Disparities In Survival Outcomes Research Articles

Abstract PO2-09-10: Addressing Breast Cancer Disparities: Co-Creating Digital Interventions with Patients, Navigators & the Community to Address Social Determinants of Health in the Memphis Statistical Area

Abstract Background: The Memphis Statistical Area, which covers counties in Arkansas, Mississippi, and Tennessee, leads in disparities in mortality rates between Black breast cancer patients compared to White counterparts1. Urban Health Education & Support Services (UHESS), in partnership with RabbleHealth, and West Cancer Center & Research Institute (WCCRI), initiated a solutions-oriented, community-based scalable initiative in January 2023 to measurably address social determinants of health (SDOH), which often drive cancer inequities that disproportionately impact individuals of marginalized communities. By leveraging a community-driven, co-creation sustainable approach, the team sought to measurably improve breast cancer equality utilizing digital enablement and the knowledge of local breast cancer survivors and leading healthcare professionals, including navigators. Methods: A four-phase approach was leveraged to 1. improve access to locally available breast cancer services in communities that are traditionally underserved and 2. measure the public health impact against root causes of breast inequities (i.e., care pathway metrics), and 3. create a repeatable, scalable model to expand to other underserved communities. In Phase 1, UHESS leveraged the Mid-South Regional Breast Cancer Coalition, which convenes ten local breast cancer patient advocacy organizations, to recruit focus groups for co-creation throughout all phases of the initiative. The working group consisted of eight representatives from a variety of Memphis-based cancer organizations, faith-based organizations, navigator programs, and WCCRI. This phase centered around establishing trust with the local patient advocacy community. In Phase 2, an initial patient survey was circulated to identify key resources that reduce health inequities and barriers to access. Human-centered design facilitators supported a series of Listen & Learn workshops with patients to convey root causes of gaps in access to relevant services and with navigators to understand professional needs of navigators and scale the ability improve patient access to resources. To co-create a solution, facilitated patient and navigator workshops were held in Phase 3 to gather patient-centric user experience and design enhancements for a digital patient engagement app. These requirements as well as navigator-defined metrics needs were digitized and organized by SDoH. Phase 4, the Deploy & Measure phase, will begin in September of 2023 and the community-based deployment model focuses on three drivers including: (a) embedding within navigator workflow, (b) activating faith-based organizations, and (c) leveraging societies. Health equity performance data will be analyzed weekly to rapidly target those ZIP codes with the greatest need. Results: Co-design efforts included over 50 members of the Greater Memphis community and final initiative results will be presented at the meeting. Planning for further research regarding community impact and model scalability is already underway. Conclusion: By leveraging a community-driven, co-creation sustainable approach, this model enables a better way to measurably improve breast cancer equality utilizing digital enablement and the knowledge of local breast cancer survivors and leading healthcare professionals, including navigators. Initiative Funding Acknowledgements: Gilead Life Sciences & Blue Cross Blue Shield of Tennessee Foundation 1. Vidal G, Bursac Z, Miranda-Carboni G, White-Means S, Starlard-Davenport A. Racial disparities in survival outcomes by breast tumor subtype among African American women in Memphis, Tennessee. Cancer Med. 2017 Jul;6(7):1776-1786. doi: 10.1002/cam4.1117. Epub 2017 Jun 14. PMID: 28612435; PMCID: PMC5504313. Citation Format: Gregory Vidal, Stacey Tinianov, Aubrey Kelly, Andrea Curry, Carla Baker. Addressing Breast Cancer Disparities: Co-Creating Digital Interventions with Patients, Navigators & the Community to Address Social Determinants of Health in the Memphis Statistical Area [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-09-10.

Racial and Ethnic Disparities in Survival Outcomes of Metastatic Renal Cell Carcinoma Patients Receiving Immunotherapy

BackgroundImmune checkpoint inhibitors (ICI) have significantly improved survival outcomes of metastatic renal cell carcinoma (mRCC). However, ethnic and racial minorities are often underrepresented in ICI clinical trials, leading to limited knowledge about ICI-specific survival outcomes for mRCC across different racial and ethnic groups. We investigated the impact of race and ethnicity on the ICI-specific survival outcomes of mRCC. MaterialsWe used The National Cancer Database (NCDB) to retrieve the data of 4858 mRCC patients diagnosed from 2014 to 2019 and receiving ICI-based regimens. We then compared survival outcomes using the Kaplan–Meier method and the Log-rank test. We analyzed the data using univariate and multivariable Cox regression analysis, adjusted for age, sex, comorbidity index, treatment centers, and grade. ResultsWhite and Asian patients had significantly longer median overall survival (mOS) than African American (AA) patients (23.2 [95% CI 21.6, 24.7; P = .001] and 22.2 [95% CI 16.4, 55.1; P = .047] vs. 14.8 [95% CI 11.9, 19.2] months, respectively). After adjustment, White patients had significantly longer median OS (adjusted hazard ratio [HR] 0.71 [95% CI 0.58, 0.84]; P = .001). There was no significant difference in the mOS between Hispanic and non-Hispanic patients (P = .39). ConclusionBlack race is an independent predictor of ICI-related survival in mRCC patients, independent of sociodemographics, clinicopathological, and treatment-related factors. Future research is required to understand the underlying reasons for these disparities, including potential genetic or biological differences and social and environmental factors.

Metformin boosts anti-tumor immunity and improves prognosis in upfront resected pancreatic cancer: an observational study.

Beyond demographic and immune factors, metabolic considerations, particularly metformin's recognized impact in oncology, warrant exploration in treating pancreatic cancer. This study aimed to investigate the influence of metformin on patient survival and its potential correlation with distinct immune profiles in PDAC tumors. We included 82 upfront resected and 66 gemcitabine-based neoadjuvant chemoradiotherapy (nCRT)-treated patients from the PREOPANC randomized controlled trial (RCT). Transcriptomic NanoString immunoprofiling was performed for a subset of 96 available resected specimens. Disparities in survival outcomes and immune profiles were apparent between metformin and non-metformin users in upfront resected patients but lacking in nCRT-treated patients. Compared to non-metformin users, upfront resected metformin users showed a higher median overall survival (OS) of 29 vs 14 months and a better 5-year OS rate of 19% vs 5%. Furthermore, metformin use was a favorable prognostic factor for OS in the upfront surgery group (HR = 0.56; 95% CI, 0.32 to 0.99). Transcriptomic data revealed that metformin users significantly underexpressed genes related to pro-tumoral immunity, including monocyte to M2 macrophage polarization and activation. Furthermore, the relative abundance of anti-inflammatory CD163+ MRC1+ M2 macrophages in non-metformin users and immune-activating CD1A+ CD1C+ dendritic cells in metformin users was heightened (P < 0.001). This study unveils immune profile changes resulting from metformin use in upfront resected pancreatic cancer patients, possibly contributing to prolonged survival outcomes. Specifically, metformin use may decrease the abundance and activity of pro-tumoral M2 macrophages and increase the recruitment and function of tumor-resolving DCs, favoring anti-tumor immunity.

