Disparities in Stage at Presentation Among Hispanic and Latinx Patients With Non-Small-Cell Lung Cancer in the United States.

PURPOSE: Hispanic and Latinx people in the United States are the fastest-growing ethnic group. However, previous studies in non-small-cell lung cancer (NSCLC) often analyze these diverse communities in aggregate. We aimed to identify differences in NSCLC stage at diagnosis in the US population, focusing on disaggregated Hispanic/Latinx individuals. METHODS: Data from the National Cancer Database from 2004 to 2018 identified patients with primary NSCLC. Individuals were disaggregated by racial and ethnic subgroup and Hispanic country of origin. Ordinal logistic regression adjusting for age, facility type, income, educational attainment, comorbidity index, insurance, and year of diagnosis was used to create adjusted odds ratios (aORs), with higher odds representing diagnosis at later-stage NSCLC. RESULTS: Of 1,565,159 patients with NSCLC, 46,616 were Hispanic/Latinx (3.0%). When analyzed in the setting of race and ethnicity, Hispanic patients were more likely to be diagnosed with metastatic disease compared with non-Hispanic White (NHW) patients: 47.0% for Hispanic Black, 46.0% Hispanic White, and 44.3% of Hispanic other patients versus 39.1% of non-Hispanic White patients (P < .001 for all). By country of origin, 51.4% of Mexican, 41.7% of Puerto Rican, 44.6% of Cuban, 50.8% of South or Central American, 48.4% of Dominican, and 45.6% of other Hispanic patients were diagnosed with metastatic disease, compared with 39.1% of NHWs. Conversely, 20.2% of Mexican, 26.9% of Puerto Rican, 24.2% of Cuban, 22.5% of South or Central American, 23.7% of Dominican, and 24.5% of other Hispanic patients were diagnosed with stage I disease, compared with 30.0% of NHWs. All Hispanic groups were more likely to present with later-stage NSCLC than NHW patients (greatest odds for Mexican patients, aOR, 1.44; P < .001). CONCLUSION: Hispanic/Latinx patients with non-small-cell lung cancer were more likely to be diagnosed with advanced disease compared with NHWs. Disparities persisted upon disaggregation by both race and country of origin, with over half of Mexican patients with metastatic disease at diagnosis. Disparities among Hispanic/Latinx groups by race and by country of origin highlight the shortcomings of treating these groups as a monolith and underscore the need for disaggregated research and targeted interventions.

Lung Cancer in Women: The Past, Present, and Future.

Lung cancer is the leading cause of cancer death for women in multiple countries including the United States. Women are exposed to unique risk factors that remain largely understudied such as indoor pollution, second-hand tobacco exposure, biological differences, gender differences in tolerability and response to therapy in lung cancer, and societal gender roles, that create distinct survivorship needs. Women continue to lack representation in lung cancer clinical trials and are typically treated with data generated from majority male patient study populations, which may be inappropriate to extrapolate and generalize to females. Current lung cancer treatment and screening guidelines do not incorporate sex-specific differences and physicians also often do not account for gender differences when choosing treatments or discussing survivorship needs. To best provide targeted treatment approaches, greater representation of women in lung cancer clinical trials and further research is necessary. Clinicians should understand the unique factors and consequences associated with lung cancer in women; thus, a holistic approach that acknowledges environmental and societal factors is necessary.

Medical Travel for Immigrant Patients With Cancer-Returning Home.

This Viewpoint describes motivations for and barriers to travel to the country of origin among immigrant patients with cancer and recommends strategies to address these motivations and barriers.

Genomic Characterization of Aggressive Breast Cancer in Younger Women.

