Risk In Cancer Survivors Research Articles

Cancer-specific Heart Failure (HF) risk score - a new risk score developed specifically to predict HF among cancer survivors

Abstract Background Heart failure (HF) is an important long-term complication in cancer survivors, especially in breast and haematological malignancies treated with anthracylines. However, screening for left ventricular dysfunction in all survivors is impractical due to potential low cost-efficiency. So we sought to develop a cancer-specific risk scoring system for HF (CRS-HF). Methods Cancer survivors (n=43,720) participating in the UK-Biobank were evaluated in this study (age 59.9 ± 7.4 years, 62.4% female). Participants were randomized into training and testing dataset with a 7:3 split. A Random Forest algorithm was applied to identify key variables that are predictive for HF incidence among cancer survivors. Results Incident HF developed in 4.3% over a median of 12.9 years. The random forest algorithm identified demographic (age, sex and body mass index), clinical (heart rate, blood pressure and cardiac history), pathology (lipids) results and other patient reported outcome measures (PROMS) that predicted HF with an accuracy of 0.872 (95%CI: 0.867-0.877) in the training set. In the testing set, the accuracy was 0.840 (95%CI: 0.832-0.848) and a reported sensitivity and specificity of 62.42% and 84.93% respectively. Our study also demonstrated that the CRS-HF performed better in ruling out non-HF incidence among survivors from breast cancer and lymphoma (accuracy: 0.858) than other cancer types (accuracy: 0.836). Conclusion The CRS-HF score is a prove-of-concept that appears to be an effective means of identifying HF risk in cancer survivors. Although initial findings demonstrate promising accuracy in forecasting HF occurrences among cancer survivors, comprehensive validation and potential refinements are warranted across diverse population cohorts.

Effects of loneliness on healthcare utilization and medical expenditures in US cancer survivors.

368 Background: Loneliness is associated with increased mortality risk in cancer survivors. However, effects of loneliness on healthcare utilization are understudied. This study examined associations of loneliness with having emergency room (ER) visit, usual source of care, and hospitalization in US adults with and without cancer history. Methods: We identified 1,844 cancer survivors and 9,517 adults without a cancer history from the 2021 Medical Expenditure Panel Survey. Loneliness was measured by 3 questions on feeling lack of companionship, left out, and isolated from others. Scores for each question were summed to create a total loneliness score, which was categorized into low/no loneliness (3-5) and high loneliness (6-9) based on previous literature. Separate logistic regression models were used to assess association of loneliness and whether having ER visit, usual source of care, and hospitalization. All models adjusted for age, region, sex, race, non-cancer health conditions, activity limitation, marital status, education, health insurance, and cancer diagnosis. We used a cancer history by loneliness interaction term to examine the differential associations of loneliness and healthcare utilization by cancer history. Results: 2,367 (23%) adults without a cancer history and 450 (22%) cancer survivors reported loneliness. All adults averagely aged over 50, with more female (non-cancer: 57.1 vs 49.9%, cancer: 68.0 vs 55.9%) and those with non-cancer health conditions ≥3 (non-cancer: 20.6 vs 15.4%, cancer: 54.0 vs 44.4%) in the loneliness group. Cancer history modified the association between loneliness and ER visit (interaction term p-value 0.04), but didn’t modify the association with having usual source of care (p=0.38) or hospitalization (p=0.87). Loneliness was associated with having ER visit (OR 1.49, 95% CI 1.11-2.00) in cancer survivors while not in non-cancer patients (OR 1.08, 95% CI 0.92-1.27). No significant association was observed between loneliness and having usual source of care or hospitalization. Conclusions: Loneliness is associated with ER visit in US cancer survivors. Findings warrant further study of impact of loneliness on clinical outcomes in cancer survivors, with the aim of enhancing strategies to mitigate loneliness and optimize healthcare utilization. Association of loneliness and healthcare utilization. No Cancer History (9,517, 85%) Cancer History (1,844, 15%) Loneliness No (7,150, 77%) Yes (2,367, 23%) No (1,394, 78%) Yes (450, 22%) Odds ratio Having ER visit Ref 1.08 (0.92-1.27) Ref 1.49 (1.11-2.00) Having usual source of care 1.08 (0.89-1.30) 0.90 (0.62-1.30) Having hospitalization 0.93 (0.79-1.09) 0.96 (0.62-1.48)

Weight Change After Cancer Diagnosis and Risk of Diabetes Mellitus: A Population-Based Nationwide Study.

Cancer survivors are at increased risk of diabetes mellitus (DM). Additionally, the prevalence of obesity, which is also a risk factor for DM, is increasing in cancer survivors. We investigated the associations between weight change after cancer diagnosis and DM risk. This retrospective cohort study used data from the Korean National Health Insurance Service. Participants who were newly diagnosed with cancer from 2010 to 2016 and received national health screening before and after diagnosis were included and followed until 2019. Weight change status after cancer diagnosis was categorized into four groups: sustained normal weight, obese to normal weight, normal weight to obese, or sustained obese. Cox proportional hazard analyses were performed to examine associations between weight change and DM. The study population comprised 264,250 cancer survivors. DM risk was highest in sustained obese (adjusted hazard ratios, 95% confidence interval: 2.17, 2.08-2.26), followed by normal weight to obese (1.66, 1.54-1.79), obese to normal weight (1.29, 1.21-1.39), and then sustained normal weight group (reference). In subgroup analyses according to cancer type, most cancers showed the highest risks in sustained obese group. Obesity at any time point was related to increased DM risk, presenting the highest risk in cancer survivors with sustained obesity. Survivors who changed from obese to normal weight had lower risk than survivors with sustained obesity. Survivors who changed from normal weight to obese showed increased risk compared to those who sustained normal weight. Our finding supports the significance of weight management among cancer survivors.