Disparities in Survival Outcomes Between Locally Advanced Cervical Squamous Cell Carcinoma and Adenocarcinoma Treated with Chemoradiotherapy.

To determine the disparities in survival outcomes between stage IIB-IVA cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) treated with chemoradiotherapy. Patients diagnosed between 2004 and 2015 were retrospectively included from the Surveillance, Epidemiology, and End Results databases. Propensity score matching (PSM) was used in this study. The primary endpoints were cervical cancer-specific survival (CCSS) and overall survival (OS). A total of 2752 patients were identified, including 87.5% (n=2408) were SCC and 12.5% (n=344) were AC. Patients with AC had inferior 5-year CCSS (67.5% vs 54.8%, P<0.001) and OS (58.4% vs 47.2%, P<0.001) compared to those with the SCC subtype. The hazard curve of cervical cancer-related death in AC peaked at 2 years (19%) and still small peaks in the 7 and 11 years of follow-up. Regarding SCC, cervical cancer-related deaths peaked at 2 years (15%) and the hazard rate was 2.0% during the six years of follow-up. The multivariate Cox regression analyses indicated that histology was an independent prognostic factor associated with survival outcomes. Patients with AC had significantly poor CCSS (P<0.001) and OS (P<0.001). Similar results were found after PSM. Our study demonstrates a significantly better prognosis for cervical SCC patients compared to those with cervical AC undergoing chemoradiotherapy. These results highlight the importance of histological subtyping in predicting treatment outcomes and tailoring therapeutic strategies.

Analysis of long non-coding RNAs associated with disulfidptosis for prognostic signature and immunotherapy response in uterine corpus endometrial carcinoma

Disulfidptosis, the demise of cells caused by the abnormal breakdown of disulfide bonds and actin in the cytoprotein backbone, has attracted attention in studies concerning disulfide-related cell death and its potential implications in cancer treatment. This study utilized bioinformatics to detect disulfidptosis associated lncRNA prognostic markers (DALPMs) with Uterine Corpus Endometrial Carcinoma (UCEC)-related to investigate the correlation between these indicators and the tumor immune microenvironment. The RNA sequencing data and somatic mutation information of patients with UCEC were obtained from the Cancer Genome Atlas (TCGA) database. Patients were randomly divided into Train and Test groups. The findings revealed a potential prognostic model comprising 14 DALPMs. Both univariate and multivariate Cox analyses demonstrated that the model-derived risk score functioned as a standalone prognostic indicator for patients. Significant disparities in survival outcomes were observed between the high- and low-risk groups as defined by the model. Differences in tumor mutational burden (TMB), tumor immune dysfunction and exclusion (TIDE), and tumor microenvironment (TME) stromal cells between patients of the high- and low-risk groups were also observed. The forecast model comprising long non-coding RNAs (lncRNAs) associated with disulfidptosis can effectively anticipate patients' prognoses.

Racial and Ethnic Differences in Acuity and Cumulative Frontline Organ Toxicity at the Time of Relapse in Pediatric Acute Myeloid Leukemia

Introduction: Racial and ethnic disparities in survival outcomes exist in pediatric acute myeloid leukemia (AML), but the role of relapse and its potential contribution to outcome disparities is unknown. We sought to examine differences in relapse-free survival (RFS) and clinical characteristics at the time of relapse by race and ethnicity using a real-world multi-institution cohort of pediatric AML patients. Methods: A retrospective cohort including all pediatric (age &amp;lt;19 years) patients treated for AML from 2011-2019 at 13 institutions in the United States was established and is being actively expanded to include diagnoses through 2023. Data collection was accomplished by detailed chart abstraction performed by trained study personnel. We additionally merged resource utilization data from the Pediatric Health Information System to ascertain patient acuity and cumulative organ toxicity. Analyses were restricted to patients identified in the medical record as Hispanic, non-Hispanic Black (NHB), and non-Hispanic White (NHW) to specifically assess historically marginalized patient populations. Other racial/ethnic groups including multi-racial were excluded due to small numbers. Kaplan-Meier survival curves were generated for RFS by race/ethnicity. Adjusted Cox models compared the hazard of relapse by race/ethnicity. Models adjusted for age at diagnosis, sex, initial risk classification, weight category at diagnosis, and acuity at initial presentation. To assess misspecification of outcome, we performed sensitivity analyses restricted to relapses occurring within 1 year of diagnosis (early RFS). Among the patients who relapsed, descriptive frequencies for clinical and treatment characteristics were reported by race/ethnicity. Results: A total of 437 pediatric patients with AML (28% Hispanic, 18% NHB, median follow-up time 3.0 years) were included in the analytic cohort. There were no statistically significant differences in RFS or early RFS by race/ethnicity (Figure 1). However, among relapsed patients, important qualitative differences were noted at the time of relapse (Table 1). Hispanic and NHB patients were older at relapse than NHW patients. Greater proportions of Hispanic and NHB patients (compared to NHW) experienced cardiovascular, respiratory, and renal failure during frontline therapy. Cumulative prevalence of organ failure in 2 or more systems since initial diagnosis was higher for both Hispanic (50%) and NHB (50%) patients compared to NHW patients (29%). Overweight/obesity at relapse was more prevalent among Hispanic (41%) and NHB (50%) compared to NHW (21%) patients. NHB patients were also more likely to present at relapse with higher acuity, defined as requiring ICU-level resources for 2 or more organ systems within 72 hours of admission, compared to NHW patients (75% vs. 57%). Conclusions: Our data suggest a similar risk of relapse by race and ethnicity. However, differences in cumulative frontline organ toxicity and acuity of presentation may lead to differential treatment at the time of relapse and drive subsequent overall survival disparities for Hispanic and NHB patients with pediatric AML. Future Directions: This was a planned interim analysis, and chart abstraction is ongoing to expand this cohort (anticipated N ~1000). We intend to pursue a series of formal mediation analyses regarding the role of relapse, cumulative organ toxicity during frontline treatment, and selection of salvage regimen on disparities in survival outcomes with the expanded cohort.

