Characterizing disparities in receipt of palliative care for Asian Americans, Native Hawaiians, and Pacific Islanders with metastatic cancer in the United States.

PURPOSE: Palliative care plays essential roles in cancer care. However, differences in receipt among individuals identifying as Asian American, Native Hawaiian, and Other Pacific Islanders (AA&NHPI) with cancer are not well-characterized, especially when these diverse groups are disaggregated. We characterized disparities in receipt of palliative care among AA&NHPI patients with AJCC Stage IV prostate, breast, or lung cancer. METHODS: We performed multivariable logistic regressions were performed in this retrospective cohort analysis, using deidentified data from the National Cancer Database (NCDB) of patients diagnosed with AJCC analytic group stage IV breast, lung, or prostate cancer (2004-2018) who were White or of Asian Indian/Pakistani, Chinese, Filipino, Hawaiian, Hmong, Japanese, Kampuchean, Korean, Laotian, Other Pacific Islander, Thai, or Vietnamese descent. We conducted multivariable logistic regression analyses in a retrospective cohort study using deidentified data from the National Cancer Database (NCDB). The study included patients diagnosed with AJCC analytic group Stage IV breast, lung, or prostate cancer between 2004 and 2018, who were White or identified as Asian Indian/Pakistani, Chinese, Filipino, Hawaiian, Hmong, Japanese, Kampuchean, Korean, Laotian, Other Pacific Islander, Thai, or Vietnamese descent. Adjusted odds ratios and 95% confidence intervals of receiving palliative care were measured when comparing White vs. AA&NHPI patients as one cohort and White vs. disaggregated AA&NHPI patients, adjusting for clinical, socioeconomic, and demographic covariates. RESULTS: Among 775,289 individuals diagnosed with cancer (median age: 68 years), no significant differences in palliative care receipt were observed between White patients and aggregated AA&NHPI patients among patients with prostate, breast, or lung cancer. However, disaggregated analyses revealed reduced palliative care receipt for breast cancer patients of Asian Indian/Pakistani descent (AOR 0.75, 95% CI, 0.60-0.94, P = 0.011) and for lung cancer patients of Chinese, Vietnamese, Thai, and Asian Indian/Pakistani descent compared to White patients (Chinese AOR 0.88, [0.81-0.94], P = 0.001; Vietnamese AOR 0.89, [0.80 to 0.99], P = 0.032; Thai AOR 0.64, [0.44-0.92], P = 0.016; Asian Indian/Pakistani AOR 0.83, [0.74-0.93], P = 0.001). Palliative care was greater for patients of Japanese and Hawaiian descent with prostate cancer (Japanese AOR 1.92, [1.32-2.75], P = 0.001; Hawaiian AOR 2.09, [1.20-3.66], P = 0.009), breast cancer (Japanese AOR 1.72, [1.21-2.43], P = 0.001; Hawaiian AOR 1.70, [1.08-2.67], P = 0.021), and lung cancer (Japanese AOR 1.92, [1.70-2.17], P < 0.001; Hawaiian AOR 2.95, [2.5-3.5], P < 0.001), as well as patients of Other Pacific Islander descent with lung cancer (AOR 1.62, [1.34-1.96], P < 0.001). CONCLUSIONS AND RELEVANCE: Our findings demonstrate disparities in receipt of palliative care upon disaggregation of diverse AA&NHPI groups, the need for disaggregated research and targeted interventions that address the unique cultural, socioeconomic, and healthcare system barriers to palliative care receipt.

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.

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.

Disparities in Primary Breast Cancer Stage at Presentation Among Hispanic Subgroups.

BACKGROUND: Although the United States (US) Hispanic population consists of diverse communities, prior breast cancer studies often analyze this group in aggregate. Our aim was to identify differences in breast cancer stage at presentation in the US population, with a particular focus on Hispanic subgroups. METHODS: Data from the National Cancer Database (NCDB) from 2004 to 2017 were used to select women with primary breast cancer; individuals were disaggregated by racial and ethnic subgroup and Hispanic country of origin. Ordinal logistic regression was used to create adjusted odds ratios (aORs) with 95% confidence intervals (CIs), with higher odds representing presentation at later-stage breast cancer. Subgroup analysis was conducted based on tumor receptor status. RESULTS: Overall, among 2,282,691 women (5.2% Hispanic), Hispanic women were more likely to live in low-income and low-educational attainment neighborhoods, and were also more likely to be uninsured. Hispanic women were also more likely to present at later-stage primary breast cancer when compared with non-Hispanic White women (aOR 1.19, 95% CI 1.18-1.21; p < 0.01). Stage disparities were demonstrated when populations were disaggregated by country of origin, particularly for Mexican women (aOR 1.55, 95% CI 1.51-1.60; p < 0.01). Disparities worsened among both racial and country of origin subgroups in women with triple-negative disease. CONCLUSION: Later breast cancer stage at presentation was observed among Hispanic populations when disaggregated by racial subgroup and country of origin. Socioeconomic disparities, as well as uncaptured disparities in access and/or differential care, may drive these observed differences. Future studies with disaggregated data are needed to characterize outcomes in Hispanic communities and develop targeted interventions.

