Towards precision cancer medicine for Aboriginal and Torres Strait Islander cancer health equity.

Delivering cancer control at scale for Aboriginal and Torres Strait Islander communities is a national priority that requires Aboriginal and Torres Strait Islander leadership and codesign, as well as significant involvement of the Aboriginal community-controlled health sector. The unique genomic variation observed among Aboriginal and Torres Strait Islander peoples may have implications for standard and precision medicine. Yet, Aboriginal and Torres Strait Islander peoples are absent from, or under-represented within, human reference genome resources, genomic studies, cancer studies, cancer cell lines, patient-derived xenografts and cancer clinical trials. Genomics-guided precision cancer medicine offers an opportunity to reduce cancer health disparities experienced by Aboriginal and Torres Strait Islander peoples through personalising prevention, diagnosis, treatment and long term management. Here, we describe what is required to ensure that Aboriginal and Torres Strait Islander peoples can receive the benefits of precision cancer medicine. Equity of access to care, an Aboriginal and Torres Strait Islander cancer workforce, and appropriate genome reference resources are important for safe and effective cancer medicine. Building Indigenous data sovereignty principles and Aboriginal and Torres Strait Islander governance into research is required to protect Aboriginal and Torres Strait Islander rights and collective interests. Aboriginal and Torres Strait Islander community engagement should be undertaken to develop an understanding of the unique cultural and ethical considerations for precision cancer research. Local and national genomic health research guidelines are needed to define a consensus best practice in genomics research with Aboriginal and Torres Strait Islander peoples.

Race and Ethnicity, Socioeconomic Factors, and Epigenetic Age Acceleration in Survivors of Childhood Cancer.

Importance: Current research in epigenetic age acceleration (EAA) is limited to non-Hispanic White individuals. It is imperative to improve inclusivity by considering racial and ethnic minorities in EAA research. Objective: To compare non-Hispanic Black with non-Hispanic White survivors of childhood cancer by examining the associations of EAA with cancer treatment exposures, potential racial and ethnic disparity in EAA, and mediating roles of social determinants of health (SDOH). Design, Setting, and Participants: In this cross-sectional study, participants were from the St Jude Lifetime Cohort, which was initiated in 2007 with ongoing follow-up. Eligible participants included non-Hispanic Black and non-Hispanic White survivors of childhood cancer treated at St Jude Children's Research Hospital between 1962 and 2012 who had DNA methylation data. Data analysis was conducted from February 2023 to May 2024. Exposure: Three treatment exposures for childhood cancer (chest radiotherapy, alkylating agents, and epipodophyllotoxin). Main Outcomes and Measures: DNA methylation was generated from peripheral blood mononuclear cell-derived DNA. EAA was calculated as residuals from regressing Levine or Horvath epigenetic age on chronological age. SDOH included educational attainment, annual personal income, and the socioeconomic area deprivation index (ADI). General linear models evaluated cross-sectional associations of EAA with race and ethnicity (non-Hispanic Black and non-Hispanic White) and/or SDOH, adjusting for sex, body mass index, smoking, and cancer treatments. Adjusted least square means (ALSM) of EAA were calculated for group comparisons. Mediation analysis treated SDOH as mediators with average causal mediation effect (ACME) calculated for the association of EAA with race and ethnicity. Results: Among a total of 1706 survivors including 230 non-Hispanic Black survivors (median [IQR] age at diagnosis, 9.5 [4.3-14.3] years; 103 male [44.8%] and 127 female [55.2%]) and 1476 non-Hispanic White survivors (median [IQR] age at diagnosis, 9.3 [3.9-14.6] years; 766 male [51.9%] and 710 female [48.1%]), EAA was significantly greater among non-Hispanic Black survivors (ALSM = 1.41; 95% CI, 0.66 to 2.16) than non-Hispanic White survivors (ALSM = 0.47; 95% CI, 0.12 to 0.81). Among non-Hispanic Black survivors, EAA was significantly increased among those exposed to chest radiotherapy (ALSM = 2.82; 95% CI, 1.37 to 4.26) vs those unexposed (ALSM = 0.46; 95% CI, -0.60 to 1.51), among those exposed to alkylating agents (ALSM = 2.33; 95% CI, 1.21 to 3.45) vs those unexposed (ALSM = 0.95; 95% CI, -0.38 to 2.27), and among those exposed to epipodophyllotoxins (ALSM = 2.83; 95% CI, 1.27 to 4.40) vs those unexposed (ALSM = 0.44; 95% CI, -0.52 to 1.40). The association of EAA with epipodophyllotoxins differed by race and ethnicity (ß for non-Hispanic Black survivors, 2.39 years; 95% CI, 0.74 to 4.04 years; ß for non-Hispanic White survivors, 0.68; 95% CI, 0.05 to 1.31 years) and the difference was significant (1.77 years; 95% CI, 0.01 to 3.53 years; P for interaction = .049). Racial and ethnic disparities in EAA were mediated by educational attainment (

