Non-cancer Causes Of Death Research Articles

Abstract C041: A systematic review of cardiovascular health among cancer survivors

Abstract Purpose: The most common non-cancer cause of death among cancer survivors is cardiovascular disease. Health behaviors (e.g., diet, physical activity, sleep, smoking) and health factors (e.g., blood pressure, hemoglobin A1C, cholesterol) associated with cancer mortality are also associated with cardiovascular mortality. The American Heart Association has termed these behaviors and factors “cardiovascular health” (CVH) or “Life’s Essential 8,” providing a metric to determine poor, intermediate, and high (ideal) CVH. Less than ideal CVH is associated with higher cancer mortality; however, little is known about the CVH of cancer survivors. The purpose of this systematic review is to examine the extant literature on CVH among cancer survivors. MethodsIn accordance with PRISMA guidelines, we are systematically examining cardiovascular health among cancer survivors (including patients) within PubMed, Scopus, CINAHL, and Embase databases without date limitations. Two reviewers are accessing articles at each level of review to determine concordance with inclusion criteria, coming to consensus via a shared discussion. Data from studies that meet inclusion criteria will be abstracted, assessed for risk of bias. and synthesized to understand themes of CVH among cancer survivors. Results To date, we have retrieved 1,990 studies from the named databases. Preliminary review of the title and abstracts suggests that CVH as a metric may be seldom used within extant literature. This review is ongoing. Conclusion: Given the co-morbid and iatrogenic nature of cardiovascular disease among cancer survivors, it is important to understand metrics that can be applied to both identify cancer survivors with increased risk of poor outcomes and educate/empower cancer survivors to make modifiable changes to reduce their risk. This review will provide much needed evidence to support future research, practice changes, and policy implications to support the long-term health of cancer survivors. Citation Format: Miriam A. Miles, Le’Andrea Anderson-Tolbert, Abigail A. Ninson, Cha-Breia Means, Tuchondriana Smith, Reagan Coleman, Laura Rogers, Joshua Joseph, Timiya S. Nolan. A systematic review of cardiovascular health among cancer survivors [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C041.

The cost of providing care by family and friends (informal care) in the last year of life: A population observational study

Introduction: Little is known about replacement costs of care provided by informal carers during the last year of life for people dying of cancer and non-cancer diseases. Aim: To estimate informal caregiving costs and explore the relationship with carer and decedent characteristics. Design: National observational study of bereaved carers. Questions included informal end-of-life caregiving into the 2017 Health Survey for England including estimated recalled frequency, duration and intensity of care provision. We estimated replacement costs for a decedent’s last year of life valuing time at the price of a substitutable activity. Spearman rank correlations and multivariable linear regression were used to explore relationships with last year of life costs. Setting/participants: Adult national survey respondents – England. Results: A total of 7997 adults were interviewed from 5767/9612 (60%) of invited households. Estimated replacement costs of personal care and other help were £27,072 and £13,697 per carer and a national cost of £13.2 billion and £15.5 billion respectively. Longer care duration and intensity, older age, death at home (lived together), non-cancer cause of death and greater deprivation were associated with increased costs. Female sex, and not accessing ‘other care services’ were related to higher costs for other help only. Conclusion: We provide a first adult general population estimate for replacement informal care costs in the last year of life of £41,000 per carer per decedent and highlight characteristics associated with greater costs. This presents a major challenge for future universal care coverage as the pool of people providing informal care diminish with an ageing population.

A population-based study of COVID-19 mortality risk in US cancer patients.

