Serum klotho levels and mortality patterns in frail individuals: unraveling the u-shaped association.

BACKGROUND: Frailty, a clinical syndrome intricately linked with the aging process, stands as a harbinger of numerous adverse outcomes, most notably mortality. This study aimed to elucidate the association between serum α-klotho concentration and mortality patterns, including all-cause and cause-specific mortality, in patients with frailty. METHODS: The study employed Cox proportional hazard models, smoothed curve fitting, and supplementary analyses, encompassing threshold effect analysis, subgroup and sensitivity analyses, to explore the relationship between α-klotho levels and mortality, including all-cause, CVD, and cancer-related mortality. RESULTS: Among the 2,608 frail individuals (mean age: 60.78 [SD 10.48] years; 59.89% female), the mortality stood at 25.35% during a median follow-up period of 6.95 years. Both unadjusted and adjusted models revealed a significant inverse association between higher serum α-klotho levels and the risk of all-cause and CVD-related mortality ([mean(95% CI) 0.68 (0.55, 0.83)] for all-cause mortality; [mean(95% CI) 0.48 (0.32, 0.74)] for CVD-related mortality, all P for trend < 0.001). Notably, log2-klotho displayed a U-shaped correlation with all-cause mortality and cancer mortality, characterized by thresholds of 9.48 and 9.55, respectively. The robustness of these findings was consistently supported by subgroup and sensitivity analyses. CONCLUSION: This study unveils a U shaped association between serum α-klotho levels and both all-cause and cancer-related mortality among middle-aged and elderly individuals with frailty in the United States. The identified serum α-klotho thresholds, at 714.8 pg/ml for all-cause mortality and 750.6 pg/ml for cancer-related mortality, hold promise as potential targets for interventions aimed at mitigating the risks of premature death and cancer within this vulnerable population.

The Healthy Eating Index-2015 and All-Cause/Cause-Specific Mortality: A Systematic Review and Dose-Response Meta-Analysis.

This meta-analysis was undertaken to determine the predictive value of Healthy Eating Index (HEI)-2015 in all-cause, cancer-cause, and cardiovascular disease (CVD)-cause mortality. This review was registered with PROSPERO as CRD42023421585. PubMed and Web of Science were searched for articles published by September 15, 2023. The hazard ratio (HR) was calculated with exact confidence intervals (CIs) of 95%. Statistical heterogeneity among studies was measured by Cochran's Q test (χ2) and the I2 statistic. Eighteen published studies were finally identified in this meta-analysis. The results showed that the HEI-2015 was associated with all-cause mortality either as a categorical variable (HR: 0.80; 95% CI: 0.79, 0.82) or continuous variable (HR: 0.90; 95% CI: 0.88, 0.92). The HEI-2015 was also associated with cancer-cause mortality as categorical variable (HR: 0.81; 95% CI: 0.78, 0.83) or continuous variable (HR: 0.90; 95% CI: 0.81, 0.99). The categorical HEI-2015 was also independently correlated with decreasing CVD-cause mortality (HR: 0.81; 95% CI: 0.75, 0.87). A nonlinear dose-response relation between the HEI-2015 and all-cause mortality was found. In the linear dose-response analysis, the risk of mortality from cancer decreased by 0.42% per 1 score increment of the HEI-2015 and the risk of CVD-cause mortality decreased by 0.51% with the increment of the HEI-2015 per 1 score. Our analysis indicated a significant relationship between the HEI-2015 and all-cause, cancer-cause, and CVD-cause mortality.

Carga global de câncer aumenta em meio à crescente necessidade de serviços

A Agência Internacional de Pesquisa sobre o Câncer (IARC) da Organização Mundial da Saúde (OMS) divulgou as estimativas mais recentes da carga global de câncer. A OMS também publicou os resultados de uma pesquisa com 115 países, que mostra que a maioria deles não financia adequadamente os serviços prioritários de câncer e cuidados paliativos como parte da cobertura universal de saúde (UHC na sigla em inglês).

