Regression Model Selection Research Articles

A New Survival Regression Model with Application to HIV Data

A New Survival Regression Model with Application to HIV Data

The Optimal Radiotherapy Strategy for Patients With Small Cell Lung Cancer and Brain Metastasis: A Retrospective Analysis.

Extensive-stage small cell lung cancer (ES-SCLC) is a notoriously aggressive malignancy frequently associated with brain metastases (BMs), presenting substantial therapeutic challenges. This study delves into the effectiveness of immunotherapy combined with diverse radiotherapy, especially the influence of brain radiotherapy (BRT) on survival outcomes in the immunotherapy era. ES-SCLC patients treated at Xiangya Hospital and Xiangya Boai Hospital from February 2020 to June 2024 were retrospectively included. The study focused on patients receiving immune checkpoint inhibitors (ICIs). Metrics included overall survival (OS) and progression-free survival (PFS), employing univariate and multivariate Cox regression models for statistical analysis. A total of 393 patients with ES-SCLC who received ICIs were included in the study. Within the entire cohort, the presence of baseline BMs did not statistically affect OS or PFS. However, thoracic radiotherapy (TRT) was identified as a favorable prognostic factor for both OS and PFS. BRT demonstrated a beneficial effect on OS across both the general cohort and the baseline_BMs subgroup. In patients from the baseline_BMs subgroup who had previously undergone TRT, ICIs plus BRT did not significantly improve OS compared to ICIs alone. Conversely, for patients who had not received prior TRT, adding BRT to ICIs significantly enhanced OS. Among the patients who underwent BRT, 71 received whole brain radiotherapy (WBRT) while 19 opted for stereotactic radiosurgery (SRS). No significant differences in OS and PFS were observed between the SRS and WBRT modalities. The sequence of ICIs relative to BRT was found to influence PFS adversely. Administering BRT before ICIs (RT-ICI) was associated with worse PFS compared to administering ICIs followed by BRT (ICI-RT). Additionally, no significant differences in OS and PFS were noted among the three subgroups defined by varying intervals between ICIs and BRT. For patients without baseline BMs, TRT and prophylactic cranial irradiation were associated with delayed onset of brain metastases. Our study underscores the importance of optimizing treatment strategies and considering the timing and integration of radiotherapy and immunotherapy to improve outcomes for patients with ES-SCLC, particularly those at risk of or presenting with BMs.

Survival Regression Model Allowing for Exposure-Mediator Interaction: Analysis of Kenya Demographic Health Survey (KDHS) 2014 Data

Although infant and under-five mortality rates have decreased over the past decade, Kenya, like many other African nations, did not achieve the Millennium Development Goal (MDG) 4 target. To accelerate progress towards reaching Sustainable Development Goal 3 by 2030, it is essential to understand the factors influencing under-five child mortality (UFCM), taking into account all potential confounding variables and effect modifiers. The child mortality rate serves as a key health indicator for any country. This study used data from the 2014 Kenya Demographic and Health Survey (KHDS). This paper introduces the concept of decomposing the total effect of an independent variable into three components: a direct effect, an indirect effect, and an interactive effect. We attempt to account for the direct effect of an independent variable on the outcome, then proceed to check the effect of the presence of a possible mediator and, furthermore, the possible interactions between an exposure variable and a mediator variable. The outcome variable was UFCM, and the study was to determine the effect of mother’s education on UFCM, in the presence of mediators such as mother’s income and the effect via the interaction between mother’s education and maternal income was estimated. To capture the effect of mediation and interactions in the context of survival analysis, an Aalen additive model, including a product term for the exposure and mediator term, was developed. The methods were further illustrated with practical approach to KDHS data. KDHS has data on a broad scope of risk factors for UFCM. Computations for all data sets was implemented using the freely available R-software package. This analysis suggests that while a significant portion of the impact of maternal education on UFCM is mediated by increasing maternal income, it is the interaction between maternal education and maternal income that leads to a reduction in UFCM. Interventions targeting an increase in income among mothers with no education level would yield a greater reduction in UFCM than interventions targeting mothers with a higher education level. The total effect was ascribed to an interaction between the mother’s education level and maternal income, and part of it is attributable to pure indirect effect, and a given proportion is attributable to pure direct effect. The majority of the total effect (70%)is attributed to the interaction between change from no education level to primary education level and maternal income. 22% is associated with the pure direct effect, while 8% is linked to the pure indirect effect. Interventions with a given increase in income among those with no education level would yield a greater reduction in UFCM than interventions targeting mothers with a higher education level.