P.023 Review of imaging changes, cognitive decline, and dementia risk in cancer survivors after chemotherapy

Background: Cancer survival rates in Canada have been improving, leading to a steady increase in the number of survivors entering the typical ages of dementia onset. Yet, some cancer treatments (e.g. chemotherapy) are neurotoxic and adversely affect normal brain functioning. We conducted a review to examine changes observed in brain imaging and cognitive measures in survivorship, and long-term risk of dementia among cancer survivors. Methods: 91 Primary studies were selected from PubMed. Inclusion criteria were studies investigating the changes in brain imaging, cognition, and future dementia risk among adult survivors who received chemotherapy. Study quality was assessed based on 1) prospective, controlled design, 2) sample size, and 3) validated imaging and cognitive metrics. Results: Imaging studies identified MRI-based structural grey and white matter changes and functional network changes among survivors. Cognitive studies reported heterogeneous impairments in attention, memory, and executive function. In studies that examined dementia risk among cancer survivors, 67% reported lower risk of dementia, while 33% reported no association or a higher risk. Conclusions: While short-term cognitive impairment with associated changes on brain imaging is widely reported, findings concerning future or long-term cognitive impairment are mixed. Studies are warranted to identify potential connections between short-term and long-term cognitive function after cancer treatment.

Association between physical activity changes and risk of incident ischemic stroke following cancer diagnosis: A nationwide retrospective cohort study.

Physical inactivity is prevalent after cancer treatment, which could increase ischemic stroke risk in cancer survivors. This study investigated the association between physical activity change from pre- to post-diagnosis and ischemic stroke risk among cancer survivors. Using data from the Korean National Health Insurance Service database, 269,943 cancer survivors (mean [SD] age, 56.3 [12.1] years; 45.7% male) with no history of cardiovascular disease were evaluated based on changes in physical activity from pre- to post-diagnosis. Using the Fine-Gray model, subdistribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for ischemic stroke risk were calculated, considering death as a competing risk. After cancer diagnosis, 62.0% remained inactive, 10.1% remained active, 16.6% became active, and 11.4% became inactive. During a mean (SD) follow-up of 4.1 (2.0) years, being active both pre- and post-diagnosis was associated with a 15% decreased risk of ischemic stroke (sHR, 0.85; 95% CI, 0.75-0.96), compared with those who remained inactive. Cancer survivors who became active and inactive post-diagnosis showed a 16% and 11% lower ischemic stroke risk (sHR, 0.84; 95% CI, 0.75-0.93; sHR, 0.89; 95% CI, 0.79-0.99), respectively, than those who remained inactive. Analysis by the primary cancer site did not substantially differ from the main findings. Physical activity is associated with reduced ischemic stroke risk among cancer survivors. The potential benefits of physical activity are not limited to individuals who were physically active before cancer diagnosis, thus preventive strategies against ischemic stroke should emphasize physical activity throughout the cancer journey.

The association between serum methylmalonic acid, cobalamin-related biomarkers, and long-term mortality risk in cancer survivors: a prospective cohort study

BackgroundElevated serum methylmalonic acid (MMA), a marker of cobalamin (vitamin B12) deficiency, has been linked to cancer progression. However, the impact of MMA or cobalamin on mortality risk in cancer survivors remains unknown. ObjectivesTo explore the relationship between MMA, serum, dietary, and supplement of cobalamin, MMA metabolism-related genes, and poor prognosis in adult cancer survivors. MethodsWe analyzed data from 1988 cancer survivors aged ≥20 y. Patients were selected from the National Health and Nutrition Examination Survey and followed up until December 31, 2019. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for mortality risk assessment. Genomic analysis identified MMA metabolism-related genes linked to early death in a 33-cancer-type cohort from The Cancer Genome Atlas. ResultsAmong 1988 participants, 872 deaths occurred over a 10-year follow-up. Higher serum MMA levels were significantly linked to increased long-term mortality risk (tertile 3 compared with tertile 1: adjusted HR: 1.37; 95% CI: 1.11, 1.70; P-trend < 0.001). No associations were found between serum, dietary, and supplement of cobalamin and cancer survivor mortality (each P-trend > 0.143). However, MMA-associated mortality was notable in patients without deficiency. When combining cobalamin and MMA categories, multivariate-adjusted HR (95% CI) for all-cause mortality was 2.06 (95% CI: 1.60, 2.65) in participants with >250 nmol/L and cobalamin >295.1 pmol/L compared with those with MMA ≤250 nmol/L and cobalamin >295.1 pmol/L. Moreover, reduced transcriptional levels of MMA metabolism-related genes, indicating decreased mitochondrial MMA metabolism capability, are linked to an unfavorable prognosis in certain cancer types. ConclusionsSerum MMA was associated with long-term mortality risk in adult cancer survivors, which was more significant among individuals with higher levels of serum cobalamin. These findings suggest that mortality related to MMA was attributed to the insufficient flux of MMA metabolism, not cobalamin deficiency.

