bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of biophysics-based biomarker with tumor volumetric response in breast cancer treated with immunotherapy.
Authors: Cook Daniel , Pfeiffer John R. , Peterson Joseph R. , Liadis Nicole , Biancalana Matthew , Lopez Dorys , Cole John A. , Antony Anuja K.
Published: June 2023

608

Background: The treatment landscape of triple negative breast cancer (TNBC) has rapidly changed in recent years, with immuno-oncology (IO) therapies, such as immune checkpoint inhibitors, leading to improvement in patient outcomes. However, the number of patients who benefit is less than 15%, and the therapy itself can prompt severe immune-related adverse events. Breast cancer tumor volume measurements derived from magnetic resonance imaging (MRI) have proven to be a strong predictor of outcome (survival) in patients who either achieve pathological complete response (pCR) or have residual cancer burden (RCB) (ACRIN6657/CALGB150007 I-SPY1). Using an integrative computational approach, we developed both the TumorIO biomarker and the TumorIO Score to predict response to IO therapy in breast cancer patients. Here, we assess the volumetric response in IO-treated patients and its relationship with the TumorIO Score. Methods: We assessed the relationship between breast tumor volumetric response to IO therapy and the TumorIO Score, a previously developed metric that relates probability of IO responsiveness to spatially-resolved tumor biology. We grouped patients into TumorIO Score high vs. low populations, and compared final volumes assessed by MRI and percent response to therapy between groups. Results: We analyzed the volumetric response of IO-treated patients from the I-SPY2 trial and from an independent cohort (total n = 67). Over 96% of the IO-treated patients in the I-SPY2 trial (n = 55) had a greater than 90% volumetric response, while in the independent cohort (n = 12) only 50% of patients had greater than 90% volumetric response. Across both cohorts, 95.8% of patients with a high TumorIO Score achieved > 90% reduction in tumor volume. Additionally, we identified three patients in our cohort that appeared not to respond to IO therapy, who were later classified as progressor, pseudo-progressor, and non-responder patients. The TumorIO biomarker was able to differentiate these three patients, as it associates a unique distinctive biological phenomenon with either response or lack of response. Conclusions: The TumorIO Score provides a novel technology to address several challenges in neoadjuvant IO therapy, namely: predicting which patients are likely to have pCR in response to IO therapy, as well as identifying patients likely to have a substantial volumetric response to IO. Additionally, this method may facilitate subcategorizing patients likely to show radiological pseudo-progression prior to IO administration, although a larger cohort is needed to validate these findings.
Artificial intelligence (AI) analysis of tumor-infiltrating lymphocytes (TILs) in hematoxylin and eosin (H&E) slides to explore immune phenotypes in papillary thyroid cancer.
Authors: Nam Myungwoo , Chung Liam Il-Young , Kim Leeseul , Park Gahee , Kim Sukjun , Song Sanghoon , Ock Chan-Young , Chae Young Kwang
Published: June 2023

6100

Background: Different biomarkers have been discovered to predict response to immunotherapy but the variability of response exists. TILs are a potential biomarker as infiltration of CD8+ T cells in the tumor microenvironment(TME) was related to treatment response to PD-1 blockade. Advanced well-differentiated papillary thyroid cancer(PTC) has limited standard-of-care treatment options and can exhibit a poor prognosis when exhausted. Our study aimed to classify the TME of PTC according to TILs. Methods: Using the TCGA PTC data, samples were classified into three immune phenotypes (immune-’desert’, immune-’excluded’, and ‘inflamed’) based on peri-tumor lymphocyte density from analysis of H&E slides using an AI model(Lunit SCOPE). Immune and stromal cell infiltration was inferred using xCell. Cytolytic scores(CYT) and thyroid differentiation scores(TDS) were calculated using mRNA expression. Results: Total of 383 samples were included. Immune phenotype analysis showed 183(47.7%) ‘desert’, 133(34.7%) ‘excluded’, and 67(17.4%) ‘inflamed’. Median age at diagnosis was the lowest in ‘inflamed’(inflamed 41.5 vs excluded 47 vs desert 50, p = 002). TNM stages were as follows in the order of stages 1 to 4: inflamed 49/4/8/3, excluded 64/13/32/16, and desert 86/28/40/19. BRAF V600E mutation was most prevalent in ‘excluded’(97/133, 72%), followed by ‘inflamed’(32/67, 47.7%) and ‘desert’(51/183, 27.8%). CYT was the highest in ‘inflamed’(median: inflamed 186 vs excluded 53 vs desert 39, p < 0.001). TDS was the highest in ‘desert’(median: inflamed -0.3 vs excluded -0.69 vs desert 0.73, p < 0.001). The 6 cell types with the most statistically significant difference in infiltration were activated dendritic cells(aDCs), DCs, B cells, epithelial cells(EpCs), CD8+ central memory T cells, and CD4+ memory T cells. The ‘inflamed’ showed the highest median value for all of these cells except EpCs. The cells with the highest median value in ‘excluded’ included EpCs, sebocytes, and immature DCs. The cells with the highest median value in ‘desert’ were lymphatic endothelial cells(ECs), ECs, and osteoblasts. Three immune phenotypes were associated with differential outcomes in disease-free survival(log-rank for trend, p-value = 0.01). There was no difference in overall survival. Conclusions: Our results suggest that 15% of PTC can have immune features which were related to a higher rate of response to immunotherapy across different tumor types. A previous study showed that PTC with a low TDS or BRAF V600E mutation is related to increased immune response indices. In our study, TDS or BRAF V600E mutation status could not distinguish the ‘inflamed’ from other phenotypes. This suggests that immune phenotype classification through TILs can provide distinct information about the TME of PTC.
Use of PROMIS to capture patient reported outcomes over time for patients on I-SPY2.
Authors: Jacob Saya , Yu Hongmei , Wolf Denise M. , Chattopadhyay Aheli , Brain Susie , Simmons Carol , Ruddy Kathryn Jean , Kang Irene , Blaes Anne Hudson , Somani Amrita B , Hershman Dawn L. , Esserman Laura , Melisko Michelle E.
Published: June 2023

