Development, characterization, and replication of proteomic aging clocks: Analysis of 2 population-based cohorts.

BACKGROUND: Biological age may be estimated by proteomic aging clocks (PACs). Previous published PACs were constructed either in smaller studies or mainly in white individuals, and they used proteomic measures from only one-time point. In this study, we created de novo PACs and compared their performance to published PACs at 2 different time points in the Atherosclerosis Risk in Communities (ARIC) study of white and black participants (around 75% white and 25% black). MEDTHODS AND FINDINGS: A total of 4,712 plasma proteins were measured using SomaScan in blood samples collected in 1990 to 1992 from 11,761 midlife participants (aged 46 to 70 years) and in 2011 to 2013 from 5,183 late-life participants (aged 66 to 90 years). The de novo ARIC PACs were constructed by training them against chronological age using elastic net regression in two-thirds of healthy participants in midlife and late life and validated in the remaining one-third of healthy participants at the corresponding time point. We also computed 3 published PACs. We estimated age acceleration for each PAC as residuals after regressing each PAC on chronological age. We also calculated the change in age acceleration from midlife to late life. We examined the associations of age acceleration and change in age acceleration with mortality through 2019 from all-cause, cardiovascular disease (CVD), cancer, and lower respiratory disease (LRD) using Cox proportional hazards regression in participants (irrespective of health) after excluding the training set. The model was adjusted for chronological age, smoking, body mass index (BMI), and other confounders. We externally validated the midlife PAC using the Multi-Ethnic Study of Atherosclerosis (MESA) Exam 1 data. The ARIC PACs had a slightly stronger correlation with chronological age than published PACs in healthy participants at each time point. Associations with mortality were similar for the ARIC PACs and published PACs. For late-life and midlife age acceleration for the ARIC PACs, respectively, hazard ratios (HRs) per 1 standard deviation were 1.65 and 1.38 (both p < 0.001) for all-cause mortality, 1.37 and 1.20 (both p < 0.001) for CVD mortality, 1.21 (p = 0.028) and 1.04 (p = 0.280) for cancer mortality, and 1.46 and 1.68 (both p < 0.001) for LRD mortality. For the change in age acceleration, HRs for all-cause, CVD, and LRD mortality were comparable to the HRs for late-life age acceleration. The association between the change in age acceleration and cancer mortality was not significant. The external validation of the midlife PAC in MESA showed significant associations with mortality, as observed for midlife participants in ARIC. The main limitation is that our PACs were constructed in midlife and late-life participants. It is unknown whether these PACs could be applied to young individuals. CONCLUSIONS: In this longitudinal study, we found that the ARIC PACs and published PACs were similarly associated with an increased risk of mortality. These findings suggested that PACs show promise as biomarkers of biological age. PACs may be serve as tools to predict mortality and evaluate the effect of anti-aging lifestyle and therapeutic interventions.

Frailty and pre-frailty associated with long-term diminished physical performance and quality of life in breast cancer and hematopoietic cell transplant survivors.

Physical frailty as a sign of accelerated aging is not well characterized in breast cancer (BC) and hematopoietic cell transplant (HCT) survivors and its correlation with outcomes and quality of life (QOL) is not defined. We conducted a prospective study to determine the prevalence of frailty in adult BC and HCT survivors, examine its impact on QOL, and determine its association with p16INK4a, a molecular biomarker for biological aging. The study included 59 BC and 65 HCT survivors. Median age was 60 years (range 27-81), 68.5% were female and 49.2% were 18-59 vs. 51.8% ≥60 years old. A total of 71 (57.3%) were "fit" (frailty score 0) vs. 53 (42.7%) were pre-frailty/frail (frailty scores ≥1), and of the latter 17 (32.1%) were BC and 36 (67.9%) HCT patients. On multivariate analysis, patients >60 years were twice as likely to be frail (OR 2.04, 95% CI, 0.96-4.33; p=0.07), HCT were more likely to be frail compared to BC patients, and female HCT had 2.43 (95% CI, 0.92-6.40) and male HCT patients had 3.25 (95% CI, 1.37-7.72) times higher risk of frail; p=0.02. Frailty was associated with significant decline in QOL, measured by Medical Outcomes Study (MOS) Short Form 36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS), and FACT (Functional Assessment of Cancer Therapy) scores. p16INK4a expression was higher in those who were frail, older than 60, and with higher expression in frail vs. fit patients who are 18-59 years. Our study highlights the high prevalence of frailty in survivors with detrimental effects on physical and overall wellbeing, and supports an association between frailty and the senescence marker p16INK4a.

