Comparison of outcomes for Hispanic and non-Hispanic patients with advanced renal cell carcinoma in the International Metastatic Renal Cell Carcinoma Database.

BACKGROUND: Existing data on the impact of Hispanic ethnicity on outcomes for patients with renal cell carcinoma (RCC) is mixed. The authors investigated outcomes of Hispanic and non-Hispanic White (NHW) patients with advanced RCC receiving systemic therapy at large academic cancer centers using the International Metastatic Renal Cell Carcinoma Database (IMDC). METHODS: Eligible patients included non-Black Hispanic and NHW patients with locally advanced or metastatic RCC initiating systemic therapy. Overall survival (OS) and time to first-line treatment failure (TTF) were calculated using the Kaplan-Meier method. The effect of ethnicity on OS and TTF were estimated by Cox regression hazard ratios (HRs). RESULTS: A total of 1563 patients (181 Hispanic and 1382 NHW) (mostly males [73.8%] with clear cell RCC [81.5%] treated with tyrosine kinase inhibitor [TKI] monotherapy [69.9%]) were included. IMDC risk groups were similar between groups. Hispanic patients were younger at initial diagnosis (median 57 vs. 59 years, p = .015) and less likely to have greater than one metastatic site (60.8% vs. 76.8%, p < .001) or bone metastases (23.8% vs. 33.4%, p = .009). Median OS and TTF was 38.0 months (95% confidence interval [CI], 28.1-59.2) versus 35.7 months (95% CI, 31.9-39.2) and 7.8 months (95% CI, 6.2-9.0) versus 7.5 months (95% CI, 6.9-8.1), respectively, in Hispanic versus NHW patients. In multivariable Cox regression analysis, no statistically significant differences were observed in OS (adjusted hazard ratio [HR], 1.07; 95% CI, 0.86-1.31, p = .56) or TTF (adjusted HR, 1.06; 95% CI, 0.89-1.26, p = .50). CONCLUSIONS: The authors did not observe statistically significant differences in OS or TTF between Hispanic and NHW patients with advanced RCC. Receiving treatment at tertiary cancer centers may mitigate observed disparities in cancer outcomes.

Disparities in Lung Cancer Clinical Trial Discussion and Enrollment at a Safety Net Hospital.

BACKGROUND: In the United States, less than 5% of all adult cancer patients enroll in clinical trials. Few studies explore participation in cancer clinical trials at safety net hospitals, which disproportionately care for minoritized, low-income, uninsured, and underinsured populations. Our study aims to investigate disparities in clinical trial discussions and enrollment among lung cancer patients at Boston Medical Center, the largest safety net hospital in New England. METHODS: We included 1121 patients diagnosed with lung cancer between January 2015 and December 2020. Electronic Medical Records (EMR) were queried, and patients were categorized into three groups: (1) clinical trial discussed and the patient enrolled, (2) clinical trial discussed but the patient not enrolled, and (3) clinical trial not discussed. Sociodemographic variables such as age, gender, race, ethnicity, city, primary language, median household income, medical insurance type, and education level were also collected. Chi-squared,t test, and multivariate regression analysis was done using SPSS version 26.0. RESULTS: Of the 1121 patients, clinical trials were discussed in 141 patients (12.6%), of which 22 (15.6%) were enrolled. Clinical trial discussions were conducted more with younger patients (68.19 vs 71.37, p = .001), but on multivariate analysis there was no significant difference (OR = 1.023; 95% CI 0.998-1.048; p = .068). There was no significant difference in clinical trial discussion or enrollment between the other sociodemographic factors. CONCLUSION: Additional study of barriers to cancer clinical trial discussion and enrollment at safety net institutions can serve as a prerequisite to ameliorating racial disparities observed on a national scale.

Prevalence of Variants of Uncertain Significance in Patients Undergoing Genetic Testing for Hereditary Breast and Ovarian Cancer and Lynch Syndrome.

