Performance of a targeted methylation-based multi-cancer early detection test by race/ethnicity.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3071-3071
Author(s):  
Wai Hong Wilson Tang ◽  
Habte Aragaw Yimer ◽  
Mohan K. Tummala ◽  
Spencer Shao ◽  
Gina G. Chung ◽  
...  

3071 Background: Disparities in cancer screening and outcomes based on factors such as gender, socioeconomic status, and race/ethnicity are well documented.1 The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) was designed to develop and validate a blood-based multi-cancer early detection (MCED) test analyzing plasma cell-free DNA (cfDNA) to detect cancer signals across multiple cancer types and simultaneously predict cancer signal origin. Findings stratified by race/ethnicity from the third and final CCGA validation sub-study are reported. Methods: CCGA is a prospective, multicenter, case-control, observational study with longitudinal follow-up (overall N = 15,254). In this pre-specified exploratory analysis from the third substudy, key objectives were to evaluate test performance for cancer signal detection (specificity, overall sensitivity, and sensitivity by clinical stage) among racial/ethnic groups. Plasma cfDNA from evaluable samples was analyzed using a targeted methylation bisulfite sequencing assay and a machine learning approach. Overall, 4077 participants comprised the independent validation set with confirmed status (cancer: n = 2823; non-cancer: n = 1254). The groups stratified by race/ethnicity were White Non-Hispanic, Black Non-Hispanic, Other Non-Hispanic (including but not limited to Asian, Native Hawaiian, Pacific Islander, American Indian, Alaska Native), Hispanic (all races), and Other/unknown. The study was not powered to detect statistical differences between groups. Results: Cancer and non-cancer groups were predominantly White (2316/2823, 82.0% and 996/1254, 79.4%, respectively). Across racial/ethnic groups, specificity for cancer signal detection was 99.6% (White Non-Hispanic: 992/996, 95% confidence interval [99.0-99.8%]), 100.0% (Black Non-Hispanic: 85/85 [95.7-100.0%]), 100.0% (Other Non-Hispanic: 33/33 [89.6-100.0%]), 98.1% (Hispanic: 101/103 [93.2-99.5%]), and 100% (Other/unknown: 37/37 [90.6-100.0%]). Despite slight differences in cancer type and staging across racial/ethnic groups, overall sensitivity for cancer signal detection among groups ranged from 43.9% to 63.0% (White Non-Hispanic: 50.5%, 1169/2316 [48.4-52.5%], Black Non-Hispanic: 53.9%, 104/193 [46.8-60.8%], Other Non-Hispanic: 43.9%, 25/57 [31.8-56.7%], Hispanic: 63.0%, 121/192 [56.0-69.5%], and Other/unknown: 52.3%, 34/65 [40.4-64.0%]). For all racial/ethnic groups, sensitivity generally increased with clinical stage (with limited exceptions at Stage IV in some groups with small sample sizes). Conclusions: The MCED test demonstrated consistent specificity and sensitivity across racial/ethnic groups, though results are limited by sample size for some groups. These findings indicate broad applicability and support clinical implementation of this MCED test on a population scale. 1. Zavela et al. Brit J Cancer 2021. Clinical trial information: NCT02889978.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3072-3072
Author(s):  
Habte Aragaw Yimer ◽  
Wai Hong Wilson Tang ◽  
Mohan K. Tummala ◽  
Spencer Shao ◽  
Gina G. Chung ◽  
...  

