Non-cancer Mortality Research Articles

Changes in vaccination uptake against pneumococcal disease, influenza, and coronavirus disease 2019 (COVID-19) before and after a Head and Neck cancer diagnosis

BackgroundPneumonia is one of the main contributors to non-cancer mortality among patients with head and neck cancer (HNC). This study aimed to determine the vaccine uptake for pneumococcal polysaccharide and conjugate vaccines, quadrivalent influenza vaccines, and mRNA COVID-19 vaccines before and after an HNC diagnosis. Furthermore, the study investigated the timing of vaccination after a cancer diagnosis. Materials & methodsThis register based multicentre study included Danish patients ≥ 18y diagnosed with HNC between 2018 and 2021. The vaccine uptake was assessed by calculating cumulative incidence (CI), while the timing of vaccination after an HNC diagnosis was explored by calculating incidence rates of vaccination the first and second half year after a cancer diagnosis. ResultsThe cumulative incidence of vaccine uptake for pneumococcal vaccines was estimated to be 8 % and 16 % one year before and after an HNC diagnosis, respectively. The CIs were 36 % and 38 % for quadrivalent influenza vaccines, respectively, whereas the CIs of vaccine uptake for mRNA COVID-19 vaccines were 60 % and 89 %. The IR of mRNA COVID-19 vaccinations the first half year after HNC diagnosis were 273 per 1000 person-months of follow-up (PMFU) and 111 per 1000 PMFU the second half year, respectively (IRR: 0.38, p < 0.001). Comparing the same periods, the IR of quadrivalent influenza vaccination was 28 per 1000 PMFU and 51 per 1000 PMFU (IRR: 1.95, 0 < 0.001). The IRs of pneumococcal vaccinations were 11 per 1000 PMFU and 14 per 1000 PMFU (IRR 1.28, p = 0.21). ConclusionsAlthough our study shows a significant increase in pneumococcal and COVID-19 vaccine uptake after HNC diagnosis, a gap remains in vaccine uptake before diagnosis, underscoring the need for increased awareness of vaccination options and recommendations. Our findings could serve as a reference for future recommendations.

Abstract 4860: Recommendations for enhancing inclusion and management of esophagus cancer clinical trials: Insights on mortality of esophagus cancer as a second primary malignancy

Abstract Background: Esophagus cancer as a second primary malignancy (esophagus-2) is increasingly common, but its prognosis is poorly understood. This study aims to examine the overall, non-cancer related and cancer-specific survival of patients diagnosed with esophagus-2 compared to the first primary esophagus cancer (esophagus-1). Methods: We included primary esophagus cancer patients diagnosed from 1975 to 2020 in the Surveillance, Epidemiology, and End Results program. Esophagus-2 was identified in patients with a previous diagnosis of non-esophageal primary malignancy. Hazard ratios of overall, esophagus cancer-specific and non-cancer related mortality were estimated among patients with esophagus-2 compared to esophagus-1, adjusting for age, sex, tumor stage and other demographic and clinical characteristics. Results: A total of 74521 and 14820 patients were identified as esophagus-1 and esophagus-2. Esophagus-2 patients suffered lower risk of esophagus cancer-specific mortality in initial 5 years but similar risk thereafter, independent of tumor characteristics and treatment. In the first 5 years after diagnosis, patients with esophagus-2 had similar risk of overall mortality with those with esophagus-1 but increased risk thereafter. As for non-cancer related mortality, esophagus-2 patients had higher risk all along. Conclusion: Patients diagnosed with esophagus-2 face a favorable esophagus cancer-specific survival within the early period after diagnosis. However, patients with esophagus-2 are more liable to die of non-cancer cause. A conservative approach to manage esophagus-2 solely based on malignancy history is not supported but effort should be put into surveillance, prevention and management of the comorbidities and complications for the first malignancy. Citation Format: Haiyu Zhou, Jinhang Leng, Hongrui Qiu, Qizhi Huang, Jinqiang Zhang. Recommendations for enhancing inclusion and management of esophagus cancer clinical trials: Insights on mortality of esophagus cancer as a second primary malignancy [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 4860.

Upfront surgery versus definitive radiotherapy: competing risk analyses for cancer-specific and noncancer mortality in oropharyngeal cancer.