Interaction effect of self-efficacy and joint problems on hearing aid abandonment among older adults

Objective We assessed the interaction between self-efficacy and joint problems and self-efficacy and visual problems on the risk of hearing aid abandonment in older adults. Design A retrospective cohort study comprising older adults who received hearing aids in Chile was conducted. Hearing aid self-efficacy was measured using the S-MARS-HA questionnaire, while joint and visual problems were assessed through self-reported questions. Survival regression models were conducted to investigate the interaction between self-efficacy and joint problems, as well as self-efficacy and visual problems. Study sample The study included 355 older adults who received hearing aids through the Chilean public health sector. Results A significant interaction effect indicated that the relationship between self-efficacy and the risk abandonment was influenced by joint problems (p < 0.05). In the subpopulation with joint problems, self-efficacy was associated with a reduced risk of hearing aid abandonment (HR = 0.81), whereas in the subpopulation without joint problems, the protective effect was more pronounced (HR = 0.52). The interaction between self-efficacy and visual problems was not significant. Conclusions The interaction between self-efficacy and joint problems was associated with the risk of abandonment. Addressing limitations associated with joint problems and individuals’ confidence in using their hearing aids could reduce the abandonment.

Elevated fibrinogen-albumin ratio is an adverse prognostic factor for patients with primarily resected gastroesophageal adenocarcinoma

PurposeSerum fibrinogen and albumin play important roles in systemic inflammation and are implicated in tumor progression. The fibrinogen-to-albumin ratio (FAR) has shown a prognostic impact in several malignancies. This study aims to assess the prognostic value of the pretherapeutic FAR in patients with adenocarcinoma of the gastroesophageal junction (AEG) who underwent upfront resection.MethodsConsecutive patients who underwent surgical resection at the Department of Surgery at the Medical University of Vienna between 1992 and 2014 were included into this study. Optimal cut-off values were determined with the receiver-operating characteristic (ROC) curve, uni- and multivariate analyzes were calculated by the Cox proportional hazard regression model for overall survival (OS).ResultsAmong 135 included patients, the majority were male (79.26%), with a mean age of 66.53 years. Elevated FAR correlated significantly (p = 0.002) with shorter OS in univariate analysis, also confirmed as independent prognostic factor (p = 0.005) in multivariable analysis. The ROC curve of FAR (AUC = 0.744) outperformed fibrinogen (AUC = 0.738) and albumin (AUC = 0.378) in predicting OS for AEG patients.ConclusionThe FAR serves as an independent prognostic factor for OS in patients undergoing primarily resection for AEG. Given its routine availability and ease of calculation, FAR could help in diagnosis and treatment selection for AEG patients. Further validation studies are warranted to confirm these findings conclusively.

Impact of the Preservation of Residual Kidney Function on Hemodialysis Survival: Results from the BISTRO Trial.

Preservation of residual kidney function (RKF) in dialysis patients has been associated with improved survival. RKF in the BISTRO trial was relatively well preserved and here we describe its association with survival during the trial and extended follow-up. RKF, measured as the average urea and creatinine clearance (GFR) or 24-hour urine volume was assessed at baseline, one, two and three months and three-monthly up to 2 years in incident haemodialysis patients. Time to event survival data or competing events (transplantation, modality change) were obtained for 50 months post enrolment via data linkage with the UK Renal Registry. Cox proportional hazards regression survival models, including those incorporating change in GFR from baseline as a time-varying variable and joint regression models for longitudinal and survival data (longitudinal models for GFR or urine volume) were used to explore the relationship of RKF preservation with survival. Analyses were adjusted for age, sex, comorbidity and ethnicity. 2919 measures of RKF were made in 387 patients from 32 UK dialysis units. Higher age and comorbidity score associated with increased mortality in all models. Baseline GFR reduced the risk of death (Hazard Ratio: 0.918 95%CI: 0.844, 0.999) per ml/min/1.73m2. A greater fall in GFR and urine volume from baseline was associated with a non-significant increased risk of death as visualised on spline plots. In the joint survival models higher GFR (adjusted HR: 0.88 95%CI 0.80, 0.97) or urine volume (adjusted HR: 0.75 95%CI 0.57, 0.95 per L) at any time point associated with better survival. Lower RKF during the first two years of haemodialysis is associated with an increased death risk for up to 50 months following dialysis initiation. This adds to a growing body of evidence that interventions to preserve RKF should be developed and tested in clinical trials.

Clinicogenomic predictors of outcomes in patients with hepatocellular carcinoma treated with immunotherapy.

Immune checkpoint inhibitor (ICI) combinations extend overall survival (OS) while anti-PD-1/L1 monotherapy is non-inferior to sorafenib in treatment-naïve, patients with advanced hepatocellular carcinoma (HCC). Clinicogenomic features are posited to influence patient outcomes. The primary objective of this retrospective study was to define the clinical, pathologic, and genomic factors associated with outcomes to ICI therapy in patients with HCC. Patients with histologically confirmed advanced HCC treated with ICI at Memorial Sloan Kettering Cancer Center from 2012 to 2022 were included. Association between clinical, pathological, and genomic characteristics were assessed with univariable and multivariable Cox regression model for progression-free survival (PFS) and OS. Two-hundred and forty-two patients were treated with ICI-based therapy. Patients were predominantly male (82%) with virally mediated HCC (53%) and Child Pugh A score (70%). Median follow-up was 28 months (0.5-78.4). Median PFS for those treated in 1st line, 2nd line and ≥ 3rd line was 4.9 (range: 2.9-6.2), 3.1 (2.3-4.0), and 2.5 (2.1-4.0) months, respectively. Median OS for those treated in 1st line, 2nd line, and ≥ 3rd line was 16 (11-22), 7.5 (6.4-11), and 6.4 (4.6-26) months, respectively. Poor liver function and performance status associated with worse PFS and OS, while viral hepatitis C was associated with favorable outcome. Genetic alterations were not associated with outcomes. Clinicopathologic factors were the major determinates of outcomes for patients with advanced HCC treated with ICI. Molecular profiling did not aid in stratification of ICI outcomes. Future studies should explore alternative biomarkers such as the level of immune activation or the pretreatment composition of the immune tumor microenvironment.