Hereditary Breast and Ovarian Cancer (HBOC) and Lynch Syndrome (LS) are the most common inherited cancer syndromes identified with genetic testing. Testing, though, commonly reveals variants of uncertain significance (VUSs). This is a retrospective observational study designed to determine the prevalence of pathogenic mutations and VUSs in patients tested for HBOC and/or LS and to explore the characteristics of the VUS population. Patients 18-80 years old that met NCCN criteria for HBOC and/or LS genetic screening were tested between 2006 and 2020 at Mount Auburn Hospital in Cambridge, Massachusetts. A total of 663 patients were included in the study, with a mean age of 50 years old and 90% being females. Pathogenic mutations were identified in 12.5% and VUSs in 28.3%. VUS prevalence was associated with race (p-value = 0.019), being particularly higher in Asian populations. Patients with a personal history of breast cancer or family history of breast or ovarian cancer were more likely to have a VUS (personal breast: OR: 1.55; CI: 1.08-2.25; family breast: OR: 1.68; CI: 1.08-2.60, family ovarian OR: 2.29; CI: 1.04-5.45). In conclusion, VUSs appear to be detected in almost one third patients tested for cancer genetic syndromes, and thus future work is warranted to determine their significance in cancer development.

Trends in Lung Cancer Incidence and Mortality (1990-2019) in the United States: A Comprehensive Analysis of Gender and State-Level Disparities.

PURPOSE: Lung cancer is the leading cause of cancer-related deaths in the United States. This study aims to analyze lung cancer incidence, mortality, and related statistics from 1990 to 2019, focusing on national- and state-level trends and exploring potential disparities between sexes. METHODS: The Global Burden of Disease database was used to extract tracheal, bronchus, and lung cancer mortality data from 1990 to 2019 for both males and females and across all states of the United States. Age-standardized incidence rates, age-standardized mortality rates, disability-adjusted life years (DALYs), and mortality-to-incidence indices (MIIs) were studied to assess for gender-based, geographic, and temporal disparities. Joinpoint regression analysis was performed to further evaluate trends. RESULTS: The incidence of these cancers in the United States decreased between 1990 and 2019 by 23.35%, with a more significant decline in males (37.73%) than females (1.41%). Similarly, for mortality, a decrease was observed for both sexes combined (26.83%), but much more significantly for males (40.23%) than females (6.01%). The MIIs decreased overall, but there were variations across states. DALYs decreased for both sexes combined, with males experiencing a larger reduction, but an increase was noted in some states for females. CONCLUSION: This analysis reveals diverse trends pertaining to the incidence, mortality, and disability burden associated with lung cancer by sex and states in the United States, emphasizing the need for targeted interventions to reduce disparities. These findings contribute to our understanding of the current landscape of lung cancer and can inform future strategies for prevention, early detection, and management.

Burden of AML, 1990-2019: Estimates From the Global Burden of Disease Study.

PURPOSE: AML accounts for 80% of acute leukemia in adults. While progress has been made in treating younger patients in the past 2 decades, there has been limited improvement for older patients until recently. This study examines the global and European Union (EU) 15+ trends in AML between 1990 and 2019. METHODS: We extracted age-standardized incidence rates (ASIRs), age-standardized death rates (ASMRs), and disability-adjusted life years, stratified by sex from the Global Burden of Disease Study database, and mortality-to-incidence ratio (MIR) were computed. Trends were compared using Joinpoint regression. RESULTS: The findings show a global increase in AML incidence for both sexes from 1990 to 2019. In the EU15+ countries, most countries exhibited an increase in ASIR for both sexes. Joinpoint revealed that globally for male patients, ASIR steadily increased until 2010, remained stable until 2015 followed by a decline till 2019. Similar trends were observed in female patients. For ASMR, although there was an increase globally and in most EU15+ countries, there was a statistically significant decrease in mortality rates globally and in the majority of EU15+ countries in recent years. MIR improved in both sexes globally. On age stratification, AML burden was highest among older groups (55 years and older), while the lowest rates were observed in younger than 20 years. CONCLUSION: The findings from our study indicate a global rise in AML incidence and mortality in both sexes and decrease in MIR from 1990 to 2019 suggesting a better survival. However, on Joinpoint analysis, there is no change in MIR in women in the past decade and past 4 years in men indicating plateau in survival trends despite recent advances.