The optimal treatment strategy for oropharyngeal cancer (OPC) is undetermined. We aim to compare the survival outcomes of OPC patients treated with upfront surgery versus definitive radiotherapy (RT). A total of 8057 cases were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer-specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray's test. Univariate and multivariate Fine-Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity-score-matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)-negative and HPV-positive cohorts. In the HPV-negative cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted subdistribution hazard ratio [SHR], 1.31; 95% confidence interval [CI], 1.05-1.64; P = 0.017) and noncancer mortality (adjusted SHR, 1.59; 95% CI 1.13-2.25; P = 0.008). In the HPV-positive cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted SHR, 1.51; 95% CI 1.23-1.85; P < 0.001) and noncancer mortality (adjusted SHR, 1.53; 95% CI 1.11-2.12; P = 0.009). Upfront surgery is a superior treatment modality compared with definitive RT in terms of lowering cancer-specific and noncancer mortality in OPC patients, regardless of HPV status. Further prospective clinical trials are needed to confirm our findings.

Perspectives on the Cardiovascular and Metabolic Effects of Androgen Deprivation Therapy in Prostate Cancer.

Cardiovascular disease (CVD) is the leading cause of non-cancer mortality in men with prostate cancer. This review summarizes the existing and emerging literature examining the cardiometabolic effects of androgen deprivation therapy (ADT) in prostate cancer. The evidence behind the metabolic effects of ADT is derived from older studies and has not been validated in modern cohorts. Most of the newer studies focus on the risk of cardiovascular disease (CVD) with ADT. Recently published studies like the HERO and PRONOUNCE trials have once again sparked debate about the effects of different types and durations of ADT on cardiovascular outcomes. The link between ADT and CVD is inherently complex with a majority of the evidence collected from population-based or non-randomized trials without enriching for high-risk populations. Ongoing clinical trials may provide more informative data to guide the cardiovascular care of prostate cancer survivors.

A comprehensive study on non-cancer-related mortality risk factors in elderly gastric cancer patients post-curative surgery.

The increasing incidence of gastric cancer in the elderly underscores the need for an in-depth understanding of the challenges and risks associated with surgical interventions in this demographic. This study aims to investigate the risk factors and prognostic indicators for non-cancer-related mortality following curative surgery in elderly gastric cancer patients. This retrospective analysis examined 684 patients with pathological Stage I-III gastric cancer who underwent curative resection between January 2012 and December 2021. The study focused on patients aged 70years and above, evaluating various clinical and pathological variables. Univariate analysis was utilized to identify potential risk factors with to non-cancer-related mortality and to access prognostic outcomes. Out of the initial 684 patients, 244 elderly patients were included in the analysis, with 33 succumbing to non-cancer-related causes. Univariate analysis identified advanced age (≥ 80years), low body mass index (BMI) (< 18.5), high Charlson Comorbidity Index (CCI), and the presence of overall surgical complications as significant potential risk factors for non-cancer related mortality. These factors also correlated with poorer overall survival and prognosis. The most common cause of non-cancer-related deaths were respiratory issues and heart failure. In elderly gastric cancer patients, managing advanced age, low BMI, high CCI, and minimizing postoperative complications are essential for reducing non-cancer-related mortality following curative surgery.

Associations between income and survival in cholangiocarcinoma: A comprehensive subtype-based analysis.

Socioeconomic determinants of health are incompletely characterized in cholangiocarcinoma (CCA). We assessed how socioeconomic status influences initial treatment decisions and survival outcomes in patients with CCA, additionally performing multiple sub-analyses based on anatomic location of the primary tumor. Observational study using the 2018 submission of the Surveillance, Epidemiology, and End Results (SEER)-18 Database. In total, 5,476 patients from 2004-2015 with a CCA were separated based on median household income (MHI) into low income (< 25th percentile of MHI) and high income (> 25th percentile of MHI) groups. Seventy-three percent of patients had complete follow up data, and were included in survival analyses. Survival and treatment outcomes were calculated using R-studio. When all cases of CCA were included, the high-income group was more likely than the low-income to receive surgery, chemotherapy, and local tumor destruction modalities. Initial treatment modality based on income differed significantly between tumor locations. Patients of lower income had higher overall and cancer-specific mortality at 2 and 5 years. Non-cancer mortality was similar between the groups. Survival differences identified in the overall cohort were maintained in the intrahepatic CCA subgroup. No differences between income groups were noted in cancer-specific or overall mortality for perihilar tumors, with variable differences in the distal cohort. Lower income was associated with higher rates of cancer-specific mortality and lower rates of surgical resection in CCA. There were significant differences in treatment selection and outcomes between intrahepatic, perihilar, and distal tumors. Population-based strategies aimed at identifying possible etiologies for these disparities are paramount to improving patient outcomes.

