The Cardioprotective and Anticancer Effects of SGLT2 Inhibitors: JACC: CardioOncology State-of-the-Art Review.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally approved for type 2 diabetes mellitus, have demonstrated efficacy in reducing cardiovascular events, particularly heart failure, in patients with and without diabetes. An intriguing research area involves exploring the potential application of SGLT2 inhibitors in cardio-oncology, aiming to mitigate the cardiovascular adverse events associated with anticancer treatments. These inhibitors present a unique dual nature, offering both cardioprotective effects and anticancer properties, conferring a double benefit for cardio-oncology patients. In this review, the authors first examine the established cardioprotective effects of SGLT2 inhibitors in heart failure and subsequently explore the existing body of evidence, including both preclinical and clinical studies, that supports the use of SGLT2 inhibitors in the context of cardio-oncology. The authors further discuss the mechanisms through which SGLT2 inhibitors protect against cardiovascular toxicity secondary to cancer treatment. Finally, they explore the potential anticancer effects of SGLT2 inhibitors along with their proposed mechanisms.

Endothelial dysfunction in breast cancer survivors on aromatase inhibitors: changes over time.

BACKGROUND: Breast cancer is estimated to comprise about 290,560 new cases in 2022. Aromatase inhibitors (AIs) are recommended as adjuvant treatment for estrogen-receptor positive (ER+) breast carcinoma in postmenopausal women, which includes approximately two-thirds of all women with breast cancer. AIs inhibit the peripheral conversion of androgens to estrogen by deactivation of the aromatase enzyme, leading to a reduction in serum estrogen level in postmenopausal women with ER+ breast carcinoma. Estrogen is known for its cardiovascular (CV) protective properties through a variety of mechanisms including vasodilation of blood vessels and inhibition of vascular injury resulting in the prevention of atherosclerosis. In clinical trials and prospective cohorts, the long-term use of AIs can increase the risk for hypertension and hyperlipidemia. Studies demonstrate mixed results as to the impact of AIs on actual CV events and overall survival. METHODS: A single arm longitudinal study of 14 postmenopausal women with ER+ breast cancer prescribed adjuvant AIs at the University of Minnesota (UMN). Subjects with a history of known tobacco use, hypertension, hyperlipidemia, and diabetes were excluded to eliminate potential confounding factors. Participants underwent routine labs, blood pressure assessments, and vascular testing at baseline (prior to starting AIs) and at six months. Vascular assessment was performed using the EndoPAT 2000 and HDI/PulseWave CR-2000 Cardiovascular Profiling System and pulse contour analysis on two occasions as previously described. Vascular measurements were conducted by one trained vascular technician. Assessments were performed in triplicate, and the mean indices were used for analyses. All subjects were on an AI at the follow-up visit. The protocol was approved by the UMN Institutional Review Board and all participants were provided written informed consent. Baseline and follow-up characteristics were compared using Wilcoxon signed-rank tests. Analyses were performed using R version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria). RESULTS: After six months of AI treatment, EndoPAT® ratio declined to a median 1.12 (Q1: 0.85, Q3: 1.86; p = 0.045; Figure 1) and median estradiol levels decreased to 2 pg/mL (Q1: 2, Q3: 3; p=0.052). There was no evidence of association between change in EndoPAT® and change in estradiol level (p = 0.91). There were no statistically significant changes in small or large arterial elasticity. CONCLUSIONS: We hypothesize that long-term use of AI can lead to persistent endothelial dysfunction, and further investigation is necessary. In our study, patients were on AI for approximately 5-10 years. As a result, we do not have data on whether these changes, such as EndoPAT® ratio and the elasticity of small and large arterial, are reversible with discontinuation of AI. These findings set the stage for a larger study to more conclusively determine the association between AI exposure and cardiovascular outcomes. Further studies should evaluate for multivariate associations withmodifiable risk factors for CV disease.

Trajectories of Health Care Contact Days for Patients With Stage IV Non-Small Cell Lung Cancer.