Types of Racism and Health Disparities and Inequalities among Cancer Patients: An Editorial Reflection of Articles in This Special Issue of IJERPH.

Racism has been a long-standing influential factor that has negatively impacted both past and current health disparities within the United Sates population. Existing problems of racism and its impact on both health disparities and health inequalities were only amplified during the COVID-19 pandemic. The pandemic allowed both clinicians and researchers to recognize a growing list of health concerns at the macro-, meso-, and micro-level among underserved racially minoritized patients with specific chronic illnesses such as cancer. Based on these concerns, this Special Issue was designed to highlight the challenges of cancer screening, cancer treatment, and cancer-centered educational outreach among racially minoritized communities.

Racial and Ethnic Disparities in Cancer Occurrence and Outcomes in Rural United States: A Scoping Review.

BACKGROUND: Cancer is the second-leading cause of death in the United States. Most studies have reported rural versus urban and Black versus White cancer disparities. However, few studies have investigated racial disparities in rural areas. OBJECTIVE: We conducted a literature review to explore the current state of knowledge on racial and ethnic disparities in cancer attitudes, knowledge, occurrence, and outcomes in rural United States. METHODS: A systematic search of PubMed and Embase was performed. Peer-reviewed articles published in English from 2004-2023 were included. Three authors independently reviewed the articles and reached a consensus. RESULTS: After reviewing 993 articles, a total of 30 articles met the inclusion criteria and were included in the present review. Studies revealed that underrepresented racial and ethnic groups in rural areas were more likely to have low cancer-related knowledge, low screening, high incidence, less access to treatment, and high mortality compared to their White counterparts. CONCLUSION: Underrepresented racial and ethnic groups in rural areas experienced a high burden of cancer. Improving social determinants of health may help reduce cancer disparities and promote health.

A scoping review of racial, ethnic, socioeconomic, and geographic disparities in the outcomes of older adults with cancer.

INTRODUCTION: Cancer health disparities are widespread. Nevertheless, the disparities in outcomes among diverse survivors of cancer ages 65 years and older ("older") have not been systematically evaluated. METHODS: We conducted a scoping review of original research articles published between January 2016 and September 2023 and indexed in Medline (Ovid), Embase, Scopus, and CINAHL databases. We included studies evaluating racial, ethnic, socioeconomic disadvantaged, geographic, sexual and gender, and/or persons with disabilities disparities in treatment, survivorship, and mortality among older survivors of cancer. We excluded studies with no a priori aims related to a health disparity, review articles, conference proceedings, meeting abstracts, studies with unclear methodologies, and articles in which the disparity group was examined only as an analytic covariate. Two reviewers independently extracted data following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis reporting guidelines. RESULTS: After searching and removing duplicates, 2573 unique citations remained and after screening 59 articles met the inclusion criteria. Many investigated more than one health disparity, and most focused on racial and ethnic (n = 44) or socioeconomic (n = 25) disparities; only 10 studies described geographic disparities, and none evaluated disparities in persons with disabilities or due to sexual and gender identity. Research investigating disparities in outcomes among diverse older survivors of cancer is increasing gradually-68% of eligible articles were published between 2020 and 2023. Most studies focused on the treatment phase of care (n = 28) and mortality (n = 26), with 16 examined disparities in survivorship, symptoms, or quality of life. Most research was descriptive and lacked analyses of potential underlying mechanisms contributing to the reported disparities. CONCLUSION: Little research has evaluated the effect of strategies to reduce health disparities among older patients with cancer. This lack of evidence perpetuates cancer inequities and leaves the cancer care system ill equipped to address the unique needs of the rapidly growing and increasingly diverse older adult cancer population.