3072 Background: The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) previously demonstrated that a blood-based multi-cancer early detection (MCED) test utilizing cell-free DNA (cfDNA) sequencing in combination with machine learning could detect cancer signals across multiple cancer types and predict cancer signal origin. Cancer classes were defined within the CCGA study for sensitivity reporting. Separately, cancer types defined by the American Joint Committee on Cancer (AJCC) criteria, which outline unique staging requirements and reflect a distinct combination of anatomic site, histology and other biologic features, were assigned to each cancer participant using the same source data for primary site of origin and histologic type. Here, we report CCGA ‘cancer class’ designation and AJCC ‘cancer type’ assignment within the third and final CCGA3 validation substudy to better characterize the diversity of tumors across which a cancer signal could be detected with the MCED test that is nearing clinical availability. Methods: CCGA is a prospective, multicenter, case-control, observational study with longitudinal follow-up (overall population N = 15,254). Plasma cfDNA from evaluable samples was analyzed using a targeted methylation bisulfite sequencing assay and a machine learning approach, and test performance, including sensitivity, was assessed. For sensitivity reporting, CCGA cancer classes were assigned to cancer participants using a combination of the type of primary cancer reported by the site and tumor characteristics abstracted from the site pathology reports by GRAIL pathologists. Each cancer participant also was separately assigned an AJCC cancer type based on the same source data using AJCC staging manual (8th edition) classifications. Results: A total of 4077 participants comprised the independent validation set with confirmed status (cancer: n = 2823; non-cancer: n = 1254 with non-cancer status confirmed at year-one follow-up). Sensitivity was reported for 24 cancer classes (sample sizes ranged from 10 to 524 participants), as well as an “other” cancer class (59 participants). According to AJCC classification, the MCED test was found to detect cancer signals across 50+ AJCC cancer types, including some types not present in the training set; some cancer types had limited representation. Conclusions: This MCED test that is nearing clinical availability and was evaluated in the third CCGA substudy detected cancer signals across 50+ AJCC cancer types. Reporting CCGA cancer classes and AJCC cancer types demonstrates the ability of the MCED test to detect cancer signals across a set of diverse cancer types representing a wide range of biologic characteristics, including cancer types that the classifier has not been trained on, and supports its use on a population-wide scale. Clinical trial information: NCT02889978.


2019 ◽  
Vol 6 (2) ◽  
Author(s):  
Priya Bhagwat ◽  
Shashi N Kapadia ◽  
Heather J Ribaudo ◽  
Roy M Gulick ◽  
Judith S Currier

Abstract Background Racial/ethnic disparities in HIV outcomes have persisted despite effective antiretroviral therapy. In a study of initial regimens, we found viral suppression varied by race/ethnicity. In this exploratory analysis, we use clinical and socioeconomic data to assess factors associated with virologic failure and adverse events within racial/ethnic groups. Methods Data were from AIDS Clinical Trial Group A5257, a randomized trial of initial regimens with either atazanavir/ritonavir, darunavir/ritonavir, or raltegravir (each combined with tenofovir DF and emtricitabine). We grouped participants by race/ethnicity and then used Cox-proportional hazards regression to examine the impact of demographic, clinical, and socioeconomic factors on the time to virologic suppression and time to adverse event reporting within each racial/ethnic group. Results We analyzed data from 1762 participants: 757 self-reported as non-Hispanic black (NHB), 615 as non-Hispanic white (NHW), and 390 as Hispanic. The proportion with virologic failure was higher for NHB (22%) and Hispanic (17%) participants compared with NHWs (9%). Factors associated with virologic failure were poor adherence and higher baseline HIV RNA level. Prior clinical AIDS diagnosis was associated with virologic failure for NHBs only, and unstable housing and illicit drug use for NHWs only. Factors associated with adverse events were female sex in all groups and concurrent use of medications for comorbidities in NHB and Hispanic participants only. Conclusions Clinical and socioeconomic factors that are associated with virologic failure and tolerability of antiretroviral therapy vary between and within racial and ethnic groups. Further research may shed light into mechanisms leading to disparities and targeted strategies to eliminate those disparities.


2021 ◽  
Author(s):  
Ruby Castilla-Puentes ◽  
Jacqueline Pesa ◽  
Caroline Brethenoux ◽  
Patrick Furey ◽  
Liliana Gil Valletta ◽  
...  