PURPOSE: Although breast cancer (BC) risk increases with age, BC in younger women is more aggressive with higher mortality compared with older women. We characterize the genomic landscape of BCs in younger women. METHODS: Clinicopathologic, molecular, and genomic differences across age groups (< 40 years, 40-60 years, > 60 years) in female BC patients were investigated in two large cohorts [AACR-GENIE8.1 (n = 11,594) and METABRIC (n = 2509)]. Cox-proportional regression analyzed the prognostic impact of age groups for disease-specific survival (DSS) and recurrence-free survival (RFS) in METABRIC and progression-free survival (PFS) in GENIE cohorts. Chi-squared test was used to assess statistical associations between genomic alterations and age groups. RESULTS: Survival analysis showed that women < 40 years had shorter DSS [hazard ratio (HR): 1.52, p = 0.005], RFS (HR: 1.4, p = 0.006), and PFS (HR: 1.82, p = 0.0003) compared with women 40-60 years, and shorter RFS (HR: 1.5, p = 0.001) and PFS (HR: 2.95, p < 0.0001) compared with women > 60 years. Molecular subtypes in the METABRIC cohort showed women < 40 years were enriched with basal, and HER2+ subtypes, and less enriched with luminal A and B subtype (p < 0.0001). Characterization of genomic alterations in both cohorts demonstrated that BCs in women < 40 years were more enriched with TP53 mutations (FDR < 0.0001), BRCA1 mutations (FDR = 0.01), ERBB2 amplifications (FDR < 0.001), CDK12 amplifications (FDR < 0.001), and PPM1D amplifications (FDR < 0.001). In contrast, BCs in older women (> 60 years) were more enriched with PIK3CA, KMT2C, and CDH1 mutations (FDR < 0.0001). CONCLUSIONS: BCs in young women are associated with shorter survival and more aggressive genomic features, including mutations in TP53 and BRCA1, and amplifications in ERBB2 and CDK12. These findings have the potential to impact clinical trial design and treatment.

Disparities in Diagnosis, Treatment Access, and Time to Treatment Among Hispanic Men With Metastatic Prostate Cancer.

PURPOSE: Reporting racial/ethnic disparities in aggregate obscures within-group heterogeneity. We sought to identify disparities in diagnosis and treatment in Hispanic subpopulations with metastatic prostate cancer (mPCa). METHODS: We disaggregated men with prostate adenocarcinoma from the National Cancer Database from 2004 to 2017 by racial subgroup and Hispanic background. We assessed (1) presenting with mPCa, (2) receiving any treatment, and (3) receiving delayed treatment beyond 90 days. Logistic regression and adjusted odds ratios (aOR) were reported. RESULTS: Hispanic men had greater odds of presenting with mPCa (aOR, 1.54; 95% CI, 1.50 to 1.58; P < .001) compared with non-Hispanic White (NHW) men. All Hispanic racial subgroups were more likely to present with mPCa, with the highest risk in Hispanic Black (HB) men (aOR, 1.68; 95% CI, 1.46 to 1.93; P < .01). Men from all Hispanic backgrounds had higher odds of presenting with mPCa, especially Mexican men (aOR, 1.99; 95% CI, 1.86 to 2.12; P < .01). Hispanic men were less likely to receive any treatment (aOR, 0.60; 95% CI, 0.53 to 0.67; P < .001), and this effect was particularly strong for Hispanic White patients (aOR, 0.58; 95% CI, 0.52 to 0.66; P < .001) and Dominican men (aOR, 0.52; 95% CI, 0.28 to 0.98; P = .044). Hispanic men were more likely to experience treatment delays compared with NHW men (aOR, 1.38; 95% CI, 1.26 to 1.52; P < .001) and in particular HB (aOR, 1.83; 95% CI, 1.22 to 2.75; P = .002) and South/Central American men (aOR, 1.48; 95% CI, 1.07 to 2.04; P = .018). CONCLUSION: Differences exist in stage at presentation, treatment receipt, and delays in treatment on disaggregation by racial subgroup and Hispanic heritage. We need to study the potential mechanisms of the observed variations to help develop targeted interventions.

Determinants of widespread metastases and of metastatic tropism in patients with prostate cancer: A genomic analysis of primary and metastatic tumors.