611

Background: Patient reported outcomes (PROs) capture direct feedback from patients in clinical trials. The NIH Patient-Reported Outcomes Measurement Information System (PROMIS) is an open source and validated PRO platform. Data on PROMIS score trajectories over time for breast cancer patients undergoing neoadjuvant chemotherapy (NAC) are limited. Methods: We administered paper surveys to patients enrolled on the I-SPY2 trial, a multicenter, randomized phase 2 trial comparing novel agents to standard NAC in high-risk breast cancer. PRO domains included PROMIS Physical Function, Anxiety, Depression, Applied Cognition and Fatigue. Surveys were administered at baseline (post-consent), C1D1, inter-regimen (~12 wks into NAC), pre-surgery and at 1, 6, 12, and 24 months post-surgery. Responses were scored using the HealthMeasures Scoring Service to generate a standardized T score, with a score of 50 representing the general US population mean. Higher Anxiety, Depression and Fatigue scores represent worse symptoms; higher Physical Function and Applied Cognition scores represent better symptoms. We calculated average scores by time-point and compared changes from baseline to various grouped time points using a paired t-test. Results: From 1/2012 to 7/2020, 1631 patients enrolled in I-SPY 2 with 959 completing the baseline survey. 62% had at least two “on-treatment” surveys, and 52% had at least one follow-up time-point. Average baseline PROMIS scores for Physical Function, Anxiety, Depression, Applied Cognition and Fatigue were 46.7, 55.1, 47.2, 53.3 and 46.0 respectively. Between baseline and the latest on-treatment time point we observed improvement in Anxiety (-5.2) and worsening in Physical Function, Applied Cognition and Fatigue (-5.4, -6.9 and +8.2 respectively). Between baseline and the latest post-surgery time point, we saw improved Anxiety (-5.9) and worsened Physical Function, Applied Cognition and Fatigue (-5.9, -3.6 and +4.3). Depression changed minimally. Conclusions: Using PROMIS, patients on I-SPY2 experienced worse Physical Function, Applied Cognition and Fatigue but improved Anxiety during and after treatment compared to baseline. While changes in Applied Cognition and Fatigue recovered partially after treatment, Physical Function scores did not, suggesting potential for longer term impact on quality of life. Clinical trial information: NCT01042379 . [Table: see text]
Risk of early mortality in patients with cancer experiencing adverse financial events.
Authors: Khan Hiba , Li Li , Yu Kaiyue , Fedorenko Catherine R. , Kreizenbeck Karma L. , Khor Sara , Kestner Shannon , Ramsey Scott David , Shankaran Veena
Published: June 2023

6503

Background: Patients with cancer are at higher risk for experiencing severe adverse financial events (AFEs) compared to similar individuals without cancer. Among persons with cancer, those experiencing bankruptcy have poorer survival. In this study, we sought to determine whether AFEs less severe than bankruptcy have an increased risk of death among patients with cancer. Methods: Records for all patients diagnosed with a solid tumor between 2013 and 2018 were identified through the Western Washington State SEER cancer registry and were linked to quarterly credit reports from TransUnion. Patients who survived at least 2 years from date of diagnosis were included. Cancer patients experiencing any AFE, defined as third-party collections, charge-offs, delinquent mortgage payments, tax liens, foreclosures, and repossessions within 2 years of diagnosis were compared with cancer cases who did not experience these events. After adjusting for age, sex, race, area deprivation index, rural/urban status, marital status, AFE at diagnosis, cancer type, and stage of cancer, we fit a Cox proportional hazards model to examine the relationship between AFEs and overall survival, and also fit a separate model for each cancer type. Results: A total of 64,637 patients were diagnosed with cancer between 2013 and 2018, and survived 2 years post-diagnosis. The overall population was 84% white, 53% female, and had a median age of 64. 12,698 patients experienced any severe financial event. The adjusted hazard ratio for mortality among patients who did versus did not experience an AFE was 1.22 (95% CI, 1.145-1.299, p <0.001), with age >65, Asian/Pacific Islander race, greater area deprivation index, and higher stage of cancer associated with increased risk for mortality. Among differing cancer types, patients with prostate cancer who experienced an AFE had the highest risk of death compared with patients with prostate cancer who did not experience an AFE (HR 1.703,95% CI, 1.395 to 2.08, p <0.001). Conclusions: Patients with cancer who experience severe AFEs within 2 years of diagnosis are at higher risk for mortality after adjusting for sociodemographic and clinical factors. When comparing within separate cancer groups, this association is strongest among patients with prostate cancer. Current analysis is limited by restricting population to those who survived at least 2 years after diagnosis; future work will expand population to include patients who died at any time point. Further research should investigate mechanisms for this increased mortality risk, to inform potential interventions and policy solutions, especially among the prostate cancer population. [Table: see text]
Health insurance continuity and survival among children, adolescents, and young adults with blood cancer: An analysis based on SEER-Medicaid data.
Authors: Ji Xu , Zhang Elyse Xinyue , Bai Shasha , Stock Wendy , Yabroff Robin , Mertens Ann C. , Castellino Sharon M.
Published: June 2023

