Mesothelioma: Scientific clues for prevention, diagnosis, and therapy.

Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.

Urinary glyphosate levels and association with mortality in the 2013-16 National Health and Nutrition Examination Survey.

OBJECTIVES: Glyphosate is the most commonly used herbicide in the USA; however, its safety is still under debate. We assessed glyphosate levels and their association with overall mortality in a representative sample of the US adult population from the 2013 to 2016 National Health and Nutrition Examination Survey. METHODS: We extracted data on urinary glyphosate (N = 2910) measured by ion chromatography isotope-dilution tandem mass spectrometry. Associations between glyphosate concentrations and demographic, lifestyle and other exposures were analyzed. Data were linked to public-use Mortality Files for 2019. RESULTS: The mean (STD) glyphosate level was 0.53 (0.59) ng/ml, with 25.7% of the subjects having glyphosate levels at or below the detection limit. At multivariate analysis, age and creatinine were associated with glyphosate urinary levels (both P < 0.0001). There was a borderline association between glyphosate levels and mortality (HRadj 1.33; 95% CI 0.99-1.77 P = 0.06). When 3,5,6-trichloropyridinol was excluded from the Cox model, glyphosate exhibits a significant association with mortality (HRadj 1.33; 95% CI 1.00-1.77; P = 0.0532). CONCLUSIONS: These nationally representative data suggest that recent exposure to glyphosate could be associated with increased mortality. More studies are necessary to understand population-level risk associated with the product, given its widespread use in agriculture.

Association of human papillomavirus genotype and phylogenic clade with oropharyngeal cancer outcomes.

BACKGROUND: Human papillomavirus (HPV)+ oropharynx cancer (OPC) has a more favorable prognosis than HPV-negative disease, but the impact of specific HPV genotype and phylogenic clade on patient outcomes is not well understood and has profound implications for treatment de-intensification. METHODS: The objective of this single-institution cohort study was to investigate the association of HPV genotype (16 vs high-risk non-16) and clade (A9 vs A7) with OPC outcomes. The primary endpoints were overall survival (OS) and event-free survival (EFS) in patients with M0 disease treated with curative intent. RESULTS: The cohort included 598 patients (87% HPV16, 98% A9). Compared to those with HPV16 OPC, individuals with non-HPV16 OPC had a higher age, comorbidity index, and proportion of non-whites, HIV+ patients, T4 tumors, and stage IV disease (AJCC 7th edition). Non-HPV16 genotype was associated with worse OS in univariate (HR = 2.17, 95% CI, 1.24-3.80, P = .0066), but not in multivariate analysis (HRadj = 0.84, 95% CI, 0.43-1.62, P = .5921). A7 clade was associated with worse OS in univariate (HR = 4.42, 95% CI, 1.60-12.30, P = .0041), but not in multivariate analysis (HRadj = 2.39, 95% CI, 0.57-9.99, P = .2325). Neither HPV genotype (HR = 1.60, 95% CI, 0.99-2.60, P = .0566) nor phylogenic clade (HR = 2.47, 95% CI, 0.91-6.72, P = .0761) was associated with EFS. CONCLUSION: Non-HPV16 genotype and A7 clade were associated with worse OS and trended toward worse EFS in univariate analyses. The survival differences were more pronounced by phylogenic clade than by HPV16 status, suggesting that the former may be a more useful classification for future studies. However, neither HPV16 status nor phylogenic clade was prognostic when adjusting for patient and tumor covariates, raising the question as to whether possible differences in outcomes are related to distinct clinical profiles rather than inherent viral properties.

The association between food insecurity and colorectal cancer screening: 2018-2021 New York State Behavioral Risk Factor Surveillance System (BRFSS).