In this study, we provide the largest analysis to date of a US-based cancer cohort to characterize death from COVID-19. A total of 4 020 669 patients across 15 subtypes living with cancer in 2020 and included in the National Cancer Institute's Surveillance, Epidemiology, and End Results database were abstracted. We investigated prognostic factors for death due to COVID-19 using a Cox proportional hazards model and calculated hazard ratios (HRs). Standardized mortality ratios were calculated using observed mortality counts from Surveillance, Epidemiology, and End Results and expected mortality based on US mortality rates. A total of 291 323 patients died, with 14 821 (5.1%) deaths attributed to COVID-19 infection. The COVID-19 disease-specific mortality rate was 11.81/10 000-persons years, and the standardized mortality ratio of COVID-19 was 2.30 (95% confidence interval [CI] = 2.26 to 2.34; P < .0001). COVID-19 ranked as the second leading cause of death following ischemic heart disease (5.2%) among 26 noncancer causes of death. Patients who are older (80 years and older vs 49 years and younger: HR = 21.47, 95% CI = 19.34 to 23.83), male (vs female: HR = 1.46, 95% CI = 1.40 to 1.51), unmarried (vs married: HR = 1.47, 95% CI = 1.42 to 1.53), and Hispanic or non-Hispanic African American (vs non-Hispanic White: HR = 2.04, 95% CI = 1.94 to 2.14 and HR = 2.03, 95% CI = 1.94 to 2.14, respectively) were at greatest risk of COVID-19 mortality. We observed that people living with cancer are at 2 times greater risk of dying from COVID-19 compared with the general US population. This work may be used by physicians and public health officials in the creation of survivorship programs that mitigate the risk of COVID-19 mortality.

Abstract 3462: Mendelian randomization analysis of 27 cardiometabolic trait related polygenic scores identifies genetic risk for cardiometabolic and cardiovascular events in a large prospective study of breast cancer survivors

Abstract Background: CVD is the most common cause of non-cancer death in breast cancer patients. Due to cancer treatment-related cardiotoxicities, breast cancer survivors are at increased risk of cardiometabolic disease (CMD) and cardiovascular disease (CVD). In addition to treatment-related factors, behavioral risk factors such as diet, smoking, and obesity are shared between CVD and breast cancer. While clinical factors influencing the risk of CVD in breast cancer patients are well studied, the effects of genetic factors are less known. Methods: To investigate genetic factors contributing to risk of CMD and CVD in women with a history of breast cancer, we performed a Mendelian randomization analysis to explore the relationships between 27 polygenic scores (PGS) for CMD and CVD phenotypes selected from the PGS Catalog and literature and 13 incident CMD and CVD events in a large prospective cohort of 3,699 breast cancer survivors in the Pathways Study. Fine-Gray sub-distribution hazard ratios (HRs) and 95% confidence intervals (CIs) associated with one standard deviation of PGS were derived with adjustment for epidemiologic, clinical, and treatment factors. The time scale was defined as time since date of breast cancer diagnosis to first of incident event, health plan disenrollment, death, or end of study (12/31/2019). The proportional hazards assumption was tested using Schoenfeld residuals, and no violation was found. Results: We identified 19 PGS-CMD/CVD associations that met Bonferroni significance (P&amp;lt;1.17 × 10−4). Five PGS were associated with increased risk of dyslipidemia: apolipoprotein B (HR=1.52, 95% CI,1.38-1.65), LDL cholesterol (1.49, 1.36-1.63), total cholesterol (1.43, 1.31-1.56), triglyceride levels (1.24, 1.14-1.34), and coronary artery disease (1.22, 1.13-1.33). Four PGS were associated with increased risk of hypertension: systolic blood pressure (1.36, 1.25-1.48), diastolic blood pressure (1.21, 1.11-1.32), fasting glucose adjusted for BMI (1.19, 1.09-1.30), and hypertension (1.41, 1.29-1.54). PGS for atrial fibrillation was associated with increased risk of arrhythmia (1.40, 1.25-1.57) and any cardiovascular disease (1.22, 1.12-1.32). PGS for coronary artery disease and myocardial infarction were both associated with increased risk of ischemic heart disease (1.43, 1.21-1.70 and 1.38, 1.17-1.62, respectively). Conclusion: Our study provides strong evidence for the potential use of PGS to predict the risk of CVD and CMD in women with a history of breast cancer. Future studies may explore the use of PGS to identify women with breast cancer at high risk of CVD-related outcomes and strategies to mitigate this risk. Citation Format: Peter N. Fiorica, Haiyang Sheng, Cecile A. Laurent, Janise M. Roh, Valerie S. Lee, Alexa Zimbalist, Isaac J. Ergas, Qianqian Zhu, Richard K. Cheng, Eileen Rillamas-Sun, Carlos Iribarren, Jamal S. Rana, Mai Nguyen-Huynh, Dawn L. Hershman, Lawrence H. Kushi, Christine B. Ambrosone, Marilyn L. Kwan, Heather Greenlee, Song Yao. Mendelian randomization analysis of 27 cardiometabolic trait related polygenic scores identifies genetic risk for cardiometabolic and cardiovascular events in a large prospective study of breast cancer survivors [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 3462.