A qualitative exploration of the non-financial costs of cancer care for Aboriginal and Torres Strait Islander Australians.

OBJECTIVE: Knowledge is growing about cancer care and financial costs for Aboriginal and Torres Strait Islander people. However, much remains unknown about the true costs of cancer care, encompassing financial, emotional, and spiritual aspects. We aimed to explore and explain how non-financial costs affect the health-seeking behaviours of these clients. METHODS: Following Indigenous research protocols, this research was led by Aboriginal and Torres Strait Islander researchers and guided by Indigenous Hospital Liaison Officers. In-depth interviews and focus groups were conducted with 29 participants (Aboriginal and Torres Strait Islander cancer clients, their carers, and cancer-care professionals) at two Queensland public hospitals. RESULTS: Four interwoven themes encompass non-financial costs of healthcare: leaving home and family; loss of control during cancer treatment; health of the spirit; social costs. The Aboriginal relational concept of 'being held' is useful in considering client, family, and carer as central to care with the Indigenous Hospital Liaison Officer two-way interpreting between the care and client team. IMPLICATIONS FOR PUBLIC HEALTH: Framing the reasons that clients and carers have difficulty in engaging in treatment as 'costs' enables a focus on how the health system itself is implicated in the disengagement of Aboriginal and Torres Strait Islander clients from treatment.

Disparities in Cancer Screening in Sexual and Gender Minority Populations: A Secondary Analysis of Behavioral Risk Factor Surveillance System Data.

OBJECTIVES: To describe cancer screening characteristics and better understand individual-, environmental-, and organizational-level barriers of sexual and gender minority (SGM) populations. . SAMPLE & SETTING: This study was conducted using a combined sample from the Behavioral Risk Factor Surveillance System (BRFSS) national dataset from 2014 and 2016. METHODS & VARIABLES: Chi-square tests for independence and logistic regression analysis tests were performed to determine whether relationships existed between SGM status and demographics. RESULTS: Black respondents or those who reported their race as other, were female, had some college or technical school or more, and had healthcare coverage were less likely to present for cancer screening. SGM respondents who were in good or better health; were unmarried; were aged 18-44 years or 45-55 years; or were Asian, Native American, or Hawaiian, or reported their race as other, had higher odds of screening for cancer. IMPLICATIONS FOR NURSING: Disparities in cancer screening among SGM populations are not well documented. These findings will inform structured education and preventative interventions to improve screening participation among SGM populations.

Creating and Implementing a Community Engagement Strategy for the 2022-2027 Illinois Comprehensive Cancer Control Plan Through an Academic-State Public Health Department Partnership.