6504

Background: Many previously uninsured patients do not receive Medicaid coverage until the point of, or after, cancer diagnosis, which may delay access to life-saving therapies. We examined whether continuous Medicaid coverage prior to diagnosis (vs. gaining Medicaid at, or after, diagnosis) provides a survival benefit in children and adolescents/young adults (AYAs) newly diagnosed with blood cancer. Methods: Using the linked SEER cancer registry-Medicaid enrollment data, we assessed coverage during the six months prior to, the month of, and the six months after cancer diagnosis (13-month window) in 29,873 children and AYAs (aged 0-39 years) diagnosed with blood cancer in 2006-2013. To measure insurance continuity, we categorized patients who had: (1) continuous Medicaid (enrolled for ≥6 months prior to through diagnosis), (2) newly gained Medicaid at/after diagnosis (enrollment only at or ≤6 months after diagnosis), (3) other patterns of noncontinuous Medicaid, (4) private insurance, (5) other insurance, or (6) uninsured/unknown insurance. The last three groups contain patients in SEER not linked to Medicaid enrollment data; these patients’ insurance at diagnosis was available in SEER. Kaplan-Meier (KM) survival curve of 5-year overall survival was stratified by insurance continuity category. Associations between insurance continuity and survival were examined using Cox proportional hazard models, for all blood cancers combined and by cancer type (leukemia, lymphoma, myeloma). Models also adjusted for age, sex, race/ethnicity, rurality, neighborhood socioeconomic status, and diagnosis year. Results: Of our sample, 44.1% had private insurance, followed by Medicaid (28.3%), other insurance (9.6%), and no insurance (3.9%) or unknown insurance (14.1%). Of Medicaid-insured patients, 44.9% had continuous Medicaid, 38.9% gained Medicaid at/after diagnosis, and 16.2% experienced other noncontinuous patterns. The KM-estimated 5-year survival probability was 89.3% for privately insured patients, followed by other insurance (88.1%), continuous Medicaid (78.2%), other patterns of noncontinuous Medicaid (74.3%), and newly gained Medicaid at/after diagnosis (70.6%; p<0.001). In multivariable analysis, patients who newly gained Medicaid at/after diagnosis had a hazard ratio (HR) for death of 2.63 (95%CI=2.42-2.87), whereas patients with continuous Medicaid and those with other noncontinuous patterns had HRs of 2.08 (95%CI=1.90-2.28) and 2.31 (95%CI=2.04-2.60), respectively, compared to privately insured patients. This finding persisted across blood cancer types. Conclusions: Less than half of Medicaid-insured children and AYAs with blood cancer had continuous insurance coverage prior to and following cancer diagnosis. Lacking continuous Medicaid coverage was associated with inferior survival.
Association of medical debt and cancer mortality in the US.
Authors: Hu Xin , Zheng Zhiyuan , Shi Kewei Sylvia , Yabroff Robin , Han Xuesong
Published: June 2023

6505

Background: Medical debt is associated with non-medical and medical financial hardship, such as food and housing insecurity, as well as delaying or forgoing recommended health care. This study examines county level associations between medical debt and cancer mortality in the US. Methods: We conducted a county level ecological study, using 2018 medical debt data from the Urban Institute linked with 2015-2019 mortality data from the National Centers for Health Statistics. All US counties with non-missing information on medical debt and other covariates were included. Primary outcomes were age-adjusted mortality rates per 100,000 person-years for all malignant cancers and by cancer type. Multivariable linear mixed models were used to estimate the association of percent of population with medical debt with cancer mortality, adjusting for county level sociodemographic characteristics. Additional analyses examined the association between median amount of medical debt per person and cancer mortality for the subset of counties with these data. Models were weighted by county level population size, with standard errors clustered at the state level. Results: Among 2,943 counties, an average of 19.8% of the population had medical debt, ranging from 0% to 53.6% across counties. Higher percentages of the population with medical debt were observed in non-metro areas, counties with higher percentages of non-Hispanic Black people, adults without high school education, living below poverty level, uninsured, or unemployed. One percentage point increase in the population with medical debt was associated with a 1.12 (95% CI=1.02-1.22) increase in age-adjusted mortality rate (per 100,000 person-years) for all malignant cancers, a 0.47 (95% CI=0.43-0.52) increase for lung cancer, a 0.09 (95% CI=0.07-0.11) increase for colorectal cancer, and a 0.06 (95% CI=0.04-0.07) increase for female breast cancer. Among 1,949 counties with the amount of medical debt available, each $100 increase in median medical debt was associated with a 0.86 (95% CI=0.52-1.21) increase in age-adjusted mortality rate for all malignant cancers. Associations between increases in median medical debt and increased mortality rates were statistically significant for major cancer types. Conclusions: Medical debt is associated with significantly higher cancer mortality at the county level. Policies increasing access to affordable health care may improve cancer outcomes. [Table: see text]
Practice- and provider-level inequities in next-generation sequencing (NGS) testing by race/ethnicity for patients (pts) with advanced non-small cell lung cancer (aNSCLC) treated in the community setting.
Authors: Vidal Gregory A. , Jain Neha , Fisher Aaron , Sheinson Daniel , Lofgren Katherine T , Ma Esprit , Yu Elaine , Comment Leah , Miksad Rebecca A. , Daniel Davey B.
Published: June 2023