PURPOSE: To assess the association between food insecurity and colorectal cancer screening uptake in screening eligible participants in New York State. METHODS: We analyzed 28,154 adults who participated in New York State Behavioral Risk Factor Surveillance System (BRFSS) from 2018 to 2021, were age-eligible for colorectal cancer screening based on the USPSTF guidelines at the time of survey administration and answered a version of the administered survey that included the module on food insecurity. Participants were defined as food insecure if they self-reported being always, usually, or sometimes stressed about having enough money to buy nutritious meals in the past 12 months. We compared demographic, healthcare access, overall health status, food insecurity by colorectal cancer screening status. Multivariable analyses were performed to assess the association of food insecurity and colorectal cancer screening status after adjusting for relevant covariates. Weighted analyses were performed using survey procedures to obtain population estimates. RESULTS: Food insecurity was statistically significantly associated a decreased likelihood of being up to date on colorectal cancer screening (ORadj 0.83, 95% CI [0.72, 0.94]) and being ever screened for colorectal cancer (ORadj 0.74, 95% CI [0.64, 0.87]) after adjusting for overall health status, healthcare coverage, interview year, age, race/ethnicity, sex, educational attainment, and income. Health status, health coverage, age, and Non-Hispanic Black race/ethnicity showed positive, statistically significant association with ever being screened and with being up to date for colorectal cancer screening. Lower income, lower educational attainment, and non-Hispanic Asian race/ethnicity were statistically significant inverse predictors of ever being screened and being up to date on screening. CONCLUSION: This project assessed the association between food insecurity and colorectal cancer screening uptake using the BRFSS survey. Food insecurity may be an important predictor for colorectal cancer screening uptake in eligible adults in the United States. The results from the study can inform future interventions and policies designed to improve participation in routine colorectal cancer screening.

Patients With Surgically Resectable Lung Cancer Who Opt for Radiation Have Worse Outcomes.

BACKGROUND: Surgery has been the standard procedure for resectable primary LC. Survival after stereotactic body radiation therapy, another treatment, is significantly biased due to preponderance of data from patients deemed unsuitable for surgery. We examined survival of patients refusing surgery in favor of radiation therapy. METHODS: We used the Surveillance, Epidemiology, and End Results database to identify patients with primary Stage I NSCLC diagnosed between 2007 and 2016. Patients were excluded if it was unknown if they were recommended for surgery or if surgery was contraindicated. Multiple predictors were assessed: radiation versus surgery, age at diagnosis, sex, race/ethnicity, health insurance status, marital status, tumor size, and histology. A multivariate analysis was performed to estimate hazard ratios and generate Kaplan-Meier survival curves. RESULTS: When adjusted for confounding variables, survival was greater for patients undergoing surgical resection than those refusing surgery in favor of radiation (HRadj 2.66; 95% CI: 2.27-3.11, p < 0.001) or for those receiving no standardized treatment (HRadj 4.43; 95% CI: 3.57-5.50, p < 0.001). CONCLUSIONS: SBRT is an effective treatment for inoperable early LC but there is limited data comparing outcomes against surgical resection. When eligible for both, patients refusing surgery and choosing radiation had worse survival when adjusting for variables including age, tumor size, and histology, and suggests that surgical resection is a superior treatment modality.

TERT and BRAF V600E mutations in thyroid cancer of World Trade Center Responders.

The 2-fold excess thyroid cancer risk reported in multiple World Trade Center (WTC) disaster exposed cohorts cannot entirely be explained by surveillance and physician bias thus highlighting the need to investigate the potential consequences of the dust exposure, containing carcinogenic and endocrine disruptive elements, on the thyroid. This study investigated the presence of TERT promoter and BRAF V600E mutations in 20 WTC-exposed versus 23 matched non-exposed thyroid cancers as potential mechanism explaining the excess risk. Although no significant difference in BRAF V600E mutation was found, TERT promoter mutations were significantly more prevalent in WTC thyroid cancer versus non-exposed thyroid cancers (P = 0.021). The odds of a TERT promoter mutation was significantly higher in the WTC versus the non-WTC thyroid cancers after adjustment [ORadj: 7.11 (95% CI: 1.21-41.83)]. These results may indicate that exposure to the mixture of pollutants present in the WTC dust resulted in an excess thyroid cancer risk and potentially more aggressive thyroid cancer, warranting investigating WTC responders on thyroid-associated symptoms during their health checkups. Future studies should include long-term follow-up to provide important insights in whether thyroid-specific survival is negatively affected by WTC dust exposure and whether this is because of the presence of one or more driver mutations.