The Use of Joint Models in Analysis of Aggregate Endpoints in RERF Cohort Studies.

In radiation risk estimation based on the Radiation Effects Research Foundation (RERF) cohort studies, one common analysis is Poisson regression on radiation dose and background and effect modifying variables of an aggregate endpoint such as all solid cancer incidence or all non-cancer mortality. As currently performed, these analyses require selection of a surrogate radiation organ dose, (e.g., colon dose), which could conceptually be problematic since the aggregate endpoint comprises events arising from a variety of organs. We use maximum likelihood theory to compare inference from the usual aggregate endpoint analysis to analyses based on joint analysis. These two approaches are also compared in a re-analysis of RERF Life Span Study all cancer mortality. We show that, except for a trivial difference, these two analytic approaches yield identical inference with respect to radiation dose response and background and effect modification when based on a single surrogate organ radiation dose. When repeating the analysis with organ-specific doses, an interesting issue of bias in intercept parameters arises when dose estimates are undefined for one sex when sex-specific outcomes are included in the aggregate endpoint, but a simple correction will avoid this issue. Lastly, while the joint analysis formulation allows use of organ-specific doses, the interpretation of such an analysis for inference regarding an aggregate endpoint can be problematic. To the extent that analysis of radiation risk for an aggregate endpoint is of interest, the joint-analysis formulation with a single surrogate dose is an appropriate analytic approach, whereas joint analysis with organ-specific doses may only be interpretable if endpoints are considered separately for estimating dose response. However, for neither approach is inference about dose response well defined.

Cause-specific mortality in a population-level cohort of diffuse large B-cell lymphoma following chemotherapy in the early 21st century.

Diffuse large B-cell lymphoma (DLBCL) is a severe non-Hodgkin's lymphoma. Life expectancy has improved with rituximab, but cause-specific mortality data is lacking. Using the Surveillance, Epidemiology, and End Results (SEER) database to study 27,449 individuals aged 20-74 years diagnosed with primary DLBCL who received chemotherapy between 2000 and 2019, we calculated standardized mortality rate (SMR) and excess absolute risk (EAR) and examined the connection between age, sex, time after diagnosis, and cause of death. Based on 12,205 deaths, 68.7% were due to lymphoma, 20.1% non-cancer causes, and 11.2% other cancers. Non-cancer mortality rates (SMR 1.2; EAR, 21.5) increased with DLBCL compared to the general population. The leading non-cancer death causes were cardiovascular (EAR, 22.6; SMR, 1.6) and infectious (EAR, 9.0; SMR, 2.9) diseases with DLBCL. Risks for non-cancer death and solid neoplasms are highest within the first diagnosis year, then decrease. Among socioeconomic factors, being white, being married, and having a higher income were favorable factors for reducing non-cancer mortality. To improve survival, close surveillance, assessment of risk factors, and early intervention are needed.

The association between Life's Essential 8 and all-cause, cancer and non-cancer mortality in US Cancer Survivors: A retrospective cohort study of NHANES

ObjectiveTo investigate Life's Essential 8 (LE8), a measure of cardiovascular health (CVH), associations with mortality outcomes in cancer survivors. MethodsA prospective cohort study included 1818 cancer survivors aged ≥20 years (weighted population: 13,204,583) from National Health and Nutrition Examination Survey (NHANES) 2005–2018. Linked to mortality data through 2019, LE8 data were gathered through self-reports and lab tests. An LE8 score of 80–100 is considered high CVH, 60–79 is moderate CVH, and 0–59 is low CVH. Multivariable Cox proportional hazards regression models were employed to evaluate the associations between LE8 and all-cause, cancer-specific and non-cancer mortality. Subsequently, subgroup analyses were conducted to assess the relationship between LE8 and mortality rates across various subgroups. ResultsAt baseline, there were 1818 cancer survivors. In a 15-year follow-up, 2548 deaths occurred: 601 from cancer, 647 from heart disease, and 1300 from other causes. Multivariable models showed high CVH associated with lower hazard ratios for all-cause, cancer-specific and non-cancer mortality vs. low CVH. Cumulative mortality rates increased during follow-up, more so in the low CVH group. Subgroup analysis revealed significant LE8 interactions with age or Poverty Income Ratio (PIR) for all-cause mortality. Additionally, significant interactions between LE8 and PIR were identified for cancer-specific and non-cancer mortality risks (P for interaction <0.05). ConclusionAmong U.S. cancer survivors, higher CVH is independently linked to lower all-cause, cancer-specific, and non-cancer mortality risks. The new CVH definition shows promise as a primary prevention strategy to reduce mortality rates in U.S. cancer survivors.