Single vs. multiple fraction non-inferiority trial of stereotactic ablative radiotherapy for the comprehensive treatment of oligo-metastases/progression: SIMPLIFY-SABR-COMET.

BACKGROUND: Radiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience. METHODS: This study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival. DISCUSSION: This study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023.

Age Differences in the Association of Sleep Duration Trajectory With Cancer Risk and Cancer-Specific Mortality: Prospective Cohort Study.

BACKGROUND: Baseline sleep duration is associated with cancer risk and cancer-specific mortality; however, the association between longitudinal patterns of sleep duration and these risks remains unknown. OBJECTIVE: This study aimed to elucidate the association between sleep duration trajectory and cancer risk and cancer-specific mortality. METHODS: The participants recruited in this study were from the Kailuan cohort, with all participants aged between 18 and 98 years and without cancer at baseline. The sleep duration of participants was continuously recorded in 2006, 2008, and 2010. Latent mixture modeling was used to identify shared sleep duration trajectories. Furthermore, the Cox proportional risk model was used to examine the association of sleep duration trajectory with cancer risk and cancer-specific mortality. RESULTS: A total of 53,273 participants were included in the present study, of whom 40,909 (76.79%) were men and 12,364 (23.21%) were women. The average age of the participants was 49.03 (SD 11.76) years. During a median follow-up of 10.99 (IQR 10.27-11.15) years, 2705 participants developed cancers. Three sleep duration trajectories were identified: normal-stable (44,844/53,273, 84.18%), median-stable (5877/53,273, 11.03%), and decreasing low-stable (2552/53,273, 4.79%). Compared with the normal-stable group, the decreasing low-stable group had increased cancer risk (hazard ratio [HR] 1.39, 95% CI 1.16-1.65) and cancer-specific mortality (HR 1.54, 95% CI 1.18-2.06). Dividing the participants by an age cutoff of 45 years revealed an increase in cancer risk (HR 1.88, 95% CI 1.30-2.71) and cancer-specific mortality (HR 2.52, 95% CI 1.22-5.19) only in participants younger than 45 years, rather than middle-aged or older participants. Joint analysis revealed that compared with participants who had a stable sleep duration within the normal range and did not snore, those with a shortened sleep duration and snoring had the highest cancer risk (HR 2.62, 95% CI 1.46-4.70). CONCLUSIONS: Sleep duration trajectories and quality are closely associated with cancer risk and cancer-specific mortality. However, these associations differ with age and are more pronounced in individuals aged <45 years. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TNRC-11001489; http://tinyurl.com/2u89hrhx.

Dietary patterns linked to lower odds of malnutrition are associated with all-cause and cancer mortality in adults with cancer.