Cause of death among gastric cancer survivors in the United States from 2000 to 2020.

A number of studies have been conducted to explore the survival of gastric cancer (GC) patients, while studies about non-cancer causes of death in patients with GC are not well-conducted. The aim of this study was to deeply investigate the causes of death (COD) in GC patients, especially non-cancer ones. The Surveillance, Epidemiology and End Results (SEER) database was used to extract information including demographics, tumor characteristics and causes of death of GC patients meeting the inclusion criteria. The patients were stratified by demographic and clinical parameters. Standardized mortality ratios (SMRs) were calculated for all causes of death at different follow-up periods. A total of 116,437 patients with GC diagnosed between 2000 and 2020 were retrieved from the SEER database. Of these, 85,827 deaths occurred during the follow-up period, most of which occurred within 1 year after GC diagnosis. GC (n = 49,746; 58%) was the leading COD, followed by other cancer (n = 21,135; 25%) and non-cancer causes (n = 14,946; 17%). Diseases of heart were the most common non-cancer cause of death, accounting for 30%, followed by cerebrovascular diseases (n = 917; 6%) and chronic obstructive pulmonary disease (n = 900; 6%). Although gastric cancer remains the most common cause of death in gastric cancer patients, it should not be ignored that the risk of non-cancer causes tends to increase with the length of the latency period. These findings may provide important insights into the healthcare management of gastric cancer patients at various follow-up intervals.

Cardiovascular-specific mortality and risk factors in colorectal Cancer patients: A cohort study based on registry data of over 500,000 individuals in the US

BackgroundColorectal cancer (CRC) is one of the most common cancers worldwide, and recent studies have found that CRC patients are at increased risk for cardiovascular disease (CVD). This study aimed to investigate competing causes of death and prognostic factors among a large cohort of CRC patients and to describe cardiovascular-specific mortality in relation to the US standard population. MethodsThis registry-based cohort study identified patients diagnosed with CRC between 1973 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database in the US. Cumulative mortality functions, conditional standardized mortality ratios, and cause-specific hazard ratios were calculated. ResultsOf the 563,298 eligible CRC patients included in this study, 407,545 died during the follow-up period. CRC was the leading cause of death, accounting for 49.8% of all possible competing causes of death. CVD was the most common non-cancer cause of death, accounting for 17.8% of total mortality. This study found that CRC patients have a significantly increased risk of cardiovascular-specific mortality compared to the US standard population, with the risk increasing with age and extended survival time. ConclusionThis study highlights the need to develop multidisciplinary prevention and management strategies for CRC and CVD to improve CRC patients' survival and quality of life.

Cause of death during nasopharyngeal carcinoma survivorship: a population-based analysis.

Recently, the survival rate of nasopharyngeal carcinoma (NPC) patients has improved greatly due to developments in NPC treatments. But cause-specific mortality in NPC patients remains unclear. This study aims to investigate the common causes of death in NPC patients. Eligible patients with NPC were included from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized mortality ratios(SMRs) were calculated to compare death rates in NPC patients with those in the general population. A total of 3475 patients with NPC were included, of whom 1696 patients died during the follow-up period. 52.83% of deaths were caused by NPC, followed by other cancers (28.13%) and non-cancer causes (18.46%). The proportion of patients who died of NPC decreased over survival time. Moreover, non-cancer causes of death increase from 12.94% to 51.22% over time after 10 years of diagnosis. Heart diseases was the most common non-cancer cause of death in NPC patients. Although NPC remains the leading cause of death after NPC diagnosis, other non-NPC causes of death represent an increased number of death in NPC patients. These findings support the involvement of multidisciplinary care for follow-up strategy in NPC patients.