Importance: Patients with stage IV non-small cell lung cancer (NSCLC) experience substantial morbidity and mortality. Contact days (ie, the number of days with health care contact outside the home) measure how much of a person's life is consumed by health care, yet little is known about patterns of contact days for patients with NSCLC. Objective: To describe the trajectories of contact days in patients with stage IV NSCLC and how trajectories vary by receipt of cancer-directed treatment in routine practice. Design, Setting, and Participants: A retrospective, population-based decedent cohort study was conducted in Ontario, Canada. Participants included adults aged 20 years or older who were diagnosed with stage IV NSCLC (January 1, 2014, to December 31, 2017) and died (January 1, 2014, to December 31, 2019); there was a maximum 2-year follow-up. Data analysis was conducted from February 22 to August 16, 2023. Exposure: Systemic cancer-directed therapy (yes or no) and type of therapy (chemotherapy vs immunotherapy vs targeted therapy). Main Outcomes and Measures: Contact days (days with health care contact, outpatient or institution-based, outside the home) were identified through administrative data. The weekly percentage of contact days and fitted models with cubic splines were quantified to describe trajectories from diagnosis until death. Results: A total of 5785 decedents with stage IV NSCLC were included (median age, 70 [IQR 62-77] years; 3108 [53.7%] were male, and 1985 [34.3%] received systemic therapy). The median overall survival was 108 (IQR, 49-426) days, median contact days were 36 (IQR, 21-62), and the median percentage that were contact days was 33.3%. A median of 5 (IQR, 2-10) days were spent with specialty palliative care. Patients who did not receive systemic therapy had a median overall survival of 66 (IQR, 34-130) days and median contact days of 28 (IQR, 17-44), of which a median of 5 (IQR, 2-9) days were spent with specialty palliative care. Overall and for subgroups, normalized trajectories followed a U-shaped distribution: contact days were most frequent immediately after diagnosis and before death. Patients who received targeted therapy had the lowest contact day rate during the trough (10.6%; vs immunotherapy, 15.4%; vs chemotherapy, 17.7%). Conclusions and Relevance: In this cohort study, decedents with stage IV NSCLC had a median survival in the order of 3.5 months and spent 1 in every 3 days alive interacting with the health care system outside the home. These results highlight the need to better support patients and care partners, benchmark appropriateness, and improve care delivery.

A pilot randomized controlled trial of an online intervention for Hodgkin lymphoma survivors to increase knowledge about late effects and recommended screening.

BACKGROUND: Hodgkin lymphoma (HL) survivors who received chest radiotherapy are at risk for breast cancer and cardiovascular disease, but screening adherence is low. We assessed the acceptability/feasibility of a web-based educational intervention and its impact on knowledge of health risks and screening. METHODS: HL survivors were randomized to either an interactive online educational intervention or handouts only. Surveys were completed at baseline and 3 months post-intervention. We described the acceptability/feasibility of the intervention and compared knowledge between groups. RESULTS: Fifty-two HL survivors participated; 27 in the intervention group and 25 in the control group. Eighteen (66%) intervention participants completed the intervention and reported high acceptability (89-100%). At baseline, adherence to breast cancer screening was low across all participants. Post-intervention, those in the intervention group more often than controls correctly identified breast cancer and echocardiogram screening guidelines (35% vs. 28%, P = 0.02 and 82% vs. 52%, P = 0.04) and reported knowing how to address potential complications from cancer treatments (87% vs. 64%, P = 0.03). We detected no increase in screening behavior post-intervention. CONCLUSION: Online education modules for high-risk HL survivors are an acceptable method to improve knowledge of health risks and screening guidelines. Future interventions should focus on improving screening uptake in this population. IMPLICATIONS FOR CANCER SURVIVORS: Web-based learning can be useful in increasing cancer survivor knowledge of their unique risks and screening recommendations but does not necessarily change patient behavior. Involvement in a cancer survivorship program can help assess individual barriers and monitor uptake of screening.

Logistic burdens of cancer care: A qualitative study.