OBJECTIVES: Dietary patterns, characterised by protein, polyunsaturated fatty acids, and vitamin D, reduce the odds of malnutrition in cancer survivors. However, it is unclear whether these dietary patterns also improve prognosis. This study prospectively examined associations between dietary patterns linked to lower odds of malnutrition and the risk of all-cause and cancer mortality in adult cancer survivors from the UK Biobank cohort. DESIGN: Prospective observational study. SETTING AND PARTICIPANTS: Cancer survivors from the UK Biobank (mean ± SD, 7.1 ± 6.3 years since diagnosis) were included (n = 2415; 59.7 ± 7.1 years; 60.7% female). MEASUREMENTS: Dietary intake was estimated using the Oxford WebQ 24-h dietary assessment. Dietary patterns ('high oily fish and nuts', and 'low oily fish') were derived using reduced rank regression (response variables: protein (g/kg/day), polyunsaturated fatty acids (g/day) and vitamin D (µg/day)). Cox proportional hazard models estimated hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cancer mortality. Nonlinear relationships were examined using restricted cubic splines. Models were adjusted for demographic and health characteristics. Sub-group analyses investigated relationships in sub-samples of adults with i) high nutritional risk (lung, gastrointestinal, haematological, or head and neck tumours) and ii) recent cancer diagnosis (cancer diagnosis within two years prior to assessment). RESULTS: Deaths due to all-causes (n = 305) and cancer (n = 249) were identified during a median 10.4 (IQR: 10.2-10.8) years follow-up. There were no statistically significant linear associations between the dietary patterns and all-cause or cancer mortality. However, a U-shaped association between the 'high oily fish and nuts' pattern, characterised by higher intake of oily fish and nuts and seeds, and all-cause mortality (p-non-linearity = 0.004) was identified, as well as with all-cause (p-non-linearity = 0.006) and cancer mortality (p-non-linearity = 0.035) in adults with a high nutritional risk cancer diagnosis (lung, gastrointestinal, haematological, or head and neck tumours), indicating that both above and below mean intake was associated with increased risk. The 'low oily fish' pattern, characterised by lower oily fish but higher potato intake, also had a non-linear association with all-cause mortality (p-non-linearity = 0.046) where lower but not higher than mean intake increased mortality risk. No dietary patterns were significantly associated with mortality in adults with a recent cancer diagnosis. CONCLUSION: 'High oily fish and nuts' or 'low oily fish' dietary patterns that were protective against malnutrition were associated with risk of all-cause and cancer mortality in adults with cancer. Future research should assess the efficacy of these dietary patterns in the acute treatment period when malnutrition is most prevalent.

Cancer mortality and morbidity among patients with schizophrenia: A hospital-based cohort study, 1992-2020.

OBJECTIVE: Due to the inconsistency of the evidence about the cancer risk among patients with schizophrenia, the aim of this study was to analyse cancer mortality and morbidity in patients with schizophrenia treated in a single centre in Lithuania during the study period of 1992-2020. MATERIALS AND METHODS: A retrospective cohort study was conducted in Vilnius Republican Psychiatric Hospital, the biggest specialised psychiatric hospital in Lithuania, with approximately 5000 hospital admissions annually. The patients' cohort was established by identifying all patients with the diagnosis of schizophrenia (ICD-10 code F20) in the hospital database from 1 January 1992 until 31 December 2017. The cancer cases and cancer deaths in the cohort were identified in the Lithuanian Cancer Register through linkage procedures. The analysis of risk was based on a comparison of observed and expected numbers of cancers and deaths. Expected number of cancer cases were calculated by multiplication of the exact person-years under observation in the cohort by sex, calendar year and a 5-year age-group-specific national incidence and mortality rate. All statistical analyses were carried out using STATA 15 statistical software. RESULTS: During the follow-up, out of 8553 patients, 673 cases of cancer were diagnosed in both sexes. Statistically significantly lower risk for overall cancer incidence was observed in men (SIR 0.74, 95% CI 0.66-0.83), but not in women (SIR 1.07, 95% CI 0.97-1.18). Statistically significant lower overall cancer mortality risk was observed in men (SMR 0.82, 95% CI 0.70-0.96), while in the women's group, risk of cancer deaths was significantly higher compared to the general population (SMR 1.28, 95% CI 1.11-1.48). We observed lower risk for pancreatic cancer (SIR 0.36, 95% CI 0.14-0.96), non-melanoma skin cancer (SIR 0.54, 95% CI 0.33-0.88) and prostate cancer (SIR 0.69, 95% CI 0.55-0.87) in men and higher risk for malignant neoplasm of liver (SIR 2.58, 95% CI 1.53-4.36) and skin melanoma (SIR 2.03, 95% CI 1.12-3.66) in men and for breast cancer (SIR 1.38, 95% CI 1.14-1.66) and corpus uteri cancer (SIR 1.56, 95% CI 1.18-2.07) in women. CONCLUSIONS: The current results of our study indicate lower risk of overall cancer incidence and mortality in male patients with schizophrenia, while female patients had a higher mortality risk, alongside variations in the risk of different cancer types. This information is important not only for patients, but for healthcare specialists to develop effective disease-specific preventive interventions and programmes.