BACKGROUND The prevalence of depression symptoms in the United States is >3 times higher mid–COVID-19 versus pre-pandemic. Racial/ethnic differences in mindsets around depression and the potential impact of the COVID-19 pandemic are not well characterized. OBJECTIVE To describe attitudes, mindsets, key drivers, and barriers related to depression pre– and mid–COVID-19 by race/ethnicity using digital conversations about depression mapped to health belief model (HBM) concepts. METHODS Advanced search, data extraction, and AI-powered tools were used to harvest, mine, and structure open-source digital conversations of US adults who engaged in conversations about depression pre– (February 1, 2019-February 29, 2020) and mid–COVID-19 pandemic (March 1, 2020-November 1, 2020) across the internet. Natural language processing, text analytics, and social data mining were used to categorize conversations that included a self-identifier into racial/ethnic groups. Conversations were mapped to HBM concepts (ie, perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action, and self-efficacy). Results are descriptive in nature. RESULTS Of 2.9 and 1.3 million relevant digital conversations pre– and mid–COVID-19, race/ethnicity was determined among 1.8 million (62%) and 979,000 (75%) conversations pre– and mid–COVID-19, respectively. Pre–COVID-19, 1.3 million conversations about depression occurred among non-Hispanic Whites (NHW), 227,200 among Black Americans (BA), 189,200 among Hispanics, and 86,800 among Asian Americans (AS). Mid–COVID-19, 736,100 conversations about depression occurred among NHW, 131,800 among BA, 78,300 among Hispanics, and 32,800 among AS. Conversations among all racial/ethnic groups had a negative tone, which increased pre– to mid–COVID-19; finding support from others was seen as a benefit among most groups. Hispanics had the highest rate of any racial/ethnic group of conversations showing an avoidant mindset toward their depression. Conversations related to external barriers to seeking treatment (eg, stigma, lack of support, and lack of resources) were generally more prevalent among Hispanics, BA, and AS than among NHW. Being able to benefit others and building a support system were key drivers to seeking help or treatment for all racial/ethnic groups. CONCLUSIONS Applying concepts of the HBM to data on digital conversation about depression allowed organization of the most frequent themes by race/ethnicity. Individuals of all groups came online to discuss their depression. There were considerable racial/ethnic differences in drivers and barriers to seeking help and treatment for depression pre– and mid–COVID-19. Generally, COVID-19 has made conversations about depression more negative, and with frequent discussions of barriers to seeking care. These data highlight opportunities for culturally competent and targeted approaches to address areas amenable to change that might impact the ability of people to ask for or receive mental health help, such as the constructs that comprise the HBM.


2019 ◽  
Vol 57 (3) ◽  
pp. 177-187 ◽  
Author(s):  
Evelyn Arana ◽  
Amy Carroll-Scott ◽  
Philip M. Massey ◽  
Nora L. Lee ◽  
Ann C. Klassen ◽  
...  

Abstract Little information exists on the associations between intellectual disability (ID) and race/ethnicity on mammogram frequency. This study collected survey and medical record data to examine this relationship. Results indicated that Hispanic and Black women with ID were more likely than White women with ID to have mammograms every 2 years. Participants who live in a state-funded residence, were aged 50+, and had a mild or moderate level of ID impairment were more likely to undergo mammography compared to participants living with family or alone, were <50, and had severe ID impairment. Further research is needed to understand the mechanisms explaining disparities in mammograms between these racial/ethnic groups.


2018 ◽  
Vol 5 (1) ◽  
pp. 100-114 ◽  
Author(s):  
Edward C. Polson ◽  
Kevin D. Dougherty

Religious participation has reinforced the color line in American society for generations. Despite rising racial and ethnic diversity across U.S. communities, most Americans continue to belong to congregations composed primarily of others from their own racial/ethnic groups. Yet recent scholarship suggests that the presence of multiple racial or ethnic groups in the same congregation is increasing. The authors examine how the racial/ethnic composition of U.S. congregations is related to white attenders’ friendship networks and comfort with other racial/ethnic groups (i.e., blacks, Hispanics, and Asians). Using national survey data, the authors find that whites in multiracial congregations report more diverse friendship networks and higher levels of comfort with nonwhites than do whites in nonmultiracial congregations. However, the influence of worshipping with another race/ethnicity seems to be most pronounced for whites in congregations with Hispanics. Moreover, neighbors and friends of other races have more impact on whites’ friendship networks and attitudes than do congregations. The authors discuss implications of these findings for understanding U.S. intergroup relations and the potential of congregations to address the color line.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3069-3069
Author(s):  
Casey L O'Connell ◽  
Pedram Razavi ◽  
Roberta McKean-Cowdin ◽  
Malcolm C. Pike