Cardiopulmonary Protection for Bilateral Breast Irradiation: A Dosimetric Comparison between Proton and Photon Plans

Recent advances in cancer treatment improve cancer survivorship. Cardiovascular disease has become the leading cause of non-cancer death in breast cancer survivors. Therefore, risk of cardiopulmonary toxicities during multimodality treatment should be assessed carefully. It remains to be defined the best scenario for proton therapy to confer meaningful cardiovascular protection in the setting of breast irradiation. We hypothesized proton therapy plan provides optimal cardiopulmonary protection during bilateral breast irradiation. The study aimed to compare cardiopulmonary dosimetric parameters of proton and photon radiotherapy plans. We conducted a retrospective study and patients with bilateral breast cancer indicated for radiotherapy between January 01, 2010 and December 31, 2020 were included. All patients received whole breast or chest wall irradiation with or without regional nodal irradiation. The dose scheme was 50-50.4 Gy in 25-28 fractions. Boost was allowed if patients receiving breast conserving surgery or known risk factors. The dosimetric parameters included planning target volume, mean dose to the heart, the volume of whole lung receiving 5 Gy, 10 Gy, and 20 Gy. For photon therapy, volumetric modulated arc therapy using double partial arc plans was generated with Pinnacle 9.8, Elekta Synergy and tomotherapy helical plan was generated with Tomo Hi-Art planning system. For proton therapy, treatment planning was generated with Ray station 9A. All data was managed using SAS v.9.4 software. Analysis of variance (α = 0.05) was used to compute the dosimetry of different treatment modalities. The statistical significance was considered with a p-value <0.05. Thirty-one patients with bilateral breast cancer were included, including 12 bilateral breast irradiation patients and 6 bilateral chest wall irradiation patients. The mean dose of heart was 53.0±43.3 cGy in proton therapy while 736.6±225.1 cGy and 869.67±241.0 cGy in Tomotherapy and volumetric modulated arc therapy respectively. The volume of whole lung receiving 5 Gy was 15.4±7.91% in proton therapy while 46.1±10.8% and 46.3±2.5% in Tomotherapy and volumetric modulated arc therapy respectively. The volume of whole lung receiving 20 Gy was 7.7±4.3% in proton therapy while 15.4±5.6% and 19±3.5% in Tomotherapy and volumetric modulated arc therapy respectively. The effects of cardiopulmonary protection were more significant for chest wall irradiation over breast irradiation. Proton radiotherapy provided significant dose reduction for bilateral breast irradiation. The benefit is more significant is patients receiving bilateral chest wall irradiation. Further clinical validations will be warranted to confirm the clinical relevance of the finding.

Causes of death after testicular cancer diagnosis: a US population-based analysis

BackgroundAfter the introduction of cisplatin-based chemotherapy, the survival time of testicular cancer (TC) patients has improved dramatically. However, the overall risk of death in patients with TC remains significantly higher than in the general population. The aim of this study was to assess and quantify the causes of death after TC diagnosis.MethodIn total, 44,975 men with TC in the United States diagnosed and registered by the Surveillance, Epidemiology, and End Results (SEER) database during 2000 to 2018 were studied. In this study, standardized mortality rates (SMRs) were calculated for each cause of death in TC individuals and further analyzed in strata according to age and race.ResultOf the included participants, 3,573 (7.94%) died during the follow-up period. The greatest proportion of deaths (38.20%) occurred within 1 to 5 years after diagnosis. Most deaths occurred from TC itself and other cancers. For non-malignant conditions, the most common causes of death within 1 years after diagnosis were accidents and adverse effects (53, 4.75%) followed by diseases of heart (45, 4.04%). However, > 1 years after diagnosis, the most common noncancer causes of death were heart diseases. Results of stratified analysis show that non-Hispanic White TC participants have a lower SMR (0.68, 95% CI, 33.39–38.67) from Cerebrovascular Diseases than the general U.S. population.ConclusionsAlthough TC remains the most common cause of death after TC diagnosis, other non-TC causes of death represent a significant number of deaths among TC men. These findings help TC survivors understand the various health risks that may occur at different follow-up periods.