Socioeconomic determinants of racial disparities in survival outcomes among patients with renal cell carcinoma

PurposeRacially driven outcomes in cancer are challenging to study. Studies evaluating the impact of race in renal cell carcinoma (RCC) outcomes are inconsistent and unable to disentangle socioeconomic disparities from inherent biological differences. We therefore seek to investigate socioeconomic determinants of racial disparities with respect to overall survival (OS) when comparing Black and White patients with RCC. MethodsWe queried the National Cancer Database (NCDB) for patients diagnosed with RCC between 2004 and 2017 with complete clinicodemographic data. Patients were examined across various stages (all, cT1aN0M0, and cM1) and subtypes (all, clear cell, or papillary). We performed Cox proportional hazards regression with adjustment for socioeconomic and disease factors. ResultsThere were 386,589 patients with RCC, of whom 46,507 (12.0%) were Black. Black patients were generally younger, had more comorbid conditions, less likely to be insured, in a lower income quartile, had lower rates of high school completion, were more likely to have papillary RCC histology, and more likely to be diagnosed at a lower stage of RCC than their white counterparts. By stage, Black patients demonstrated a 16% (any stage), 22.5% (small renal mass [SRM]), and 15% (metastatic) higher risk of mortality than White patients. Survival differences were also evident in histology-specific subanalyses. Socioeconomic factors played a larger role in predicting OS among patients with SRMs than in patients with metastasis. ConclusionsBlack patients with RCC demonstrate worse survival outcomes compared to White patients across all stages. Socioeconomic disparities between races play a significant role in influencing survival in RCC.

Socioeconomic status on survival outcomes in patients with colorectal cancer: a cross-sectional study.

Colorectal cancer (CRC) is widely acknowledged as a prevalent malignancy and the second most common cause of cancer-related mortality worldwide. The aim of this study was to examine the independent impact of Median Household Income (MHI) on prognosis and survival outcomes in patients with CRC. Data from 17 cancer registries of the United States Surveillance, Epidemiology, and End Results program, with follow-up extended until November 2022 was analyzed. A Cox proportional hazards regression analysis was conducted to evaluate the influence of different levels of MHI on survival outcomes among patients with CRC. A total of 761,697 CRC patient records were retrieved from the SEER database. The Cox regression analysis results indicated that patients with higher MHI exhibited improved overall survival outcomes when compared to those with lower MHI (MMHI: P < 0.001; HMHI: P < 0.001). Regardless of the specific tumor location, gender, stage of CRC, or treatment method, higher MHI is consistently linked to improved survival outcomes. However, this association was not found to be statistically significant among American Indian/Alaska Native (MMHI: P = 0.017; HMHI: P = 0.081), Asian or Pacific Islander (MMHI: P = 0.223; HMHI: P = 0.002) and unmarried or domestic partner patients (MMHI: P = 0.311; HMHI: P = 0.011). These results emphasize the importance of considering socioeconomic factors, such as income level, in understanding and addressing disparities in survival outcomes of CRC patients.

The impact of novel therapies on disparities in survival outcomes for metastatic cancers.

e18635 Background: Real-world data have suggested that increases in overall survival (OS) for metastatic cancers over time have been driven by improvements in the groups of patients who already had the highest survival outcomes. To further investigate these identified trends, this research aimed to quantify how novel therapies for metastatic cancers impact disparities in OS outcomes. Methods: Novel therapies for metastatic breast (mBC), metastatic colorectal (mCRC), and metastatic non-small cell lung (mNSCLC) cancer, approved by the United States Food and Drug Administration (FDA) in the last 8 years based on data from phase III randomised controlled trials (RCTs), were identified. For each cancer type, 3 novel therapies were selected with inclusion based on the availability of published Kaplan-Meier data for OS, at least 100 patients in each arm of the corresponding RCT, and OS reaching less than 30% at the end of the RCT follow-up period. For each cancer type and for the novel therapies and comparator therapies separately, the published OS data were replicated from the Kaplan-Meier data and pooled using weights based on sample sizes to ensure each therapy contributed equally to the analysis. Parametric survival modelling was performed to address censoring. The disparity in OS was defined by the absolute difference between groups with the highest and lowest survival, with groups defined by stratifying OS in either 2 or 5 groups. The impact of the combined novel therapies was determined based on the change in OS disparity relative to the combined comparators. A probabilistic analysis was performed to quantify the impact of parameter uncertainty on the outcomes. Results: Novel therapies increased disparities in OS across the 3 cancers. For mBC, the disparities in OS increased by 5.4 (95%-confidence interval: 0.9; 9.9) months, which equates to a 23.0% increase from 24.2 to 29.6 months if OS was stratified in 2 groups, and by 13.9 (1.4; 26.6) months; 25.0% from 57.1 to 71.1 if OS was stratified in 5 groups. For mCRC, disparities increased by 2.8 (1.4; 4.2) months; 37.6% from 7.5 to 10.3 months and by 6.3 (2.9; 9.8) months; 38.9% from 16.5 to 22.8 months, for stratification based on 2 and 5 groups, respectively. For mNSCLC, disparities increased by 10.2 (3.3; 17.3) months; 33.6% from 31.0 to 41.3 months and by 19.5 (4.0; 35.5) months; 31.5% from 63.2 to 82.7 months, for stratification based on 2 and 5 groups, respectively. Conclusions: OS outcomes for recent FDA-approved drugs for metastatic cancers suggest that these novel therapies increase disparities in OS between the patient groups with the highest and lowest OS relative to their comparator therapies in RCTs. Although evidence in terms of these disparities is important, further research using (real-world) individual patient data is warranted to assess how, for example, socioeconomic variables affect the impact of therapies on health disparities among patient groups.