6508

Background: Inequities in NGS testing in pts with aNSCLC are well documented. Here, we examined elements of total inequity in NGS testing for pts with aNSCLC treated in the US community setting, in terms of within and between inequities at the practice and provider level. Methods: Using the nationwide, deidentified, electronic health record–derived Flatiron Health database, we studied pts with aNSCLC diagnosed in April 2018 or later and treated in the community setting. Testing quality was defined as an NGS result reported ≤60 days after advanced diagnosis. Total-practice inequity was the average percentage-point (pp) difference in the rate of testing quality for non-Latinx Black or Latinx pts compared with non-Latinx white pts. Within-practice inequity was the average pp difference in testing rates at a practice weighted by overall practice enrollment. Between-practice inequity was the covariance between a practice's overall testing rate and the extent of practice-level racial/ethnic underrepresentation. We estimated these inequities at the practice and provider levels using a Bayesian approach. Results: Our study included a total of 12,045 pts (9,981 non-Latinx white, 1,528 non-Latinx Black, and 536 Latinx pts). Both within- and between-practice inequities contributed to total inequity in NGS testing for non-Latinx Black and Latinx pts compared with non-Latinx white pts (Table). For non-Latinx Black pts, between-practice inequities were estimated as 57% (3.77 pp/6.56 pp) of the total inequity in NGS testing; for Latinx pts, the contribution of between-practice inequity was 39% (3.13 pp/8.01 pp). At the provider level, between-provider inequities were the dominant contributor to total inequity in NGS testing for both non-Latinx Black and Latinx pts, accounting for 86% (5.88 pp/6.87 pp) of total provider-level inequity for non-Latinx Black pts and 64% (5.36 pp/8.43 pp) for Latinx pts. Conclusions: Inequities within and between practices, as well as between providers, are meaningful contributors to total inequity in NGS testing. Additional healthcare equity initiatives are needed to identify potential causes for lagging practices/providers to address inequities in NGS testing. [Table: see text]
Mediators of racial/ethnic inequities in clinical trial participation among US patients with cancer, 2011-2022.
Authors: Guadamuz Jenny , Wang Xiaoliang , Altomare Ivy , Calip Gregory Sampang
Published: June 2023

6511

Background: In 2024, the US Food & Drug Administration will require drug sponsors to implement plans to improve racial/ethnic diversity in clinical trials. While minoritized populations are less likely to participate in cancer trials, it is unknown whether social determinants of health (SDOH) explain these inequities. Here we identified SDOH factors that contribute to racial/ethnic inequities in clinical trial participation among patients with 22 solid and blood cancers. Methods: This retrospective study used the nationwide Flatiron Health electronic health record-derived de-identified database of adult patients with cancer (2011-2022). Area-level SDOH ( e.g., predominant race/ethnicity [proxy for segregation]) contextualizing where patients live were defined using the American Community Survey tract data. Patients were followed from cancer-specific diagnosis to clinical study drug receipt (proxy for trial participation), death, or last recorded activity. Associations of race/ethnicity and SDOH factors on trial participation were assessed using Cox proportional hazards models adjusted for clinical factors (diagnosis year, age, sex, performance status, stage, and cancer type). To elucidate which SDOH explain racial/ethnic inequities, mediation analysis was performed using nonlinear multiple additive regression trees models. Results: This study included 233,556 patients (median age: 68 years, 50.0% women; 65.6% non-Latinx [NL] White, 8.5% NL Black, 5.0% Latinx). Black and Latinx patients were more likely to live in marginalized areas ( i.e., disproportionately minoritized, low socioeconomic status, limited English proficiency, and low vehicle ownership) than White patients. Overall, 4.9% of patients participated in trials. Fewer patients from community practices or in marginalized neighborhoods participated in trials. Black (3.4%; hazard ratio [HR] 0.55, 95% confidence interval [CI]: 0.51- 0.60) and Latinx patients (3.6%; HR 0.57, CI: 0.52-0.63) were less likely to participate in trials than White patients (5.8%). Black-White trial inequities were substantially mediated (58%, CI: 47%-68%) by practice type ( e.g., community vs. academic center, 13%, CI: 10%-15%) and area-level SDOH ( e.g., segregation [33%, CI: 25%-44%] and vehicle ownership [12%, CI: 8%-15%]). Mediators explained 55% (CI: 38%-71%) of the Latinx-White trial participation inequity; area-level SDOH—including segregation (29%, CI: 13%-37%), limited English proficiency (15%, CI: 9%-25%), and vehicle ownership (8%, CI: 5%-12%)—were the most important mediators. Conclusions: SDOH factors, especially manifestations of structural racism such as segregation, explained a substantial proportion of racial/ethnic inequities in trial participation among patients with cancer. These findings can inform targeted efforts to increase racial/ethnic diversity in cancer trials.
Enhancement in line of therapy (LoT) derivation from real-world data (RWD) from electronic health records (EHR) via integration of medical claims data.
Authors: Agrawal Smita , P B Avinash , George Rohini , Singh Neeraj , Soni Megha , Chakkrapani Sangavai , Priya Vandana , Vaidya Vivek Prabhakar
Published: June 2023