Trends in prostate cancer incidence among Black men in the Caribbean and the United States.

BACKGROUND: Prostate cancer incidence is highest for Black men of the African diaspora in the United States and Caribbean. Recent changes in recommendations for prostate cancer screening have been shown to decrease overall prostate cancer incidence and increase the likelihood of late stage disease. However, it is unclear how trends in prostate cancer characteristics among high risk Black men differ by geographic region during the changes in screening recommendations. METHODS: In this study, we used population-based prostate cancer registry data to describe age-adjusted prostate cancer incidence trends from 2008 to 2015 among Black men from six geographic regions. We obtained data on incident Black prostate cancer patients from six cancer registries (in the United States: Florida, Alabama, Pennsylvania, and New York; and in the Caribbean: Guadeloupe and Martinique). After age standardization, we used descriptive analyses to compare the demographics and tumor characteristics by cancer registry site. The Joinpoint regression program was used to compare the trends in incidence by site. RESULTS: A total of 59,246 men were analyzed. We found the highest incidence rates (per 100,000) for prostate cancer in the Caribbean countries (181.99 in Martinique and 176.62 in Guadeloupe) and New York state (178.74). Incidence trends decreased significantly over time at all sites except Martinique, which also showed significantly increasing rates of late stage (III/IV) and Gleason score 7+ tumors. CONCLUSIONS: We observed significant differences in prostate cancer incidence trends among Black men after major changes prostate screening recommendations. Future studies will examine the factors that differentially influence prostate cancer trends among the African diaspora.

A 20-year Follow-up of the International Early Lung Cancer Action Program (I-ELCAP).

Background The low-dose CT (≤3 mGy) screening report of 1000 Early Lung Cancer Action Program (ELCAP) participants in 1999 led to the International ELCAP (I-ELCAP) collaboration, which enrolled 31 567 participants in annual low-dose CT screening between 1992 and 2005. In 2006, I-ELCAP investigators reported the 10-year lung cancer-specific survival of 80% for 484 participants diagnosed with a first primary lung cancer through annual screening, with a high frequency of clinical stage I lung cancer (85%). Purpose To update the cure rate by determining the 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening in the expanded I-ELCAP cohort. Materials and Methods For participants enrolled in the HIPAA-compliant prospective I-ELCAP cohort between 1992 and 2022 and observed until December 30, 2022, Kaplan-Meier survival analysis was used to determine the 10- and 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening. Eligible participants were aged at least 40 years and had current or former cigarette use or had never smoked but had been exposed to secondhand tobacco smoke. Results Among 89 404 I-ELCAP participants, 1257 (1.4%) were diagnosed with a first primary lung cancer (684 male, 573 female; median age, 66 years; IQR, 61-72), with a median smoking history of 43.0 pack-years (IQR, 29.0-60.0). Median follow-up duration was 105 months (IQR, 41-182). The frequency of clinical stage I at pretreatment CT was 81% (1017 of 1257). The 10-year lung cancer-specific survival of 1257 participants was 81% (95% CI: 79, 84) and the 20-year lung cancer-specific survival was 81% (95% CI: 78, 83), and it was 95% (95% CI: 91, 98) for 181 participants with pathologic T1aN0M0 lung cancer. Conclusion The 10-year lung cancer-specific survival of 80% reported in 2006 for I-ELCAP participants enrolled in annual low-dose CT screening and diagnosed with a first primary lung cancer has persisted, as shown by the updated 20-year lung cancer-specific survival for the expanded I-ELCAP cohort. © RSNA, 2023 See also the editorials by Grenier and by Sequist and Olazagasti in this issue.