Disparities in Survival Outcomes among Racial/Ethnic Minorities with Head and Neck Squamous Cell Cancer in the United States

Racial/ethnic (R/E) minorities with head and neck squamous cell carcinoma (HNSCC) have worse survival outcomes compared to White patients. While disparities in patient outcomes for R/E minorities have been well documented, the specific drivers of the inferior outcomes remain poorly understood. This was a population-based retrospective cohort study that analyzed HNSCC patients using the National Cancer Database (NCDB) from 2000-2016. Patient outcomes were stratified by R/E groups including White, Black, Hispanic, Native American/Other, and Asian. The main outcome in this study was overall survival (OS). Univariate time-to-event survival analyses were performed using the Kaplan-Meier product limit estimates and the log-rank test to evaluate the differences between strata. There were 304,138 patients with HNSCC identified in this study, of which 262,762 (86.3%) were White, 32,528 (10.6%) were Black, 6191 were Asian (2.0%), and 2657 were Native American/Other (0.9%). Black R/E minorities were more likely to be uninsured (9% vs. 5%, p < 0.0001), have Medicaid insurance (22% vs. 8%, p < 0.0001), be in a lower income quartile (<30,000, 42% vs. 13%, p < 0.0001), have metastatic disease (5% vs. 2%, p < 0.001), and have a total treatment time 6 days longer than White patients (median 107 vs. 101 days, p < 0.001). The 5-year OS for White, Black, Native American/Other, and Asian patients was 50.8%, 38.6%, 51.1%, and 55.8%, respectively. Among the oropharynx HNSCC patients, the 5-year OS rates in p16+ White, Black, and Asian patients were 65.7%, 39.4%%, and 55%, respectively. After a multivariate analysis, Black race was still associated with an inferior OS (HR:1.09, 95% CI: 1.03-1.15, p = 0.002). This large cohort study of HNSCC patients demonstrates that Black race is independently associated with worse OS, in part due to socioeconomic, clinical, and treatment-related factors.

Abstract P1-06-02: The effect of race on pathologic complete response rates and overall survival in patients with triple negative breast cancer

Abstract Introduction: Despite the recent overall improvement in survival for patients with breast cancer, racial disparities in outcomes persist. While studies have demonstrated that socioeconomic factors and access to treatment play a role, differences in tumor biology may also contribute. Black women are significantly more likely to develop triple negative breast cancer (TNBC), the deadliest of the breast cancer subtypes, with more TNBC patients progressing to incurable, metastatic disease than patients with any other breast cancer subtype. Studies have demonstrated that TNBC patients who achieve a pathologic complete response (pCR), defined as no residual invasive cancer in the breast or lymph nodes after neoadjuvant chemotherapy (NAC), have improved survival. We hypothesize that rates of pCR and overall survival (OS) in patients with TNBC may differ by race/ethnicity, which may account in part for the disparities in outcomes observed. Methods: Adult female patients with stage I-III TNBC diagnosed in 2010-2019 who received NAC followed by surgery were identified from the National Cancer Database (NCDB). Race/ethnicity was defined as Hispanic (H), Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Non-Hispanic Asian (NHA), and Non-Hispanic Other (NHO). pCR was defined as no invasive cancer in either the breast or axilla (ypT0/is,N0) at surgery. Logistic regression was used to estimate the association of race/ethnicity with achievement of pCR after adjustment for covariates. Unadjusted OS was estimated using the Kaplan-Meier method, and the log-rank test was used to compare groups. Cox Proportional Hazards models were used to estimate the association of race/ethnicity and achievement of pCR with OS after adjustment for covariates. Additional interaction and subgroup analyses were also conducted. Results: Of the 40,890 patients identified, 29.8% (n=12,173) demonstrated pCR after NAC. The unadjusted 5-year OS rates for those who achieved pCR were significantly higher compared to patients with no pCR (0.917, 95% CI 0.911-0.923 vs 0.667, 95% CI 0.661-0.673, log-rank p&amp;lt; 0.001). Hispanic patients were more likely to achieve pCR (OR 1.19, 95% CI 1.08-1.31, p=0.001), and NHB patients were less likely to achieve pCR (OR 0.89, 95% CI 0.83-0.95, p=0.001) compared to NHW, even after adjustment. Unadjusted OS was also notably lower for NHB patients compared to every other race group (5-year OS rate: NHB 0.709 vs NHW 0.746 vs NHO 0.771 vs H 0.772 vs NHA 0.816, log-rank p&amp;lt; 0.001); however, this difference did not persist after adjustment for patient and disease factors, including achievement of pCR. Interval from diagnosis to start of chemotherapy (OR 0.95, 95% CI 0.94-0.96, p&amp;lt; 0.001) and duration after chemotherapy start to surgery (OR 1.02, 95% CI 1.02-1.03, p&amp;lt; 0.001) were associated with the odds of achieving pCR. Overall, the effect of achieving pCR on OS did not differ by race/ethnicity (interaction p=0.10). Discussion: Achieving pCR after NAC in patients with TNBC is associated with a significant improvement in OS. Yet, rates of pCR appear to differ based on race/ethnicity, with NHB patients demonstrating significantly lower rates of pCR than NHW patients, which may contribute to the disparities in survival outcomes observed. In addition to addressing socioeconomic factors and access to treatment, further research examining whether biological differences exist based on race that influence response of TNBC to current standard therapies is essential for improving survival outcomes for this disproportionately affected patient population. Citation Format: Hannah E. Woriax, Samantha M. Thomas, Jennifer K. Plichta, Laura H. Rosenberger, Astrid Botty van de bruele, Akiko Chiba, Gayle DiLalla, Carolyn Menendez, E Shelley Hwang, Maggie L. DiNome. The effect of race on pathologic complete response rates and overall survival in patients with triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-06-02.

Structural racism in clinical research limits its validity and applicability

The current sociocultural pressures to re-examine structural racism in society and in medicine have inspired researchers to question the assumptions that underpin clinical research and to more deliberately ask questions about the disparities in cancer outcomes based on race or ethnicity with a more intersectional lens.1 Sumit Gupta and colleagues2 present a provocative study on racial and ethnic disparities in survival outcomes in children with acute lymphocytic leukaemia who participated in Children's Oncology Group clinical trials between 2004 and 2019, showing that racial disparities in the outcome of acute lymphocytic leukaemia persist, despite overall advances in its management.