Approaches to Prevent and Manage Cardiovascular Disease in Patients Receiving Therapy for Prostate Cancer.

Prostate cancer (PCa) is amongst the most common cancers in men worldwide. Cardiovascular (CV) risk factors and CV disease (CVD) are common comorbidities in this patient population, posing a challenge for PCa-directed therapies which can cause or worsen CVRFs and CVDs. Herein, we summarize the approaches to prevent and manage CVD in patients with PCa receiving therapy. While patients with locally advanced and metastatic PCa benefit from hormonal therapy, these treatments can potentially cause CV toxicity. Androgen receptor targeting therapies, such as androgen deprivation therapy (ADT), can induce metabolic changes and directly impact cardiovascular function, thereby reducing cardiorespiratory fitness and increasing CV mortality. Moreover,more than half of the PCa patients have poorly controlled CV risk factors at baseline. Hence, there is an urgent need to address gaps in preventing and managing CVD in PCa patients. Screening and optimizing CV risk factors and CVD in patients undergoing ADT are essential to reduce CV mortality, the leading non-cancer cause of death in PCa survivors. The risk of CV morbidity and mortality can be further mitigated by considering the patient's cardiovascular risk profile when deciding the choice and duration of ADT. A multidisciplinary team-based approach is crucial to achieve the best outcomes for PCa patients undergoing therapy.

Causes of death among patients with cutaneous melanoma: a US population-based study

Research on mortality outcomes and non-cancer-related causes of death in patients with cutaneous melanoma (CM) remains limited. This study aimed to identify the prevalence of non-cancer-related deaths following CM diagnosis. The data of 224,624 patients diagnosed with malignant CM in the United States between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We stratified our cohort based on their melanoma stage at diagnosis and further calculated standardized mortality ratios (SMRs) for each cause of death, comparing their relative risk to that of the general US population. The total number of fatalities among melanoma patients was 60,110, representing 26.8% of the total cases. The percentage of deaths is directly proportional to the disease stage, reaching 80% in distant melanoma. The highest fatalities among the localized melanoma group (25,332; 60.5%) occurred from non-cancer causes, followed by melanoma-attributable deaths (10,817; 25.8%). Conversely, melanoma is the leading cause of death in regional and distant melanoma cohorts. Cardiovascular and cerebrovascular diseases were the most prevalent non-cancer causes of death among the three disease-stage cohorts. Compared to the general population, we did not observe an increased risk of death due to non-cancer causes in the localized CM cohort, while patients diagnosed with regional and distant CMs had a statistically significant higher risk of death from all the reported major causes of death.

High risk of non-cancer mortality in bladder cancer patients: evidence from SEER-Medicaid

PurposeThe objective of this study was to investigate non-cancer causes of death and associated risk factors after bladder cancer (BC) diagnosis.MethodsEligible BC patients were obtained from the SEER database. SEER*Stat software 8.3.9.2 was used to calculate the standardized mortality ratios (SMRs). The proportions of different non-cancer cause of death were calculated and analyzed in different follow-up periods. Multivariate competing risk model was used to analyze the risk factors for death of BC and non-cancer diseases.ResultsIn total, 240,954 BC patients were included and 106,092 patients experienced death, with 37,205 (35.07%), 13,208 (12.45%) and 55,679 (52.48%) patients experienced BC, other cancer and non-cancer disease-related deaths, respectively. Overall SMR for BC patients who died from non-cancer diseases was 2.42 (95% CI [2.40–2.44]). Cardiovascular diseases were the most common non-cancer cause of death, followed by respiratory diseases, diabetes mellitus, and infectious diseases. Multivariate competing risk analysis identified the following high-risk factors for non-cancer mortality: age > 60 years, male, whites, in situ stage, pathological type of transitional cell carcinoma, not receiving treatment (including surgery, chemotherapy, or radiation), and widowed.ConclusionsCardiovascular diseases are the leading non-cancer cause of death in BC patients, followed by respiratory disease, diabetes mellitus and infectious diseases. Physicians should pay attention to the risk of death from these non-cancer diseases. Also, physicians should encourage patients to engage in more proactive self-surveillance and follow up.