INTRODUCTION: Emerging evidence suggests that metastasis is better described as a spectrum of disease rather than a binary state. A greater understanding of the genomic features that determine extent and location of metastatic spread may inform risk stratification and monitoring. Here, we identify genomic alterations from primary prostate carcinomas that are predictive of wide-spread metastatic potential. METHODS: Genomic and clinical data from 1,312 patients with primary prostate carcinoma were extracted from the MSK-MET cohort through cBioPortal. Metastatic site counts and overall survival (OS) data were publicly available and used as the primary outcomes. Primary tumor samples were profiled using the MSK-IMPACT targeted sequencing platform. We focused on 58 genes frequently altered in prostate cancer. Cox proportional hazard analyses defined hazard ratios (HRs) and 95% confidence intervals (CIs) for overall mortality in patients with different metastatic outcomes. RESULTS: Out of the 1,312 patients in our cohort, 939 (71%) developed metastases, of whom 113 (8.6%) had metastases to 5 or more distinct anatomical sites (defining wide-spread metastases, WSM). Bone was the most common site of metastasis (36%), and 80% of patients with liver metastases had 4 or more additional sites of metastasis. Among patients with metastasis, increasing number of metastatic sites was associated with increased risk of death (HR: 1.8, 95%CI: 1.63-1.99, P < 0.001). Alterations in the following genes were enriched in tumors from patients with WSM vs. others: TP53 (40% vs. 20%, P < 0.0001), FOXA1-amplification (8% vs. 3%, P = 0.02), AR-amplification (4.4% vs. 1%, P = 0.01), RB1-deletion (5.3% vs. 0.7%, P = 0.001), and BRCA2-deletion (4.4% vs. 0.7%, P = 0.01). Univariable survival analysis showed all these alterations were predictive of OS (P < 0.05). On multivariable analysis, only TP53 mutations, and FOXA1 and AR amplifications were independent prognostic factors. FOXA1 (n = 37) and AR (n = 13) amplifications were mutually exclusive and patients with these experienced very poor OS (HR: 3.57, 95%CI:2.26-5.6, P < 0.001]. CONCLUSIONS: We identified genomic alterations (TP53 mutations, FOXA1/AR amplification, RB1/BRCA2 deletion) from primary prostate carcinomas that are predictive of wide-spread metastases and poor outcome.

Non-small cell lung cancer disparities in stage at presentation and treatment for Asian American, Native Hawaiian, and Pacific Islander women.

BACKGROUND AND OBJECTIVES: Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPI) represent the fastest-growing group in the United States. While described in aggregate, great variations exist within the community. We aimed to determine whether there were differences in stage at presentation and treatment status among AANHPI women with non-small cell lung cancer (NSCLC). METHODS: Between 2004 and 2016, we identified 522 361 female patients with newly diagnosed NSCLC from the National Cancer Database. Multivariable logistic regression models were used to define adjusted odds ratios (aORs) of presenting with stage IV disease and not receiving treatment. RESULTS: AANHPI women were more likely to present with stage IV disease compared to White (54.32% vs. 40.28%, p < 0.001). Aside from Hawaiian, Pakistani, and Hmong women, all other ethnic groups had greater odds of presenting with stage IV disease than White women. AANHPI women <65 years were more likely to present with stage IV disease (p = 0.030). Only Vietnamese women showed a significant difference (aOR = 1.30 [1.06-1.58], p = 0.010) for likelihood of receiving treatment compared to White. CONCLUSIONS: Differences in stage at presentation and treatment status in women with NSCLC were observed among AANHPI ethnic groups when populations were disaggregated.

Localized prostate cancer disparities in risk group at presentation and access to treatment for Hispanic men.

BACKGROUND: Despite great heterogeneity amongst Hispanic groups, prostate cancer studies often report Hispanic patients in aggregate. We sought to identify differences in prostate cancer risk group at presentation and treatment status among Hispanic subgroup populations. METHODS: Patients with localized prostate adenocarcinoma diagnosed from 2004-2017 were identified in the National Cancer Database (NCDB) and disaggregated by racial subgroup and Hispanic country of origin. Ordinal logistic regression defined adjusted odds ratios (AORs) with 95% CI of (1) presenting at progressively higher risk group and (2) receiving treatment with intermediate-unfavorable or high-risk disease. RESULTS: In our sample (n = 895,087), Hispanic men had greater odds of presenting with higher-risk localized prostate cancer compared with non-Hispanic White men (AOR = 1.18 95% CI 1.16-1.21, p < 0.001). Additionally, Hispanic Black men were less likely to present with higher-risk disease than non-Hispanic Black men. Disparities also existed when disaggregated by country of origin, particularly for Mexican men. Amongst men with unfavorable-risk disease, Hispanic men were less likely to receive treatment than non-Hispanic White men (95% CI 0.57-0.67, p < 0.001). The odds of Hispanic Black patients receiving treatment was 2.00 times the odds (95% CI 1.17-3.41 p = 0.011) of non-Hispanic Black patients receiving treatment. Upon disaggregation by country of origin, disparities persisted, particularly for Mexican men. CONCLUSION: We found marked heterogeneity when risk group at presentation and treatment for higher-risk disease were disaggregated by racial subgroup and country of origin. Our findings support further collection of disaggregated data in Hispanic communities and study of potential mechanisms underlying the observed differences.