Racial Disparities in Survival Outcomes of Patients With Serous Epithelial Ovarian Cancer: A Retrospective Cohort Analysis.

To identify racial disparities in five-year survival rates in women affected by serous epithelial ovarian carcinoma in the United States (US). This retrospective cohort study analyzed data from the 2010 to 2016 Surveillance, Epidemiology, and End Results (SEER) program database. Women with a primary malignancy of serous epithelial ovarian carcinoma, using International Classification of Diseases for Oncology (ICD-O) Topography Coding and ICD-O-3 Histology Coding, were included in this study. Race and ethnicity were combined into the following groups: Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Non-Hispanic Asian/Pacific Islander (NHAPI), Non-Hispanic Other (NHO), and Hispanics. Cancer-specific survival was measured at five years post-diagnosis. A comparison of baseline characteristics was assessed using Chi-squared tests. Unadjusted and adjusted Cox regression models were used to calculate hazard ratios (HR) and corresponding 95% confidence intervals (CI). From 2010 to 2016, there were 9,630 women with a primary diagnosis of serous ovarian carcinoma identified in the SEER database. A higher proportion of Asian/PI women (90.7%) were diagnosed with high-grade malignancy (poorly differentiated/undifferentiated) compared to NHW women (85.4%). NHB women (9.7%) were less likely to undergo surgery when compared to NHW women (6.7%). Hispanic women had the highest proportion of uninsured women (5.9%), while NHW and NHAPI had the lowest (2.2% each). A higher proportion of NHB (74.2%) and Asian/PI (71.3%) women presented with the distant disease compared to NHW women (70.2%). After adjustment for age, insurance, marital status, stage, metastases, and surgical resection, NHB women had the highest hazard of death within five years compared to NHW women (adjusted (adj) HR 1.22, 95% CI 1.09-1.36, p<0.001). Hispanic women also had lower five-year survival probabilities compared to NHW women (adj HR 1.21, 95% CI 1.12-1.30, p<0.001). Patients undergoing surgery had significantly increased survival probability compared to those who did not (p<0.001). As expected, women with Grade III and Grade IV disease both had significantly lower five-year survival probabilities compared to Grade I (p<0.001). This study reveals that there is an association between race and overall survival in patients with serous ovarian carcinoma, with NHB and Hispanic women having the highest hazards of death compared to NHW women. This adds to the existing body of literature as survival outcomes in Hispanic patients relative to NHW patients are not well documented. Because of the potential interplay between overall survival and several factors including race, future studies should aim to investigate other socioeconomic factors that may be impacting survival.

Disparities in survival outcomes among Black patients with HPV-associated oropharyngeal cancer.

Patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma(HPV-OPSCC) have a favorable prognosis and excellent overall survival (OS), and studies have demonstrated these findings in cohorts of predominantly White patients. Racial/ethnic (R/E) minorities, particularly Black patients, with head and neck squamous cell carcinoma (HNSCC) have worse survival outcomes compared with White patients. In this study, we aimed to determine if Black patients with HPV-OPSCC have a similar favorable prognosis to the White population. This was a population-based retrospective cohort study that analyzed HNSCC patients using the National Cancer Database from 2010 to 2016. We identified patients with Stage I-IV HPV- OPSCC who were treated with radiation, surgery, chemotherapy, or a combination of modalities. Patient outcomes were stratified by R/E groups including White Versus Black patients. The main outcome in this study was OS. Analyses for proportions of categorical variables were performed using a χ2 or Fisher's exact test. Univariate and multivariate time-to-event survival analyses were performed using Kaplan-Meier product limit estimates and log-rank test to test the differences between strata. A Cox proportional hazards regression model was used to assess the association between covariates and risk of death (OS).We identified 9256 OPSCC patients who met inclusion criteria and were treated between 2010 and 2016, of which 7912 were White (85.5%) and 1344 were Black (14.5%). A total of 1727 were HPV-OPSCC, of which 1598 were White (92.5%) and 129 (7.5%) were Black. By race, the 5-year OS for White versus Black OPSCC patients was 42% versus 23%, respectively (log-rank, p < 0.0001). Among HPV-positive OPSCC patients, the 5-year OS for White versus Black patients was 65% versus 39% (log-rank, p < 0.0001). Among HPV-negativepatients, the 5-year OS for White versus Black patients was 36% versus 13% (log-rank, p < 0.0001). On multivariate analysis, after accounting for age, sex, insurance status, income, Charlson-Deyo score, receipt of surgery, distance from facility, and total treatment time, Black race trended toward, but was not associated with worse survival. Hazard ratio(HR:1.24, 95% confidence interval[CI] 0.85-1.81, p = 0.255). This national cohort study of OPSCC patients demonstrates that Black patients with HPV-OPSCC have a poor prognosis and OS similar to HPV-negative White patients. This may be partly due to socioeconomic barriers such as insurance and income. Further work is needed to better understand the specific drivers of inferior survival outcomes in this specific patient population.