Cancer mortality in Germany-born Americans and Germans.

INTRODUCTION: Comparing cancer mortality and associated risk factors among immigrant populations in a host country to those in their country of origin reveals disparities in cancer risk, access to care, diagnosis, and disease management. This study compares cancer mortality between the German resident population and Germany-born individuals who migrated to the US. METHODS: Cancer mortality data from 2008-2018 were derived for Germans from the World Health Organization database and for Germany-born Americans resident in four states (California, Florida, Massachusetts, and New York) from respective Departments of Vital Statistics. We calculated age-standardized mortality rates (ASMRs) using the European standard population and standardized mortality ratios (SMR) compared to the German resident population along with 95% confidence intervals (CIs). RESULTS: Germany-born American males had lower ASMRs (253.8 per 100,000) than German resident population (325.6 per 100,000). The difference in females was modest, with ASMRs of 200.7 and 203.7 per 100,000, respectively. For all cancers, Germany-born American males had an SMR of 0.72 (95% CI: 0.70-0.74) and females 0.98 (95% CI: 0.95-1.00). Male SMRs among Germany-born Americans were significantly below one for oral cavity, stomach, colorectal, liver, lung, prostate, and kidney cancer. Among females, SMRs were below one for oral cavity, stomach, colorectal, gallbladder, breast, cervix uteri, and kidney cancer. For both sexes, SMRs were over one for bladder cancer (1.14 for males, 1.21 for females). Mortality was higher for lung cancer (SMR: 1.68), non-Hodgkin's lymphoma (1.18) and uterine cancer (1.22) among Germany-born American females compared to the German resident population. CONCLUSION: Germany-born American males but not females showed lower cancer mortality than German resident population. Disparities may stem from variations in risk factors (e.g., smoking and alcohol use) as well as differences in screening practices and participation, cancer treatment, besides some residual potential "healthy immigrant effect".

Cancer mortality in childhood and adolescence: analysis of trends and spatial distribution in the 133 intermediate Brazilian regions grouped by macroregions.

OBJECTIVE: To assess the magnitude, trend, and spatial patterns of childhood and adolescent cancer mortality between 1996 and 2017 in 133 Brazilian intermediate regions by using socioeconomic and healthcare services indicators. METHODS: This is an ecological study for analyzing the trend of mortality from cancer in childhood and adolescence through time series. Data on deaths were extracted from the Brazilian Mortality Information System. Data on population were extracted from the 1991, 2000, and 2010 demographic censuses of the Brazilian Institute of Geography and Statistics, with interpolation for intercensal years. Time series were delineated for mortality by type of cancer in each intermediate region. Such regions were grouped by macroregions to present the results. The calculation and interpretation of mortality trends use the Prais-Winsten autoregression procedure. RESULTS: Mortality rates for all neoplasms were higher in the Northern region (7.79 deaths per 100 thousand population), while for leukemias, they were higher in the Southern region (1.61 deaths per 100 thousand population). In both regions, mortality was higher in boys and in the 0-4 age group. The trend was decreasing (annual percent change [APC] - -2.11 [95%CI: -3.14; - 1.30]) for all neoplasms in the Brazilian regions and stationary (APC - -0.43 [95%CI: -1.61; 2.12]) for leukemias in the analyzed period. CONCLUSION: The mortality rate for all neoplasms showed higher values in regions with smaller numbers of ICU beds in the public healthcare system.

Health-related quality of life among cancer survivors: pre-existing chronic conditions are to be given priority.