Malignant pleural mesothelioma characteristics and outcomes: A SEER-Medicare analysis.

BACKGROUND: Pleural mesothelioma is rare cancer linked to asbestos exposure. Previous research has indicated that female individuals have better survival than male individuals, but this has never been examined in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. MATERIALS AND METHODS: Malignant pleural mesothelioma cases diagnosed from 1992 to 2015 were queried from the linked SEER-Medicare database. Multivariable logistic regression was used to assess the clinical and demographic factors associated with sex. A multivariable Cox proportional hazards model and propensity matching methods were used to assess sex differences in overall survival (OS) while accounting for potential confounders. RESULTS: Among 4201 patients included in the analysis, 3340 (79.5%) were males and 861 (20.5%) females. Females were significantly older, with more epithelial histology than males were, and had significantly better OS, adjusted for confounders (adjusted hazard ratio, 0.83, 95% confidence interval: 0.76-0.90). Other variables independently associated with improved survival included younger age at diagnosis, having a spouse/domestic partner, epithelial histology, lower comorbidity score, and receipt of surgery or chemotherapy. CONCLUSIONS: The study describes sex differences in mesothelioma occurrence, treatment, and survival and is the first to examine SEER-Medicare. It provides directions for future research into potential therapeutic targets.

Longitudinal Assessment of Association Between Tobacco Use and Tobacco Dependence Among Adults: Latent Class Analysis of the Population Assessment of Tobacco and Health Study Waves 1-4.

INTRODUCTION: With increasing tobacco product varieties, understanding tobacco use (TU) profiles and their associations with tobacco dependence (TD) has also become increasingly challenging. AIMS AND METHODS: We aimed to identify TU profiles and their associations with TD over time, and to identify subgroups with high risk of TD. We included 3463 adult recent tobacco users who had complete TU and TD data across waves 1-4 of the Population Assessment of Tobacco and Health (PATH) study. We used a composite index of TD and a summed TD score from an established 16-item TD measure. We applied a latent class analysis to identify TU profiles based on participants' usage of eight common tobacco product groups at each survey wave and to check the stability of the TU profiles over time. We then used generalized estimating equations regressions to evaluate the longitudinal TU-TD association, adjusting for potential confounders. RESULTS: We identified three distinct TU profiles that remained consistent across four survey waves: Dominant cigarette users (62%-68%), poly users with high propensity of using traditional cigarettes, e-cigarettes, and cigars (24%-31%), and dominant smokeless product users (7%-9%). Covariate-adjusted models showed that TD was significantly lower among the poly users and the dominant smokeless users, compared to that among the dominant cigarette users. CONCLUSIONS: Both TU profiles and their associations with TD were stable over time at the population level. Poly users and smokeless product users were consistently associated with lower TD than cigarette-dominant users, suggesting the need for tailored tobacco cessation interventions for users with different TU profiles. IMPLICATIONS: The finding of consistent TU profiles across four survey waves extends the current literature in capturing TU patterns in an evolving tobacco product landscape. The finding of the overall higher level of TD among the cigarette-dominant users compared to the other TU latent profiles (the Cig+eCig+Cigar dominant poly users and the dominant smokeless product users) can help identify high-risk groups for potential interventions. Our application of innovative statistical methods to high-quality longitudinal data from the PATH study helps improve the understanding of the dynamic TU-TD relationship over time.

Epidemiologic roadblocks in studying elongated mineral particles and mesothelioma risk.