Racial and Ethnic Disparities in Survival Outcomes in Chronic Myeloid Leukemia

Introduction Minority populations within the United States bear a disproportionate burden of health disparities, which has been demonstrated across studied malignancies. The effect that race plays on treatment access and overall survival (OS) in chronic myeloid leukemia (CML) is poorly understood. Using a large national database, we aim to identify how racial and ethnic identity effects access to treatment and survival outcomes in CML Methods Using the National Cancer Database we identified CML patients (pts) diagnosed from 2004-2019. Demographic and treatment characteristics were compared for White, Black, Asian, Hispanic and other minority populations, with race and ethnicity self-identified by pts. Excluding pts who were managed with upfront allogeneic stem cell transplant, Kaplan Meier and adjusted Cox regression survival analysis were used to compare OS by race and ethnicity, with repeat analysis for the <65 year (yr) old cohort. Multivariable Cox regression was adjusted for age, Charlson-Deyo comorbidity index, sex, insurance, and zip code income and education level quartiles to compare OS by race. Results We identified 38,763 pts diagnosed with CML, of which 81% (N=17,739) identified as White, 12% (N=4,672) Black, 3% (N=1,125) Asian, and 4% (N=1,422) identified as Other race. 3,304 pts (9%) were Hispanic ethnicity. The median age of all CML pts was 57 yrs (interquartile range [IQR] 44-70), with White pts presenting at an older age (median 59 yrs [IQR 45-71]) than other races, with a median age of 53 yrs [IQR 40-64] in the Black population and a median age in the Asian and Other races of 50 (IQR 35-63). Compared to White pts, Black pts were more likely to reside in low-income zip codes (44% vs. 16% of White pts), be uninsured (11% vs. 6%), insured by Medicaid (19% vs. 8%) and be treated at academic centers (47% vs. 36%). Hispanic pts presented at a younger age (median 46 yrs [IQR 34-59] vs 58 yrs [IQR 45-71 yrs] in the non-Hispanic population), and were more likely to reside in low-income areas (29% vs 19%), be uninsured (21% vs 5%), or Medicaid insured (23% vs 9%), all p<0.001. All races were equally likely to receive disease directed therapy at diagnosis. The median OS for all CML cases was 14.4 yrs (95% confidence interval (CI) 13.9-14.9), with a 1-, 5- and 10- yr OS of 90%, 73%, and 60%, respectively. The 5-yr OS for both White and Black pts was 73% (p=0.114), with 82% 5-yr OS for Asian pts (p<0.001), and 84% for other races (p<0.001). In pts <65 yrs old, the White population had a 1-, 5- and 10-yr OS of 96%, 87%, and 78%, which was significantly longer than in the Black population, at 94%, 87%, and 78%, p<0.001. On Cox regression adjusted for age, Black race was associated with reduced OS (HR 1.24 [95% CI 1.17-1.31], p<0.001) while pts who identified as either Asian race (HR 0.84 [95% CI 0.73-0.97], p=0.020) or other race (HR 0.79 [95% CI 0.69-0.90], p<0.001) were found to have significantly improved OS, referenced to the White population. On Cox regression adjusted for age, race, ethnicity, comorbidity and socioeconomic features, Black race was not associated with worse outcomes over White race (HR 1.03 [95% CI 0.96-1.10), p=0.378). Asian or Other race, and Hispanic ethnicity were associated with significantly improved OS, with HR 0.82 (95% CI 0.71-0.96), HR 0.79 (95% CI 0.67-0.64) and HR 0.77 (95% CI 0.70-0.85), respectively, all p<0.05. Characteristics associated with reduced OS included age (HR 1.05 [1.05-1.06], p<0.001), increased comorbidity burden (HR 1.32 [0.29-1.35], p<0.001), uninsured status (HR 1.98 [1.78-2.20], p<0.001), Medicaid (HR 2.16 [1.98-2.36], p<0.001), Medicare (HR 1.56 [1.47-1.66], p<0.001), and residing is areas with low income (HR 1.17 [95% CI 1.08-1.27) and low education level (HR 1.19 [95% CI 1.09-1.29]), all p<0.001. Discussion We present the largest study to date examining the influence of race and ethnicity on OS in CML pts. Despite advances in diagnosis and treatment options over the past decade, pts from traditionally underserved populations, including Black, uninsured, and low-income populations, continue to have reduced OS. Black pts have particularly poor survival when compared to White pts of similar ages, however, when adjusted for socioeconomic features associated with healthcare access, the survival gap improves. This indicates that access to treatment remains a significant barrier in this population, highlighting the need for targeted actions to improve outcomes in this population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

IBCL-462 Racial-Ethnicity Gap in Survival among Non-Hodgkin Lymphoma Survivors

Non-Hodgkin lymphoma (NHL) is one of the most common cancers in the United States. It is one of the leading causes of cancer-specific morbidity and mortality. An explanation for the significant racial/ethnicity disparity in survival among NHL survivors has been attributed to disparity in access to treatment modalities. We determined if patients' race/ethnicity is an independent predictor of survival following a diagnosis of NHL. We utilized the SEER Registry to identify patients with a primary diagnosis of NHL from 2007 to 2015. Our primary outcome of interest was the patients' survival following a diagnosis of NHL. We determined cancer-specific survival at 1, 3, and 5 years stratified by patients' race/ethnicity. We used Cox regression to determine if the race/ethnicity disparity continues after controlling for disease stage, age, sex, and treatment modalities. There were 171,778 primary cases of NHL in the study period. The majority of the patients were Non-Hispanic Whites (NHW), 72.1%, Non-Hispanic Blacks (NHB), 7.8%, Hispanics, 12.0%, Non-Hispanic Asians, or Pacific Islanders (NHAPI), and 0.5% Non-Hispanic American Indians/Alaska Natives (NHAIAN). There were 54.9% males vs. 45.1% females. The mean age of the study population was 64.7± 16.6 years. Survival at 1, 3 and 5 years by patients' race/ethnicity was, NHW (90.3%, 84.0%, 81.2%), NHB (86.6%, 79.6%, 76.1%), Hispanics (87.4%, 81.5%, 78. 6%). NHB had the worst overall survival (OR=1.53; 95% CI 1.47-1.60), Hispanics (OR=1.23; 95% CI 1.19-1.28), NHAIP (1.26; 95% CI 1.20-1.32) and NHAIAN (OR=1.23; 95%CI 1.04-1.46). There is significant racial disparity in survival outcomes following NHL diagnosis. This disparity persisted even after controlling for patients' insurance type, disease stage, and treatment modalities. Further research is needed to unravel the role of genetics in the racial gap seen in outcomes among NHL survivors.

Disparities in Survival Outcomes of Out-of-Hospital Cardiac Arrest Patients between Urban and Rural Areas and the Identification of Modifiable Factors in an Area of South Korea

This retrospective study aimed to compare the survival outcomes of adult out-of-hospital cardiac arrest (OHCA) patients between urban (Busan, Ulsan, Changwon) and rural (Gyeongnam) areas in South Korea and identify modifiable factors in the chain of survival. The primary and secondary outcomes were survival to discharge and modifiable factors in the chain of survival were identified using logistic regression analysis. In total, 1954 patients were analyzed. The survival to discharge rates in the whole region and in urban and rural areas were 6.9%, 8.7% (Busan 8.7%, Ulsan 10.3%, Changwon 7.2%), and 3.4%, respectively. In the urban group, modifiable factors associated with survival to discharge were no advanced airway management (adjusted odds ratio (aOR) 2.065, 95% confidence interval (CI): 1.138–3.747), no mechanical chest compression (aOR 3.932, 95% CI: 2.015–7.674), and an emergency medical service (EMS) transport time of more than 8 min (aOR 3.521, 95% CI: 2.075–5.975). In the rural group, modifiable factors included an EMS scene time of more than 15 min (aOR 0.076, 95% CI: 0.006–0.883) and an EMS transport time of more than 8 min (aOR 4.741, 95% CI: 1.035–21.706). To improve survival outcomes, dedicated resources and attention to EMS practices and transport time in urban areas and EMS scene and transport times in rural areas are needed.