Abstract Abstract 3069 Poster Board III-6 Background Acute lymphoblastic leukemia (ALL) is an aggressive malignancy whose incidence declines through adolescence and then increases steadily with age. Prognosis appears to be inversely related to age among adults. We sought to explore the impact of race/ethnicity on incidence and survival among adults with ALL in the United States (US). Methods We examined trends in incidence and survival among adults with ALL in the US using the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program which includes data from 17 SEER registries. We calculated the incidence rates for the most recent time period (2001-2005) because the classification for ALL subtypes was more complete during this time. For the survival analysis we used the data collected between 1975 and 2005. We categorized race/ethnicity into 5 mutually exclusive categories: non-Hispanic whites (NHW), Hispanic whites (HW), African Americans (AA), Asian/Pacific Islanders (API) and American Indians/Native Alaskans (AI/NA). Hispanic ethnicity was defined using SEER's Hispanic-origin variable which is based on the NAACCR Hispanic Identification Algorithm (NHIA); 11 patients dually coded as black and Hispanic were included in the AA group for our analyses. Few ALL cases were identified among AI/NA, so that group is not represented in the final analyses. We included ALL cases coded in the SEER registry using the International Classification of Disease for Oncology (ICD-0-3) as 9827-9829 and 9835-9837. We excluded cases of Burkitt's leukemia (n=228), cases that were not confirmed by microscopic or cytologic tests (n=132), cases that were reported only based on autopsy data (n=3) and cases whose race/ethnicity were unknown (n=20). The average annual incidence rates per 100,000 for 2001-2005, age-adjusted to the 2000 US standard population were calculated using SEER*Stat Version 6.4.4 statistical software. We used multivariate Cox hazard models stratified by SEER registry and age category to estimate the hazard ratios (HR) and 95% confidence intervals (95% CI) for relative survival of adult ALL cases across race/ethnicity, sex and cell of origin (B- or T-cell). All models were adjusted for the diagnosis era, and use of non-CNS radiation. The model also included an interaction term for age and diagnosis era. We performed a separate stratified analysis of the impact of race/ethnicity on survival within age subgroups (20-29, 30-39, 40-59, 60-69, 70+). Results The highest incidence rate (IR) of ALL was observed for HW (IR: 1.60; 95% CI: 1.43-1.79). HW had a significantly higher IR across all age categories as compared to the other racial/ethnic groups, while AA had the lowest IR. In particular, the observed rate of B-cell ALL among HW (IR 0.77; 95% CI 0.69-0.87) was more than twice that of NHW (IR: 0.29; 95% CI: 0.27-0.32) and more than three times the rate observed among AA (IR: 0.20; 95% CI: 0.15-0.26). In contrast, we did not observe statistically significant variability in the rates of T-cell ALL across race/ethnic groups (overall IR: 0.12; 95% CI: 0.11-0.14). Survival was significantly poorer among AA (HR: 1.26; 95% CI: 1.09-1.46), HW (HR: 1.21; 95% CI: 1.09-1.46), and API (HR: 1.18; 95% CI: 1.06-1.32) compared to NHW with all subtypes of ALL. Among adults younger than 40 with B-cell ALL, survival was significantly poorer among AA (HR: 1.60; 95% CI:1.021-2.429) and HW (HR: 1.53; 95% CI:1.204-1.943) with a non-signficant trend among API (HR: 1.22; 95% 0.834-1.755) compared to NHW. Survival differences between the different racial/ethnic groups were no longer statistically significant among adults with B-cell ALL over the age of 40. For T-cell ALL, survival was significantly poorer among AA (HR: 1.61; 95% CI: 1.22-2.10), HW (HR: 1.49; 95% CI: 1.14-1.93) and API (HR: 1.57; 95% CI: 1.13-2.13), as compared to NHW. A similar survival pattern by age (adults above and below age 40 years) was observed for T-cell as described for B-cell, with AA under 40 having a particularly dismal prognosis (HR: 2.89; 95% CI 1.96-4.17) compared to NHW. Conclusions The incidence rate of B-cell ALL among adults in the US is higher among HW than other ethnic groups. Survival is significantly poorer among AA and HW than among NHW under the age of 40 with B-cell ALL. Survival is also significantly poorer among AA, HW and API than among NHW with T-cell ALL in adults under 40. Survival trends appear to converge after the age of 40 among all racial/ethnic groups. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 380-380 ◽  
Author(s):  
Rachel M Lee ◽  
Yuan Liu ◽  
Mohammad Yahya Zaidi ◽  
Adriana Carolina Gamboa ◽  
Maria C. Russell ◽  
...  