Value-based payment models and management of newly diagnosed prostate cancer.

To examine the effect of urologist participation in value-based payment models on the initial management of men with newly diagnosed prostate cancer. Medicare beneficiaries with prostate cancer diagnosed between 2017 and 2019, with 1 year of follow-up, were assigned to their primary urologist, each of whom was then aligned to a value-based payment model (the merit-based incentive payment system [MIPS], accountable care organization [ACO] without financial risk, and ACO with risk). Multivariable mixed-effects logistic regression was used to measure the association between payment model participation and treatment of prostate cancer. Additional models estimated the effects of payment model participation on use of treatment in men with very high risk (i.e., >75%) of non-cancer mortality within 10 years of diagnosis (i.e., a group of men for whom treatment is generally not recommended) and price-standardized prostate cancer spending in the 12 months after diagnosis. Treatment did not vary by payment model, both overall (MIPS-67% [95% CI 66%-68%], ACOs without risk-66% [95% CI 66%-68%], ACOs with risk-66% [95% CI 64%-68%]). Similarly, treatment did not vary among men with very high risk of non-cancer mortality by payment model (MIPS-52% [95% CI 50%-55%], ACOs without risk-52% [95% CI 50%-55%], ACOs with risk-51% [95% CI 45%-56%]). Adjusted spending was similar across payment models (MIPS-$16,501 [95% CI $16,222-$16,780], ACOs without risk-$16,140 [95% CI $15,852-$16,429], ACOs with risk-$16,117 [95% CI $15,585-$16,649]). How urologists participate in value-based payment models is not associated with treatment, potential overtreatment, and prostate cancer spending in men with newly diagnosed disease.

Abstract B022: Understanding and addressing disparities in cancer therapy induced inflammation and associated endothelial dysfunction

Abstract Nearly 4 million breast cancer survivors live in the United States (U.S.). Continued improvements of cancer therapies (CTx), including targeted treatment options such as anti-HER2 therapy combined with traditional systemic CTx like anthracyclines (ANTs) have made adverse cardiovascular events the leading cause of non-cancer related mortality among BC survivors. Toxicities can be acute and/or reversible (e.g., anti-her2) or may persist for years (ANTs)). Most efforts focus on managing and defining the mechanism of cardiac damage in response to CTx. Yet, systemic vascular function, including microvascular endothelial function, is not only a predictor but also a contributor to a significant number of cardiovascular complications that is mostly overlooked in response to CTx. Little to no mechanistic evidence exists how CTx impacts the human circulation and endothelial function. Systemic inflammation (e.g., Interleukin levels or TLR signaling) is elevated in cancer and CV disease alike, yet the connection of CTx induced endothelial dysfunction has not been explored in breast cancer patients. Black/African American women are at higher risk for cardio-toxicity. Existing literature suggest significant racial differences in immune signaling and microvascular function perhaps explaining varying risk for CV toxicity post-CTx. However, contributing biological, social and environmental factors remain ill defined. The Discovery and Elimination of Cardio-Oncology Disparities for Equity (DECODE) in the Heartland center addresses critical gaps in the literature by testing if an exercise intervention can lower systemic inflammatory load to improve endothelial function and CV risk itself. We propose to: 1) quantify physiological and molecular differences in inflammation and endothelial function before and following CTx among 120 Black/African American and non-Hispanic White women with invasive, non-metastatic BC; 2) test the feasibility and efficacy of an exercise intervention during CTx designed to mitigate the adverse effects of treatment on exercise capacity and QoL; and 3) examine the influence of multi-level socio-ecological factors (individual, interpersonal, institutional, environmental) on inflammation, microvascular endothelial function, QoL and response to the exercise intervention among participants. This presentation presents DECODE’s novel translational study design and methodologies. Citation Format: Melinda Stolley, Andreas Beyer, Kirsten Beyer, Alison Kriegel, David Gutterman, Shane Phillips, Sherry Ann Brown, Kent Hoskins, Rodney Sparapani, Michael Widlansky, Amanda Kong. Understanding and addressing disparities in cancer therapy induced inflammation and associated endothelial dysfunction [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B022.