6514

Background: Clinical RWD derived from EHRs is becoming increasingly important for clinical research, trial design, regulatory decisions etc. These applications require identification of lines of therapy (LoT) which are typically not captured in EHR and must be abstracted from other clinical and medication data. EHR data has significant missingness which can be complemented with other data sources such as medical claims data. In this study, we demonstrate how our proprietary line of therapy algorithms for solid cancers show significant improvements when built using integrated EHR and claims data when compared to EHR data alone. Methods: For this analysis, ConcertAI’s RWD360 dataset integrated with a large administrative open-claims dataset (>90% overlap) for 14 solid cancer indications (Breast, Bladder, Lung, Prostate, Pancreas, Melanoma, Liver, Head & Neck, Renal, Colorectal, Melanoma, Ovarian, Thyroid, Endometrial) was used. The date of advanced/metastatic diagnosis used as the index date for LoTs was derived from the EHR data and medications from both EHR and claims data were used. We ran our LoT algorithms on EHR data with and without claims data and evaluated the impact of integrating claims data on the quantity and quality of LoT output. Results: The inclusion of medication data from claims significantly increased (7-22%) the number of patients for which LoTs could be extracted from the EHR data. Furthermore, we observed increases in number of lines per patient, length of lines and medications per line across cohorts. The distance between index date and 1st line start date was shortened in a subset (2-12%) of patients as a result. In a small fraction of cases, we even observed removal of false lines as some of the lines moved to adjuvant/neoadjuvant setting by filling in missing medication from claims. Overall, 7-39% patients in the LoT cohorts were impacted by addition of claims. Results for a few cancer types are presented in Table 1. We also compared the top LoTs derived from the integrated dataset against the standard of care for that cancer and observed very good concordance. Conclusions: Deriving LoTs by integrating data from multiple data sources such as EHR and claims can significantly improve its accuracy. [Table: see text]
The Man Van: Mobile targeted case finding for prostate cancer.
Authors: Moghul Masood , Croft Fionnuala , Kinsella Netty , Cahill Declan , James Nicholas D.
Published: June 2023

6522

Background: Early intervention is potentially lifesaving in prostate cancer. The debate for screening continues with recent developments suggesting the arguments in favour are becoming stronger however, barriers to access remain. The Man Van project is designed to address these with a highly novel community-based targeting of high-risk groups on a mobile unit. Methods: A bespoke mobile health vehicle was moved to 8 community-based locations in areas of high deprivation indices in London, UK, inviting men for a health check consisting of: general health questionnaires, blood pressure, height/weight, HbA1c for diabetes and a PSA test. Telemedicine was used to inform patients of outcomes. Direct referrals to secondary care was performed. Community engagement was utilised to increase uptake using: primary healthcare centres, religious organisations and community centres. Results: Between December 2021 and December 2022, 618 men were seen at our Man Van clinics at a range of community settings (non-attendance rate 24%). The highest uptake was in locations where there was collaboration with primary care to recruit patients. The median age of attendees was 56 years, range 25-87. 43% of attendees were non-white (20% black). The median BMI was 27.7, range 16.2-50.5. 422 PSA tests were performed with 14 prostate cancers (3.3%) found till date. 9 (64%) of these cancers were grade group 2 (all > 5% pattern 4) or 3. Of patients diagnosed with prostate cancer the median age was 59 years, range 48-73, 10 were black (71%), median PSA 6.85 g/L, range 0.81-45, median IPSS score was 9.5, range 2-31, median IIEF-5 was 16, range 1-25. The IPSS score was significantly higher (P < 0.05) in men diagnosed with prostate cancer. 1 bladder (G3pT1) and 1 oesophageal cancer (T3N2M1) were also found. 3 patients had either HGPIN or ASAP, 3 patients had renal stones, 2 urethral strictures were found. 334 HbA1c tests were performed with 18 diabetics diagnosed (5.4%). 46 patients (7.4%) required input for benign urinary symptoms and 20 for erectile dysfunction (3.2%). Primary care referrals were as follows: 171 for hypertension (27.6%), 43 for an elevated BMI (7.0%), 37 for mental health issues (6.0%), 43 for excess alcohol intake (7.0%), 51 for smoking cessation assistance (8.3%). Significantly more patients 45 years were referred for primary care follow-up versus < 45 years (P < 0.01). Service evaluation questionnaires showed overwhelmingly positive support for the service. Conclusions: The Man Van initiative is a novel method of linking primary and secondary care for a range of health checks, including PSA. By improving community awareness and access in high-risk groups we demonstrate high uptakes for health checks including for prostate cancer and a willingness to engage with health improvement measures. As well as comparatively high levels of prostate cancers diagnosed at early stages, high levels of other health conditions were found; improving the economic value of the service.
Analysis and optimization of equitable US cancer clinical trial center access by travel time.
Authors: Lee Hassal , Bates Alexander , Marshall Andrea , Callier Shawneequa , Chambwe Nyasha , Janowitz Tobias
Published: June 2023