380 Background: Inequities in cancer survival are well documented. Whether disparities in overall survival (OS) result from inherent racial differences in underlying disease biology or socioeconomic factors (SEF) is not known. Our aim was to define the association of race/ethnicity and SEF with OS in pts with cholangiocarcinoma (CCA). Methods: Pts with CCA of all sites and stages in the National Cancer Data Base (2004-14) were included. Racial/ethnic groups were defined as non-Hispanic White (NH-W), non-Hispanic Black (NH-B), Asian, and Hispanic. Income and education were based on census data for pts’ zip code. Income was defined as high (³$63,000) vs low ( < $63,000). Primary outcome was OS. Results: 27,151 pts were included with a mean age of 68 yrs; 51% were male. 78% were NH-W, 8% NH-B, 6% Asian, and 6% Hispanic. 56% had Medicare, 33% private insurance, 7% Medicaid, and 4% were uninsured. 67% had high income. 21% lived in an area where > 20% of adults did not finish high school. NH-B and Hispanic pts had more unfavorable SEF including uninsured status, low income, and less formal education than NH-W and Asian pts (all p < 0.001). They were also younger, more likely to be female and to have metastatic disease (all p < 0.001). Despite this, NH-B race and Hispanic ethnicity were not associated with decreased OS. Male sex, older age, non-private insurance, low income, lower education, non-academic facility, location outside the Northeast, higher Charlson-Deyo score, worse grade, larger tumor size, and higher stage were all associated with decreased OS (all p < 0.001). On MV analysis, along with adverse pathologic factors, type of insurance (p = 0.003), low income (p < 0.001), and facility type and location of treatment (p < 0.001) remained associated with decreased OS; non-white race/ethnicity was not. Conclusions: Disparities in survival exist in CCA, however they are not driven by race/ethnicity. Non-privately insured and low-income pts had decreased OS, as did pts treated at non-academic centers and outside the Northeast. This suggests that decreased ability to access and afford care results in worse outcomes, rather than biological differences amongst racial/ethnic groups.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24092-e24092
Author(s):  
Monica F. Chen ◽  
Daniel K. Manson ◽  
Ariel Yuan ◽  
Katherine D. Crew

e24092 Background: Trastuzumab improves breast cancer survival but is associated with an increased risk of heart failure. Identifying risk factors associated with trastuzumab induced cardiotoxicity (TIC) would allow for more targeted and intensive screening for at-risk patients. Hypertension is one of the most consistent predictors of TIC. Racial/ethnic minorities are at higher risk of cardiovascular disease but are under-represented in studies of TIC. The objective of this study was to evaluate the relationship between race/ethnicity and risk of TIC among a diverse cohort of patients with HER2-positive early-stage breast cancer. Methods: We conducted a retrospective cohort study of patients treated at Columbia University between 2007 and 2016 for stage I-III breast cancer with adjuvant or neoadjuvant trastuzumab who had at least two echocardiograms. Mild TIC was defined as a ≥10% decline in left ventricular ejection fraction (LVEF); moderate TIC ≥15% decline; severe TIC ≥20% or decline in LVEF to < 50%. Diagnosis of hypertension, average systolic and diastolic blood pressure, and number of hypertension medications was assessed 1- year pre-treatment, during treatment, and 1-year post-treatment. We generated descriptive statistics and used multivariable logistic regression to evaluate demographic and clinical factors associated with TIC. Results: Of 279 patients evaluated, 36.6% were non-Hispanic white, 18.3% non-Hispanic black, 34.8% Hispanic, and 10.4% Asian. The average baseline LVEF was 60% and did not significantly differ between racial/ethnic groups. Mild TIC developed in 33.3% of patients, moderate TIC 18.6%, severe TIC 15.8%, and 14.7% with LVEF decline to < 50%. Patients with hypertension were at increased odds of developing TIC (OR = 2.41, 95% CI = 1.15-3.93; p = 0.02). Prevalence of hypertension was 53% among non-Hispanic white women, 69% non-Hispanic black, 53% Hispanic, and 39% Asian. Incidence of TIC did not differ significantly between racial/ethnic groups. Forty percent of patients with hypertension were not on any medications before initiating trastuzumab. Conclusions: There was no difference in TIC based upon race/ethnicity despite higher rates of hypertension among racial/ethnic minorities compared to non-Hispanic whites. However, a high portion of patients with hypertension were not on any medications before treatment. Increased screening and treatment of hypertension among patients receiving HER2-positive targeted therapy for early-stage breast cancer may be warranted.