Clinical characteristics, racial inequities, and outcomes in patients with breast cancer and COVID-19: A COVID-19 and cancer consortium (CCC19) cohort study.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical trial number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701.

Cystic fibrosis-related mortality in the United States from 1999 to 2020: an observational analysis of time trends and disparities.

Cystic fibrosis transmembrane conductance regulator modulators have revolutionized cystic fibrosis (CF) care in the past decade. This study explores the CF-related mortality trends in the US from 1999 to 2020. We extracted CF-related mortality data from the CDC WONDER database. CF age-standardized mortality rates (ASMRs) were identified by ICD-10 code E84 and were stratified by demographic and geographical variables. Temporal trends were analyzed using Joinpoint modeling. CF-related ASMRs decreased from 1.9 to 1.04 per million population (p = 0.013), with a greater reduction in recent years. This trend was replicated in both sexes. The median age of death increased from 24 to 37 years. CF mortality rates decreased across sex, white race, non-Hispanic ethnicity, census regions, and urbanization status. Incongruent trends were reported in non-white races and Hispanic ethnicity. A lower median age of death was observed in women, non-white races, and Hispanic ethnicity. SARS-CoV-2 infection was the primary cause of death in 1.7% of CF decedents in 2020. The national CF-related mortality rates declined and the median age of death among CF decedents increased significantly indicating better survival in the recent years. The changes were relatively slow during the earlier period of the study, followed by a greater decline lately. We observed patterns of sex, ethnic, racial, and geographical disparities associated with the worsening of the gap between ethnicities, narrowing of the gap between races and rural vs. urban counties, and closing of the gap between sexes over the study period.

Disparities in US Lung Cancer Clinical Trial Enrollment.

BACKGROUND: Disparities within clinical trial enrollment are well-documented, reducing the generalizability of results. Although nearly 30 years have passed since Congress passed the NIH Revitalization Act to encourage the participation of minoritized populations in clinical trials, these patients continue to be underrepresented. This study aimed to investigate lung cancer clinical trial enrollment disparities for race/ethnicity, sex, and age. METHODS: We queried the National Institutes of Health: US National Library of Medicine database of clinical trials for all US-based lung cancer clinical trials completed between 2004 and 2021 and collected data on race and ethnicity, gender, and age breakdown. This data was compared to Surveillance, Epidemiology, and End Results (SEER) database data. Independent sample t-tests and Kruskal-Wallis's approach were used to analyze the data. RESULTS: Of 311 eligible trials with exclusive US enrollment, 136 (44%) reported race and ethnicity breakdown for the patient cohort representing 9869 patients. Hispanic, Non-Hispanic American Indian/Alaska Native, Non-Hispanic Black, and Non-Hispanic Unreported participants were underrepresented (p = 0.001, p = 0.005, p = 0.014, p = 0.002, respectively). Non-Hispanic White participants were overrepresented (p = 0.018). Disparities worsened from 2017 to 2021 for Hispanic patients (p = 0.03). No significant differences were found for sex or age. CONCLUSIONS: Disparities for clinical lung cancer trial enrollment have not shown statistically significant improvement since 2004, and representation remains unequal, especially for racial and ethnic minorities.

Gender differences in leukemia outcomes based on health care expenditures using estimates from the GLOBOCAN 2020.

BACKGROUND: Leukemia contributes significantly to the global cancer burden. Due to the importance of evaluating improvements in leukemia outcomes, the current study aimed to examine the variations in mortality-to-incidence ratio (MIR) between genders and association of MIR with the health expenditures in selected countries. METHODS: The leukemia incidence and mortality rates were extracted from the GLOBOCAN 2020 database. In total, 56 countries were included based on the data quality reports and the exclusion of missing data. The associations of MIR and changes in MIR over time ([Formula: see text]MIR) with the human development index (HDI), current health expenditure (CHE) per capita, and current health expenditure as a percentage of gross domestic product (CHE/GDP) were investigated using Spearman's rank correlation coefficient. RESULTS: In 2020, an estimated 474,519 new cases of leukemia were diagnosed globally, and 311,594 deaths occurred due to the disease. Male patients exhibited a higher incidence and mortality of leukemia compared to females on a global scale. Our analysis revealed that the MIRs were the highest and lowest in Egypt (0.79) and the United States (0.29), respectively. Remarkably, countries with greater HDI, higher CHE per capita, and a higher CHE/GDP tended to have lower MIR in both genders and within gender-specific subgroups. The δMIR demonstrated a significant negative correlation with HDI and CHE per capita, whereas no significant associations were observed among female patients for CHE/GDP. Besides, all three indicators showed trends towards negative correlations with δMIR among males, though these trends were not statistically significant (p>0.05). CONCLUSIONS: Generally, leukemia MIRs tended to be most favorable (i.e., lower) in countries with high HDI and high health expenditure. The gender differences observed in leukemia outcomes may reflect the potential influence of social, material, behavioral, and biological factors.

Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19.

Importance: Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking. Objective: To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022. Exposure: Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19. Main Outcomes and Measures: Main outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up. Results: Of 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13). Conclusions and Relevance: In this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19-related thromboembolism in patients with cancer.

New drug approvals in prostate cancer and their effect on the treatment landscape.

Prostate cancer is the most frequently diagnosed non-skin cancer and the second leading cause of cancer-related mortality in men in the United States. Over the past decade, the treatment landscape for advanced prostate cancer has rapidly shifted. For decades, androgen deprivation therapy has been the cornerstone of systemic treatment for patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, more recently, we have seen the emergence of doublet and triplet combinations in the mHSPC setting. At the same time, there is an expanding list of treatments for patients with metastatic castration-resistant prostate cancer (mCRPC), including hormonal treatments, chemotherapy, immunotherapy, bone-targeted agents, radioligand therapy, and targeted therapy. The shifting of the treatment landscape for advanced prostate cancer has raised many questions regarding patient selection, therapy choice, and sequencing of different approved agents, particularly in the mCRPC setting with the earlier use of chemotherapy and androgen receptor signaling inhibitors. Since then, multiple trials have been conducted to improve the management of mHSPC and delay its progression to mCRPC. This review article discusses various clinical trials that focus on novel therapeutic targets for prostate cancer and how the initiation of newer clinical trials has affected older therapies and trials.

Pulmonary hypertension associated mortality in the United States from 2003 to 2020: an observational analysis of time trends and disparities.

Background: Pulmonary hypertension (PH) is an independent risk factor for morbidity and mortality. In the last two decades, significant advances have been made in management of World Health Organization (WHO) group 1 PH. However, there are no approved targeted pharmacotherapies for PH secondary to left-sided heart diseases or chronic hypoxic lung diseases which are thought to account for more than 70-80% of the disease burden. No recent investigation has analyzed and compared the mortality burden related to WHO group 1 PH with the mortality burden with WHO groups 2-5 PH at the national level in the United States (US). We hypothesize that WHO group 1 PH-related mortality has improved over the last two decades in comparison to WHO groups 2-5 PH. Methods: In this study, we used data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) the underlying cause of death database to study age-standardized mortality rates related to PH in the US from 2003 to 2020. Results: A total of 126,526 deaths were recorded from PH in the US between 2003 and 2020. Across the study period, PH-related ASMR increased from 17.81 per million population in 2003 to 23.89 in 2020 with a percentage change (PC) of +34%. However, there are contrasting mortality trends in WHO group 1 PH when compared to WHO groups 2-5 PH. Data demonstrated a decline in mortality from group 1 PH regardless of gender. In contrast, an increase in mortality from WHO groups 2-5 PH was observed, accounting for the major proportion of the overall PH mortality burden in recent years. Conclusions: PH-related mortality continues to an increase primarily due to increase in mortality attributed to WHO groups 2-5 PH. These findings have notable public health implications. Screening and risk assessment tools for secondary PH, risk factor modification, and novel management strategies are vital to improve outcomes.

Clinical Characteristics, Racial Inequities, and Outcomes in Patients with Breast Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Cohort Study.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1,383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32 - 1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70 - 6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83 - 12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63 - 3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20 - 2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66 - 3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89 - 22.6]). Hispanic ethnicity, timing and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to Non-Hispanic White patients.

Trends in pulmonary tuberculosis mortality between 1985 and 2018: an observational analysis.