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.

Cause-specific mortality among patients with renal cell carcinoma in the United States from 2000 to 2018.

There has been little focus on the non-cancer causes of death in patients with renal cell carcinoma (RCC). Therefore, we aimed to assess the frequency and risk of different causes of death, stratified by tumor stage, and demographics, after a diagnosis of RCC in the United States. Data on eligible patients with RCC from January 1, 2000, to December 31, 2018, in the United States were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized mortality ratios for causes of death were calculated using the SEER*Stat software 8.3.9.2 for the overall population and stratified subgroups. A total of 165,969 patients with RCC were included and 60,290 (36.3%) died during follow-up. The majority of deaths were due to kidney cancer (51.3%) but a significant proportion was non-cancer causes (37.6%). The proportion of deaths attributed to RCC decreased with increasing follow-up with non-cancer causes becoming dominant after the fifth year following RCC diagnosis. Overall, cardiovascular diseases and cerebrovascular diseases were the most common non-RCC-related causes of death. AJCC stage I and localized RCC had the most deaths attributed to non-cancerous causes (66.2% and 61.2%, respectively) while AJCC stage IV and distant RCC had the most deaths due to RCC (86.2% and 86.5%, respectively). A large proportion of RCC patients die of non-cancerous causes especially early-stage patients and advanced-stage patients who survive >5 years. Coordination of multidisciplinary care with relevant specialists depending on the stage of the disease is needed to better prevent death overtime from non-cancer causes.

Adverse cardiovascular effect following gonadotropin-releasing hormone antagonist versus GnRH agonist for prostate cancer treatment: A systematic review and meta-analysis.

Androgen deprivation therapy is the mainstay of medical treatment for prostate cancer (Pca); however, it is associated with an increased risk of adverse cardiovascular (CV) events and death. To date, CV death has been the leading noncancer cause of death in Pca patients. Both GnRH antagonists (an emerging class of drugs) and GnRH agonists (most frequently prescribed) are efficacious against Pca. However, the adverse effects, especially the adverse CV effect between them remain unclear. Through a literature search using MEDLINE, EMBASE and the Cochrane Library, all available studies comparing the safety of CV risk between GnRH antagonists and GnRH agonists in Pca patients were extracted. Comparisons of outcomes of interest between these two classes of drugs were calculated using the risk ratio (RR). Subgroup analyses were performed depending on the study design and preexisting CV disease at baseline. Nine randomized controlled clinical trials (RCTs) and five real-world observational studies comprising 62160 Pca patients were included in our meta-analysis. Patients receiving GnRH antagonists experienced fewer CV events (RR: 0.66, 95% CI:0.53-0.82, P<0.001), CV death (RR:0.4, 95% CI: 0.24-0.67, P<0.001) and myocardial infarctions (RR: 0.71, 95% CI: 0.52-0.96, P=0.03). No difference was found in the incidence of stroke and heart failure. Moreover, GnRH antagonists were associated with fewer CV events in patients with preexisting CV disease but not in those without preexisting CV disease in the RCT series. GnRH antagonists appear to offer favorable safety in terms of adverse CV events and CV death compared with GnRH agonists among men diagnosed with Pca, especially those who had established CV disease at baseline. https://inplasy.com/inplasy-2023-2-0009/, identifier INPLASY202320009.

A troubled heart: Mood disorder history longitudinally predicts faster cardiopulmonary aging in breast cancer survivorship.