INTRODUCTION: Comprehensive cancer control (CCC) plans are state-level blueprints that identify regional cancer priorities and health equity strategies. Coalitions are encouraged to engage with community members, advocacy groups, people representing multiple sectors, and working partners throughout the development process. We describe the community and legislative engagement strategy developed and implemented during 2020-2022 for the 2022-2027 Illinois CCC plan. METHODS: The engagement strategies were grounded in theory and evidence-based tools and resources. It was developed and implemented by coalition members representing the state health department and an academic partner, with feedback from the larger coalition. The strategy included a statewide town hall, 8 focus groups, and raising awareness of the plan among state policy makers. RESULTS: A total of 112 people participated in the town hall and focus groups, including 40 (36%) cancer survivors, 31 (28%) cancer caregivers, and 18 (16%) Latino and 26 (23%) African American residents. Fourteen of 53 (26%) focus group participants identified as rural. Participants identified drivers of cancer disparities (eg, lack of a comprehensive health insurance system, discrimination, transportation access) and funding and policy priorities. Illinois House Resolution 0675, the Illinois Cancer Control Plan, was passed in March 2022. CONCLUSION: The expertise and voices of community members affected by cancer can be documented and reflected in CCC plans. CCC plans can be brought to the attention of policy makers. Other coalitions working on state plans may consider replicating our strategy. Ultimately, CCC plans should reflect health equity principles and prioritize eliminating cancer disparities.

Disparities in Socioeconomic Factors Mediate the Impact of Racial Segregation Among Patients With Hepatopancreaticobiliary Cancer.

BACKGROUND: Structural racism within the U.S. health care system contributes to disparities in oncologic care. This study sought to examine the socioeconomic factors that underlie the impact of racial segregation on hepatopancreaticobiliary (HPB) cancer inequities. METHODS: Both Black and White patients who presented with HPB cancer were identified from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2005-2015) and 2010 Census data. The Index of Dissimilarity (IoD), a validated measure of segregation, was examined relative to cancer stage at diagnosis, surgical resection, and overall mortality. Principal component analysis and structural equation modeling were used to determine the mediating effect of socioeconomic factors. RESULTS: Among 39,063 patients, 86.4 % (n = 33,749) were White and 13.6 % (n = 5314) were Black. Black patients were more likely to reside in segregated areas than White patients (IoD, 0.62 vs. 0.52; p < 0.05). Black patients in highly segregated areas were less likely to present with early-stage disease (relative risk [RR], 0.89; 95 % confidence interval [CI] 0.82-0.95) or undergo surgery for localized disease (RR, 0.81; 95% CI 0.70-0.91), and had greater mortality hazards (hazard ratio 1.12, 95% CI 1.06-1.17) than White patients in low segregation areas (all p < 0.05). Mediation analysis identified poverty, lack of insurance, education level, crowded living conditions, commute time, and supportive income as contributing to 25 % of the disparities in early-stage presentation. Average income, house price, and income mobility explained 17 % of the disparities in surgical resection. Notably, average income, house price, and income mobility mediated 59 % of the effect that racial segregation had on long-term survival. CONCLUSION: Racial segregation, mediated through underlying socioeconomic factors, accounted for marked disparities in access to surgical care and outcomes for patients with HPB cancer.

Cancer Distribution Among Asian, Native Hawaiian, and Pacific Islander Subgroups - United States, 2015-2019.

Non-Hispanic Asian (Asian) and non-Hispanic Native Hawaiian and Pacific Islander (NHPI) persons represent growing segments of the U.S. population (1). Epidemiologic cancer studies often aggregate Asian and NHPI persons (2,3); however, because Asian and NHPI persons are culturally, geographically, and linguistically diverse (2,4), subgroup analyses might provide insights into the distribution of health outcomes. To examine the frequency and percentage of new cancer cases among 25 Asian and NHPI subgroups, CDC analyzed the most current 2015-2019 U.S. Cancer Statistics data.* The distribution of new cancer cases among Asian and NHPI subgroups differed by sex, age, cancer type, and stage at diagnosis (for screening-detected cancers). The percentage of cases diagnosed among females ranged from 47.1% to 68.2% and among persons aged <40 years, ranged from 3.1% to 20.2%. Among the 25 subgroups, the most common cancer type varied. For example, although breast cancer was the most common in 18 subgroups, lung cancer was the most common cancer among Chamoru, Micronesian race not otherwise specified (NOS), and Vietnamese persons; colorectal cancer was the most common cancer among Cambodian, Hmong, Laotian, and Papua New Guinean persons. The frequency of late-stage cancer diagnoses among all subgroups ranged from 25.7% to 40.3% (breast), 38.1% to 61.1% (cervical), 52.4% to 64.7% (colorectal), and 70.0% to 78.5% (lung). Subgroup data illustrate health disparities among Asian and NHPI persons, which might be reduced through the design and implementation of culturally and linguistically responsive cancer prevention and control programs, including programs that address social determinants of health.