2020 ◽  
Author(s):  
Alexandra Sara Aringer ◽  
Jimmy Calanchini

People with mental illness are often stereotyped as dangerous, unstable, or unreliable, and these stereotypes perpetuate prejudice against those who are already vulnerable. However, many of these stereotypes are Eurocentric due to a lack of diversity within psychology. The present, preregistered research investigates whether depictions of mental illness are idiosyncratic to various racial/ethnic groups, or if these perceptions generalize across groups. Participants reported their endorsement of a series of mental illness descriptions (e.g., “This person spontaneously explodes in outbursts of anger”) as they apply to African Americans, Asian Americans, Hispanic/Latinxs, Caucasians, as well as to individuals with unspecified race/ethnicity. Exploratory factor analyses of these descriptions revealed three factors that describe mentally ill people -- ashamed, self-destructive, irresponsible -- and participants’ perceptions of mental illness on these three factors varied by racial/ethnic groups. Participants rated Asian Americans as more ashamed, but less self-destructive and irresponsible than other racial/ethnic groups. Conversely, participants rated Caucasians as less ashamed, but more self-destructive and irresponsible than other racial/ethnic groups. Perceptions of mental illness did not differ between Hispanic/Latinxs and African Americans. Additional analyses indicate that, compared to Caucasian participants, non-Caucasian participants rated mentally ill members of their ingroup as more ashamed but less self-destructive and irresponsible. This research indicates that participants from different racial/ethnic groups vary in the extent to which they ascribe different facets of mental illness to their ingroup versus outgroups. Implications for Eurocentric versus more diverse perceptions of mental illness are discussed.


Author(s):  
Melissa Flores ◽  
John M Ruiz ◽  
Emily A Butler ◽  
David A Sbarra

Abstract Background and Purpose Hispanic ethnic density (HED) is associated with salubrious health outcomes for Hispanics, yet recent research suggests it may also be protective for other groups. The purpose of this study was to test whether HED was protective for other racial-ethnic groups. We tested whether social support or neighborhood social integration mediated the association between high HED and depressive symptoms (CES-D) and physical morbidity 5 years later. Lastly, we tested whether race-ethnicity moderated both main and indirect effects. Methods We used Waves 1 (2005–2006), and 2 (2010–2011) from The National Social Life, Health, and Aging Project, a national study of older U.S. adults. Our sample was restricted to Wave 1 adults who returned at Wave 2, did not move from their residence between waves, and self-identified as Hispanic, non-Hispanic White (NHW), or non-Hispanic Black (NHB; n = 1,635). We geo-coded respondents’ addresses to a census-tract and overlaid racial–ethnic population data. Moderated-mediation models using multiple imputation (to handle missingness) and bootstrapping were used to estimate indirect effects for all racial–ethnic categories. Results Depressive symptoms were lower amongst racial-ethnic minorities in ethnically (Hispanic) dense neighborhoods; this effect was not stronger in Hispanics. HED was not associated with physical morbidity. Sensitivity analyses revealed that HED was protective for cardiovascular events in all racial–ethnic groups, but not arthritis, or respiratory disease. Social support and neighborhood social integration were not mediators for the association between HED and outcomes, nor were indirect effects moderated by race–ethnicity. Conclusions This study offers some evidence that HED may be protective for some conditions in older adults; however, the phenomena underlying these effects remains a question for future work.


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