Patient-Reported Morbidity Instruments: A Systematic Review.

OBJECTIVES: Although comorbidities play an essential role in risk adjustment and outcomes measurement, there is little consensus regarding the best source of this data. The aim of this study was to identify general patient-reported morbidity instruments and their measurement properties. METHODS: A systematic review was conducted using multiple electronic databases (Embase, Medline, Cochrane Central, and Web of Science) from inception to March 2018. Articles focusing primarily on the development or subsequent validation of a patient-reported morbidity instrument were included. After including relevant articles, the measurement properties of each morbidity instrument were extracted by 2 investigators for narrative synthesis. RESULTS: A total of 1005 articles were screened, of which 34 eligible articles were ultimately included. The most widely assessed instruments were the Self-Reported Charlson Comorbidity Index (n = 7), the Self-Administered Comorbidity Questionnaire (n = 3), and the Disease Burden Morbidity Assessment (n = 3). The most commonly included conditions were diabetes, hypertension, and myocardial infarction. Studies demonstrated substantial variability in item-level reliability versus the gold standard medical record review (κ range 0.66-0.86), meaning that the accuracy of the self-reported comorbidity data is dependent on the selected morbidity. CONCLUSIONS: The Self-Reported Charlson Comorbidity Index and the Self-Administered Comorbidity Questionnaire were the most frequently cited instruments. Significant variability was observed in reliability per comorbid condition of patient-reported morbidity questionnaires. Further research is needed to determine whether patient-reported morbidity data should be used to bolster medical records data or serve as a stand-alone entity when risk adjusting observational outcomes data.

Primary Care Physician and Patient Perceptions of Reimbursement for Total Knee and Hip Replacement.

BACKGROUND: The opinions of nonspecialists and patients will be important to determining reimbursements for specialists such as orthopedic surgeons. In addition, primary care physician (PCP) perceptions of reimbursements may affect utilization of orthopedic services. METHODS: We distributed a web-based survey to PCPs, asking how much they believed orthopedic surgeons were reimbursed for total hip arthroplasty (THA) and total knee arthroplasty (TKA). We also proctored a paper-based survey to postoperative patients, asking how much orthopedic surgeons should be reimbursed. RESULTS: There was a significant difference between perceived and actual reimbursement values for THA and TKA. Hospital-affiliated PCPs estimated higher reimbursements for both THA ($1657 vs $838, P < .0001 for Medicaid and $2246 vs $1515, P = .018 for Medicare) and TKA ($1260 vs $903, P = .052 for Medicaid and $2022 vs $1514, P = .049 for Medicare). Similarly, larger practices estimated higher reimbursements for both THA ($1861 vs $838, P < .0001 for Medicaid and $2635 vs $1515, P = .004 for Medicare) and TKA ($1583 vs $903, P = .005 for Medicaid and $2380 vs $1514, P = .011 for Medicare). Compared to PCPs, patients estimated that orthopedic surgeons should be paid 4 times higher for both THA ($9787 vs $2235, P < .0001) and TKA ($9088 vs $2134, P < .0001). CONCLUSION: PCPs believe that reimbursements for orthopedic procedures are higher than actual values. The effect that these perceptions will have on efforts at cost reform and utilization of orthopedic services requires further study.

Modifiable Lifestyle Risk Factors in Adult Survivors of Childhood Cancer: A Nationally Representative Study.

OBJECTIVE: Given the vulnerable health condition of adult childhood cancer survivors, it is essential that they develop positive health behaviors to minimize controllable health risks. Therefore, we evaluated if adult survivors of non-childhood cancer and childhood cancer differ in the odds of each modifiable risk factor compared with each other and compared with the general population. METHODS: This nationally representative study leveraged the National Health Interview Survey (NHIS) sample from 2000 to 2018 and the Behavioral Risk Factor Surveillance System (BRFSS) sample from 2016 to 2021. Our study population included adults diagnosed with cancer when they were ≤14 years of age. Outcomes included physical activity, body mass index (BMI), current smoking, ever-smoking, alcohol use, and binge drinking. RESULTS: Insufficient physical activity was not statistically significant in the BRFSS, but in the NHIS, childhood cancer survivors had significantly more insufficient physical activity compared with non-childhood cancer survivors (aOR 1.29, P=0.038) and the general population (aOR 1.40, P=0.006). Childhood cancer survivors also had a higher likelihood of being significantly underweight (aOR 1.84, P=0.018) and having ever-smoked (aOR 1.42, P=0.001) compared with the general population in the NHIS. There was a significantly higher likelihood of smoking among childhood cancer survivors in the BRFSS (aOR 2.02, P=0.004). CONCLUSIONS: The likelihoods of many risky behaviors between adult childhood cancer survivors and general population controls were comparable, although rates of physical activity may be decreased, and rates of smoking may be increased among childhood cancer survivors. Targeted interventions are needed to promote healthy behaviors in this vulnerable population.

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.

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.

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.

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.

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.