Radiotherapy Deserts: The Impact of Race, Poverty, and the Rural-Urban Continuum on Density of Providers and the Use of Radiation Therapy in the US.

PURPOSE: Prior efforts to characterize disparities in radiation therapy access and receipt have not comprehensively investigated interplay between race, socioeconomic status, and geography relative to oncologic outcomes. This study sought to define these complex relationships at the US county level for prostate cancer (PC) and invasive breast (BC) cancer to build a tool that facilitates identification of "radiotherapy deserts"-regions with mismatch between radiation therapy resources and oncologic need. METHODS AND MATERIALS: An ecologic study model was constructed using national databases to evaluate 3,141 US counties. Radiation therapy resources and use densities were operationalized as physicians to persons at risk (PPR) and use to persons at risk (UPR): the number of attending radiation oncologists and Medicare beneficiaries per 100,000 persons at risk, respectively. Oncologic need was defined by "hot zone" counties with ≥2 standard deviations (SDs) above mean incidence and death rates. Univariable and multivariable logistic regressions examined links between PPR and UPR densities, epidemiologic variables, and hot zones for oncologic outcomes. Statistics are reported at a significance level of P < .05. RESULTS: The mean (SD) PPR and UPR densities were 2.1 (5.9) and 192.6 (557.6) for PC and 1.9 (5.3) and 174.4 (501.0) for BC, respectively. Counties with high PPR and UPR densities were predominately metropolitan (odds ratio [OR], 2.9-4.4), generally with a higher percentage of Black non-Hispanic constituents (OR, 1.5-2.3). Incidence and death rate hot zones were largely nonmetropolitan (OR, 0.3-0.6), generally with a higher percentage of Black non-Hispanic constituents (OR, 3.2-6.3). Lower PPR density was associated with death rate hot zones for both types of cancer (OR, 0.8-0.9); UPR density was generally not linked to oncologic outcomes on multivariable analysis. CONCLUSIONS: The study found that mismatch between oncologic need with PPR and UPR disproportionately affects nonmetropolitan communities with a higher percentage of Black non-Hispanic constituents. An interactive web platform (bit.ly/densitymaps) was developed to visualize "radiotherapy deserts" and drive targeted investigation of underlying barriers to care in areas of highest need, with the goal of reducing health inequities in this context.

Understanding the role of access in Hispanic cancer screening disparities.