Impact of Cancer Diagnosis on Appropriate Use of Antithrombotic Medications in Individuals with Cardiovascular Diseases

Introduction: Cancer and Cardiovascular disease (CVD) often coexist and CVD is the leading cause of non-cancer mortality in people with cancer. Antithrombotic medications used to manage CVD are associated with increased bleeding risk, particularly in people with cancer. Appropriate management of CVD is therefore essential in individuals with cancer, both to decrease recurrent CVD as well as to prevent bleeding. In this study, we assessed utilization patterns of antithrombotic medications for CVD following a new diagnosis of cancer. Methods: Among people receiving primary care at the University of Vermont Medical Center from 2010 to 2019, we identified a cohort of 4,010 subjects with baseline CVD, identified from problem lists or billing codes within the first year of follow-up. Exclusion criteria included baseline cancer diagnosis (cancer known at the time of inclusion in the cohort or within the first year of follow-up) or a known history of venous thrombosis. Incident cancer was defined as new diagnosis of cancer after the first year of follow-up and did not include people with non-melanomatous skin cancers. We used the National Cancer Institute list of ICD-9 and ICD-10 codes for different cancer diagnoses. Patient's use of antithrombotics, prescribed or non-prescribed, were captured using computable phenotypes developed from the electronic outpatient medication reconciliation record and validated using chart review. People with baseline CVD who were diagnosed with cancer after the first year of follow up were matched 1:1 by sex and age with people with CVD and no cancer. We used logistic regression to estimate the odds ratio (OR) and 95% confidence intervals (95% CI) of persistent guideline-directed use of antithrombotic medications for 6 months after a new cancer diagnosis versus a matched time-period in those without incident cancer (use of antiplatelets in those with a history of atherosclerotic CVD and use of anticoagulation in those with a history of atrial fibrillation). Results: We identified 4,010 individuals with baseline CVD, 841 of whom (20%) developed incident cancer during follow-up. Distribution of CVD and antithrombotic use in the age- and sex-matched population are presented in Table 1. 2/3 of the population had coronary artery disease and about 30% had atrial fibrillation or flutter. About 65% of individuals were on any antiplatelet therapy and 18% were on anticoagulation for CVD. 41% of people with baseline CVD, and incident cancer diagnosis were still on antiplatelet therapy 6 months after their cancer diagnosis as opposed to 38 % in the matched population without a cancer diagnosis. 33% of individuals with incident cancer were still on anticoagulation for atrial fibrillation or flutter as opposed to 28% of the matched population without cancer. Both of these differences were statistically significant with OR=1.55 (95% CI, 1.15-2.1) for antiplatelets, and OR=1.56 (95% CI, 1.05,2.31) for anticoagulants, compared to those with no cancer diagnosis (Table 2). Conclusion: Surprisingly, our study found that incident cancer in individuals with baseline CVD was associated with increased adherence to antithrombotic therapy. We had hypothesized that incident cancer would be associated with lower use of antithrombotic therapy. This result could be related to increased interaction with medical specialists following a cancer diagnosis. The impact of increased adherence to antithrombotics on bleeding however, will need to be further investigated.

Leisure-time physical activity, daily sitting time, and mortality among US skin cancer survivors.

