Supplementary Table S1 shows the sample size, person-years of follow-up, and numeric values of increasing observed/expected ratio of multiple primary cancers with county-level smoking prevalence.

Figure S4. Observed/Expected Ratio of the Occurrence of Multiple Primary Cancers by County-Level Smoking Prevalence by Age Groups and Race/Ethnicity among Males and Females.

QuestionDo disparities in cancer survival that are generally seen in the broader US population exist among Black veterans compared with veterans who are not Black receiving care through the Veterans Health Administration (VHA)?FindingsIn this systematic review of 39 studies representing 603 256 veterans, including a meta-analysis of 29 studies with sufficient outcome data, Black veterans with cancer receiving care through the VHA had similar or better overall survival and cancer-specific survival compared with those whose race was categorized as either White or non-Black.MeaningThese results suggest that equity in outcomes for Black veterans with cancer is being achieved for those receiving care through the VHA. This systematic review and meta-analysis of studies of US veterans receiving cancer care through the Veterans Health Administration compares outcomes for Black veterans compared with veterans from other racial groups. ImportanceIn the US, Black patients with cancer consistently experience worse survival compared to White patients, even after adjusting for age, sex, and disease stage. Whether these disparities exist among patients receiving care in the Veterans Health Administration (VHA), an integrated health system designed to provide near-equal access to care, remains uncertain.ObjectiveTo evaluate whether overall survival (OS) and cancer-specific survival (CSS) differ between Black veterans and those with other race receiving cancer care through VHA.Data SourcesPubMed was searched from January 2015 through April 2022. Reference lists from identified studies were also reviewed.Study SelectionStudies of US veterans receiving cancer care through the VHA were included if they reported OS or CSS by race and provided hazard ratios (HRs). Dual independent rating of titles and abstracts was conducted for inclusion.Data Extraction and SynthesisA random-effects model was used to pool effect sizes, the Paule-Mandel estimator was used to calculate the heterogeneity variance tau 2, and Knapp-Hartung adjustments were used to calculate the confidence interval of the pooled effect. Review and meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline.Main Outcomes and MeasuresOS and CSS were compared between Black veterans and those who were not Black using pooled HRs.ResultsOf 101 studies identified, 39 met inclusion criteria and 29 provided sufficient data for meta-analysis. The reported outcomes represented 603 256 veterans with cancer treated between 1983 and 2017, with a mean 29.0% (range, 8.9%-55.0%) of patients categorized as Black. All studies compared race by Black compared with White, except for 7 of 20 prostate cancer studies, which compared race by Black compared with non-Black. Black veterans were found to have better OS (HR, 0.93; 95% CI, 0.89-0.97) and CSS (HR, 0.94; 95% CI, 0.90-0.98). Survival advantages for Black veterans were observed across several cancer types, including bladder, laryngeal, lung, oropharyngeal, prostate, and plasma cell cancers. Between-study heterogeneity was low to moderate.Conclusions and RelevanceIn this systematic review and meta-analysis of peer-reviewed publications reporting the outcomes of veterans receiving cancer care through VHA, survival outcomes were generally similar or better for Black compared with White or non-Black veterans. These findings suggest that integrated health care systems providing near-equitable access to comprehensive cancer care can substantially reduce or eliminate disparities in cancer outcomes.

Background Socioenvironmental deprivation and discrimination are associated with poorer cancer outcomes, yet their combined impact remains understudied. This study examines the independent and combined impact of these factors on cancer-related outcomes.Methods Survey data (2018-2020) from 7977 participants across 6 National Cancer Institute-designated cancer centers assessed perceived discrimination (PD), area-level deprivation, lifestyle factors (smoking and obesity), and self-reported breast and colorectal cancer screening behaviors. Multivariate and multilevel logistic regression models estimated associations and the interclass correlation (ICC) quantified variation attributable to area-level factors.Results High PD was associated with 2.28 times higher odds of current smoking (95% CI = 1.71 to 3.05) and 1.33 times higher odds of obesity (95% CI = 1.03 to 1.72), compared with those with low PD. Living in socially deprived areas increased the odds of smoking by 1.51 (95% CI = 1.20 to 1.89), relative to socially privileged areas. ICC estimates that 4% of the variation in the association between high PD on smoking, and 2% of the variation between medium PD and obesity, were attributable to area-level factors. Neither PD nor neighborhood disadvantage were significantly associated with being up-to-date on cancer screenings.Conclusions PD and neighborhood deprivation independently increase risk of smoking and obesity, both cancer risk factors, but were not significantly associated with screening behaviors. Area-level factors explain modest variation in these associations.Impact Findings highlight the importance of integrating both social experience (PD) and structural conditions (neighborhood deprivation) in cancer prevention research. For practice and policy, results underscore the need for multilevel strategies and targeted prevention efforts to reduce behavioral cancer risk.