Cancer treatment often creates logistic conflicts with everyday life priorities; however, these challenges and how they are subjectively experienced have been largely unaddressed in cancer care. Our goal was to describe time and logistic requirements of cancer care and whether and how they interfered with daily life and well-being. We conducted interviews with 20 adults receiving cancer-directed treatment at a single academic cancer center. We focused on participants' perception of the time, effort, and energy-intensiveness of cancer care activities, organization of care requirements, and preferences in how to manage the logistic burdens of their cancer care. Participant interview transcripts were analyzed using an inductive thematic analysis approach. Burdens related to travel, appointment schedules, healthcare system navigation, and consequences for relationships had roots both at the system-level (e.g. labs that were chronically delayed, protocol-centered rather than patient-centered bureaucratic requirements) and in individual circumstances (e.g. greater stressors among those working and/or have young children versus those who are retired) that determined subjective burdensomeness, which was highest among patients who experienced multiple sources of burdens simultaneously. Our study illustrates how objective burdens of cancer care translate into subjective burden depending on patient circumstances, emphasizing that to study burdens of care, an exclusive focus on objective measures does not capture the complexity of these issues. The complex interplay between healthcare system factors and individual circumstances points to clinical opportunities, for example helping patients to find ways to meet work and childcare requirements while receiving care.

Accelerated Aging in Cancer Survivors: Cellular Senescence, Frailty, and Possible Opportunities for Interventions.

The population of cancer survivors has markedly increased due to the rapid improvements in cancer treatment. However, cancer survivors experience accelerated aging, which leads to chronic diseases and other age-related conditions, such as frailty. Those conditions may persist years after cancer diagnosis and treatment. Cellular senescence, a hallmark of aging, is one of the mechanisms that contribute to accelerated aging in cancer survivors. Several aging measures, including measures based on clinical markers and biomarkers, have been proposed to estimate the aging process, and some of them have shown associations with mortality and frailty in cancer survivors. Several anti-aging interventions, including lifestyle changes and anti-aging drugs, have been proposed. Future research, particularly in large-scale studies, is needed to determine the efficiency of these aging measures and anti-aging interventions before considering their application in clinics. This review focuses on the mechanisms of cellular senescence and accelerated aging in cancer survivors, assessment of the aging process using clinical markers and biomarkers, and the high prevalence of frailty in that population, as well as possible opportunities for anti-aging interventions. A deeper understanding of aging measures and anti-aging interventions in cancer survivors will contribute to the development of effective strategies to mitigate accelerated aging in cancer survivors and improve their quality of life.

Health Care Contact Days Among Older Cancer Survivors.

PURPOSE: Health care contact days-days spent receiving health care outside the home-represent an intuitive, practical, and person-centered measure of time consumed by health care. METHODS: We linked 2019 Medicare Current Beneficiary Survey and traditional Medicare claims data for community-dwelling older adults with a history of cancer. We identified contact days (ie, spent in a hospital, emergency department, skilled nursing facility, or inpatient hospice or receiving ambulatory care including an office visit, procedure, treatment, imaging, or test) and described patterns of total and ambulatory contact days. Using weighted Poisson regression models, we identified factors associated with contact days. RESULTS: We included 1,168 older adults representing 4.51 million cancer survivors (median age, 76.4 years, 52.8% women). The median (IQR) time from cancer diagnosis was 65 (27-126) months. In 2019, these adults had mean (standard deviation) total contact days of 28.4 (27.6) and ambulatory contact days of 24.2 (23.6). These included days for tests (8.0 [8.8]), imaging (3.6 [4.1]), visits with any clinicians (12.4 [11.5]), and visits with primary care clinicians (4.4 [4.7]), and nononcology specialists (7.1 [9.4]) specifically. Sixty-four percent of days with a nonvisit ambulatory service (eg, a test) were not on the same day as a clinician visit. Factors associated with more total contact days included younger age, lower income, more chronic conditions, poor self-rated health, and tendency to "go to doctor as soon as feel bad." CONCLUSION: Older adult cancer survivors spent nearly 1 month of the year receiving health care outside the home. This care was largely ambulatory, often delivered by nononcologists, and varied by factors beyond clinical characteristics. These results highlight the need to recognize patient burdens and improve survivorship care delivery, including through care coordination.

Comparisons of financial hardship in cancer care by family structure and among those with and without minor children using nationally representative data.