To investigate the long-term effect of sitting time and physical activity after a skin cancer diagnosis. A cohort of a nationally representative sample of skin cancer survivors (n=862) and non-cancer adults (n=13691) ≥50 years from the US National Health and Nutrition Examination Survey. Mortality data were linked through December 31, 2019. During up to 13.2 years of follow-up (median, 6.3 years; 94,093 person-years), 207 deaths (cancer: 53) occurred in skin cancer survivors and 1970 (cancer: 414) in non-cancer adults. After adjusting for covariates and skin cancer type, being active was associated with lower risks of all-cause (HR=0.69; 95% CI: 0.47 to 1.00) and non-cancer (HR=0.59; 95% CI: 0.36 to 0.97) mortality compared to being inactive among skin cancer survivors. Meanwhile, sitting 8 h/d was associated with higher risks of all-cause (HR=1.72; 95% CI: 1.11 to 2.67) and non-cancer (HR=1.76; 95% CI: 1.07 to 2.92) mortality compared to sitting <6 h/d. In the joint analysis, inactive skin cancer survivors sitting >8 h/d had the highest mortality risks from all-cause (HR=2.26; 95% CI: 1.28 to 4.00) and non-cancer (HR=2.11; 95% CI,1.10 to 4.17). Additionally, the associations of LTPA and sitting time with all-cause and cause-specific mortality did not differ between skin cancer survivors and non-cancer adults (all P for interaction>0.05) CONCLUSION: The combination of prolonged sitting and lack of physical activity was associated with elevated risks of all-cause and non-cancer deaths among US skin cancer survivors. Skin cancer survivors could benefit from maintaining a physically active lifestyle.

Abstract 15351: Characteristics of Veterans Enrolled in a Nationwide Home Telemonitoring Blood Pressure (BP) Program

Background: Guidelines recommend home BP monitoring for the diagnosis and management of hypertension. The Veterans Affairs (VA) has a robust nationwide home BP monitoring telehealth (HT) program. Aims: We aimed to determine factors associated with being enrolled in the VA’s HT program using a nationwide cohort. Methods: Veterans with hypertension and a primary care (PC) visit between 4/2013 and 9/2015 were identified and classified as telehealth if they enrolled in the HT program and were issued a home-telehealth BP monitor. Control patients were not enrolled. Patient characteristics including the care assessment needs (CAN) score (validated probability for mortality or hospitalization in the following year) were extracted from the electronic health record (EHR). Results: Over 33 months, 29,927 (2.5%) veterans were enrolled in the HT program and 1,160,506 (97.5%) veterans with hypertension were not enrolled. Compared to controls, HT patients were of similar age (median 66 years), were more likely to be female (5.6% vs 4.6%), be of Black race (28.7% vs 20.1%), have a higher index median systolic BP (158.4 vs 153 mmHg), have a greater number of PC visits in the 2 years prior (11 vs 7 visits), have a higher median probability of a mortality or hospitalization event within 1 year (13% vs 7%) and were on a greater number of antihypertensive medications than those not enrolled (Table). These veterans were seen by 9,301 PC providers, who enrolled the following percentages of their hypertensive patients (% of patients by % of providers): 0% by 22%, &lt;2% by 24.1%, 2-5% by 28.9%, 5-10% by 16.4%, 10-20% by 6.9% and &gt;20% by 1.7%. Conclusion: The VA’s HT program is used by a limited number of Veterans. Those enrolled are sicker and have a greater burden of hypertension than those not enrolled. Most providers have a small percentage of their panel of patients enrolled. This preliminary report comes from a study evaluating the effect of HT on BP control, cardiovascular events, and non-cancer mortality.

Joint association of sedentary behavior and vitamin D status with mortality among cancer survivors

BackgroundSedentary behavior and vitamin D deficiency are independent risk factors for mortality in cancer survivors, but their joint association with mortality has not been investigated.MethodsWe analyzed data from 2914 cancer survivors who participated in the National Health and Nutrition Examination Survey (2007–2018) and followed up with them until December 31, 2019. Sedentary behavior was assessed by self-reported daily hours of sitting, and vitamin D status was measured by serum total 25-hydroxyvitamin D (25(OH)D) levels.ResultsAmong 2914 cancer survivors, vitamin D deficiency was more prevalent in those with prolonged daily sitting time. During up to 13.2 years (median, 5.6 years) of follow-up, there were 676 deaths (cancer, 226; cardiovascular disease, 142; other causes, 308). The prolonged sitting time was associated with a higher risk of all-cause and noncancer mortality, and vitamin D deficiency was associated with a higher risk of all-cause and cancer mortality. Furthermore, cancer survivors with both prolonged sitting time (≥ 6 h/day) and vitamin D deficiency had a significantly higher risk of all-cause (HR, 2.05; 95% CI: 1.54–2.72), cancer (HR, 2.33; 95% CI, 1.47–3.70), and noncancer mortality (HR, 1.91; 95% CI, 1.33–2.74) than those with neither risk factor after adjustment for potential confounders.ConclusionsIn a nationally representative sample of U.S. cancer survivors, the joint presence of sedentary behavior and vitamin D deficiency was significantly associated with an increased risk of all-cause and cancer-specific mortality.