Elongated mineral particles (EMPs) are a type of both occupational and environmental exposures that have generated interest in the scientific community due to their potential health effects. Their possible association with mesothelioma represents an area of concern. We provide an overview of the current challenges around epidemiological assessments of EMP exposure and mesothelioma risk, including methodological aspects that need to be addressed when designing and analyzing a study on EMP exposure and mesothelioma. Future work is needed to investigate the relationship between EMPs and mesothelioma, focused on an improved definition of EMP exposure and accounting for other concomitant sources of carcinogen exposure.

Non-asbestiform elongate mineral particles and mesothelioma risk: Human and experimental evidence.

The presentations in this session of the Monticello II conference were aimed at summarizing what is known about asbestiform and non-asbestiform elongate mineral particles (EMPs) and mesothelioma risks based on evidence from experimental and epidemiology studies. Dr. Case discussed case reports of mesothelioma over the last several decades. Dr. Taioli indicated that the epidemiology evidence concerning non-asbestiform EMPs is weak or lacking, and that progress would be limited unless mesothelioma registries are established. One exception discussed is that of taconite miners, who are exposed to grunerite. Drs. Mandel and Odo noted that studies of taconite miners in Minnesota have revealed an excess rate of mesothelioma, but the role of non-asbestiform EMPs in this excess incidence of mesothelioma is unclear. Dr. Becich discussed the National Mesothelioma Virtual Bank (NMVB), a virtual mesothelioma patient registry that includes mesothelioma patients' lifetime work histories, exposure histories, biospecimens, proteogenomic information, and imaging data that can be used in epidemiology research on mesothelioma. Dr. Bernstein indicated that there is a strong consensus that long, highly durable respirable asbestiform EMPs have the potential to cause mesothelioma, but there is continued debate concerning the biodurability required, and the dimensions (both length and diameter), the shape, and the dose associated with mesothelioma risk. Finally, Dr. Nel discussed how experimental studies of High Aspect Ratio Engineered Nanomaterials have clarified dimensional and durability features that impact disease risk, the impact of inflammation and oxidative stress on the epigenetic regulation of tumor suppressor genes, and the generation of immune suppressive effects in the mesothelioma tumor microenvironment. The session ended with a discussion of future research needs.

Global DNA methylation of WTC prostate cancer tissues show signature differences compared to non-exposed cases.

There is increased incidence of prostate cancer (PC) among World Trade Center (WTC)-exposed responders and community members, with preliminary evidence suggestive of more aggressive disease. While previous research is supportive of differences in DNA methylation and gene expression as a consequence of WTC exposure, as measured in blood of healthy individuals, the epigenetics of WTC PC tissues has yet to be explored. Patients were recruited from the World Trade Center Health Program. Non-WTC PC samples were frequency matched on age, race/ethnicity and Gleason score. Bisulfite-treated DNA was extracted from tumor tissue blocks and used to assess global DNA methylation with the MethylationEPIC BeadChip. Differential and pathway enrichment analyses were conducted. RNA from the same tumor blocks was used for gene expression analysis to further support DNA methylation findings. Methylation data were generated for 28 samples (13 WTC and 15 non-WTC). Statistically significant differences in methylation were observed for 3,586 genes; on average WTC samples were statistically significantly more hypermethylated (P = 0.04131). Pathway enrichment analysis revealed hypermethylation in epithelial mesenchymal transition (EMT), hypoxia, mitotic spindle, TNFA signaling via NFKB, WNT signaling, and TGF beta signaling pathways in WTC compared to non-WTC samples. The androgen response, G2M and MYC target pathways were hypomethylated. These results correlated well with RNA gene expression. In conclusion, long-term epigenic changes associated with WTC dust exposure were observed in PC tissues. These occurred in genes of critical pathways, likely increasing prostate tumorigenesis potential. This warrants analysis of larger WTC groups and other cancer types.

Disparities in clinical and demographic characteristics among Asian/Pacific Islander and Non-Hispanic White newly diagnosed lung cancer patients.