Abstract 2238: Reducing cardiovascular disease risk in cancer survivors: Impact of a 16-week circuit-based interval exercise intervention

Abstract Introduction: Obesity and physical inactivity pose a significant health concern for cancer survivors in developing comorbid conditions such as type 2 diabetes, hypertension, and metabolic syndrome that lead to a heightened risk of cardiovascular disease (CVD). Therefore, regular physical activity plays a central role in reducing the risk of CVD. The Framingham risk score (FRS) is an established assessment of CVD risk that combines six risk factors including age, gender, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure, diabetes, and smoking status. The objective of the study was to investigate the effects of a 16-week circuit, interval-based exercise training intervention on FRS and the 10-year FRS-predicted risk of developing CVD among breast, prostate, and colorectal cancer survivors. Methods: This single center, pilot randomized controlled trial consisted of 90 sedentary, overweight or obese (BMI &amp;gt; 25.0 kg/m2) survivors of breast, prostate or colorectal cancers, randomized to exercise (n=60) or usual care (n=30). The 16-week intervention comprised supervised moderate to vigorous intensity aerobic (65-85% of VO2max) and resistance (65-85% of 1-repetition maximum) exercise sessions conducted in a circuit-based interval fashion, occurring three times per week. Blood samples were obtained at baseline and post-intervention time points to measure fasting plasma levels of HDL-C and LDL-C, along with resting systolic blood pressure and diagnosis of diabetes. Paired t-test and repeated measure ANOVA were used to determine between-group differences. Results: Participants (age 63.2 ± 10.8 years) were diagnosed with breast (35%), prostate (30%), and colorectal (35%) cancers and consisted of 55% female participants, participants had a mean BMI of 34.7±5.9, and 85% were obese. Chemotherapy and/or radiation therapy was completed by 75% of participants. Retention and adherence rates to exercise were high (100% and 92%, respectively). Compared to usual care, circuit, interval-based exercise significantly reduced total FRS (between group mean difference, -12.0 points p&amp;lt;0.001) and 10-year CVD risk (-10.0%; p&amp;lt;0.001). Conclusions: This study underscores the critical role of circuit-based, interval exercise interventions in mitigating the elevated cardiovascular risk faced by sedentary, overweight, or obese cancer survivors. The significant reduction in FRS components highlights the potential of structured exercise programs to enhance cardiovascular health, thereby reducing the burden of comorbid conditions and CVD risk in cancer survivors. Citation Format: Amber J. Normann, Rebekah L. Wilson, Cami N. Christopher, Mary K. Norris, Simone Cuomo, Christina M. Dieli-Conwright. Reducing cardiovascular disease risk in cancer survivors: Impact of a 16-week circuit-based interval exercise intervention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2238.

Disparities in Cardiovascular Disease-Related Outcomes Among Cancer Survivors in the United States: A Systematic Review of the Literature

Cancer and cardiovascular disease (CVD) are major causes of morbidity and mortality in the United States (US). Cancer survivors have increased risks for CVD and CVD-related mortality due to multiple factors including cancer treatment-related cardiotoxicity. Disparities are rooted in differential exposure to risk factors and social determinants of health (SDOH), including systemic racism. This review aimed to assess SDOH's role in disparities, document CVD-related disparities among US cancer survivors, and identify literature gaps for future research. Following the Peer Review of Electronic Search Strategies (PRESS) guidelines, MEDLINE, PsycINFO, and Scopus were searched on March 15, 2021, with an update conducted on September 26, 2023. Articles screening was performed using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, a pre-defined Population, Exposure, Comparison, Outcomes, and Settings (PECOS) framework, and the Rayyan platform. A modified version of the Newcastle-Ottawa Scale was used to assess the risk of bias, and RAW Graphs for alluvial charts. This review is registered with PROSPERO under ID #CRD42021236460. Out of 7,719 retrieved articles, 24 were included, and discussed diverse SDOH that contribute to CVD-related disparities among cancer survivors. The 24 included studies had a large combined total sample size (n=7,704,645; median=19,707). While various disparities have been investigated, including rural-urban, sex, socioeconomic status, and age, a notable observation is that non-Hispanic Black cancer survivors experience disproportionately adverse CVD outcomes when compared to non-Hispanic White survivors. This underscores historical racism and discrimination against non-Hispanic Black individuals as fundamental drivers of CVD-related disparities. Stakeholders should work to eliminate the root causes of disparities. Clinicians should increase screening for risk factors that exacerbate CVD-related disparities among cancer survivors. Researchers should prioritise the investigation of systemic factors driving disparities in cancer and CVD and develop innovative interventions to mitigate risk in cancer survivors.