Atherosclerotic Cardiovascular Disease Risk and Longitudinal Risk Factor Management Among Patients With Breast Cancer

BackgroundCardiovascular disease is the leading cause of noncancer mortality for breast cancer survivors. Data are limited regarding patient-level atherosclerotic cardiovascular disease (ASCVD) risk estimation and preventive medication use. This study aimed to characterize ASCVD risk and longitudinal preventive medication use for a cohort of patients with nonmetastatic breast cancer. Patients and MethodsThis retrospective cohort study included 326 patients at an academic medical center in Boston, Massachusetts diagnosed with nonmetastatic breast cancer or ductal carcinoma in situ from January 2009 through December 2015. Patient demographics, clinical characteristics, laboratory studies, medication exposure, and incident cardiovascular outcomes were collected. Estimated 10-year ASCVD risk was calculated for all patients from nonlaboratory clinical parameters. ResultsMedian follow up time was 6.5 years (IQR 5.0, 8.1). At cancer diagnosis, 23 patients (7.1%) had established ASCVD. Among those without ASCVD, 10-year estimated ASCVD risk was ≥20% for 77 patients (25.4%) and 7.5% to <20% for 114 patients (37.6%). Two-hundred and sixteen patients (66.3%) had an indication for lipid-lowering therapy at cancer diagnosis, 123 of whom (57.0%) received a statin during the study. Among 100 patients with ASCVD or estimated 10-year ASCVD risk ≥20%, 92 (92.0%) received an antihypertensive medication during the study. Clinic blood pressure >140/90 mmHg was observed in 33.0% to 55.6% of these patients at each follow up assessment. ConclusionA majority of patients in this breast cancer cohort had an elevated risk of ASCVD at the time of cancer diagnosis. Modifiable ASCVD risk factors were frequently untreated or uncontrolled in the years following cancer treatment.

Third mortality follow-up of the Mallinckrodt uranium processing workers, 1942–2019

Introduction Mallinckrodt Chemical Works was a uranium processing facility during the Manhattan Project from 1942 to 1966. Thousands of workers were exposed to low-dose-rates of ionizing radiation from external and internal sources. This third follow-up of 2514 White male employees updates cancer and noncancer mortality potentially associated with radiation and silica dust. Materials and methods Individual, annualized organ doses were estimated from film badge records (n monitored = 2514), occupational chest x-rays (n = 2514), uranium urinalysis (n = 1868), radium intake through radon breath measurements (n = 487), and radon ambient measurements (n = 1356). Silica dust exposure from pitchblende processing was estimated (n = 1317). Vital status and cause of death determination through 2019 relied upon the National Death Index and Social Security Administration Epidemiological Vital Status Service. The analysis included standardized mortality ratios (SMRs), Cox proportional hazards, and Poisson regression models. Results Vital status was confirmed for 99.4% of workers (84.0% deceased). For a dose weighting factor of 1 for intakes of uranium, radium, and radon decay products, the mean and median lung doses were 65.6 and 29.9 mGy, respectively. SMRs indicated a difference in health outcomes between salaried and hourly workers, and more brain cancer deaths than expected [SMR: 1.79; 95% confidence interval (CI): 1.14, 2.70]. No association was seen between radiation and lung cancer [hazard ratio (HR) at 100 mGy: 0.93; 95%CI: 0.78, 1.11]. The relationship between radiation and kidney cancer observed in the previous follow-up was maintained (HR at 100 mGy: 2.07; 95%CI: 1.12, 3.79). Cardiovascular disease (CVD) also increased significantly with heart dose (HR at 100 mGy: 1.11; 95%CI: 1.02, 1.21). Exposures to dust ≥23.6 mg/m3-year were associated with nonmalignant kidney disease (NMKD) (HR: 3.02; 95%CI: 1.12, 8.16) and kidney cancer combined with NMKD (HR: 2.46; 95%CI: 1.04, 5.81), though without evidence of a dose-response per 100 mg/m3-year. Conclusions This third follow-up of Mallinckrodt uranium processors reinforced the results of the previous studies. There was an excess of brain cancers compared with the US population, although no radiation dose-response was detected. The association between radiation and kidney cancer remained, though potentially due to few cases at higher doses. The association between levels of silica dust ≥23.6 mg/m3-year and NMKD also remained. No association was observed between radiation and lung cancer. A positive dose-response was observed between radiation and CVD; however, this association may be confounded by smoking, which was unmeasured. Future work will pool these data with other uranium processing worker cohorts within the Million Person Study.