6524

Background: Racially minoritized and socioeconomically disadvantaged populations are underrepresented in cancer clinical trials. Data-driven, quantitative approaches are required to address this inequity. Here, we systematically analyze the geographical distribution of self-identified racial and socioeconomic demographics within commuting distance to cancer clinical trial centers and all hospitals U.S.-wide. Methods: We calculate self-identified racial and socioeconomic demographics of populations living within 30-, 60-, and 120-minute one-way driving commute times from U.S. cancer clinical trial centers and all U.S. hospitals. Data sources include the U.S. 2020 census (for race and socioeconomic data), OpenStreetMaps (for calculation of commuting times), NCT trial registry (for cancer clinical trial quantification), NCI Designated Cancer Centers List, Nature Index of Cancer Research Health Institutions and National Homeland Infrastructure Foundation-Level Data (for U.S.-wide hospital and cancer clinical trial center identification). Data analysis was conducted in R, and Ggplot2 used for all data visualizations. Results: Analysis of clinical trial numbers between 2012–2022 identified 78 high-volume U.S. cancer trial centers. Compared to U.S. national averages, these centers are in areas with socioeconomically more affluent populations (+27.6K USD (95% CI +23.1 to 32.8K) median income unpaired mean difference; -0.073 (95% CI -0.063 to -0.084) deprivation index unpaired mean difference), with higher proportions of affluent self-identified White individuals (+10.1% unpaired mean difference (95% CI +6.8 to +13.7%)). The top 10th percentile of all U.S. hospitals (N=7,623) show a range of absolute sum difference from 2.4% to 35% from equal racial representation of White, Black/African American and Asian/Mixed/Other groups. For each U.S. city above 500,000 inhabitants, we compile map overlays that display all prospective hospitals within commutable distance to racially diverse and socioeconomically disadvantaged populations. These maps may inform the design of future clinical trials or investigations in enrollment and retention strategies for clinical trials. Conclusions: Our analysis identifies biases in the sociodemographics of populations living within commuting distance to U.S.-based cancer trial sites and enables the determination of more equitably commutable prospective satellite hospital sites that could be mobilized for enhanced racial and socioeconomic representation in clinical trials. Other recruitment barriers still need to be tackled to ensure racial and socioeconomic demographics within the geographical vicinity of a clinical site can translate to equitable trial participant representation.
Are enrollment criteria for phase II and III clinical trials in acute myeloid leukemia arbitrarily restrictive?
Authors: Hantel Andrew , Walsh Thomas , Clancy Dillon , Luskin Marlise Rachael , DeAngelo Daniel J. , Lathan Christopher S. , Abel Gregory A.
Published: June 2023

6525

Background: Ethical clinical research requires fair subject selection and a favorable risk-benefit ratio. Enrollment criteria can unfairly exclude patients if they are not based in safety. There are few data regarding variability within criteria, which can also represent unfair exclusion, or for acute myeloid leukemia (AML). Methods: We assessed enrollment criteria use and variability for frontline phase II and III therapeutic AML trials from 2010-2019 listed on Clinicaltrials.gov. Drug safety profiles were obtained from protocols, publications, and FDA labels. FDA publications guided a standardized abstraction and coding process. Associations between criteria and safety profiles were identified using X2 and t-tests. Regression modeling identified differences in infectious disease (ID) exclusion by sponsor adjusted for trial phase, year, size, and safety profiles. Results: 190 trials were eligible; 159 (84%) were phase II and 32 (17%) phase III. Trials were sponsored by the National Institutes of Health (NIH; 50; 26%), industry (109; 57%), and academic investigators (AI; 108; 57%). Exclusions and variability are shown in the table. ID exclusions were for HIV (96; 51%) and hepatitis B (60; 32%) and C (64; 34%). Older adults were considered as over 60 (42 trials; 39%), 65 (23; 21%), 70 (13; 12%), or 75 years (18; 17%). There was no association between QTc limits and the use of QTc prolonging drugs (criteria presence p=0.2; mean 450 vs 474 ms, p=0.3) or renal function limits and nephrotoxic drugs (presence p=0.2; mean 1.65 vs 1.67 ULN, p=0.8). Hepatitis B and C exclusions were associated with the use of drugs linked to viral reactivation (OR 2.1 [95% CI 1.1,3.9], 2.0 [95% CI 1.1,3.7]). This was not the case for HIV (OR 1.2 [95% CI 0.7,2.2]). Industry sponsorship was independently associated with hepatitis B and C exclusion (OR 3.0 [95% CI 1.2,7.3], 3.3 [95% CI 1.4,4.7]) and AI sponsorship with HIV exclusion (OR 2.5 [95% CI 1.4,5.5]). Conclusions: There is substantial variability in enrollment criteria for AML clinical trials. Many criteria are related to risks, but some exclusions and variability are not clearly based in safety. Avoiding arbitrary exclusions will likely enhance trial representativeness and enrollment rates. [Table: see text]
Evaluating social vulnerability impact on care and prognosis of head & neck-nervous system cancers in the US.
Authors: Lutfallah Salim , Fei-Zhang David , Chelius Daniel , D'Souza Jill , Paludo Jonas , Ruff Michael W. , Rastatter Jeffrey , Sheyn Anthony
Published: June 2023

6526

Background: In the current literature, the association between social determinants of health (SDH) and head & neck-nervous system cancer (HNNsC) is limited by the narrow scope of SDH assessed and the broad classifications of HNNsC. Our study utilizes the CDC-Social Vulnerability Index (SVI) to assess both the individual and collective impact of four social determinant themes on various HNNsC in US adults. Methods: This study utilized the SEER database to evaluate 116,373 adult patients from 1975-2017 who presented with HNNsC. Patients were assigned SVI scores based on county-of-residence at the time of diagnosis, encompassing total-SVI score and 4 sub-scores of socioeconomic status, minority-language status, household composition, and housing-transportation. Using these scores, univariate linear regressions were used to assess patient care (months of follow-up) and prognosis (months of survival). Results: As total-SVI score increased, decreases in months of follow-up (MOF) and months of survival (MOS) were observed for many HNNsC tumors (p less than 0.001) when comparing the lowest to highest vulnerability cohorts. There was a decrease ranging from 3.55-36.6% in the MOF, with the largest decreases occurring in embryonal, anaplastic oligodendroglioma, and anaplastic ependymoma tumor types, with the largest sub-score contribution coming from socioeconomic status for these three disease classes. Similarly, there was a decrease ranging from 6.90-45.81% in the MOS, with the largest decreases occurring in anaplastic ependymoma, anaplastic astrocytoma, and pilocytic astrocytoma tumor types with the largest sub-score contribution coming from socioeconomic status for these three disease classes. Increases in vulnerability within SDH themes contributed significantly to these total-SVI trends in MOF and MOS, with each social determinant impacting different disease classes to varying extents. Socioeconomic status was the most impactful sub-score for MOF in nine of fourteen disease classes, followed by housing-transportation and household composition, each leading the impact of two of fourteen disease classes, and minority-language status leading the impact of one of fourteen disease classes. Similarly, socioeconomic status was the most impactful sub-score for MOS in eight of fourteen disease classes, followed by housing-transportation leading the impact of three of fourteen disease classes, household composition leading the impact of two of fourteen disease classes, and minority-language status leading the impact of one of fourteen disease classes. Conclusions: The results of this study show that with increasing social vulnerability, there is a significant decrease in both the care (follow-up) and the prognosis (survival) of US adults with HNNsC and highlight which SDH contributes more to disparities.
Racial disparities in utilization of first line targeted therapies for metastatic breast cancer.
Authors: Martei Yehoda M. , Chen Kan , Mamtani Ronac , Shulman Lawrence N. , Hubbard Rebecca A. , Clark Amy Sanders
Published: June 2023