INTRODUCTION: While demographic risk factors of cancer-related financial hardships have been studied, having minor children or being single have rarely been assessed in the context of healthcare-related financial hardships. METHODS: Using data from the 2015 to 2018 National Health Interview Survey, we assessed financial hardship (material and psychological hardship; behavioral coping due to costs: delaying/foregoing care, reducing prescription costs, or skipping specialists or follow-up care) among adults aged 18-59 years with cancer (N = 2844) by minor child parenting status and family structure. In a secondary analysis, we compared this group with individuals without cancer. Using logistic regression models, we compared those with and without children aged <18 years, further distinguishing between those who were single versus one of two or more adults in the family. RESULTS: Compared to individuals from families with two or more adults/without children, single adults with children more often reported cancer-related financial hardships, for example material hardship (45.9% vs. 38.8%), and reducing prescription costs, (50.7% vs. 34.4%, adjusted OR 1.57, 95% CI 1.07-2.28). Single adults without minor children and those from families with two or more adults/with minor children also reported greater financial hardships on some dimensions. Associations were similar among those without cancer, but the overall magnitude of financial hardships was lower compared to those with cancer. CONCLUSIONS: Our findings suggest that having minor children, and being a single adult are risk factors for cancer-related financial hardship. Financial vulnerability associated with family structure should be taken into consideration in healthcare, and especially cancer care.

Association of antibiotic exposure with residual cancer burden in HER2-negative early stage breast cancer.

Antibiotic exposure during immunotherapy (IO) has been shown to negatively affect clinical outcomes in various cancer types. The aim of this study was to evaluate whether antibiotic exposure in patients with high-risk early-stage HER2-negative breast cancer (BC) undergoing treatment with neoadjuvant pembrolizumab impacted residual cancer burden (RCB) and pathologic complete response (pCR) in the pembrolizumab-4 arm of the ISPY-2 clinical trial. Patients received pembrolizumab for four cycles concurrently with weekly paclitaxel for 12 weeks, followed by four cycles of doxorubicin plus cyclophosphamide every 2 or 3 weeks. Patients who received at least one dose of systemic antibiotics concurrently at the time of immunotherapy (IO) were included in the antibiotic exposure group (ATB+). All other participants were included in the control group (ATB-). RCB index and PCR rates were compared between the ATB+ and ATB- groups using t-tests and Chi-squared tests, and linear and logistic regression models, respectively. Sixty-six patients were included in the analysis. 18/66 (27%) patients were in the ATB+ group. Antibiotic use during IO was associated with a higher mean RCB index (1.80 ± 1.43 versus 1.08 ± 1.41) and a lower pCR rate (27.8% versus 52.1%). The association between antibiotic use and the RCB index remained significant in multivariable linear regression analysis (RCB index-coefficient 0.86, 95% CI 0.20-1.53, P = 0.01). Our findings suggest that concurrent antibiotic exposure during neoadjuvant pembrolizumab in HER2-negative early-stage BC is associated with higher RCB. Further validation in larger cohorts is needed to confirm these findings.

Advancing the care of individuals with cancer through innovation & technology: Proceedings from the cardiology oncology innovation summit 2020 and 2021.

As cancer therapies increase in effectiveness and patients' life expectancies improve, balancing oncologic efficacy while reducing acute and long-term cardiovascular toxicities has become of paramount importance. To address this pressing need, the Cardiology Oncology Innovation Network (COIN) was formed to bring together domain experts with the overarching goal of collaboratively investigating, applying, and educating widely on various forms of innovation to improve the quality of life and cardiovascular healthcare of patients undergoing and surviving cancer therapies. The COIN mission pillars of innovation, collaboration, and education have been implemented with cross-collaboration among academic institutions, private and public establishments, and industry and technology companies. In this report, we summarize proceedings from the first two annual COIN summits (inaugural in 2020 and subsequent in 2021) including educational sessions on technological innovations for establishing best practices and aligning resources. Herein, we highlight emerging areas for innovation and defining unmet needs to further improve the outcome for cancer patients and survivors of all ages. Additionally, we provide actionable suggestions for advancing innovation, collaboration, and education in cardio-oncology in the digital era.

Coverage for evidence-based cancer survivorship care services.