PURPOSE: Racial disparities persist among lung cancer patients but have not been adequately studied among Asian/Pacific Islander (API) subgroups, which are heterogeneous. This study compared clinical and demographic characteristics at diagnosis of API subgroups and NHW patients. METHODS: NHW and API adults diagnosed with lung cancer were identified from the Surveillance, Epidemiology, and End Results database (1990-2015). API was divided into eight subgroups: Chinese, Japanese, Filipino, Hawaiian/Pacific Islander, Korean, Vietnamese, Asian Indian/Pakistani, and Other. Multivariable multinomial logistic regression models were used to assess adjusted associations of clinical and demographic factors with API/subgroups. RESULTS: There were 522,702 (92.6%) NHW and 41,479 (7.4%) API lung cancer patients. API were less likely to be diagnosed at the age of ≥ 80 years (ORadj 0.53, 95% CI 0.48-0.58 for ≥ 80 vs. ≤ 39 years) than NHW. However, Japanese patients were more often diagnosed at ≥ 80 years compared to other ethnic subgroups. API were less often female (ORadj 0.85, 95% CI 0.83-0.86), and unmarried (ORadj 0.71, 95% CI 0.68-0.74); however, among API, Japanese, Hawaiian/Pacific Islander, Korean, and Vietnamese were more often unmarried, compared to Chinese patients. API were more frequently diagnosed at stage IV, compared to stage I (ORadj 1.31, 95% CI 1.27-1.35). API had significantly less squamous cell carcinoma (ORadj 0.54, 95% CI 0.52-0.56, compared to adenocarcinoma); among API, Japanese, Filipino, Hawaiian/Pacific Islander, Korean, Asian Indian/Pakistani, and Other were more likely than Chinese patients to present with squamous cell histology (range: ORadj[Other] 1.24, 95% CI 1.09-1.41; ORadj[Hawaiian/Pacific Islander] 2.47, 95% CI 2.22-2.75). CONCLUSION: At diagnosis, there are significant differences in demographic and clinical characteristics between NHW, API, and API subgroups. Treating API patients as a single population may overlook biological, environmental, and behavioral differences that might be beneficial in designing prevention strategies and treatment.

Assessing influenza vaccination success to inform COVID-19 vaccination campaign.

Given recent downward trends in daily rates of COVID-19 vaccinations, it is important to reassess strategies to reach those most vulnerable. The success and efficacy of vaccination campaigns for other respiratory illnesses, such as influenza, may help inform messaging around COVID-19 vaccinations. This cross-sectional study examines the individual-level factors associated with, and the spatial distribution of, predictors of COVID-19 severity, and uptake of influenza and hepatitis B (as a negative control) vaccines across NYC. Data were obtained from the 2018 Community Health Survey (CHS), including self-reported influenza and hepatitis B vaccine uptake, diabetes, asthma, hypertension, body mass index (BMI), age, race/ethnicity, educational attainment, borough, and United Hospital Fund (UHF) neighborhood of residence. A CDC-defined COVID-19 severity risk score was created with variables available in the CHS, including diabetes, asthma, hypertension, BMI ≥ 30 kg/m2 , and age ≥65 years old. After adjustment, there was a significant positive association between COVID-19 severity risk score and influenza vaccine uptake (1: ORadj = 1.49, 95% CI 1.28-1.73; 2: ORadj = 1.99; 95% CI: 1.65-2.41; 3+: ORadj = 2.89; 95% CI: 2.32-3.60, compared to 0). Hepatitis B vaccine uptake was significantly inversely associated with COVID-19 severity risk score (1: ORadj = 0.67; 95% CI: 0.57-0.79; 2: ORadj = 0.54; 95% CI: 0.44-0.66; 3+: ORadj = 0.45; 95% CI: 0.36-0.56, compared to 0). The influenza vaccination campaign template is effective at reaching those most at risk for serious COVID-19 and, if implemented, may help reach the most vulnerable that have not yet been vaccinated against COVID-19.

Modulation of chemoimmunotherapy efficacy in non-small cell lung cancer by sex and histology: a real-world, patient-level analysis.