BACKGROUND: Hispanic populations in the United States experience numerous barriers to care access. It is unclear how cancer screening disparities between Hispanic and non-Hispanic White individuals are explained by access to care, including having a usual source of care and health insurance coverage. METHODS: A secondary analysis of the 2019 National Health Interview Survey was conducted and included respondents who were sex- and age-eligible for cervical (n = 8316), breast (n = 6025), or colorectal cancer screening (n = 11,313). The proportion of ever screened and up to date for each screening type was compared.  Regression models evaluated whether controlling for reporting a usual source of care and type of health insurance (public, private, none) attenuated disparities between Hispanics and non-Hispanic White individuals. RESULTS: Hispanic individuals were less likely than non-Hispanic White individuals to be up to date with cervical cancer screening (71.6% vs. 74.6%) and colorectal cancer screening (52.9% vs. 70.3%), but up-to-date screening was similar for breast cancer (78.8% vs. 76.3%). Hispanic individuals (vs. non-Hispanic White) were less likely to have a usual source of care (77.9% vs. 86.0%) and more likely to be uninsured (23.6% vs. 7.1%). In regressions, insurance fully attenuated cervical cancer disparities. Controlling for both usual source of care and insurance type explained approximately half of the colorectal cancer screening disparities (adjusted risk difference: -8.3 [-11.2 to -4.8]). CONCLUSION: Addressing the high rate of uninsurance among Hispanic individuals could mitigate cancer screening disparities. Future research should build on the relative successes of breast cancer screening and investigate additional barriers for colorectal cancer screening. PLAIN LANGUAGE SUMMARY: This study uses data from a national survey to compare cancer screening use those who identify as Hispanic with those who identify as non-Hispanic White. Those who identify as Hispanic are much less likely to be up to date with colorectal cancer screening than those who identify as non-Hispanic White, slightly less likely to be up to date on cervical cancer screening, and similarly likely to receive breast cancer screening. Improving insurance coverage is important for health equity, as is further exploring what drives higher use of breast cancer screening and lower use of colorectal cancer screening.

Equitable Representation of Latinos in Clinical Research Is Needed to Achieve Health Equity in Cancer Care.

PURPOSE: Identify key barriers that keep Latinos from participating in clinical trials (CTs) and interventions proven effective in increasing their representation in clinical research. METHODS: Utilize our own extensive research experience and review the literature to: identify key barriers, summarize strategies that have been proven effective in increasing Latino representation in CTs, issue a call to action for programs/practices and practitioners to implement what is proven effective, and make recommendations for further research to address current gaps. RESULTS: Participation barriers are complex, multifactorial, and exist at different levels, including study design (eg, protocol complexity, patient exclusion criteria, trial duration and frequency), healthcare system barriers (eg, lack of minority staff), patient-related factors (eg, lack of awareness, low health literacy, language, social determinants of health [SDoH]), and medical team issues (eg, lack of cultural competence, lack of referrals, implicit bias, provider/patient communication). Research has shown that the most effective strategies to increase participation of underrepresented minorities in CTs include culturally sensitive educational tools aimed at community members, patients, and physicians, and strategies to address the multiple SDoH and other barriers to participation facing cancer patients and the factors that influence patient decision-making. CONCLUSION: Raising awareness or offering clinical trials to everyone will not alone increase Latino participation. Other key barriers at different levels must also be addressed, especially SDoH and patients' contextual factors. To achieve equitable participation of Latinos and other underrepresented groups in clinical research, comprehensive approaches that address interrelated multilevel and multifactorial barriers to participation can produce a substantial, sustained impact-ensuring everyone equitably benefits from scientific advances in cancer treatment, improved cancer outcomes and quality of life, and reduced health care costs.

Strategies to Increase Participation of African Populations in Clinical Trials.

Conducting clinical research in low- and middle-income countries is essential to address the global impact of cancer. In 2017, ASCO convened an Academic Global Oncology Task Force that recommended an increase in global oncology research to enhance the field of oncology through research and education. The emerging crisis of cancer in Africa demands a similar global commitment to workforce development, infrastructure building, and access to care that will provide a platform for impactful and relevant research efforts. In the words of the African Organisation for Research and Training in Cancer, it is time to "transform cancer control in Africa through collaboration in education, research, (and) delivery of equitable and timely interventions to minimize the impact of cancer." Although there are some initiatives aimed at developing research capacity to host trials in Africa, there is now a need to establish strategic partnerships with the aim of achieving harmonized, accredited clinical trial units capable of running trials according to Good Clinical Practice standards.

Trends in Cancer Mortality Among Black Individuals in the US From 1999 to 2019.