SARS-CoV-2 Infection and Related Hospitalization among Cancer Survivors.

Little is known about SARS-CoV-2 infection and COVID-19 severity among a growing population of cancer survivors. We describe the association of infection and related hospitalization by recency of cancer diagnosis in a large U.S. cohort. Participants were sent electronic surveys between April 2020 and January 2021 to collect information on SARS-CoV-2 infection and potential COVID-19-related risk factors. SARS-CoV-2 infections were identified using survey report of a COVID-19-positive test and electronic health record data. Cumulative incidence of SARS-CoV-2 infection was estimated up to 365 days from baseline survey and stratified by recency of cancer diagnosis. Among those with SARS-CoV-2 infection, we used logistic regression to estimate the association between recency of cancer diagnosis and hospitalization within 30 days of infection. Cumulative incidence of SARS-CoV-2 infection at 365 days was 3.3% [95% confidence interval (CI), 3.2%-3.5%] among those without cancer history and ranged from 2.8% (95% CI, 2.3%-3.5%) to 3.7% (95% CI, 2.9%-4.7%) among those with a history of cancer depending on recency. There was no statistically significant difference in odds of hospitalization within 30 days following SARS-CoV-2 infection by cancer diagnosis recency. Our null findings are consistent with other studies on COVID-19 infection risk in cancer survivors, where COVID-19 severity and sequelae were independent of cancer history and were likely associated with factors such as intensive care unit admission, noncancer comorbid conditions, and long-term care residency. This study can inform COVID-19 risk-counseling of cancer survivors and their caregivers as we continue to contend with COVID-19.

The Effect of Cardiac Rehabilitation on Quality of Life and 6-Minute Walk Test in Breast Cancer Survivors

Background Breast cancer (BC) is the most diagnosed cancer in women, contributing to 24.6% of malignancies in females and responsible for 15% of all cancer-related deaths among women worldwide.[1] Over the last 20 years, BC survival rates have significantly improved.[1] However, this survivorship is often marked by fatigue, poor quality of life (QoL), reduced functional capacity along with treatment-related adverse effects.[2] The implementation of a model similar to cardiac rehabilitation (CR) program as a preventive strategy may provide a potential solution to improve functional capacity, quality of life and reduce cardiovascular disease (CVD) risk in cancer survivors.[3] Objective to investigate the effect of 12-week completed cardiac rehabilitation program on quality of life (using FACT-B questionnaire) and 6-minute walk test in breast cancer survivors. Patients and Methods In this 2-arm parallel prospective, randomized, controlled clinical trial, sixty breast cancer survivors 3 months to 1 year after completion of chemotherapy were recruited at Ain Shams University hospitals and divided into two groups Study group (n = 30); participated in 12-week CR program and Control group (n = 30) did not participate in CR program but still received the usual cancer care. Cardiac rehabilitation program consisted of education, diet control, drug adherence, 12 weeks exercise sessions, Behavior and psychosocial management, Sexual activity education Smoking cessation. Functional capacity was assessed before and after study period by sixminute walk test (6MWT) and exercise test (using modified Bruce protocol). All patients were personally interviewed for assessment of quality of life before and after study period using (FACT-B) questionnaire. In addition patients underwent echocardiography assessment before and after study period. Result Sixty female breast cancer survivors were enrolled. Nine patients dropped from CR program, some due to social commitments (n = 2), others due to long distance issues (n = 2), and the remaining were not interested in continuing the program (n = 5). There were no significant differences between the two groups regarding age, baseline BMI, hemoglobin (Hb) levels, medical history, chemotherapy protocol, and radiation. When comparing two groups, the study group showed significant increase in age-predicted 6MWD (p = 0.02), ET (p &amp;lt; 0.001), METs (p &amp;lt; 0.001), QoL score (p &amp;lt; 0.001), along with significant decrease in SBP (p &amp;lt; 0.001), HR (p &amp;lt; 0.001), RPP (p &amp;lt; 0.001). Conclusion The results of this study demonstrated that completed cardiac rehabilitation program improves functional capacity and quality of life in breast cancer survivors. Recommendation We recommend that multicomponent supervised cardiac rehabilitation program should be incorporated within the usual care of breast cancer survivor

Association of dietary total antioxidant capacity and its distribution across three meals with all-cause, cancer, and non-cancer mortality among cancer survivors: the US National Health and Nutrition Examination Survey, 1999-2018.