6528

Background: This study evaluated whether there were racial disparities in utilization (decomposed as change in proportion of eligible patients initiating therapy over time and time to treatment initiation (TTI)) to CDK4/6 inhibitors and pertuzumab since FDA approval as first line (1L) treatment for ER+/HER2- and HER2+ metastatic breast cancer (MBC), respectively. Methods: This cohort study used the nationwide Flatiron Health electronic health record-derived de-identified database. Included women were ≥18 years old, diagnosed with de novo or recurrent MBC, who received 1L therapy, and documented as non-Hispanic White (NHW) or non-Hispanic Black/African American (NHB). Two cohorts were generated for patients with ER+/HER2- MBC diagnosed 3/2015-10/2021 and HER2+ MBC diagnosed 7/2012-9/2021. We estimated temporal trends in the proportion of NHW and NHB patients receiving respective therapy using logistic regression with natural cubic splines for time trends and tested for changes in uptake over time within each group as well as differences in trends between groups. A similar model was used for TTI among treatment initiators, using linear regression models. In addition to time and race, regression models included age, ECOG performance status, insurance, Medicaid expansion status, practice type, and proportion of black patients per practice among patients who met both cohort criteria. Results: 8318 patients (NHW=7006; NHB=1312) met ER+/HER2- cohort criteria and 2321 (NHW=1915; NHB=406) met HER2+ cohort criteria. There was a significant change over time in the proportion of NHW (p<0.0001) and NHB (p<0.0001) initiating 1L CDK4/6 inhibitors (Table). Temporal trends were also significantly different between NHW and NHB (p<0.0001). Higher ECOG performance status (OR=0.85 per unit increase, 95%CI 0.80-0.90; p<0.001) and an increasing proportion of black patients seen at practice (OR=0.45, 95%CI 0.29-0.71; p<0.001) were independent predictors of lower odds of initiating CDK4/6 inhibitors. Overall, 43% NHW vs 41% NHB received pertuzumab respectively. There was no significant difference in uptake trends for pertuzumab between NHW and NHB (p=0.41). There was no significant difference in the temporal trends of TTI for either CDK4/6 inhibitors (p=0.74) or pertuzumab (p=0.84). Conclusions: Utilization of CDK4/6 inhibitors steadily increased over time, however > 25% of eligible patients did not receive the drug, and less than half of individuals who met indication for pertuzumab were prescribed it. Racial disparities were significant for oral CDK4/6 inhibitors but not for intravenous pertuzumab. [Table: see text]
Outcomes of Black (B) versus White (W) patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT) with or without orteronel (Ort): Analysis of pt-level data from SWOG-1216 phase 3 trial.
Authors: Sayegh Nicolas , Swami Umang , Jo Yeonjung , Gebrael Georges , Haaland Benjamin , Gupta Shilpa , Plets Melissa , Hussain Maha H. A. , Quinn David I. , Lara Primo N , Thompson Ian M , Agarwal Neeraj
Published: June 2023

6532

Background: Despite more aggressive prostate cancer (PCa) at presentation and higher mortality in real world, B pts with metastatic hormone resistant PCa did not have inferior outcomes than W pts when both were enrolled in clinical trials (PMID: 33951180). In the phase 3 S1216 trial, treatment with Ort, a novel CYP17 axis inhibitor, significantly improved progression-free survival (PFS) but not overall survival (OS) compared to bicalutamide (Bic) in pts with mHSPC receiving ADT. This trial enrolled the greatest number of B pts in a phase 3 trial in this setting to-date. We hypothesized that given comparable access to care as experienced in a clinical trial, outcomes in B pts would be similar to those of W pts in the mHSPC setting. Methods: Eligibility: Pts with mHSPC were enrolled. Only pts self-identifying as B or W were included in this analysis. PFS and OS for each group were estimated using Kaplan-Meier method. A multivariate analysis (MVA) adjusting for disease characteristics was conducted using a Cox proportional hazards model. Results: Among 1279 participants, 135 (10.6%) were B; 1077 (84.2%) were W. B and W were equally distributed between treatment arms, and had respectively similar proportion of pts with Gleason score ≥8 (61.3 vs 62.1%), Zubrod score ≥2 (5.1 vs 3.4%) and extensive disease (48.1 vs 48.7%). However, B pts, as compared to W, were younger (65.8 vs 68.4 yrs, p=0.001) and had a higher median baseline PSA (54.7 vs 26.7 ng/mL; p<0.001). PSA responses (≤ 0.2 ng/mL) at month 7 were similar in both groups (p=0.296). Overall, B vs W had similar median PFS (2.3 vs 2.9 yrs, p=0.71) and OS (5.5 vs 6.3 yrs, p=0.65). MVA confirmed similar PFS and OS after adjusting for known prognostic factors (Table). No interaction between race and treatment was observed (P-value interaction PFS= 0.77 and OS= 0.91). Conclusions: We demonstrate that even though B pts present with more aggressive disease in mHSPC setting, they did not have statistically significant worse OS and PFS than W pts and treatment effect was also similar for both racial groups. Equitable access to care may negate historical differences in outcomes among B vs W pts with advanced PCa. Funding: NIH/NCI/NCTN grant U10CA180888, U10CA180819; and Millennium Pharmaceuticals (Takeda Oncology). Univariate and MVA of PFS and OS. [Table: see text]
County-level jail incarceration and cancer mortality in the US.
Authors: Zhao Jingxuan , Kajeepeta Sandhya , Han Xuesong , Nogueira Leticia M , Zheng Zhiyuan , Fan Qinjin , Shi Kewei Sylvia , Yabroff Robin
Published: June 2023