Supplementary Table S2 shows the sample size, person-years of follow-up, and numeric values of increasing observed/expected ratio of multiple primary cancers with county-level smoking prevalence by age groups.

Supplementary Figure S2 shows the observed/expected ratio of multiple primary cancers increases with county-level smoking prevalence among survivors of both smoking-related cancers and non-smoking-related cancers.

Figure S3. Observed/Expected Ratio of the Occurrence of Multiple Primary Cancers by County-Level Smoking Prevalence and Poverty Levels among Males and Females.

Since 2021, the American Cancer Society has published its biennial report on the status of cancer disparities in the United States. In this 2025 report, the authors provide updated data on disparities in cancer occurrence and outcomes by sex, race, ethnicity, socioeconomic status (SES [educational attainment as a proxy]), and geographic location (including urbanicity of county of residence and congressional district), along with contributors to these disparities, including major cancer risk factors, screening, and select social determinants of health (SDOH) and health‐related social needs. The authors found substantial disparities across the cancer continuum, including risk factors, incidence, stage at diagnosis, receipt of care, survival, and mortality for many cancers and in evaluated SDOH by race and ethnicity, educational attainment, and geographic location. During 2019 through 2023, Black and American Indian/Alaska Native populations had the highest cancer mortality rates, both overall and for the leading causes of cancer death. Cancer mortality rates were also consistently higher among adults with lower SES. However, differences in cancer mortality were substantially larger by education than by race, indicating that SES plays a major role in driving racial disparities in cancer mortality. Overall cancer mortality rates were higher in Black adults than in White adults with the same education level by 7%–28% among males and by 2%–43% among females. Within each race, however, overall cancer mortality rates were higher in adults with ≤12 years of education than in those with ≥16 years of education by 143%–192% among males and by 71%–140% among females. Mortality from all cancers combined was 21% higher in nonmetropolitan than in large metropolitan counties, with the greatest differences for lung (45%) and cervical (36%) cancers and the smallest for prostate, female breast, and pancreatic cancers (7%–8%). By congressional district, the highest cancer mortality rates both overall and for lung, colorectal, and breast cancers were largely found in the South and East North‐Central division of the Midwest; however, for prostate cancer, there was no distinct geographic pattern. Sociodemographic groups that had higher cancer mortality generally had higher exposure to risk factors, lower health insurance coverage, and limited access to cancer prevention, early detection, and treatment compared with groups that had lower cancer mortality, largely reflecting fundamental disparities in SDOH. Mitigating cancer disparities in the United States requires intersectoral stakeholder engagement, targeted funding, effective policies at the federal, state, and local levels, and broad implementation of evidence‐based interventions, such as expanding health insurance coverage, including through strengthening Marketplaces and protecting and expanding access to Medicaid.

Supplementary Figure S1 shows the observed/expected ratio of multiple primary cancers increases with county-level smoking prevalence using 2000-2003 and 2014-2016 smoking prevalence.

Individual and community-level transportation barriers are known drivers of health disparities, especially in rural areas. In a 2021-2022 community-based project to improve cancer screening at federally qualified health centers in Virginia, Department of Transportation policy governing road signage emerged as an unexpected but actionable barrier. Following successful advocacy for road signs directing patients to a rural federally qualified health center, screening rates increased. This highlights the need to recognize unexpected access barriers and engage nontraditional partners, such as transportation agencies, to reduce regulatory-level barriers. (Am J Public Health. 2026;116(2):175-179. https://doi.org/10.2105/AJPH.2025.308285).