BACKGROUND: Pulmonary tuberculosis (TB) is a major source of global morbidity and mortality. Latent infection has enabled it to spread to a quarter of the world's population. The late 1980s and early 1990s saw an increase in the number of TB cases related to the HIV epidemic, and the spread of multidrug-resistant TB. Few studies have reported pulmonary TB mortality trends. Our study reports and compares trends in pulmonary TB mortality. METHODS: We utilized the World Health Organization (WHO) mortality database from 1985 through 2018 to analyze TB mortality using the International Classification of Diseases-10 codes. Based on the availability and quality of data, we investigated 33 countries including two countries from the Americas; 28 countries from Europe; and 3 countries from the Western Pacific region. Mortality rates were dichotomized by sex. We computed age-standardized death rates per 100,000 population using the world standard population. Time trends were investigated using joinpoint regression analysis. RESULTS: We observed a uniform decrease in mortality in all countries across the study period except the Republic of Moldova, which showed an increase in female mortality (+ 0.12 per 100,000 population). Among all countries, Lithuania had the greatest reduction in male mortality (-12) between 1993-2018, and Hungary had the greatest reduction in female mortality (-1.57) between 1985-2017. For males, Slovenia had the most rapid recent declining trend with an estimated annual percentage change (EAPC) of -47% (2003-2016), whereas Croatia showed the fastest increase (EAPC, + 25.0% [2015-2017]). For females, New Zealand had the most rapid declining trend (EAPC, -47.2% [1985-2015]), whereas Croatia showed a rapid increase (EAPC, + 24.9% [2014-2017]). CONCLUSIONS: Pulmonary TB mortality is disproportionately higher among Central and Eastern European countries. This communicable disease cannot be eliminated from any one region without a global approach. Priority action areas include ensuring early diagnosis and successful treatment to the most vulnerable groups such as people of foreign origin from countries with a high burden of TB and incarcerated population. Incomplete reporting of TB-related epidemiological data to WHO excluded high-burden countries and limited our study to 33 countries only. Improvement in reporting is crucial to accurately identify changes in epidemiology, the effect of new treatments, and management approaches.

Management of Lobular Neoplasia Diagnosed by Core Biopsy.

Lobular neoplasia (LN) involves proliferative changes within the breast lobules. LN is divided into lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH). LCIS can be further subdivided into three subtypes: classic LCIS, pleomorphic LCIS, and LCIS with necrosis (florid type). Because classic LCIS is now considered as a benign etiology, current guidelines recommend close follow-up with imaging versus surgical excision. The goal of our study was to determine if the diagnosis of classic LN on core needle biopsy (CNB) merits surgical excision. This is a retrospective, observational study conducted at Mount Auburn Hospital, Cambridge, MA, from May 17, 2017, through June 30, 2020. We reviewed the data of breast biopsies conducted at our hospital over this period and included patients who were diagnosed with classic LN (LCIS and/or ALH) and excluded patients having any other atypical lesions on CNB. All known cancer patients were excluded. Of the 2707 CNBs performed during the study period, we identified 68 women who were diagnosed with ALH or LCIS on CNB. CNB was performed for an abnormal mammogram in the majority of patients (60; 88%) while 7(10.3%) had an abnormal breast magnetic resonance imaging study (MRI), and 1 had an abnormal ultrasound (US). A total of 58 patients (85%) underwent excisional biopsy, of which 3 (5.2%) showed malignancy, including 2 cases of DCIS and 1 invasive carcinoma. In addition, there was 1 case (1.7%) with pleomorphic LCIS and 11 cases with ADH (15.5%). The management of LN found on core biopsy is evolving, with some advocating surgical excision and others recommending observation. Our data show a change in diagnosis with excisional biopsy in 13 (22.4%) of patients with 2 cases of DCIS, 1 invasive carcinoma, 1 pleomorphic LCIS, and 9 cases of ADH, diagnosed on excisional biopsy. While ALH and classic LCIS are considered benign, the choice of ongoing surveillance versus excisional biopsy should be made with shared decision making with the patient, with consideration of personal and family history, as well as patient preferences.