Breast cancer survivors live longer due to more advanced cancer treatments; however, cardiovascular disease (CVD) is the leading non-cancer cause of death in breast cancer survivors. Previous studies have shown that depression is associated with an increased risk of CVD development. This study investigated whether depressive symptoms or mood disorder history, either independently or in combination with cardiotoxic treatments, predicted older cardiopulmonary age using a novel index-the Age Based on Exercise Stress Test (ABEST)-among breast cancer survivors. Breast cancer survivors (N = 80, ages 26-72, stage I-IIIA) were assessed an average of 53 days (SD = 26) post-surgery, but before adjuvant treatment, and again an average of 32 (SD = 6) months thereafter. At both visits, they reported depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D), completed the Structured Clinical Interview for DSM-V, and engaged in an exercise stress test to obtain ABEST scores. Controlling for treatment type, age, education, trunk fat, antidepressant use, and time between visits, longitudinal analyses showed that breast cancer survivors with a mood disorder history had worsening ABEST scores over time, compared to their peers without this history (p = .046). Change in physical activity between Visits 1 and 2 did not mediate this relationship (95% CI: -0.16-0.51). Ancillary analyses provided some additional support for the primary finding, such that those with a mood disorder history trended toward greater decreases in Vo2max, although results were marginally non-significant (p = .095). There were no cross-sectional relationships between depressive symptoms or mood disorder history and ABEST scores (ps>.20). Treatment type did not modulate observed relationships (ps>.22). Breast cancer survivors with a mood disorder history may experience faster cardiopulmonary aging compared to their peers without such a history, raising risk for CVD.

Causes of death in endometrial cancer survivors: A Surveillance, Epidemiology, and End Result-based analysis.

Increasing attention has been paid to the survival of endometrial cancer (EC) patients, but the non-cancer causes of death from EC are rarely reported. This study primarily aimed to investigate the non-cancer causes of death in patients with EC. The study collected relevant data, including age, tumour stage and treatment mode, on patients diagnosed with endometrial malignancies from 2000 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) Programme. We analysed the standardised mortality ratio (SMR) to determine the cause of death. The study included 135,831 patients with EC. During the follow-up, 46,604 (34.3%) patients died, of whom 42.9%, 15.6% and 41.5% died of EC, other cancers and non-cancer causes, respectively. As the diagnosis time increased, the number of EC-associated mortalities gradually decreased. The most common non-cancer causes of death were heart disease, cerebrovascular disease and diabetes. Regarding the general population of the United States, patients with EC died of heart disease (SMR: 1.06; 95% confidence interval [CI]: 1.03-1.09), diabetes (SMR: 1.56; 95% CI: 1.47-1.65) and septicaemia (SMR: 1.40; 95% CI: 1.28-1.52), which were statistically significant. For patients with EC, the number of deaths from non-cancer causes (mainly heart disease, cerebrovascular disease and diabetes mellitus) is equivalent to that of EC. In addition, compared with the general population, EC survivors have a higher risk of death from sepsis and diabetes. These discoveries support how survivors can avoid future-related health risks. By doing this, clinicians can improve the quality of life and chances of the survival of patients with EC.

Research on the Effects of Chemotherapy on Survival Outcomes for Older Patients with Primary Triple-Negative Breast Cancer after Surgery: A Propensity Score Matching and Competing Risk Analysis of the SEER Database

Background: The population of older women (≥70 years old) with triple-negative breast cancer (TNBC) is increasing, but there are few prognostic studies for these patients. In the study, we explored the effects of chemotherapy on breast cancer-specific death (BCSD) and other cause-specific death (OCSD) in older patients with TNBC. Methods: In accordance with the inclusion and exclusion criteria, we extracted primary TNBC older patients (≥70 years old) from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2019. We used propensity score matching (PSM), cumulative incidence function (CIF) and multivariate Fine and Gray competitive risk analyses to explore the effects of chemotherapy on survival for older patients with primary TNBC after surgery. Results: After one-to-one matched PSM analysis, we identified 2478 primary TNBC patients (≥70 years old) finally. CIF analysis showed that the 3-year, 5-year and 8-year mortalities were 15.34%, 20.30% and 23.73% for BCSD, and 7.36%, 13.20% and 23.02% for OCSD. The survival analysis showed that patients who received chemotherapy had a better overall survival than those who did not received chemotherapy (hazard ratio 0.72, 95% confidence interval 0.63–0.82, p &lt; 0.001). There was no difference in BCSD between older patients with chemotherapy and no chemotherapy. The OCSD rate for patients with chemotherapy was lower than that of those with no chemotherapy (Gray’s test, p &lt; 0.001). Diseases of heart were the most common cause of death in elderly patients with TNBC. After multivariate Fine and Gray competitive risk, age in diagnosis, race black, tumor grade, T status, N status and receiving radiotherapy were proven to be independent predictive factors of BCSD. Meanwhile, age in diagnosis, radiotherapy status, and chemotherapy status were proven to be independent predictive factors of OCSD. Conclusions: For older patients (≥70 years old) with TNBC, chemotherapy improved overall patient survival by reducing the rates of OCSD, but not by reducing the rates of BCSD. The impact of non-cancer causes of death on the prognosis of older cancer patients should not be ignored.