Abstract Background: Racial disparities continue to exist in lung cancer, while Black individuals tend to smoke less than Whites, indicating potentially additional factors contribute to lung cancer risk. Our previous work showed that social stressors, including neighborhood violent crime, can shape tumor biology via stress-responsive mechanisms. In this study, we investigated how neighborhood violent crime influences tumor microenvironment with a focus on how glucocorticoid receptor activity impacts the spatial pattern of M2 macrophages and CD8+ T cells as indicators of hot and cold immune phenotypes. Methods: We analyzed 15 lung tumor spatial transcriptomic samples to quantify pathway activity and cell type associations using gene set co-regulation analysis (GESECA). Spatial co-localization was assessed using univariate and bivariate local Moran’s I (p < 0.05). To enhance spatial resolution beyond the Visium spot size, we extracted latent spatial features using non-negative matrix factorization (NMF), estimated empirical variograms to characterize spatial autocorrelation, and applied ordinary kriging to generate high-resolution spatial maps. Results: Neighborhood violent crime rates were positively correlated with glucocorticoid receptor activity, as evidenced by high expression of genes involved in the glucocorticoid biosynthesis pathway activity (p < 0.05). Regions with elevated glucocorticoid receptor activity also showed higher abundance of epithelial cells, especially in tumors from high-crime neighborhoods. High-resolution spatial maps further revealed that tumors from high-violent crime neighborhoods displayed strong co-localization between M2 macrophages and CD8+ T cells, suggesting that CD8+ T cells are surrounded by immunosuppressive myeloid cells, creating a functionally “cold” tumor microenvironment. In contrast, tumors from low-violent crime neighborhoods showed more mutually exclusive spatial patterns of M2 macrophages and CD8+ T cells, reflecting a “hot” tumor microenvironment. Conclusions: Our findings suggest that exposure to social stressors, such as neighborhood violent crime, may influence tumor biology by altering stress-responsive pathways and reshaping immune spatial architecture. The distinct hot and cold immune microenvironment may indicate differential treatment effectiveness across neighborhood contexts, potentially contributing to lung cancer disparities. Different immunotherapy strategies depending on immune tumor microenvironment to improve treatment effectiveness. Citation Format: Sabrina Akter, Aiman Soliman, Robert A. Winn, Zeynep Madak-Erdogan, Sage J. Kim. Stress-responsive glucocorticoid receptor signaling shapes the immune tumor microenvironment in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1416.

Supplementary Table S3 shows the sample size, person-years of follow-up, and numeric values of increasing observed/expected ratio of multiple primary cancers with county-level smoking prevalence by racial/ethnic groups.

BACKGROUND:As the number of cancer survivors in the United States grows, multiple primary cancer (MPC) has become an increasing public health concern. Understanding geographic variation in MPC incidence can inform targeted public health strategies. In this study, we aimed to examine associations between MPC incidence and county-level cigarette smoking (smoking) prevalence. METHODS:We conducted a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results 17 registries, representing 26.5% of the U.S. population. The cohort included 6,364,027 individuals diagnosed with an initial primary cancer between 2000 and 2021, followed through December 2021. County-level smoking prevalence was the primary exposure. The main outcome was MPC incidence, assessed using observed-to-expected ratios across strata of smoking prevalence. Analyses were stratified by sex, age, and race/ethnicity. RESULTS:Observed-to-expected ratios of MPC increased with higher county-level smoking prevalence, from 1.02 (95% CI, 1.01-1.03) among males and 1.24 (95% CI, 1.22-1.25) in females in low-prevalence counties to 1.34 (95% CI, 1.31-1.38) and 1.53 (95% CI, 1.49-1.58), respectively, in high-prevalence counties. Robust relationships were observed among individuals diagnosed with their initial cancer at ages 45 to 64. CONCLUSION:County-level smoking prevalence is positively associated with MPC incidence. These findings support the need for targeted, community-level tobacco control interventions to reduce MPC risk. IMPACT:By linking county-level smoking prevalence to MPC risk, this study highlights the potential utility of community-level data in identifying high-risk populations and guiding tobacco control and survivorship interventions.

ABSTRACT Background Cancer survivors are increasingly living beyond 5 years post‐diagnosis and are projected to exceed 26,000,000 in the United States (US) by 2040. Research is needed on racial and ethnic differences in long‐term survival. Methods In this retrospective cohort study of 10,895,183 individuals diagnosed with cancer from the US population‐based Surveillance Epidemiology and End Result (SEER) data (2000–2021), we compared survival outcomes up to 15 years post‐diagnosis across 6 mutually exclusive racial/ethnic groups: Hispanics, and non‐Hispanic White, Black, Asian, American Indian/Alaska Native (AI/AN), and Native Hawaiian and other Pacific Islander (NHPI). Results Overall, Hispanic and non‐Hispanic Black, Asian, AI/AN, and NHPI cancer survivors had persistently poorer survival outcomes compared to non‐Hispanic White cancer survivors. AI/AN men and women, NHPI men, and Black women experienced the poorest outcomes. Survival gaps widened over time. By year 15, male AI/AN and NHPI and female AI/AN and Blacks were more than 25% more likely to die compared to their White counterparts. These disparities were most pronounced among individuals with advanced‐stage cancers and persisted across counties with various income levels. Racial/ethnic differences varied by cancer site. Conclusions Long‐term survival disparities by race and ethnicity persist and widen beyond 5 years post‐diagnosis, particularly among non‐Hispanic AI/AN individuals, NHPI men, and Black women. These trends are not solely explained by income or cancer stage, highlighting the need for long‐term, risk‐based and tailored survivorship care to reduce racial and ethnic differences in cancer outcomes.