The effect of the antioxidant capacity of diet and its distribution across three meals on mortality risk among cancer patients remains unexplored. We aimed to prospectively investigate the association of dietary total antioxidant capacity (DAC) and its distribution across three meals with all-cause, cancer, and noncancer mortality among cancer survivors. We included 5,009 patients with cancer from the National Health and Nutrition Examination Survey conducted between 1999 and 2018. The adjusted hazard ratio (aHR) was estimated using the survey-weighted Cox proportional hazards model. During a median follow-up of 7.9 years, 1811 deaths, including 575 cancer-related deaths, were recorded. Among cancer survivors, compared with participants in the lowest quartile of total DAC from three meals, those in the highest quartile had a 24% decreased risk of noncancer mortality (aHR = 0.76, 95% confidence interval [CI]: 0.60-0.92), but not of all-cause and cancer mortality (each p trend >0.1). However, this association became insignificant for total DAC after excluding dinner DAC. In addition, higher dinner DAC rather than breakfast or lunch DAC was associated with a 21% lower risk of all-cause mortality (aHR = 0.79, 95% CI: 0.65-0.98) and 28% lower risk of noncancer mortality (aHR = 0.72, 95% CI: 0.57-0.90). Similar associations were found for ΔDAC (dinner DAC - breakfast DAC) with noncancer mortality (aHR = 0.56, 95% CI: 0.38-0.83), but DAC was not associated with cancer mortality (p trend >0.3). Among cancer survivors, total DAC from three meals was associated with reduced noncancer mortality, with the primary effect attributable to increased DAC intake from dinner. Our findings emphasize that DAC consumption from dinner should be advocated to reduce mortality risk in cancer survivors.

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

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. To estimate the calibration and discrimination ofthe PCEs in cancer survivors compared to non-cancer participants in the Atherosclerosis Risk in Communities (ARIC) study. 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 1year 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. 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). The PCEs overestimated ASCVD risk in all participants. The performance of the PCEs was similar in cancer survivors and cancer-free participants. Our findings suggest that ASCVD risk prediction tools tailored to survivors of adult cancers may not be needed.

Abstract 4361: The plasma proteome as a cardiovascular disease risk assessment tool in cancer survivors

Abstract Cardiovascular disease (CVD) is the most common non-cancer cause of death in cancer survivors and there is an unmet clinical need for easy, accurate, and safe CVD prognostic risk-stratification in adult cancer survivors. This study investigated whether a previously validated 27-plasma protein prognostic model for four-year cardiovascular (CV) events could have such a utility. We used the 27-plasma protein model to predict the four-year risk of a CV event (myocardial infarction, stroke, transient ischemic attack, heart failure hospitalization, death) in 906 participants with a prior history or active malignancy of any type of cancer and compared predictive results to follow-up CV outcome data. The participants were from the BASEL VIII or ARIC (visit 3) studies with a medically adjudicated prior diagnosis of cancer. BASEL VIII is an observational cohort study in patients with suspected coronary artery disease. ARIC is a multi-site cohort study funded by the NHLBI, NCI, and NPCR investigating risk factors for CV health. A subset analysis was conducted to assess model performance in participants with no prior history of CVD and those with stable CVD. The 27-plasma protein model accurately stratified participants into 4 distinct and non-overlapping (95% CI) risk bins. The median time to event for all cancer survivors who had an event in this study was 1.3 years. Observed 4-year event rates across the 4 risk bins (low, medium-low, medium-high, and high) were 11.0%, 17.3%, 31.2% and 60.2%, respectively, which were higher than stratified event rates from our previously published metacohort analyses (5.6%, 11.2%, 20.0% and 43.4%, respectively) in participants with elevated CVD risk factors (e.g., prior events, diabetes, kidney disease and suspected coronary artery disease). The plasma protein model accurately predicted 4-year CVD risk with a C-index of 0.71 (0.68, 0.74) and 4-year AUC of 0.74 (0.69, 0.79). Performance of the protein model was comparable between participants with no prior history of CVD (C-Index: 0.69; AUC: 0.71) and stable CVD (C-Index: 0.69; AUC: 0.72), demonstrating the model accurately predicts CV event risk in cancer survivors regardless of cardiovascular history. Cancer survivors in this cohort can be distinguished with 4-year CV event rates as high as 60.2%, underscoring the urgent need for an easy and accurate risk stratification tool for this population. Prognostic protein testing may provide a novel tool for CVD risk assessment in adult cancer survivors. Citation Format: Emma V. Troth, Matthew Ayala, Jessica Chadwick, Erin Hales, Michael Hinterberg, Jessica N. Kuzma, Clare Paterson, Rachel Ostroff, Joan E. Walter, Christian Mueller, Josef Coresh. The plasma proteome as a cardiovascular disease risk assessment tool in cancer survivors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4361.

Abstract 4397: Chemotherapy-induced peripheral neuropathy and falls in cancer survivors relate to digital balance and gait impairments