Racial Disparities in Survival Among Non-Hodgkin Lymphoma Patients: An Analysis of the SEER Database (2007-2015).

IntroductionAlthough disparities in cancer survival exist across different races/ethnicity, the underlying factors are not fully understood.AimTo identify the interaction between race/ethnicity and insurance type and how this influences survival among non-Hodgkins lymphoma (NHL) patients.MethodsWe utilized the SEER (Surveillance, Epidemiology, and End Results) Registry to identify patients with a primary diagnosis of NHL from 2007 to 2015. Our primary outcome of interest was the hazard of death following a diagnosis of NHL. In addition, we utilized the Cox regression model to explore the interaction between race and insurance type and how this influences survival among NHL patients.ResultsThere were 44,609 patients with NHL who fulfilled the study criteria. The mean age at diagnosis was 50.9 ± 10.8 years, with a mean survival of 49.8± 34.5 months. Among these patients, 64.8% were non-Hispanic Whites, 16% were Hispanics, and 10.8% were Blacks. In addition, 76.5% of the study population had private insurance, 16.6% had public insurance, and 6.9% were uninsured. Blacks had the worst survival (HR=1.66; 95% = 1.55-1.78). Patients on private insurance had better survival compared to those with public insurance (HR=2.11; 95% CI=2.00-2.24)ConclusionThe racial and socioeconomic disparity in survival outcomes among patients with NHL persisted despite controlling for treatment modalities, age, and disease stage.

Poverty, race, ethnicity, and survival among U.S. children with non-metastatic osteosarcoma treated on EURAMOS-1: A report from the Children’s Oncology Group.

10004 Background: Children living in poverty and those who identify as a race/ethnicity other than non-Hispanic White experience higher rates of relapse and lower overall survival across many pediatric cancers. Racial, ethnic and socioeconomic disparities have not been comprehensively investigated in osteosarcoma. We leveraged data from US-enrolled patients on the recent international EURAMOS-1 trial to investigate disparities in survival outcomes. Aim: Identify if race/ethnicity, household or neighborhood poverty exposure are associated with event-free survival (EFS) or overall survival (OS) in patients with non-metastatic osteosarcoma enrolled at a US-center on EURAMOS-1. Methods: Retrospective cohort study of US patients aged 5-21 years enrolled on EURAMOS-1 with a diagnosis of non-metastatic, primary osteosarcoma. Poverty was the primary exposure defined at the household- (sole coverage with Medicaid or CHIP public insurance versus other) and neighborhood- (Census-defined high-poverty ZIP code with &gt;20% of residents living at &lt;100% Federal Poverty Level vs other) levels. Race and ethnicity were categorized to reflect structural inequities and historically marginalized populations, as Hispanic, non-Hispanic Black (NHB), non-Hispanic Other (NHO), and non-Hispanic White (NHW). OS and EFS as a function of time from trial enrollment were estimated using the Kaplan-Meier method. Hypotheses of associations between risks for EFS-event, death and post-relapse death with poverty-exposures and race/ethnicity were assessed using log-rank tests. Statistical comparisons were performed excluding patients with missing values for the exposures considered. P-values &lt;=0.05 were considered significant. Results: Among 758 patients, 27% were household poverty-exposed and 29% were neighborhood-poverty exposed. Twenty-one percent of children identified as Hispanic, 17% NHB, 5% NHO and 57% NHW. Neither household- or neighborhood-poverty, nor race/ethnicity were significantly associated with risks for EFS-event or death. Post-relapse risk for death differed significantly across race/ethnicity with NHB at greatest risk compared to others (4-Year post-relapse survival 35.7% Hispanic vs. 13.0% NHB vs. 43.8% NHO vs 38.9% NHW; p=0.0046). Conclusions: Neither poverty-exposures nor race/ethnicity were associated with EFS or OS in this COG trial-enrolled cohort, suggesting equitable outcomes following standardized therapy. Despite this, non-Hispanic Black children experienced significantly inferior post-relapse survival. Investigation of mechanisms driving these post-relapse disparities, including inequities in health care delivery and access to post-relapse trial-enrollment, are paramount to ensure equity in outcomes for all children with cancer.