The National Cancer Policy Forum (NCPF) of the National Academies of Sciences, Engineering, and Medicine was founded in 2006 to serve as a trusted venue for identifying and addressing high-priority policy issues in cancer research and care. NPCF takes a comprehensive, multisectoral, and multidisciplinary approach to strategically consider the entire continuum of cancer research and cancer care. Over the past two decades, the Forum has served a uniquely important role in examining both long-standing and emerging policy issues that are relevant to reducing the burden of cancer, both through prevention and by improving the care and outcomes for those diagnosed with cancer, and exploring solutions from multiple perspectives. The Forum has fostered actionable dialogue among a broad range of participants, including patient advocacy organizations, federal agencies, academia, professional organizations, nonprofits, and industry. NCPF activities inform the cancer community and the general public about a wide range of scientific, clinical, and policy issues through workshops, webinars, and the proceedings published after these convenings. Forum activities have influenced policy through the resulting publications and by providing input to National Academies consensus studies, which provide consensus recommendations. This commentary summarizes the breadth of topics addressed by the Forum over the years and examples of the impact of the Forum activities on policies and procedures, programs and practices, and participants and people around the globe.

Lung cancer, once considered a clinical rarity, is now the leading cause of cancer-related mortality among both men and women in the United States (US) and remains the deadliest cancer worldwide. Early investigations focused on a broad range of environmental and occupational exposures as putative factors. However, the emergence of robust epidemiologic evidence in the mid-twentieth century established tobacco use, particularly cigarette smoking, as the dominant driver of lung cancer incidence. These discoveries fundamentally shaped US tobacco control policies, cancer prevention strategies, and subsequent scientific advances in thoracic oncology. Over the past three decades, innovations in screening, staging, molecular characterization, and treatment have transformed the landscape of lung cancer care and created unprecedented opportunities to improve outcomes for populations at greatest risk. Yet, the benefits in these advancements have not been equally realized. Persistent disparities in access to screening, prevention, timely diagnosis, and evidence-based care continue to disproportionately burden at-risk groups, including individuals with lower socioeconomic status and those in rural areas. Addressing these inequities requires multifaceted, cross-sector strategies that extend beyond the clinic to the social and structural determinants of health. This review aims to provide a brief history of lung cancer research, reflect on advancements in lung cancer treatment from 1990 - 2025, and highlight efforts toward continued progress in truly equitable lung cancer screening, treatment, care, and policy.

Pathway analysis results of cluster 6 genes from Supplementary Figure 4C.

Genes correlated with exposure to neighborhood violence.

Introduction Lung cancer is a leading cause of cancer-related deaths and has been associated with the microbiota of the human respiratory tract. However, the optimal sample type for studying the role of microbiota in lung cancer and the microbial hallmarks of lung cancer patients remain unclear.Methods In this study, we downloaded 16S rRNA sequencing data of 1,105 high-quality samples from 13 BioProjects, including lung tissues, bronchoalveolar lavage (BAL) fluids, and saliva, and performed a meta-analysis.Results Our results revealed that the BAL microbiota, dominated by taxa such as Sphingomonas and Pseudomonas, which are not typically abundant in the oral microbiota, served as hallmarks of individuals without lung cancer. In contrast, BAL samples from lung cancer patients showed higher relative abundances of oral-associated taxa, e.g., Streptococcus and Prevotella, with increased rates of dominance by these taxa in the BAL microbiota of lung cancer patients. Additionally, beta diversity analysis revealed significant compositional differences between the BAL microbiota of healthy individuals and those with lung cancer. Furthermore, while compositional differences were observed in the oral microbiota between healthy participants and lung cancer patients, as well as between microbiota from lung tumors and normal adjacent tissues, these differences were less pronounced than those observed in the BAL samples between healthy individuals and lung cancer patients. Cross-site correlations indicated limited associations between the relative abundances of taxa in the oral, BAL, and lung tissue microbiota, implying that differences in lower respiratory microbiota may not be directly driven by upper respiratory tract microbiota.Discussion These findings highlight distinct microbial patterns linked to lung cancer in the respiratory tract. More pronounced differences were observed in the BAL microbiota between healthy individuals and lung cancer patients, with the predominance of taxa, typically not abundant in the oral microbiota, serving as hallmarks of health.