Abstract Background and Aim: Standing postural sway and gait tests with body-worn inertial sensors provide a multitude of objective, digital balance, and gait measures that represent several different domains controlling mobility. However, it is not clear which domains of balance or gait best reflect the impact of treatment-induced peripheral neuropathy on mobility or differentiate fall risk in cancer survivors. This study aimed to determine which domains of balance and gait differed between cancer survivors who reported 1) symptoms of peripheral neuropathy versus asymptomatic survivors and 2) falls in the previous six months versus non-fallers. Methods: Both postural sway during 30 seconds of quiet stance and gait characteristics from the Instrumented Time-Up-and-Go test (ITUG) were recorded with six synchronous inertial sensors (Opals by APDM Wearable Technology, a Clario company). The sensors were placed on both shanks and wrists, and one on the lumbar spine and sternum in 425 female cancer survivors (age: 62 ± 6 years). A principal component analysis (PCA) approach was used first to identify independent domains of mobility from 14 balance and gait measures for subsequent analysis. Results: PCA analysis revealed 5 independent domains (PC1: Sway amplitude, PC2: Gait pace; PC3: Sway frequency; PC4: Gait spatial-temporal and PC5: Turning) that accounted for 81% of the variance of performance across the participants. Cancer survivors who reported neuropathy showed a significantly higher sway frequency (PC3) than asymptomatic survivors. Cancer survivors who reported falls showed a significantly larger sway area (PC1) and slower gait pace (PC2) than non-fallers. Conclusions: Wearable sensor instrumentation from short balance and gait tests capture objective digital gait and balance outcomes reflective of treatment-related neuropathy and fall risk in women treated with chemotherapy for cancer. Wearable sensors could be used for oncology clinical trials to assess the impact of cancer treatment and symptom mitigation strategies to limit changes in mobility that might lead to excess falls in people with cancer. Citation Format: Vrutangkumar Shah, Daniel Muzyka, Carolyn Guidarelli, Kristen Sowalsky, Kerri M. Winters-Stone, Fay B. Horak. Chemotherapy-induced peripheral neuropathy and falls in cancer survivors relate to digital balance and gait impairments. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4397.

Abstract P6-05-09: Cardiovascular Risk Evaluation for Breast Cancer Survivors: A Pilot Study

Abstract Introduction: Breast cancer (BC) is the most common cancer in women in the United States (US). With advances in screening and treatment, there are increasing numbers of BC survivors. Preexisting or emerging cardiovascular (CV) risk factors and some cancer therapies put BC survivors at risk for long-term CV disease (CVD). ASCO clinical practice guidelines for prevention and monitoring of cardiac dysfunction recommend treatment of CV risk factors in cancer survivors, however, the application of these guidelines in clinical practice presents several challenges. In this pilot study, we describe the feasibility of performing CVD risk assessment in a cohort of BC survivors in a single institution in an urban area that serves mostly Black/African American (AA) populations. Methods: We identified patients with early-stage BC treated between 2015 and 2022. Patients underwent CVD risk assessment including vital signs, hemoglobin A1c, lipid panel, transthoracic echocardiogram (TTE), 6-minute walk test (6MWT), troponin T, and B-type natriuretic peptide (NT-ProBNP). The primary objective of the study was to describe the feasibility of performing a CVD risk assessment. Results: Out of 69 eligible patients who were approached for the study, 50 were enrolled and completed the CVD risk assessment (72%). Among 19 patients who did not enroll or complete the risk assessment, time constraints to complete the work up was the predominant factor. The median age was 60.5 years (SD = 13.65; range 34-86), 76% self-identified as Black/AA, 14% as White, and 95% as Non-Hispanic. Half of the patients had hormone-receptor-positive BC, 34% human epidermal growth factor receptor 2 (HER2) positive disease (and received HER2-targeted therapies), and 28% triple-negative breast cancer (TNBC). In terms of treatment, 34% received anthracycline-containing regimens. CVD risk assessment results are shown in Table 1. Twenty-four (48%) of the patients had metabolic syndrome defined as the presence of 3 out of 5 CV risk factors (waist circumference, hypertension, low HDL, high triglycerides, insulin resistance). Although all patients had an ejection fraction (EF) above 55%, 7 patients (14%) had an abnormal global longitudinal strain (GLS). The median number of meters in the 6MWT was 369 (SD 94.46, range 67-531); 74% of patients walked a shorter distance than predicted by age and body mass index, indicating significant physical impairment. All patients had a troponin T value below the 99th percentile. The most frequent modifiable CVD-risk factors included obesity and hypertension. Conclusion: Performing a low-cost CVD risk assessment in a population of mostly Black/AA BC survivors was feasible in this pilot study. We identified a high prevalence of CVD risk factors, with 48% of patients meeting metabolic syndrome criteria and the majority of patients demonstrated a very high level of functional impairment measured by 6MWT. Our findings underscore the importance of survivorship care focused on CVD risk in BC survivors. Limitations include the small sample size, single-institution study, and lack of CV and BC-related outcomes. The higher incidence of TNBC could be explained by a selection bias of patients receiving cytotoxic chemotherapy and the higher incidence of TNBC in the Black/AA population. Future research will focus on implementing this assessment in the survivorship clinic and establishing interventions to decrease CVD risk in cancer survivors. Table 1. Clinical Measurements &amp; Outcomes (n=50). Citation Format: Ilana Schlam, Dipanjan Debnath, Christopher Gallagher, Asma A. Dilawari, Shruti R. Tiwari, Malate Aschalew, Hiwot Guebre-Xabiher, Stacy Malloy, Kristi Graves, Ana Barac, Ami Chitalia. Cardiovascular Risk Evaluation for Breast Cancer Survivors: A Pilot Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-09.