PURPOSE: The American Society of Clinical Oncology Cancer Survivorship Committee established a task force to determine which survivorship care services were being denied by public and private payers for coverage and reimbursement. METHODS: A quantitative survey instrument was developed to determine the clinical practice-reported rates of coverage denials for evidence-based cancer survivorship care services. Additionally, qualitative interviews were conducted to understand whether coverage denials were based on payer policies, cost-sharing, or prior authorization. RESULTS: Of 122 respondents from 50 states, respondents reported that coverage denials were common ("always," "most of the time," or "some of the time") for maintenance therapies, screening for new primary cancers or cancer recurrence. Respondents reported that denials in coverage for maintenance therapies were highest for immunotherapy (41.74%) and maintenance chemotherapy (40.17%). Coverage denials for new primary cancer screenings were highest for Hodgkin lymphoma survivors needing a PET/CT scan (49.04%) and breast cancer survivors at a high risk of recurrence who needed an MRI (63.46%), respectively. More than half of survey respondents reported denials for symptom management and supportive care services. Fertility services, dental services when indicated, and mental health services were denied "always" or "most of the time" 23.1%, 22.5%, and 12.8%, respectively. Respondents reported they often had a process in place to automatically appeal denials for evidence-based services. The denial process, however, resulted in greater stress for the patient and provider. CONCLUSION: Our study demonstrates that additional advocacy with payers is needed to ensure that reimbursement policies are consistent with evidence-based survivorship care services.

Consuming Patients' Days: Time Spent on Ambulatory Appointments by People With Cancer.

BACKGROUND: In qualitative work, patients report that seemingly short trips to clinic (eg, a supposed 10-minute blood draw) often turn into "all-day affairs." We sought to quantify the time patients with cancer spend attending ambulatory appointments. METHODS: We conducted a retrospective study of patients scheduled for oncology-related ambulatory care (eg, labs, imaging, procedures, infusions, and clinician visits) at an academic cancer center over 1 week. The primary exposure was the ambulatory service type(s) (eg, clinician visit only, labs and infusion, etc.). We used Real-Time Location System badge data to calculate clinic times and estimated round-trip travel times and parking times. We calculated and summarized clinic and total (clinic + travel + parking) times for ambulatory service types. RESULTS: We included 435 patients. Across all service day type(s), the median (IQR) clinic time was 119 (78-202) minutes. The estimated median (IQR) round-trip driving distance and travel time was 34 (17-49) miles and 50 (36-68) minutes. The median (IQR) parking time was 14 (12-15) minutes. Overall, the median (IQR) total time was 197 (143-287) minutes. The median total times for specific service type(s) included: 99 minutes for lab-only, 144 minutes for clinician visit only, and 278 minutes for labs, clinician visit, and infusion. CONCLUSION: Patients often spent several hours pursuing ambulatory cancer care on a given day. Accounting for opportunity time costs and the coordination of activities around ambulatory care, these results highlight the substantial time burdens of cancer care, and support the notion that many days with ambulatory health care contact may represent "lost days."

The development and flux of the University of Minnesota Survivorship Program: progress, challenges, and opportunities.

For the past 30 years, the University of Minnesota's Cancer Survivorship Program has been dedicated to providing exceptional care to patients who have lived the cancer experience. Our model is consultative, risk-stratified, and oncologist-led but executed predominately by advanced practice providers. Care is personalized and serves three survivor populations: children, adults, and patients who received BMT with over 500 new patients evaluated annually. As guidelines and survivorship standards have changed, our clinical programs have evolved from a focus on survivorship care plans to supportive care. The program offers a wide range of supportive services from acupuncture to nutritional services as well as several educational programs for patients. The program has a strong research legacy, notably as the birthplace of research that led to the Children's Oncology Group Guidelines as well as advancements in cardio-oncology and frailty after bone marrow transplantation. In 2021, we hosted the first annual Survivorship Research Forum, providing the opportunity and space for experts across disciplines to exchange ideas on a broad range of survivorship topics not possible at other national cancer-related conferences. With successes and challenges, we have identified opportunities for growth as our program continues to evolve and grow in our goal to improve cancer outcomes along a wide spectrum of physical, emotional, functional, and social dimensions. IMPLICATIONS FOR CANCER SURVIVORS: The University of Minnesota Cancer Survivorship Program provides care, education, and research opportunities for patients across the cancer continuum.

Impact of body mass index on pathological response after neoadjuvant chemotherapy: results from the I-SPY 2 trial.