Combined influence of nutritional and inflammatory status and depressive symptoms on mortality among US cancer survivors: Findings from the NHANES

BackgroundInflammation and nutrition and depression are interrelated, and both are related to changes in mortality rates. We investigated the association of nutritional and inflammation index or depressive symptoms with the risk of all-cause mortality or cause-specific mortality among cancer survivors. MethodsA prospective cohort of a nationally representative sample of cancer survivors, aged 40 years or older (n = 2331; weighted population, 15 248 255; 67.6 ± 11.0 years; 50.6 % males), were recruited from the US National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Advanced lung cancer inflammation index (ALI) reflected inflammation and nutritional status and Patient Health Questionnaire 9 (PHQ-9) demonstrated depressive symptoms. The independent and joint associations of ALI and PHQ-9 score with mortality outcomes were examined among cancer survivors and Cox regression analysis based on weights was used to calculate the relative risk. ResultsWe identified 605 all-cause deaths (cancer, 204; non-cancer, 401) over a median of 6.2 years of follow-up (15,385 person-years; interquartile range, 3.3–9.8 years). High ALI was observed to be consistently associated with lower risks of all-cause (hazard ratio [HR], 0.516; 95 % CI, 0.400–0.667) and non-cancer (HR, 0.414; 95 % CI, 0.291–0.588) mortality compared with low ALI in a series of adjusted models. Meanwhile, lower PHQ-9 score (0–4) was associated with lower risks of all-cause (HR, 0.686; 95 % CI, 0.521–0.903) and non-cancer (HR, 0.686; 95 % CI, 0.474–0.992) mortality compared with higher PHQ-9 score (≥10). Furthermore, joint analyses showed that high ALI was associated with a decreased risk of death among cancer survivors who were not depressive. Specifically, survivors with high ALI but not depressive symptoms had the lowest overall (HR, 0.404; 95 % CI, 0.228–0.715) risks. ConclusionIn this cohort study, we observed impact of nutritional and inflammatory status and depressive symptoms on mortality among cancer survivors, with the lowest risks of death from both all causes and non-cancer being noted among the combination of high level ALI with no depression.

Association Between Urologist Merit-Based Incentive Payment System Performance and Quality of Prostate Cancer Care.

We performed a study to evaluate the association between urologist performance in the Merit-Based Incentive Payment System (MIPS), and quality and spending for prostate cancer care. Medicare beneficiaries with prostate cancer diagnosed between 2017 and 2019 were assigned to their primary urologist. Associated MIPS scores were identified and categorized based on thresholds for payment adjustment as low (worst), moderate, and high (best). Multivariable mixed effects models were used to measure the association between MIPS performance and adherence to quality measures and price standardized spending for prostate cancer. Adherence to quality measures did not vary across MIPS performance groups for pretreatment counselling by both a urologist and radiation oncologist (low-76%, [95% CI 73%-80%], moderate-77% [95% CI 74%-79%], and high-75% [95% CI 74%-76%]) and avoiding treatment in men with a high risk of noncancer mortality within 10 years of diagnosis (low-40% [95% CI 35%-45%], moderate-39% [95% CI 36%-43%], high-38% [95% CI 36%-39%]). Men on active surveillance managed by high performers more likely received a confirmatory test (44% [95% CI 43%-46%]) compared to those managed by moderate (38% [95% CI 33%-42%]) performers, but not low performers (36% [95% CI 29%-44%]). There was no difference in adjusted spending across MIPS performance groups. Better performance in MIPS is associated with a higher rate of confirmatory testing in men initiating active surveillance for prostate cancer. However, performance was not associated with other dimensions of quality nor spending.

Long-term cancer and non-cancer associated mortality among patients with cervical cancer (1138)

Long-term cancer and non-cancer associated mortality among patients with cervical cancer (1138)