at diagnosis and sociodemographic factors are associated with breast cancer mortality. Factors underlying these associations warrant further study. Cancer 2017;123:3125-31. © 2017 American Cancer Society.