Importance: Cancer is the second leading cause of mortality in the US. Despite national decreases in cancer mortality, Black individuals continue to have the highest cancer death rates. Objective: To examine national trends in cancer mortality from 1999 to 2019 among Black individuals by demographic characteristics and to compare cancer death rates in 2019 among Black individuals with rates in other racial and ethnic groups. Design, Setting, and Participants: This serial cross-sectional study used US national death certificate data obtained from the National Center for Health Statistics and included all cancer deaths among individuals aged 20 years or older from January 1999 to December 2019. Data were analyzed from June 2021 to January 2022. Exposures: Age, sex, and race and ethnicity. Main Outcomes and Measures: Trends in age-standardized mortality rates and average annual percent change (AAPC) in rates were estimated by cancer type, age, sex, and race and ethnicity. Results: From 1999 to 2019, 1 361 663 million deaths from cancer occurred among Black individuals. The overall cancer death rate significantly decreased among Black men (AAPC, -2.6%; 95% CI, -2.6% to -2.6%) and women (AAPC, -1.5%; 95% CI, -1.7% to -1.3%). Death rates decreased for most cancer types, with the greatest decreases observed for lung cancer among men (AAPC, -3.8%; 95% CI, -4.0% to -3.6%) and stomach cancer among women (AAPC, -3.4%; 95% CI, -3.6% to -3.2%). Lung cancer mortality also had the largest absolute decreases among men (-78.5 per 100 000 population) and women (-19.5 per 100 000 population). We observed a significant increase in deaths from liver cancer among men (AAPC, 3.8%; 95% CI, 3.0%-4.6%) and women (AAPC, 1.8%; 95% CI, 1.2%-2.3%) aged 65 to 79 years. There was also an increasing trend in uterus cancer mortality among women aged 35 to 49 years (2.9%; 95% CI, 2.3% to 2.6%), 50 to 64 years (2.3%; 95% CI, 2.0% to 2.6%), and 65 to 79 years (1.6%; 95% CI, 1.2% to 2.0%). In 2019, Black men and women had the highest cancer mortality rates compared with non-Hispanic American Indian/Alaska Native, Asian or Pacific Islander, and White individuals and Hispanic/Latino individuals. Conclusions and Relevance: In this cross-sectional study, there were substantial decreases in cancer death rates among Black individuals from 1999 to 2019, but higher cancer death rates among Black men and women compared with other racial and ethnic groups persisted in 2019. Targeted interventions appear to be needed to eliminate social inequalities that contribute to Black individuals having higher cancer mortality.

Exploiting the tumor immune microenvironment and immunometabolism using mitochondria-targeted drugs: Challenges and opportunities in racial disparity and cancer outcome research.

Black and Hispanic cancer patients have a higher incidence of cancer mortality. Many factors (e.g., socioeconomic differences, insufficient access to healthcare) contribute to racial disparity. Emerging research implicates biological disparity in cancer outcomes. Studies show distinct differences in the tumor immune microenvironment (TIME) in Black cancer patients. Studies also have linked altered mitochondrial metabolism to changes in immune cell activation in TIME. Recent publications revealed a novel immunomodulatory role for triphenylphosphonium-based mitochondrial-targeted drugs (MTDs). These are synthetically modified, naturally occurring molecules (e.g., honokiol, magnolol, metformin) or FDA-approved small molecule drugs (e.g., atovaquone, hydroxyurea). Modifications involve conjugating the parent molecule via an alkyl linker chain to a triphenylphosphonium moiety. These modified molecules (e.g., Mito-honokiol, Mito-magnolol, Mito-metformin, Mito-atovaquone, Mito-hydroxyurea) accumulate in tumor cell mitochondria more effectively than in normal cells and inhibit mitochondrial respiration, induce reactive oxygen species, activate AMPK and redox transcription factors, and inhibit cancer cell proliferation. Besides these intrinsic effects of MTDs in redox signaling and proliferation in tumors, MTDs induced extrinsic effects in the TIME of mouse xenografts. MTD treatment inhibited tumor-suppressive immune cells, myeloid-derived suppressor cells, and regulatory T cells, and activated T cells and antitumor immune effects. One key biological disparity in Black cancer patients was related to altered mitochondrial oxidative metabolism; MTDs targeting vulnerabilities in tumor cells and the TIME may help us understand this biological disparity. Clinical trials should include an appropriate number of Black and Hispanic cancer patients and should validate the intratumoral, antihypoxic effects of MTDs with imaging.