BACKGROUND: It has been postulated that patient's sex impacts response to immunotherapy. Sex modulation of immunotherapy benefit, however, has not yet been explored using patient-level data, where potential confounders, as well as histologic type, can be accounted for. Here we investigated the association between sex and chemoimmunotherapy efficacy for non-small cell lung cancer (NSCLC) using a large, nation-wide dataset. PATIENTS & METHODS: Stage IV NSCLC patients diagnosed in 2015 were identified in the National Cancer Database (NCDB). Patients were treated with either chemoimmunotherapy or chemotherapy alone. The efficacy of the addition of immunotherapy treatment by sex was investigated using both an adjusted Cox proportional hazards model and propensity-score matching, in both the overall cohort and stratified by histological subtype. RESULTS: 2064 (16%) patients received chemoimmunotherapy and10,733 (84%) received chemotherapy alone. Adjusted survival analysis in the overall cohort showed that both males (hazards ratio (HR)adj: 0.80, 95% CI: 0.74-0.87) and females (HRadj: 0.83, 95% CI: 0.76-0.90) had better OS when treated with chemoimmunotherapy than chemotherapy alone, with no statistically significant interaction between sex and receipt of immunotherapy (p = 0.63). Propensity matching confirmed these results. However, for those with squamous cell histology, male patients derived more benefit from chemoimmunotherapy treatment than females (HRadj: 0.73, 95% CI: 0.58-0.91 vs HRadj: 1.03, 95% CI: 0.76-1.38; p for interaction = 0.07). CONCLUSION: Male patients with squamous cell carcinoma may derive more benefit from chemoimmunotherapy treatment. Histology likely plays an important role in how sex modulates immunotherapy efficacy.

Trends for In- and Outpatient Thyroid Cancer Surgery in Older Adults in New York State, 2007-2017.

BACKGROUND: In view of the 2013 American Thyroid Association consensus statement on outpatient thyroidectomy, the present study assessed the trends and factors associated with thyroid cancer surgery setting in older adults, using the New York Statewide Planning and Research Cooperative System database. MATERIALS AND METHODS: There were 14,495 patients with surgically treated thyroid cancer in New York State between 2007 and 2017. Trends were plotted over time and stratified by surgery type. Significance of the trend was assessed using the Mann-Kendall test. Multivariable logistic regression was used to assess independent associations with surgical setting. RESULTS: The overall outpatient surgery rate significantly increased over time (correlation coefficient 0.82; P < 0.001), for both total thyroidectomy (P < 0.001) and lobectomy (P < 0.001). Factors associated with increased odds of inpatient surgery were medium- and high-volume hospitalization (adjusted odds ratio [ORadj] 2.12, 95% confidence interval [CI] 1.93-2.32; ORadj 1.69, 95% CI 1.55-1.85, respectively) versus low volume, undergoing total thyroidectomy (ORadj 1.75, 95% CI 1.61-1.90), as well as having Medicare insurance (ORadj 1.13, 95% CI 1.02-1.24) versus private insurance. CONCLUSIONS: The present study shows that outpatient thyroidectomy is increasingly favored over inpatient thyroidectomy over time in an older patient population. A clear changepoint following 2011 preceded the publication of the American Thyroid Association statement on outpatient thyroidectomy in 2013 and was likely associated with multiple publications reporting safety of outpatient thyroid surgery and clear economic benefits.

Ecologic study of influenza vaccination uptake and COVID-19 death rate in New York City.