Abstract P108: Post-Diagnosis Body Weight Change and Cardiovascular Outcomes in Cancer Survivors

Background: The development of cancer and its treatment often entail changes in body weight. This study aimed to investigate the association of post-diagnosis body weight change with cardiovascular disease (CVD) risk in cancer survivors. Methods: From the Korean National Health Insurance database, we identified 112,565 3-year cancer survivors who had been diagnosed with cancer at age ≥20 years from 2006 through 2013 and had normal body weight (body mass index [BMI] 18.5-22.9 kg/m2) before a cancer diagnosis. In categorical analysis, participants were classified into 4 groups according to their post-diagnosis BMI: 1) obesity (BMI ≥25 kg/m2); 2) overweight (BMI 23-24.9 kg/m2); 3) normal weight (BMI 18.5-22.9 kg/m2); and 4) underweight (BMI &lt;18.5 kg/m2). In continuous analysis, post-diagnosis change in BMI was assessed by subtracting pre-diagnosis BMI from post-diagnosis BMI. The primary outcome was CVD event, defined as a composite of myocardial infarction, stroke, heart failure, or cardiovascular death. We examined the association of post-diagnosis BMI change with CVD risk using cause-specific Cox model. Results: Over a median follow-up of 5.5 years, 3,797 new CVD events occurred. The cumulative incidence of CVD according to post-diagnosis BMI was the highest in the obesity group, followed by underweight, overweight, and normal weight groups (Figure A). The findings remained broadly consistent after multivariable adjustment; being obese post-diagnosis was associated with a higher CVD risk than maintaining normal weight (HR 1.28, 95% CI 1.05-1.58). However, being underweight post-diagnosis was no more associated with the risk of CVD (HR 0.99, 95% CI 0.86-1.14) (Figure B). Similar findings were observed in a continuous analysis (Figure C). Conclusions: Weight gain after a cancer diagnosis was associated with a higher CVD risk, whereas the association was null for post-diagnosis weight loss. CVD prevention programs for cancer survivors should consider incorporating strategies for preventing weight gain.

Fracture Risk Among Older Cancer Survivors Compared With Older Adults Without a History of Cancer

The number of cancer survivors living in the US is projected to be 26.1 million by 2040. Cancer survivors may be at increased risk of bone fractures, but research is limited in several important ways. To investigate the associations of cancer diagnoses, including time since diagnosis and stage at diagnosis, with risks of pelvic, radial, and vertebral fractures (separately and combined) among older cancer survivors and compared with fracture risk among older adults without a history of cancer. Secondarily, to examine differences in risk of fracture stratified by modifiable behaviors, treatment, and cancer type. This longitudinal cohort study used data from 92 431 older adults in the US Cancer Prevention Study II Nutrition Cohort linked with 1999 to 2017 Medicare claims. Data were analyzed from July 15, 2021, to May 3, 2022. Cancer history, time since cancer diagnosis, and stage at cancer diagnosis. Hazard ratios (HRs) and 95% CIs for the risk of pelvic, radial, vertebral, and total frailty-related fractures were estimated using multivariate Cox proportional hazards regression. Stratification was used for secondary aims. Among 92 431 participants (mean [SD] age, was 69.4 [6.0] years, 51 820 [56%] women, and 90 458 [97.9%] White], 12 943 participants experienced a frailty-related bone fracture. Compared with participants without a history of cancer, cancer survivors who were diagnosed 1 to less than 5 years earlier with advanced stage cancer had higher risk of fracture (HR, 2.12; 95% CI, 1.75-2.58). The higher fracture risk in cancer survivors with recent advanced stage diagnosis (vs no cancer) was driven largely by vertebral (HR, 2.46; 95% CI, 1.93-3.13) and pelvic (HR, 2.46; 95% CI, 1.84-3.29) fracture sites. Compared with cancer survivors who did not receive chemotherapy, survivors who received chemotherapy were more likely to have a fracture; this association was stronger within 5 years of diagnosis (HR, 1.31; 95% CI, 1.09-1.57) than 5 or more years after diagnosis (HR, 1.22; 95% CI, 0.99-1.51). Although the HR for risk of fracture was lower among physically active cancer survivors 5 or more years after diagnosis (HR, 0.76; 95% CI, 0.54-1.07), this result was not statistically significant, whereas current smoking was significantly associated with higher risk of fracture (HR, 2.27; 95% CI, 1.55-3.33). Findings from this cohort study suggest that older adults with a history of cancer may benefit from clinical guidance on prevention of frailty-related fractures. If study findings are replicated, fracture prevention programs for survivors might include referrals for physical activity with cancer exercise professionals and smoking cessation programs.

Patient perspectives on testing for clonal hematopoiesis of indeterminate potential

AbstractClonal hematopoiesis of indeterminate potential (CHIP), an emerging biomarker for personalized risk-directed interventions, is increased in cancer survivors. However, little is known about patient preferences for CHIP testing. We surveyed participants in a prospective cohort study of young women with breast cancer (BC). The emailed survey included an introduction to CHIP and a vignette eliciting participants’ preferences for CHIP testing, considering sequentially: population-based 10-year risk of BC recurrence, hematologic malignancy, and heart disease; increased CHIP-associated risks; current CHIP management; dedicated CHIP clinic; and hypothetical CHIP treatment. Preference changes were evaluated using the McNemar test. The survey response rate was 82.2% (528/642). Median age at time of survey was 46 years and median time from diagnosis was 108 months. Only 5.9% had prior knowledge of CHIP. After vignette presentation, most survivors (87.1%) recommended CHIP testing for the vignette patient. Presented next with CHIP-independent, population-based risks, 11.1% shifted their preference from testing to not testing. After receiving information about CHIP-associated risks, an additional 10.1% shifted their preference to testing. Preference for testing increased if vignette patient was offered a CHIP clinic or hypothetical CHIP treatment, with 7.2% and 14.1% switching preferences toward testing, respectively. Finally, 75.8% of participants desired CHIP testing for themselves. Among participants, 28.2% reported that learning about CHIP caused at least moderate anxiety. Most young survivors favored CHIP testing, with preferences influenced by risk presentation and potential management strategies. Our findings highlight the importance of risk communication and psychosocial support when considering biomarkers for future risk in cancer survivors. This trial has been registered at www.clinicaltrials.gov as #NCT01468246.