Data quality in a survey of registered medical cannabis users with cancer: nonresponse and measurement error.

Cannabis use among individuals with cancer is best understood using survey self-report. As cannabis remains federally illegal, surveys could be subject to nonresponse and measurement issues impacting data quality. We surveyed individuals using medical cannabis for a cancer-related condition in the Minnesota Medical Cannabis Program (MCP). Although survey responders are older, there are no differences by race and ethnicity, gender, or receipt of reduced cannabis registry enrollment fee. Responders made a more recent purchase and more recently completed an independent symptom assessment for the registry than nonresponders, suggesting some opportunity for nonresponse error. Among responders, self-report and MCP administrative data with respect to age, race, gender, registry certification, and cannabis purchase history were similar. Responders were less likely to report receipt of Medicaid than would be expected based on registry low-income enrollment eligibility. Although attention should be paid to potential for nonresponse error, surveys are a reliable tool to ascertain cannabis behavior patterns in this population.

Implementation and impact of an electronic patient reported outcomes system in a phase II multi-site adaptive platform clinical trial for early-stage breast cancer.

OBJECTIVES: We describe the development and implementation of a system for monitoring patient-reported adverse events and quality of life using electronic Patient Reported Outcome (ePRO) instruments in the I-SPY2 Trial, a phase II clinical trial for locally advanced breast cancer. We describe the administration of technological, workflow, and behavior change interventions and their associated impact on questionnaire completion. MATERIALS AND METHODS: Using the OpenClinica electronic data capture system, we developed rules-based logic to build automated ePRO surveys, customized to the I-SPY2 treatment schedule. We piloted ePROs at the University of California, San Francisco (UCSF) to optimize workflow in the context of trial treatment scenarios and staggered rollout of the ePRO system to 26 sites to ensure effective implementation of the technology. RESULTS: Increasing ePRO completion requires workflow solutions and research staff engagement. Over two years, we increased baseline survey completion from 25% to 80%. The majority of patients completed between 30% and 75% of the questionnaires they received, with no statistically significant variation in survey completion by age, race or ethnicity. Patients who completed the screening timepoint questionnaire were significantly more likely to complete more of the surveys they received at later timepoints (mean completion of 74.1% vs 35.5%, P < .0001). Baseline PROMIS social functioning and grade 2 or more PRO-CTCAE interference of Abdominal Pain, Decreased Appetite, Dizziness and Shortness of Breath was associated with lower survey completion rates. DISCUSSION AND CONCLUSION: By implementing ePROs, we have the potential to increase efficiency and accuracy of patient-reported clinical trial data collection, while improving quality of care, patient safety, and health outcomes. Our method is accessible across demographics and facilitates an ease of data collection and sharing across nationwide sites. We identify predictors of decreased completion that can optimize resource allocation by better targeting efforts such as in-person outreach, staff engagement, a robust technical workflow, and increased monitoring to improve overall completion rates. TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT01042379.

Association Between Obesity and Risk of Total and Obesity-Related Cancer in People With Incident Cardiovascular Disease.