Disparities in Care Management During Terminal Hospitalization Among Adults With Metastatic Cancer From 2010 to 2017.

Importance: Many patients with metastatic cancer receive high-cost, low-value care near the end of life. Identifying patients with a high likelihood of receiving low-value care is an important step to improve appropriate end-of-life care. Objective: To analyze patterns of care and interventions during terminal hospitalizations and examine whether care management is associated with sociodemographic status among adult patients with metastatic cancer at the end of life. Design, Setting, and Participants: This retrospective, population-based cross-sectional study used data from the Healthcare Cost and Utilization Project to analyze all-payer, encounter-level information from multiple inpatient centers in the US. All utilization and hospital charge records from national inpatient sample data sets between January 1, 2010, and December 31, 2017 (n = 58 761 097), were screened. The final cohort included 21 335 patients 18 years and older at inpatient admission who had a principal diagnosis of metastatic cancer and died during hospitalization. Data for the current study were analyzed from January 1, 2010, to December 31, 2017. Exposures: Patient demographic characteristics, patient insurance status, hospital location, and hospital teaching status. Main Outcomes and Measures: Receipt of systemic therapy (including chemotherapy and immunotherapy), receipt of invasive mechanical ventilation, emergency department (ED) admission, time from hospital admission to death, and total charges during a terminal hospitalization. Results: Among 21 335 patients with metastatic cancer who had terminal hospitalizations between 2010 and 2017, the median age was 65 years (interquartile range, 56-75 years); 54.0% of patients were female; 0.5% were American Indian, 3.3% were Asian or Pacific Islander, 14.1% were Black, 7.5% were Hispanic, 65.9% were White, and 3.1% were identified as other; 58.2% were insured by Medicare or Medicaid, and 33.2% were privately insured. Overall, 63.2% of patients were admitted from the ED, 4.6% received systemic therapy, and 19.2% received invasive mechanical ventilation during hospitalization. Racial and ethnic minority patients had a higher likelihood of being admitted from the ED (Asian or Pacific Islander patients: odds ratio [OR], 1.43 [95% CI, 1.20-1.72]; P < .001; Black patients: OR, 1.39 [95% CI, 1.27-1.52]; P < .001; and Hispanic patients: OR, 1.45 [95% CI, 1.28-1.64]; P < .001), receiving invasive mechanical ventilation (Black patients: OR, 1.59 [95% CI, 1.44-1.75]; P < .001), and incurring higher total charges (Asian or Pacific Islander patients: OR, 1.35 [95% CI, 1.13-1.60]; P = .001; Black patients: OR, 1.23 [95% CI, 1.13-1.34]; P < .001; and Hispanic patients: OR, 1.50 [95% CI, 1.34-1.69]; P < .001) compared with White patients. Privately insured patients had a lower likelihood of being admitted from the ED (OR, 0.47 [95% CI, 0.44-0.51]; P < .001), receiving invasive mechanical ventilation (OR, 0.75 [95% CI, 0.69-0.82]; P < .001), and incurring higher total charges (OR, 0.64 [95% CI, 0.59-0.68]; P < .001) compared with Medicare and Medicaid beneficiaries. Conclusions and Relevance: In this study, patients with metastatic cancer from racial and ethnic minority groups and those with Medicare or Medicaid coverage were more likely to receive low-value, aggressive interventions at the end of life. Further studies are needed to evaluate the underlying factors associated with disparities at the end of life to implement prospective interventions.