Acute heart failure presentation, management and outcomes in cancer patients: a national longitudinal study.

Currently, little evidence exists on survival and quality of care in cancer patients presenting with acute heart failure (HF). To investigate the presentation and outcomes of hospital admission with acute HF in a national cohort of patients with prior cancer. This retrospective, population-based cohort study, identified 221,953 patients admitted to hospital in England for HF during 2012-2018 (12,867 with a breast, prostate, colorectal or lung cancer diagnosis in the previous 10 years). We examined the impact of cancer on 1) HF presentation and in-hospital mortality, 2) place of care, 3) HF medication prescribing, and 4) post-discharge survival, using propensity score weighting and model-based adjustment. HF presentation was similar between cancer and non-cancer patients. A lower percentage of patients with prior cancer were cared for in a cardiology ward (-2.4 percentage point difference [ppd] [95% CI -3.3, -1.6]) or were prescribed ACEi/ARB for HFrEF (-2.1 ppd [-3.3, -0.9]) than non-cancer patients. Survival after HF discharge was poor with median survival of 1.6 years in prior cancer and 2.6 years in non-cancer patients. Mortality in prior cancer patients was driven primarily by non-cancer causes (68% of post-discharge deaths). Survival in prior cancer patients presenting with acute HF was poor, with a significant proportion due to non-cancer causes of death. Despite this, cardiologists were less likely to manage cancer patients with HF. Cancer patients who develop HF were less likely to be prescribed guideline-based HF medications compared with non-cancer patients. This was particularly driven by patients with a poorer cancer prognosis.

Protocol for pyrotinib cardiac safety in patients with HER2-positive early or locally advanced breast cancer-The EARLY-MYO-BC study.

Cardiotoxicity has become the most common cause of non-cancer death among breast cancer patients. Pyrotinib, a tyrosine kinase inhibitor targeting HER2, has been successfully used to treat breast cancer patients but has also resulted in less well-understood cardiotoxicity. This prospective, controlled, open-label, observational trial was designed to characterize pyrotinib's cardiac impacts in the neoadjuvant setting for patients with HER2-positive early or locally advanced breast cancer. The EARLY-MYO-BC study will prospectively enroll HER2-positive breast cancer patients who are scheduled to receive four cycles of neoadjuvant therapy with pyrotinib or pertuzumab added to trastuzumab before radical breast cancer surgery. Patients will undergo comprehensive cardiac assessment before and after neoadjuvant therapy, including laboratory measures, electrocardiography, transthoracic echocardiography, cardiopulmonary exercise testing (CPET), and cardiac magnetic resonance (CMR). To test the non-inferiority of pyrotinib plus trastuzumab therapy to pertuzumab plus trastuzumab therapy in terms of cardiac safety, the primary endpoint will be assessed by the relative change in global longitudinal strain from baseline to completion of neoadjuvant therapy by echocardiography. The secondary endpoints include myocardial diffuse fibrosis (by T1-derived extracellular volume), myocardial edema (by T2 mapping), cardiac volumetric assessment by CMR, diastolic function (by left ventricular volume, left atrial volume, E/A, and E/E') by echocardiography, and exercise capacity by CPET. This study will comprehensively assess the impacts of pyrotinib on myocardial structural, function, and tissue characteristics, and, furthermore, will determine whether pyrotinib plus trastuzumab is a reasonable dual HER2 blockade regimen with regard to cardiac safety. Results may provide information in selecting an appropriate anti-HER2 treatment for HER2-positive breast cancer. https://clinicaltrials.gov/, identifier NCT04510532.