BACKGROUND: Cardiovascular disease (CVD) and cancer frequently co-occur due to shared risk factors such as obesity, which is linked to CVD and 14 cancer types. This study explores whether CVD pathophysiologies, combined with obesity, increase cancer risk, impacting clinical management. METHODS AND RESULTS: Data from the ARIC (Atherosclerosis Risk in Communities) study, spanning 28 years, were analyzed. The cohort included 5127 participants with incident CVD (myocardial infarction, stroke, heart failure, coronary heart disease), of whom 1511 developed a first primary cancer. Follow-up began at CVD diagnosis after Visit 1. Obesity was assessed using body mass index, waist circumference, and waist-to-hip ratio. Incidence rate differences between obesity groups were adjusted for age, sex, and center, whereas the obesity-cancer association was estimated using Fine-Gray regression adjusted for shared risk factors including smoking. Cancer incidence in obese individuals with CVD (body mass index: rate differences=226.6/100 000 person-years) was higher than in those with normal weight. Although obesity was not linked to overall cancer after adjusting for shared risk factors, it was nominally associated with obesity-related cancers. Specifically, women with CVD and obesity had increased obesity-related cancer risk (body mass index: hazard ratio, 1.67 [95% CI, 1.17-2.31]). No significant associations were found in men, even after excluding prostate cancer. CONCLUSIONS: This study suggests that obesity is linked to higher obesity-related cancer risk in women with incident CVD, independent of shared risk factors. Further research is needed to eliminate residual confounding, understand sex differences, and explore how CVD pathophysiologies and obesity together influence cancer risk.

Perceptions, prevalence, and patterns of cannabis use among cancer patients treated at 12 NCI-Designated Cancer Centers.

BACKGROUND: The legal climate for cannabis use has dramatically changed with an increasing number of states passing legislation legalizing access for medical and recreational use. Among cancer patients, cannabis is often used to ameliorate adverse effects of cancer treatment. Data are limited on the extent and type of use among cancer patients during treatment and the perceived benefits and harms. This multicenter survey was conducted to assess the use of cannabis among cancer patients residing in states with varied legal access to cannabis. METHODS: A total of 12 NCI-Designated Cancer Centers, across states with varied cannabis-access legal status, conducted surveys with a core questionnaire to assess cannabis use among recently diagnosed cancer patients. Data were collected between September 2021 and August 2023 and pooled across 12 cancer centers. Frequencies and 95% confidence intervals for core survey measures were calculated, and weighted estimates are presented for the 10 sites that drew probability samples. RESULTS: Overall reported cannabis use since cancer diagnosis among survey respondents was 32.9% (weighted), which varied slightly by state legalization status. The most common perceived benefits of use were for pain, sleep, stress and anxiety, and treatment side effects. Reported perceived risks were less common and included inability to drive, difficulty concentrating, lung damage, addiction, and impact on employment. A majority reported feeling comfortable speaking to health-care providers though, overall, only 21.5% reported having done so. Among those who used cannabis since diagnosis, the most common modes were eating in food, smoking, and pills or tinctures, and the most common reasons were for sleep disturbance, followed by pain and stress and anxiety with 60%-68% reporting improved symptoms with use. CONCLUSION: This geographically diverse survey demonstrates that patients use cannabis regardless of its legal status. Addressing knowledge gaps concerning benefits and harms of cannabis use during cancer treatment is critical to enhance patient-provider communication.

Proteomic Aging Clocks and the Risk of Mortality among Longer-Term Cancer Survivors in the Atherosclerosis Risk in Communities (ARIC) Study.

Background: We constructed a new proteomic aging clock (PAC) and computed the published Lehallier's PAC to estimate biological age. We tested PACs' associations with mortality in longer-term cancer survivors and cancer-free participants. Methods: ARIC measured 4,712 proteins using SomaScan in plasma samples collected at multiple visits, including Visit 5 (2011-13), from 806 cancer survivors and 3,699 cancer-free participants (aged 66-90). In the training set (N=2,466 randomly selected cancer-free participants), we developed the new PAC using elastic net regression and computed Lehallier's PAC. Age acceleration was calculated as residuals after regressing each PAC on chronological age after excluding the training set. We used multivariable-adjusted Cox proportional hazards regression to examine the associations of age acceleration with all-cause, cardiovascular disease (CVD), and cancer mortality. Results: Both PACs were correlated with chronological age [r=0.70-0.75]. Age acceleration for these two PACs was similarly associated with all-cause mortality in cancer survivors [hazard ratios (HRs) per 1 SD=1.40-1.42, p<0.01]. The associations with all-cause mortality were similar in cancer survivors and cancer-free participants for both PACs [p-interactions=0.20-0.62]. There were also associations with all-cause mortality in breast cancer survivors for both PACs [HRs=1.54-1.72, p<0.01] and colorectal cancer survivors for the new PAC [HR=1.96, p=0.03]. Additionally, the new PAC was associated with cancer mortality in all cancer survivors. Finally, HRs=1.42-1.61 [p<0.01] for CVD mortality in cancer-free participants for two PACs but the association was insignificant in cancer survivors perhaps due to a limited number of outcomes. Conclusion: PACs hold promise as potential biomarkers for premature mortality in cancer survivors.