BACKGROUND: The aim of this ecological study was to assess the area-level relationship between cumulative death rate for COVID-19 and historic influenza vaccination uptake in the New York City population. METHODS: Predictors of COVID-19 death included self-reported influenza vaccination in 2017, as well as four CDC-defined risk factors of severe COVID-19 infection available at the ecological level, which were diabetes, asthma, BMI 30-100 (2 kg/m2) and hypertension, in addition to race and age (65 + years). RESULTS: After adjusting for potential confounders, for every one-unit increase in influenza vaccination uptake for each zip code area, the rate of COVID-19 deaths decreased by 5.17 per 100,000 residents (p < 0.0001). CONCLUSIONS: Zip codes with a higher prevalence of influenza vaccination had lower rates of COVID-19 mortality, inciting the need to further explore the relationship between influenza vaccination uptake and COVID-19 mortality at the individual level.

A Neighborhood Analysis of Time Trends in COVID-19 Infection in NYC.

To understand how observed COVID-19 diagnostic testing disparities across New York City (NYC) have impacted infection rates and COVID-19 spread, we examined neighborhood-level factors associated with, and the spatial distribution of, antibody test and infection rates, and compared changes over time by NYC ZIP code tabulation area (ZCTA). Data were obtained from 2019 American Community Survey 5-year estimates to create an SES index by ZCTA. Other predictors obtained from 2018 census data were the proportions of white residents, Hispanic residents and residents ≥ 65 years old. Multivariable Poisson regressions were performed to assess the rate of change for antibody testing and positivity, and to assess the independent associations with SES, race and age. Results: There was a significant association between the rate of antibody tests and SES quartiles (Q1: ßadj = 0.04, Q2: ßadj = 0.03 and Q3: ßadj = - 0.03, compared to Q4), and the proportion of residents who are white (ßadj = 0.004, p < .0001), Hispanic   (ßadj = 0.001, p < .0001), and ≥ 65 years (ßadj = 0.01, p < .0001). Total number of positive antibody tests was significantly inversely associated with SES quartile (Q1: ßadj = 0.50, Q2: ßadj = 0.48 and Q3: ßadj = 0.29, compared to Q4), and proportion of white residents (ß = - 0.001, p < .0001) and ≥ 65 years (ß = - 0.02, p < .0001), and significantly positively associated with proportion of Hispanic residents (ß = 0.003, p < .0001). There are disparities in antibody testing and positivity, reflecting disproportionate impacts and undercounts of COVID-19 infection across NYC ZCTAs. Future public health response should increase testing in these vulnerable areas to diminish infection spread.

Monocyte counts and prostate cancer outcomes in white and black men: results from the SEARCH database.

PURPOSE: Circulating inflammatory markers may predict prostate cancer (PC) outcomes. For example, a recent study showed that higher peripheral blood monocyte counts were associated with aggressive PC in Asian men undergoing radical prostatectomy (RP). Herein, we investigated whether peripheral monocyte count can predict long-term PC outcomes after RP in black and white men. METHODS: We retrospectively reviewed data on 2345 men undergoing RP from 2000 to 2017 at eight Veterans Affairs hospitals. Data on monocyte count within 6 and 12 months prior to surgery were collected. The study outcomes were biochemical recurrence (BCR), castration-resistant PC (CRPC), metastasis, all-cause mortality (ACM), and PC-specific morality (PCSM). Cox-proportional hazard models were used to assess the associations between pre-operative monocyte count and the above-mentioned outcomes accounting for confounders. RESULTS: Of 2345 RP patients, 972 (41%) were black and 1373 (59%) were white men. In multivariable analyses, we found no associations between monocyte count and BCR among all men (HR: 1.36, 95%CI 0.90-2.07) or when analyses were stratified by race (HR: 1.30, 95%CI 0.69-2.46, in black men; HR:1.33, 95%CI 0.76-02.33, in white men). Likewise, no overall or race-specific associations were found between monocyte count and CRPC, metastases, ACM, and PCSM, all p ≥ 0.15. Results were similar for monocyte count measured at 12 months prior to RP. CONCLUSION: In black and white PC patients undergoing RP, peripheral monocyte count was not associated with long-term PC outcomes. Contrary to what was found in Asian populations, monocyte count was not associated with PC outcomes in this study.