Impact of COVID-19 in patients on active melanoma therapy and with history of melanoma.

INTRODUCTION: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. RESULTS: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35). CONCLUSIONS: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors.

A Diagnostic Dilemma of a Case of Granulomatosis With Polyangiitis (GPA) Presenting With Thrombotic Vasculopathy.

Granulomatosis with polyangiitis (GPA) is a rare disease with a prevalence of about three in 100,000 persons in the United States. GPA is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis affecting predominantly small-sized vessels. It can present with localized or systemic symptoms with multiple organ involvement, thus making diagnosis challenging. Common skin lesions in GPA are palpable purpura, petechiae, ulcers, and livedo reticularis. These lesions usually have underlying vasculitis with or without granuloma on histology findings. To date, there have been no previous reports about thrombotic vasculopathy in GPA before. We present a case of a 25-year-old female who presented with intermittent joint pain for weeks, purpuric rash, and mild hemoptysis for a few days. A review of systems was notable for a 15-pound weight loss in one year. Physical examination was significant for a purpuric rash on the left elbow and toe, and left knee swelling and erythema. Presenting laboratory results were notable for anemia, indirect hyperbilirubinemia, mildly elevated D-dimers, and microscopic hematuria. Chest radiograph revealed confluent airspace disease. Extensive infectious workup was negative. A skin biopsy of her left toe revealed dermal intravascular thrombi without evidence of vasculitis. The thrombotic vasculopathy did not favor vasculitis but raised concern for a hypercoagulable state. However, extensive hematologic workup was negative. Bronchoscopy findings were consistent with diffuse alveolar hemorrhage. Later, cytoplasmic ANCA (c-ANCA) and anti-proteinase 3 (PR3) antibody titers were positive. Her diagnosis was unclear since both skin biopsy and bronchoscopy were nonspecific and inconsistent with her positive antibody results. The patient eventually underwent a kidney biopsy, which showed pauci-immune necrotizing and crescentic glomerulonephritis. Finally, a diagnosis of granulomatosis with polyangiitis was made based on the kidney biopsy and positive c-ANCA. The patient was treated with steroids and IV rituximab and discharged home with outpatient rheumatology follow-up. Due to multiple signs and symptoms including thrombotic vasculopathy, there was a diagnostic dilemma requiring a multidisciplinary approach. This case highlights the importance of pattern recognition for the diagnostic framework of rare disease entities and the multidisciplinary collaborative efforts required to reach the final diagnosis.

Cancer, more than a "COVID-19 co-morbidity".

Patients with cancer represent a particularly vulnerable population at risk of adverse outcomes related to COVID-19. Collectively, the initial studies, including patients with and without cancer, confirmed that patients with cancer had a higher risk of complications and death related to COVID-19. Subsequent studies on patients with COVID-19 and cancer investigated patient and disease-related factors associated with COVID-19 severity and morality. Multiple interconnected factors include demographics, comorbidities, cancer-associated variables, treatment side effects, and other parameters. However, there is a lack of clarity on the contributions of any one factor. In this commentary, we deconvolute the data of specific risk factors associated with worse outcomes due to COVID-19 in cancer patients and focus on understanding the recommended guidelines to mitigate COVID-19 risk in this vulnerable population. In the first section, we highlight the key parameters, including age and race, cancer status, type of malignancy, cancer therapy, smoking status and comorbidities that impact outcomes for cancer patients with COVID-19. Next, we discuss efforts made at the patient, health system, and population levels to mitigate the effects of the ongoing outbreak for patients with cancer, including (1) screening, barrier and isolation strategies (2), Masking/PPE (3), vaccination, and (4) systemic therapies (e.g., evusheld) to prevent disease onset in patients. In the last section, we discuss optimal treatment strategies for COVID-19, including additional therapies for patients with COVID-19 and cancer. Overall, this commentary focuses on articles with high yield and impact on understanding the evolving evidence of risk factors and management guidelines in detail. We also emphasize the ongoing collaboration between clinicians, researchers, health system administrators and policymakers and how its role will be important in optimizing care delivery strategies for patients with cancer. Creative patient-centered solutions will be critical in the coming years, post the pandemic.