Pre-Diagnosis Diet and Physical Activity and Risk of Cardiovascular Disease Mortality among Female Cancer Survivors

Simple SummaryThe number of cancer survivors is increasing; however, cancer survivors are at an increased risk of cardiovascular diseases (CVD) and CVD mortality. Therefore, it is pertinent to understand how lifestyle choices such as dietary patterns and physical activity are associated with this risk. Little is known about the relationship of pre-cancer diagnosis diet quality and physical activity (PA) with CVD among cancer survivors. Most studies have focused on post-cancer diagnosis risk factors, without accounting for their status in the pre-diagnosis period or interaction on CVD mortality. We examined pre-cancer diagnosis diet quality and physical activity in relation with CVD mortality risk in female cancer survivors from the California Teachers Study cohort. We hypothesized that higher diet quality scores and higher physical activity levels prior to cancer diagnosis would be associated with lower risk of CVD mortality in female cancer survivors.Sub-optimal diet and physical activity (PA) levels have been associated with increased risk of cardiovascular disease (CVD) mortality. The relationship between pre-cancer diagnosis diet quality and PA level on CVD mortality risk in cancer survivors is unclear. We examined the association between pre-cancer diagnosis diet quality and leisure-time PA and their interaction on CVD mortality in cancer survivors. Diet quality was characterized by the Alternative Mediterranean Diet Index (aMED). Leisure-time PA was converted to a metabolic equivalent of task hours per week (MET-h/wk). During a median of 6.3 years of follow-up of 18,533 female cancer survivors, we identified 915 CVD deaths. aMED score was not associated with CVD mortality. PA level was inversely associated with CVD mortality (HRQ1-Q4 = 0.74; 95% CI: 0.61–0.88; Ptrend = 0.0014). Compared to cancer survivors with the lowest pre-diagnosis aMED score and PA level, cancer survivors with higher aMED scores and higher MET-hrs/wk were at a 33% lower risk of CVD mortality (HR = 0.67; 95% CI: 0.52–0.87). Overall, this study shows PA to be a strong predictor of CVD mortality in female cancer survivors. Our observations support the importance of PA throughout the lifecycle in lowering CVD mortality risk.

Pre-diagnosis Diet and Physical Activity and Risk of Cardiovascular Disease Mortality Among Female Cancer Survivors

ObjectivesBetter diet quality and higher physical activity (PA) levels have been associated with lower risk of cardiovascular disease (CVD) mortality, but the relationship between pre- cancer diagnosis diet quality and PA level on CVD mortality risk in cancer survivors is unclear. We examined the association between pre-cancer diagnosis diet quality and leisure time PA, and their interaction, on CVD mortality in cancer survivors.MethodsFemale cancer survivors who were diagnosed during follow-up and had no history of cancer, stroke, or heart attack at baseline were identified. Analyses excluded: (1) participants who lived outside California at baseline, (3) missing food frequency questionnaire (FFQ) or recreational PA data, (4) total energy intake less than 600 kilocalories/day or above 3,500 kilocalories/day or (5) survivors whose cancer was diagnosed within 1 year of the baseline questionnaire. Diet quality was characterized by the Alternative Mediterranean Diet Index (aMED). Leisure time PA was converted to metabolic equivalent of task hours per week (MET-h/wk). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards regression models.ResultsDuring a median of 6.3 years of follow-up of 18,533 female cancer survivors, we identified 915 CVD deaths. aMED did not show a significant association with CVD mortality. Pre-cancer diagnosis PA was independently associated with lower CVD mortality (HRQ1-Q4 = 0.74; 95% CI: 0.61–0.88; Ptrend < 0.0014). No significant interaction was observed between pre-cancer diagnosis aMED score and PA with CVD mortality but compared to participants with the lowest pre-diagnosis aMED score and physical activity levels, participants with higher aMED scores and higher MET-hrs/wk were at 33% lower risk of CVD mortality (HR = 0.67; 95% CI: 0.52–0.87).ConclusionsOverall, this study shows PA level to be a strong predictor of CVD mortality in female cancer survivors. Our observations support the importance of PA throughout the lifecycle in decreasing risk of CVD mortality. Primary care physicians (PCPs) should continue to relay the significance of PA level in their healthy patients prior to a potential diagnosis of cancer.Funding SourcesNational Cancer Institute of the National Institutes of Health.