Highlights from Recent Cancer Literature

Although BRCA1/2 pathogenic variants are well known to increase risk of female breast and ovarian cancers, the risk of other malignancies has not been well characterized due to small sample sizes tested. Here, Li and colleagues analyzed data from 3,184 BRCA1 and 2,157 BRCA2 carrier families from the Consortium of Investigators of Modifiers of BRCA1/2, identifying numerous differences in the spectrum of cancers. Carriers of BRCA1 pathogenic variants had significantly increased incidence of male breast, gallbladder, stomach, and colorectal cancers, without an increase in prostate cancer, while those with BRCA2 pathogenic variants had dramatically increased relative incidence of male breast cancer, along with significant increases in the incidence of stomach, pancreatic, and prostate cancer. Age-specific absolute risks were calculated across cancers separately for both BRCA1 and BRCA2.Expert Commentary: This large study of BRCA1/2 families provides a detailed risk for cancers in addition to breast and ovarian cancers, generating crucial baseline data to design age- and mutation-specific surveillance protocols.Li S, Silvestri V, Leslie G, Rebbeck TR, Neuhausen SL, Hopper JL, et al. Cancer risks associated with BRCA1 and BRCA2 pathogenic variants. Journal of Clinical Oncology; Published online January 25, 2022; doi: 10.1200/JCO.21.02112.Tumoral heterogeneity allows for resistant tumor cell clones to survive during cancer therapy, leading to relapse. Karabacak and colleagues used single cell mass cytometry on PTEN-deleted mouse models of prostate cancer to determine the evolution of kinase activities in different tumor compartments during metastasis or following drug treatment. Bone lesions in a metastatic model of prostate cancer displayed elevated PI3K/mTOR activity and overexpressed the c-Met receptor tyrosine kinase as compared with primary tumors, circulating tumor cells, and metastases. These metastases were uniquely sensitive to inhibition of c-MET as compared with metastases in other tissues. The authors also expanded on the importance of intratumoral heterogeneity by demonstrating PI3K/mTOR activity was elevated in epithelial cancer cells and diminished in mesenchymal cells within a single tumor, which was confirmed in prostate and breast patient–derived circulating tumor cells. These findings suggest differential sensitivity of different cell states to PI3K/mTOR inhibitors and provide insights into how the epithelial-to-mesenchymal transition promotes drug resistance.Expert Commentary: This study highlights intertumoral and intratumoral differences in kinase activity (PI3K/mTOR) in a mouse model of prostate cancer and suggests using combination therapies to target the differing therapeutic vulnerabilities of cancer cells in different tissue compartments.Karabacak NM, Zheng Y, Dubash TD, Burr R, Micalizzi DS, Wittner BS, et al. Differential kinase activity across tumor compartments defines sensitivity to target inhibition. Cancer Res 2022;82:1084–97.Multiple cancer types are dependent upon glutamine for survival as a key component of tumor cell metabolism and energy production. In a recent study, Huang and colleagues identified a previously unrecognized role for glutamine in cancer by demonstrating glutamine is used in γ-aminobutyric acid (GABA) production, which has mostly been studied in neuronal signaling. GABA and GAD1, the enzymes responsible for conversion of glutamine to GABA, were found to be overexpressed in lung and colorectal cancer and correlated with poor outcomes. GABA, through a GAD1- and β-catenin–dependent pathway, promoted tumor growth and suppressed CD8+ T-cell infiltration. Targeting the GABA receptor or GAD1 overcame resistance to anti-PD-1 therapy.Expert Commentary: This study suggests that targeting the GABA pathway may be an effective therapeutic strategy for a subset of cancer patients.Huang D, Wang Y, Thompson JW, Yin T, Alexander PB, Qin D, et al. Cancer-cell-derived GABA promotes β-catenin–mediated tumour growth and immunosuppression. Nat Cell Biol 2022;24:230–41.Disparities in survival outcomes exist between Black and Hispanic patients and non-Hispanic white patients. Abraham and colleagues examined biological, clinical, and socioeconomic variables in six Chicago area hospitals, assessing outcomes in acute myeloid leukemia, an aggressive hematologic cancer. While patient age and specific mutations were favorable indicators in the white population, this was not the case for other populations. Using census tract information to generate measures of racial and economic segregation, the authors assembled an outcomes dataset that included these data and other known variables. Other studies have suggested that nonbiologic factors can independently affect survival in acute myeloid leukemia. Here the variables considered to represent structural racism accounted for nearly all the disparity in survival outcomes among the defined racial groups.Expert Commentary: This study highlights the urgent need to consider structural and historic factors including socioeconomic status, neighborhood segregation and affluence, and access to community support resources when seeking to improve cancer outcomes.Abraham I, Rauscher G, Patel A, Pearse W, Rajakumar P, Burkart M, et al. Structural racism is a mediator of disparities in acute myeloid leukemia outcomes. Blood; Published online January 21, 2022; doi: 10.1182/blood.2021012830.Cancer-associated fibroblasts (CAF) are now known to have both tumor-promoting and tumor-suppressive properties, which complicates the design of therapies targeting CAFs. Prostaglandin E2 (PGE2), a lipid mediator, is known to promote tumor initiation and growth, and suppresses antitumor immunity, however, Elsakeel and colleagues further defined the role of PGE2 by studying its impact on CAF activation. Knockout of microsomal prostaglandin E synthase-1 (mPGES-1) in PyMT mice or prostanoid E receptor 3 (EP3) in CAFs constrained PGE2 signaling to inhibit mammary tumor growth, however, these changes promoted robust CAF proliferation. Disruption of PGE2 signaling in CAFs caused epithelial-to-mesenchymal transition in cancer organoids and stimulated metastasis in mice. Mechanistically, these effects were associated with a reduction in TGFβ-activated kinase–like protein (TAK1L), a negative regulator of p38 MAPK activation. Interestingly, high TAK1L expression in CAFs correlated with reduced metastasis and enhanced survival in breast cancer patients.Expert Commentary: This study suggests that PGE2 functions as a double-edged mediator, promoting tumor growth at the primary site while restricting metastasis. PGE2 targeting strategies in breast cancer may potentially benefit from EP3-selective approaches.Elsakeel E, Brüggemann M, Wagih J, Lityagina O, Elewa MAF, Han Y, et al. Disruption of prostaglandin E2 signaling in cancer-associated fibroblasts limits mammary carcinoma growth but promotes metastasis. Cancer Res 2022:82:1380–95.Ferroptosis is a cell death pathway known to be regulated by fatty acid metabolism, but the specific species of fatty acids that can induce this process are not well defined. Liao and colleagues screened which fatty acids could trigger ferroptosis in cancer cells in vitro, specifically in combination with IFNγ. Only arachidonic acid induced cell death, which could be suppressed by ferrostatin 1. Arachidonic acid–mediated cell death required ACSL4, an essential enzyme in generating phospholipids from polyunsaturated fatty acids, which, when oxidized, can induce ferroptosis. Interestingly, ACSL4-deficient tumor cells were resistant to immune control and these tumors exhibited reduced T-cell infiltration and function, and the authors observed that induction of ferroptosis required T cells. Therapeutically, systemic arachidonic acid administration enhanced tumor control when combined with checkpoint blockade therapy. In cancer patients, higher expression of ACSL4 correlated with improved response to checkpoint blockade.Expert Commentary: T cells can induce cancer cell ferroptosis through producing IFNγ in the presence of the long chain fatty acid arachidonic acid. Arachidonic acid administration may improve the efficacy of checkpoint blockade therapy.Liao P, Wang W, Wang W, Kryczek I, Li X, Bian Y, et al. CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4. Cancer Cell; Published online February 15, 2022; doi: 10.1016/j.ccell.2022.02.003.Note: Breaking Insights are written by Cancer Research editors. Readers are encouraged to consult the articles referred to in each item for full details on the findings described.