PURPOSE: Increased body mass index (BMI) has been associated with poor outcomes in women with breast cancer. We evaluated the association between BMI and pathological complete response (pCR) in the I-SPY 2 trial. METHODS: 978 patients enrolled in the I-SPY 2 trial 3/2010-11/2016 and had a recorded baseline BMI prior to treatment were included in the analysis. Tumor subtypes were defined by hormone receptor and HER2 status. Pretreatment BMI was categorized as obese (BMI ≥ 30 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and normal/underweight (< 25 kg/m2). pCR was defined as elimination of detectable invasive cancer in the breast and lymph nodes (ypT0/Tis and ypN0) at the time of surgery. Logistic regression analysis was used to determine associations between BMI and pCR. Event-free survival (EFS) and overall survival (OS) between different BMI categories were examined using Cox proportional hazards regression. RESULTS: The median age in the study population was 49 years. pCR rates were 32.8% in normal/underweight, 31.4% in overweight, and 32.5% in obese patients. In univariable analysis, there was no significant difference in pCR with BMI. In multivariable analysis adjusted for race/ethnicity, age, menopausal status, breast cancer subtype, and clinical stage, there was no significant difference in pCR after neoadjuvant chemotherapy for obese compared with normal/underweight patients (OR = 1.1, 95% CI 0.68-1.63, P = 0.83), and for overweight compared with normal/underweight (OR = 1, 95% CI 0.64-1.47, P = 0.88). We tested for potential interaction between BMI and breast cancer subtype; however, the interaction was not significant in the multivariable model (P = 0.09). Multivariate Cox regression showed there was no difference in EFS (P = 0.81) or OS (P = 0.52) between obese, overweight, and normal/underweight breast cancer patients with a median follow-up time of 3.8 years. CONCLUSION: We found no difference in pCR rates by BMI with actual body weight-based neoadjuvant chemotherapy in this biologically high-risk breast cancer population in the I-SPY2 trial.

Performance of the pooled cohort equations in cancer survivors: the Atherosclerosis Risk in Communities study.

BACKGROUND: Cancer survivors may have elevated atherosclerotic cardiovascular disease (ASCVD) risk. Therefore, we tested how accurately the American College of Cardiology/American Heart Association 2013 pooled cohort equations (PCEs) predict 10-year ASCVD risk in cancer survivors. OBJECTIVES: To estimate the calibration and discrimination of the PCEs in cancer survivors compared to non-cancer participants in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: We evaluated the PCEs' performance among 1244 cancer survivors and 3849 cancer-free participants who were free of ASCVD at the start of follow-up. Each cancer survivor was incidence-density matched with up to five controls by age, race, sex, and study center. Follow-up began at the first study visit at least 1 year after the diagnosis date of the cancer survivor and finished at the ASCVD event, death, or end of follow-up. Calibration and discrimination were assessed and compared between cancer survivors and cancer-free participants. RESULTS: Cancer survivors had higher PCE-predicted risk, at 26.1%, compared with 23.1% for cancer-free participants. There were 110 ASCVD events in cancer survivors and 332 ASCVD events in cancer-free participants. The PCEs overestimated ASCVD risk in cancer survivors and cancer-free participants by 45.6% and 47.4%, respectively, with poor discrimination in both groups (C-statistic for cancer survivors = 0.623; for cancer-free participants, C = 0.671). CONCLUSIONS: The PCEs overestimated ASCVD risk in all participants. The performance of the PCEs was similar in cancer survivors and cancer-free participants. IMPLICATIONS FOR CANCER SURVIVORS: Our findings suggest that ASCVD risk prediction tools tailored to survivors of adult cancers may not be needed.

Estimating uninsured and underinsured women eligible for Minnesota's Breast Cancer Screening Program.

Since its inception in 1991, the mission of the National Breast and Cervical Cancer Early Detection Program's (NBCCEDP) mission is to improve access to mammography. This program has demonstrated evidence showing that it has improved breast cancer screening rates for women who are uninsured and underinsured. However, the literature has shown that NBCCEDP screenings are decreasing, and only reach a portion of eligible women. Reliable estimates at the sub-county level are needed to identify and reach eligible women. Our work builds upon previous estimates by integrating uninsured and insurance status into spatially adaptive filters. We use spatially adaptive filters to create small area estimates of standardized incidence ratios describing the utilization rate of NBCCEDP services in Minnesota. We integrate the American Community Survey (2010-2014) insurance status data to account for the percentage that an individual is uninsured. We test five models that integrate insurance status by age, sex, and race/ethnicity. Our composite model, which adjusts for age, sex, and race/ethnicity insurance statuses, reduces 95% of the estimation error. We estimate that there approximately 49,913.7 women eligible to receive services for Minnesota. We also create small geography (i.e., county and sub-county) estimates for Minnesota. The integration of the insurance data improved our utilization estimate. The development of these methods will allow state programs to more efficiently use their resources and understand their reach.