PURPOSE: This study aimed to describe the health-related quality of life (HRQoL) of cancer survivors in China by the five-level EuroQol-5-dimension (EQ-5D-5L) questionnaire and to explore the impact of the comorbidity of pre-existing chronic conditions on HRQoL in cancer survivors. METHODS: Data on cancer survivors were obtained from two cross-sectional surveys conducted in Shandong Province, China. The data of the Chinese general population, the Chinese diabetes population, the Chinese hypertension population, and the Chinese urban population from the published studies were used as the controls. The χ2 test was conducted to compare the incidence of five-dimensional problems between the study and control populations. The non-parametric Mann-Whitney U test and Kruskal-Wallis test were performed to examine the differences in EQ-5D-5L utility scores. Besides, the Tobit regression model was used to examine the variables influencing the EQ-5D-5L utility score. RESULTS: One thousand fifty-one adult cancer survivors were included. Cancer survivors had significantly lower EQ-5D-5L utility scores (Z = - 15.939, P < 0.001) and EQ-VAS scores (Z = - 11.156, P < 0.001) than the general adult population. The average EQ-5D-5L utility score of hypertensive cancer survivors was lower than that of the hypertensive population (Z = - 1.610, P = 0.107), but the difference was not statistically significant. CONCLUSION: Compared to the general population, the HRQoL of cancer survivors was extremely poor in all dimensions of the EQ-5D-5L. Pre-existing chronic conditions had significant antecedent effects on the HRQoL of cancer survivors. Therefore, more attention should be paid to chronic diseases, and effective interventions should be adopted based on this.

Validity and Efficiency of Progression-Free Survival-2 as a Surrogate End Point for Overall Survival in Advanced Cancer Randomized Trials.

PURPOSE: Progression-free survival (PFS)-2, defined as the time from randomization to progression on second-line therapy, is potentially a more reliable surrogate than PFS for overall survival (OS), but will require longer follow-up and a larger sample size. We sought to compare the validity and efficiency, defined as proportional increase in follow-up time and sample size, of PFS-2 to PFS. METHODS: We performed an electronic search to identify randomized trials of advanced solid tumors reporting PFS, PFS-2, and OS as prespecified end points. Only studies that had protocols that defined measurement of PFS-2 and follow-up for patients after first disease progression were included. We compared correlations in the relative treatment effect for OS with PFS and PFS-2. We reconstructed individual patient data from survival curves to estimate time to statistical significance (TSS) of the relative treatment effect. We further computed the sample size (person-year [PY] follow-up) required to reach statistical significance. RESULTS: Across the 42 analysis units and 21,255 patients, the correlation of the relative treatment effect between OS and PFS-2, r, was 0.70 (95% CI, 0.41 to 0.80) and r = 0.46 (95% CI, 0.26 to 0.74) for OS and PFS. The median differences in TSS between OS with PFS, OS with PFS-2, and PFS with PFS-2 were 16.59 (95% CI, 4.48 to not reached [NR]), 10.0 (95% CI, 2.2 to NR), and 4.31 (95% CI, 2.92 to 13.13) months, respectively. The median difference in PYs required to reach statistical significance for PFS-2 over PFS was 156 (95% CI, 82 to 500) PYs, equivalent to an estimated median 12.7% increase in PYs. CONCLUSION: PFS-2 offers improved correlation with OS than PFS with a modest increase in follow-up time and sample size. PFS-2 should be considered as a primary end point in future trials of advanced cancers.

Trends in Cancer Mortality Disparities Between Black and White Individuals in the US, 2000-2020.

This cross-sectional study compares trends in estimated age-adjusted cancer mortality rates between non-Hispanic Black and non-Hispanic White individuals in the US from 2000 to 2020.

Ethnic disparities in cancer mortality in the capital and northeast of the State of São Paulo, Brazil 2001-17.