Distinct Profiles of DNA Repair Activity Define Favorable-risk Prostate Cancer Subtypes With Divergent Outcome.

INTRODUCTION: Understanding if divergent molecular profiles of DNA damage and repair (DDR) pathway activity, a biomarker of disease progression, exist in prostate tumors with favorable-risk features is an unmet need, which this study aim to unearth. MATERIALS AND METHODS: This was a multicenter registry genome-wide expression profiling study of prospectively collected radical prostatectomy (RP) tumor samples from 2014 to 2016. DDR activity was calculated from average expression of 372 DDR genes. Consensus hierarchical clustering was used to arrive at a robust clustering solution based on DDR gene expression patterns. Genome-wide differential expression between clusters was performed, and outcomes were evaluated across expression patterns. RESULTS: Of 5239 patients from the prospective registry, 376 had favorable-risk disease (Grade group [GG] 1 to 2, PSA prior to RP <10ng/ml, pT2 or less). DDR activity score was correlated with prognostic genomic signatures that predict for metastatic risk (r = 0.37, P < 2e-16) and high grade groups (P < .001). High DDR activity (top-quartile) was observed in 28% of patients with favorable-risk disease. In favorable-risk disease, 3 distinct clusters with varied DDR activity emerged with consensus clustering. Cluster I (compared with cluster II-III and GG3-GG5 disease) had the highest expression of all DDR sub-pathways, MYC, PAPR1, AR, and AR activity (P < .001 for all). Furthermore, cluster I was associated with poorer metastasis-free survival (MFS) and Overall survival (OS) compared with other clusters (MFS; HR: 2.43, 95%CI, [1.22-4.83], P = .01; OS; HR: 2.77, 95%CI, [1.18-6.5], P = .01). CONCLUSIONS: Cluster I is a novel subgroup of favorable-risk disease with high DDR activity, AR activity, PARP1 and chr8q/MYC expression, and poorer MFS and OS.

Chromosome 8q arm overexpression is associated with worse prostate cancer prognosis.

OBJECTIVE: Chromosome 8q arm (chr8q) is the most amplified chromosomal segment in advanced metastatic castration-resistant prostate cancer after chXq12. These regions harbor important oncogenes driving prostate cancer progression, including MYC that plays a role in various hallmarks of cancer, including cell cycle progression and immune surveillance. Herein we characterize the co-expression patterns of chr8q genes and their clinical utility in more than 7,000 radical prostatectomy samples. MATERIALS AND METHODS: Copy Number alterations of 336 genes on chr8q21 to chr8q24 were extracted from 2 primary prostate cancer cohorts (TCGA, n = 492; MSK-primary, n = 856) and 3 metastatic prostate cancer cohorts (MSK-met, N = 432; MSK-mCSPC, N = 424; SU2CPNAS, n = 444) from cBioPortal. Expression data for the 336 genes was extracted from 6,135 radical prostatectomy samples from Decipher GRID registry. For survival analysis, patients were grouped into top 10% and top 25% by band expression and were compared with the remaining cohort. Hazard ratios were calculated using Cox proportional hazards models. RESULTS: Genes on chr8q were highly co-amplified and co-expressed. Copy number alterations and overexpression of chr8q genes in primary disease were associated with higher Gleason scores, increased risk of metastases, and increased prostate cancer specific mortality. Additionally, our data demonstrated high expression of MYC alone was not associated with differences in metastases free survival while high expression of other chr8q bands was associated with decreased metastases free survival. By combining chr8q data with an established genomic classifier like Decipher, we were able to develop a new model that was better at predicting metastases than Decipher alone. CONCLUSIONS: Our findings highlight the clinical utility of chr8q data, which can be used to improve prognostication and risk prediction in localized prostate cancer.