Trajectory of Healthcare Contact Days for Veterans With Advanced Gastrointestinal Malignancy.

How and where patients with advanced cancer facing limited survival spend their time is critical. Healthcare contact days (days with healthcare contact outside the home) offer a patient-centered and practical measure of how much of a person's life is consumed by healthcare. We retrospectively analyzed contact days among decedent veterans with stage IV gastrointestinal cancer at the Minneapolis Veterans Affairs Healthcare System from 2010 to 2021. Among 468 decedents, the median overall survival was 4 months. Patients spent 1 in 3 days with healthcare contact. Over the course of illness, the percentage of contact days followed a "U-shaped" pattern, with an initial post-diagnosis peak, a lower middle trough, and an eventual rise as patients neared the end-of-life. Contact days varied by clinical factors and by sociodemographics. These data have important implications for improving care delivery, such as through care coordination and communicating expected burdens to and supporting patients and care partners.

Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer.

Importance: There has been little consideration of genomic risk of recurrence by breast cancer subtype despite evidence of racial disparities in breast cancer outcomes. Objective: To evaluate associations between clinical trial end points, namely pathologic complete response (pCR) and distant recurrence-free survival (DRFS), and race and examine whether gene expression signatures are associated with outcomes by race. Design, Setting, and Participants: This retrospective cohort study used data from the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2 (I-SPY 2) multicenter clinical trial of neoadjuvant chemotherapy with novel agents and combinations for patients with previously untreated stage II/III breast cancer. Analyses were conducted of associations between race and short- and long-term outcomes, overall and by receptor subtypes, and their association with 28 expression biomarkers. The trial enrolled 990 female patients between March 30, 2010, and November 5, 2016, with a primary tumor size of 2.5 cm or greater and clinical or molecular high risk based on MammaPrint or hormone receptor (HR)-negative/ERBB2 (formerly HER2 or HER2/neu)-positive subtyping across 9 arms. This data analysis was performed between June 10, 2021, and October 20, 2022. Exposure: Race, tumor receptor subtypes, and genomic biomarker expression of early breast cancer. Main Outcomes and Measures: The primary outcomes were pCR and DRFS assessed by race, overall, and by tumor subtype using logistic regression and Cox proportional hazards regression models. The interaction between 28 expression biomarkers and race, considering pCR and DRFS overall and within subtypes, was also evaluated. Results: The analytic sample included 974 participants (excluding 16 self-reporting as American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, or multiple races due to small sample sizes), including 68 Asian (7%), 120 Black (12%), and 786 White (81%) patients. Median (range) age at diagnosis was 47 (25-71) years for Asian, 49 (25-77) for Black, and 49 (23-73) years for White patients. The pCR rates were 32% (n = 22) for Asian, 30% for Black (n = 36), and 32% for White (n = 255) patients (P = .87). Black patients with HR-positive/ERBB2-negative tumors not achieving pCR had significantly worse DRFS than their White counterparts (hazard ratio, 2.28; 95% CI, 1.24-4.21; P = .01), with 5-year DRFS rates of 55% (n = 32) and 77% (n = 247), respectively. Black patients with HR-positive/ERBB2-negative tumors, compared with White patients, had higher expression of an interferon signature (mean [SD], 0.39 [0.87] and -0.10 [0.99]; P = .007) and, compared with Asian patients, had a higher mitotic score (mean [SD], 0.07 [1.08] and -0.69 [1.06]; P = .01) and lower estrogen receptor/progesterone receptor signature (mean [SD], 0.31 [0.90] and 1.08 [0.95]; P = .008). A transforming growth factor ß signature had a significant association with race relative to pCR and DRFS, with a higher signature associated with lower pCR and worse DRFS outcomes among Black patients only. Conclusions and Relevance: The findings show that women with early high-risk breast cancer who achieve pCR have similarly good outcomes regardless of race, but Black women with HR-positive/ERBB2-negative tumors without pCR may have worse DRFS than White women, highlighting the need to develop and test novel biomarker-informed therapies in diverse populations.