PURPOSE: There is a paucity of studies investigating cancer disparities in groups defined by ethnicity in transitioning economies. We examined the influence of ethnicity on mortality for the leading cancer types in São Paulo, Brazil, comparing patterns in the capital and the northeast of the state. METHODS: Cancer deaths were obtained from a Brazilian public government database for the Barretos region (2003-2017) and the municipality of São Paulo (2001-2015). Age-standardized rates (ASR) per 100,000 persons-years, by cancer type and sex, for five self-declared racial classifications (white, black, eastern origin (Asian), mixed ethnicity (pardo), and indigenous Brazilians), were calculated using the world standard population. RESULTS: Black Brazilians had higher mortality rates for most common cancer types in Barretos, whereas in São Paulo, white Brazilians had higher rates of mortality from breast, colorectal, and lung cancer. In both regions, lung cancer was the leading cause of cancer death among white, black, and pardo Brazilians, with colorectal cancer deaths leading among Asian Brazilians. Black and pardo Brazilians had higher cervical cancer mortality rates than white Brazilians. CONCLUSION: There are substantial disparities in mortality from different cancers in São Paulo according to ethnicity, pointing to inequities in access to health care services.

Declines in Cancer Death Rates Among Youth: United States, 2001-2021.

Since the mid-1970s, cancer death rates for youth in the United States have declined significantly despite a slow increase in incidence for some of the major types (1-3). A previous report with trends from 1999 through 2014 showed declines for all 5-year age groups of youth (0-4, 5-9, 10-14, 15-19) (4). This Data Brief updates that report by presenting trends in cancer death rates through 2021. Rates from 2001 to 2021 are presented in total and for females and males. Rates for 2001, 2011, and 2021 are presented by 5-year age groups and for White, Black, and Hispanic youth. Trends are shown for the three most common types of cancer in youth.

Progress in cancer control leads to a substantial number of cancer deaths avoided in Canada.

It is currently not known how many more cancer deaths would have occurred among Canadians if cancer mortality rates were unchanged following various modern human interventions. The objective of this study was to estimate the number of cancer deaths that have been avoided in Canada since the age-standardized overall cancer mortality rate peaked in 1988. We applied the age-specific overall cancer mortality rates from 1988 to the Canadian population for all subsequent years to estimate the number of expected deaths. Avoided cancer deaths were estimated as the difference between the observed and expected number of cancer deaths for each year. Since 1988, there have been 372 584 (standardized mortality ratio = 0.77) and 120 045 (standardized mortality ratio = 0.90) avoided cancer deaths in males and females, respectively (492 629 total). Nearly half a million cancer deaths have been avoided in Canada since the overall cancer mortality rate peaked, which demonstrates the exceptional progress made in modern cancer control in Canada.

Opportunities, challenges, and future directions for simulation modeling the effects of structural racism on cancer mortality in the United States: a scoping review.

PURPOSE: Structural racism could contribute to racial and ethnic disparities in cancer mortality via its broad effects on housing, economic opportunities, and health care. However, there has been limited focus on incorporating structural racism into simulation models designed to identify practice and policy strategies to support health equity. We reviewed studies evaluating structural racism and cancer mortality disparities to highlight opportunities, challenges, and future directions to capture this broad concept in simulation modeling research. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review Extension guidelines. Articles published between 2018 and 2023 were searched including terms related to race, ethnicity, cancer-specific and all-cause mortality, and structural racism. We included studies evaluating the effects of structural racism on racial and ethnic disparities in cancer mortality in the United States. RESULTS: A total of 8345 articles were identified, and 183 articles were included. Studies used different measures, data sources, and methods. For example, in 20 studies, racial residential segregation, one component of structural racism, was measured by indices of dissimilarity, concentration at the extremes, redlining, or isolation. Data sources included cancer registries, claims, or institutional data linked to area-level metrics from the US census or historical mortgage data. Segregation was associated with worse survival. Nine studies were location specific, and the segregation measures were developed for Black, Hispanic, and White residents. CONCLUSIONS: A range of measures and data sources are available to capture the effects of structural racism. We provide a set of recommendations for best practices for modelers to consider when incorporating the effects of structural racism into simulation models.