6535

Background: Incarceration has been linked to poor community health outcomes, such as worse preterm births and mortality in the US, although little research has examined cancer outcomes. This study examined associations of county-level jail incarceration and cancer mortality. Methods: Annual county-level local jail incarceration rates (1990-2018) were obtained from the Vera Institute of Justice. We calculated annual county-level mortality rates (2000 -2019) with invasive cancer as the underlying cause of death (ICD-10 codes: C00-C97) using National Vital Statistics System. Associations of county-level jail incarceration and cancer mortality overall, and by sex, race, and common cancer sites were examined with generalized estimating equations with Poisson distribution and standard errors clustered at county level. To assess the short-, medium-, and long-term associations, we used lagged county-level incarceration rates by 1, 5, and 10 years prior to mortality rates in separate analyses. Results: Over the 20-year study period, each 1 per 1000 increase in county jail incarceration rate was associated with a 1.2% increase in cancer mortality rate in the short-term (model with 1-year lags, rate ratio (RR): 1.012, 95% CI: 1.009–1.015) and 1.1% increase in medium-term (5-year lags (RR: 1.011, 95% CI: 1.008–1.014) and 0.8% increase long-term (10-year lags (RR: 1.008, 95% CI: 1.004–1.012). After adjusting for county-level sociodemographic characteristics, the RRs were attenuated but remained statistically significant. Jail incarceration was associated with higher cancer mortality for all common cancers included in the study (Table) and for White people, but not for Black people. The magnitude of associations was similar for medium- and long-term effects (5- and 10-year lags, respectively). Conclusions: Higher county-level jail incarceration rates were associated with higher county-level cancer mortality rates, underscoring the collateral health consequences of mass incarceration. Efforts to identify interventions to decrease the cancer mortality burden in these communities are warranted. [Table: see text]
An intersectional approach to cervical cancer screening disparities by race/ethnicity and immigrant status.
Authors: Chen Jane J. , Sarkar Indra N. , Hsu Emily , Dizon Don S.
Published: June 2023

6536

Background: Racial/ethnic minority and immigrant groups individually experience lower rates of cervical cancer (CC) screening. Although immigrants represent large proportions of racial/ethnic minorities, few studies have explored the interacting health consequences of these social categories. Intersectionality is a theoretical framework which recognizes that studying social categories independently cannot capture their cumulative effects on health. In the context of CC screening, only one study took this approach but did not analyze several important barriers to care. This study aims to analyze the joint influence of race/ethnicity and immigrant status on screening and identify barriers unique to each intersectional group. Methods: Data from the National Health Interview Survey years 2005, 2010 and 2015 were drawn from IPUMS. Analyses were restricted to those eligible for CC screening (n=17,941). Multivariable logistic regression was used to model the interactional effect of race/ethnicity and immigrant status on screening up to date (UTD) status adjusting for confounders. Variables reflecting socioeconomic status (SES), access to care, acculturation and language were separately included to see whether they explained identified disparities. Finally, amongst women not UTD on screening, reasons for this were analyzed. All analyses were adjusted for complex survey design. Results: US born Non-Hispanic Black women had higher odds of being UTD on screening (OR 1.63, 95% CI [1.23, 2.18]) while immigrant Non-Hispanic White (OR 0.45 [0.29, 0.7]), immigrant Asian (OR 0.29 [0.2, 0.42]) and immigrant Hispanic/Latinx women (OR 0.51 [0.39, 0.67]) had lower odds compared to US born Non-Hispanic White women. Adjusting for SES (OR 0.87 [0.65, 1.16]) and access (OR 1 [0.74, 1.36]) attenuated the ORs for immigrant Hispanic/Latinx women but not immigrant Asian and White women. Adjusting for acculturation attenuated the ORs for immigrant Hispanic/Latinx (OR 0.84 [0.58, 1.22]) and White women (OR 0.68 [0.42, 1.12]) only. Adjusting for language increased but did not attenuate the ORs for all immigrant groups. Analyses of reasons for not screening showed immigrant Non-Hispanic White, Black and Asian women had greater proportions selecting “Didn’t need or know needed this test” versus other groups (10-12% vs. 5.4-8.4%). Conclusions: Immigrant status continues to explain much of the CC screening disparities previously attributed to race/ethnicity. SES and access to care remain important barriers for immigrant Hispanic/Latinx women but less so for other immigrant groups. This study reveals that acculturation is an important barrier for immigrant Non-Hispanic White and Hispanic/Latinx women, possibly representing disparities in knowledge. Language barriers may also contribute in all immigrant women. Further intersectional studies are needed to identify remaining barriers.