Aging measures and cancer: Findings from the Health and Retirement Study.

Background: Compared to cancer-free persons, cancer survivors of the same chronological age (CA) have increased physiological dysfunction, i.e., higher biological age (BA), which may lead to higher morbidity and mortality. We estimated BA using eight aging metrics: BA computed by Klemera Doubal method (KDM-BA), phenotypic age (PhenoAge), five epigenetic clocks (ECs, Horvath, Hannum, Levine, GrimAge, and pace of aging (POA)), and subjective age (SA). We tested if aging constructs were associated with total cancer prevalence and all-cause mortality in cancer survivors and controls, i.e., cancer-free persons, in the Health and Retirement Study (HRS), a large population-based study. Methods: In 2016, data on BA-KDM, PhenoAge, and SA were available for 946 cancer survivors and 4,555 controls; data for the five ECs were available for 582 cancer survivors and 2,805 controls. Weighted logistic regression was used to estimate the association between each aging construct and cancer prevalence (odds ratio, OR, 95%CI). Weighted Cox proportional hazards regression was used to estimate the associations between each aging construct and cancer incidence as well as all-cause mortality (hazard ratio, HR, 95%CI). To study all BA metrics (except for POA) independent of CA, we estimated age acceleration as residuals of BA regressed on CA. Results: Age acceleration for each aging construct and POA were higher in cancer survivors than controls. In a multivariable-adjusted model, five aging constructs (age acceleration for Hannum, Horvath, Levine, GrimAge, and SA) were associated with cancer prevalence. Among all cancer survivors, age acceleration for PhenoAge and four ECs (Hannum, Horvath, Levine, and GrimAge), was associated with higher all-cause mortality over 4 years of follow-up. PhenoAge, Hannum, and GrimAge were also associated with all-cause mortality in controls. The highest HR was observed for GrimAge acceleration in cancer survivors: 2.03 (95% CI, 1.58-2.60). In contrast, acceleration for KDM-BA and POA was significantly associated with mortality in controls but not in cancer survivors. When all eight aging constructs were included in the same model, two of them (Levine and GrimAge) were significantly associated with mortality among cancers survivors. None of the aging constructs were associated with cancer incidence. Conclusion: Variations in the associations between aging constructs and mortality in cancer survivors and controls suggests that aging constructs may capture different aspects of aging and that cancer survivors may be experiencing age-related physiologic dysfunctions differently than controls. Future work should evaluate how these aging constructs predict mortality for specific cancer types.

A cross-institutional evaluation on breast cancer phenotyping NLP algorithms on electronic health records.

Objective: Transformer-based language models are prevailing in the clinical domain due to their excellent performance on clinical NLP tasks. The generalizability of those models is usually ignored during the model development process. This study evaluated the generalizability of CancerBERT, a Transformer-based clinical NLP model, along with classic machine learning models, i.e., conditional random field (CRF), bi-directional long short-term memory CRF (BiLSTM-CRF), across different clinical institutes through a breast cancer phenotype extraction task. Materials and methods: Two clinical corpora of breast cancer patients were collected from the electronic health records from the University of Minnesota (UMN) and Mayo Clinic (MC), and annotated following the same guideline. We developed three types of NLP models (i.e., CRF, BiLSTM-CRF and CancerBERT) to extract cancer phenotypes from clinical texts. We evaluated the generalizability of models on different test sets with different learning strategies (model transfer vs locally trained). The entity coverage score was assessed with their association with the model performances. Results: We manually annotated 200 and 161 clinical documents at UMN and MC. The corpora of the two institutes were found to have higher similarity between the target entities than the overall corpora. The CancerBERT models obtained the best performances among the independent test sets from two clinical institutes and the permutation test set. The CancerBERT model developed in one institute and further fine-tuned in another institute achieved reasonable performance compared to the model developed on local data (micro-F1: 0.925 vs 0.932). Conclusions: The results indicate the CancerBERT model has superior learning ability and generalizability among the three types of clinical NLP models for our named entity recognition task. It has the advantage to recognize complex entities, e.g., entities with different labels.