Risk prediction of heart diseases in patients with breast cancer: A deep learning approach with longitudinal electronic health records data.

Accurately predicting heart disease risks in patients with breast cancer is crucial for clinical decision support and patient safety. This study developed and evaluated predictive models for six heart diseases using real-world electronic health records (EHRs) data. We incorporated a trainable decay mechanism to handle missing values in the long short-term memory (LSTM) model, creating LSTM-D models to predict heart disease risk based on longitudinal EHRs data. Additionally, we deployed NLP methods to extract breast cancer phenotypes from clinical texts, integrating unstructured and structured data to enhance predictions. Our LSTM-D models outperformed baseline models in predicting congestive heart failure, coronary artery disease, cardiomyopathy, myocardial infarction, transient ischemic attack, and aortic regurgitation, with AUC scores ranging from 0.7189 to 0.9548. Observation windows of 12-24 months were found optimal for model performance. This research advances precise, personalized care strategies, enabling early intervention and improved management of cardiovascular risks in breast cancer survivors.

Multi-modality risk prediction of cardiovascular diseases for breast cancer cohort in the All of Us Research Program.

OBJECTIVE: This study leverages the rich diversity of the All of Us Research Program (All of Us)'s dataset to devise a predictive model for cardiovascular disease (CVD) in breast cancer (BC) survivors. Central to this endeavor is the creation of a robust data integration pipeline that synthesizes electronic health records (EHRs), patient surveys, and genomic data, while upholding fairness across demographic variables. MATERIALS AND METHODS: We have developed a universal data wrangling pipeline to process and merge heterogeneous data sources of the All of Us dataset, address missingness and variance in data, and align disparate data modalities into a coherent framework for analysis. Utilizing a composite feature set including EHR, lifestyle, and social determinants of health (SDoH) data, we then employed Adaptive Lasso and Random Forest regression models to predict 6 CVD outcomes. The models were evaluated using the c-index and time-dependent Area Under the Receiver Operating Characteristic Curve over a 10-year period. RESULTS: The Adaptive Lasso model showed consistent performance across most CVD outcomes, while the Random Forest model excelled particularly in predicting outcomes like transient ischemic attack when incorporating the full multi-model feature set. Feature importance analysis revealed age and previous coronary events as dominant predictors across CVD outcomes, with SDoH clustering labels highlighting the nuanced impact of social factors. DISCUSSION: The development of both Cox-based predictive model and Random Forest Regression model represents the extensive application of the All of Us, in integrating EHR and patient surveys to enhance precision medicine. And the inclusion of SDoH clustering labels revealed the significant impact of sociobehavioral factors on patient outcomes, emphasizing the importance of comprehensive health determinants in predictive models. Despite these advancements, limitations include the exclusion of genetic data, broad categorization of CVD conditions, and the need for fairness analyses to ensure equitable model performance across diverse populations. Future work should refine clinical and social variable measurements, incorporate advanced imputation techniques, and explore additional predictive algorithms to enhance model precision and fairness. CONCLUSION: This study demonstrates the liability of the All of Us's diverse dataset in developing a multi-modality predictive model for CVD in BC survivors risk stratification in oncological survivorship. The data integration pipeline and subsequent predictive models establish a methodological foundation for future research into personalized healthcare.

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.

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.

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.

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.

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.

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.

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.

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."