Cardiac Resynchronization Therapy in Ischemic Versus Nonischemic Cardiomyopathy: Patient-Level Meta-Analysis of 7 Randomized Clinical Trials

BackgroundData on whether cardiac resynchronization therapy (CRT) results in better clinical and echocardiographic outcomes in patients with nonischemic cardiomyopathy (NICM) vs ischemic cardiomyopathy (ICM) are conflicting. ObjectivesThe authors conducted this meta-analysis of 7 clinical trials of CRT to determine the association between etiology of cardiomyopathy and clinical and echocardiographic outcomes. MethodsThe authors analyzed patient-level data using Bayesian Hierarchical Weibull survival regression modeling to determine the association between etiology of cardiomyopathy and time to all-cause death or heart failure hospitalization (HFH). Linear regression was used to assess the association between etiology of cardiomyopathy and echocardiographic measurements. ResultsOf 6,252 patients included, 4,717 (75%) were men, median age was 66 years (IQR: 58-73 years), 3,704 (59%) had ICM, and 3,778 (60%) received CRT. CRT increased the time to HFH or all-cause death (HR: 0.67; 95% credible interval [CrI]: 0.56-0.82; P < 0.001) with no difference by etiology of cardiomyopathy (HR ratio: 1.06 [95% CrI: 0.87-1.29]; P = 0.57). Likewise, CRT increased the time to all-cause death (HR: 0.71 [95% CrI: 0.55-0.93]; P = 0.019) with no difference by etiology of cardiomyopathy (HR ratio: 1.06 [95% CrI: 0.80-1.43]; P = 0.70). Echocardiographic data that were available for 2,430 (39%) patients showed that CRT improvements in left ventricular ejection fraction, left ventricular end-diastolic diameter, and left ventricular end-systolic diameter were larger for patients with NICM. ConclusionsAlthough CRT led to greater increases in left ventricular ejection fraction and reductions in ventricular dimensions for patients with NICM compared with those with ICM, CRT significantly increased the time to HFH or all-cause death independently of the etiology of cardiomyopathy. Further studies on improving patient selection for CRT are needed.

Prognostic model development for risk of curve progression in adolescent idiopathic scoliosis: a prospective cohort study of 127 patients.

The study's purpose was to develop and internally validate a prognostic survival model exploring baseline variables for adolescent idiopathic scoliosis curve progression. A longitudinal prognostic cohort analysis was performed on trial data (n = 135) including girls and boys, Cobb angle 25-40°, aged 9-17 years, remaining growth > 1 year, and previously untreated. Prognostic outcome was defined as curve progression of Cobb angle of > 6° prior to skeletal maturity. 34 candidate prognostic variables were tested. Time-to-event was measured with 6-month intervals. Cox proportional hazards regression survival model (CoxPH) was used for model development and validation in comparison with machine learning models (66.6/33.3 train/test data set). The models were adjusted for treatment exposure. The final primary prognostic model included 127 patients, predicting progress with acceptable discriminative ability (concordance = 0.79, 95% confidence interval [CI] 0.72-0.86). Significant prognostic risk factors were Risser stage of 0 (HR 4.6, CI 2.1-10.1, P < 0.001), larger major curve Cobb angle (HRstandardized1.5, CI 1.1-2.0, P = 0.005), and higher score on patient-reported pictorial Spinal Appearance Questionnaire (pSAQ) (HRstandardized 1.4, CI 1.0-1.9, P = 0.04). Treatment exposure, entered as a covariate adjustment, contributed significantly to the final model (HR 3.1, CI 1.5-6.0, P = 0.001). Sensitivity analysis displayed that CoxPH maintained acceptable discriminative ability (AUC 0.79, CI 0.65-0.93) in comparison with machine learning algorithms. The prognostic model (Risser stage, Cobb angle, pSAQ, and menarche) predicted curve progression of > 6° Cobb angle with acceptable discriminative ability. Adding patient report of the pSAQ may be of clinical importance for the prognosis of curve progression.

Survival Analysis of Patients with Covid-19 Using Parametric Models in the Presence of Frailty Variable: A Prospective Cohort Study

Introduction: This study was performed to investigate the survival analysis of patients using parametric models in the presence of fragility variables. Methods: The data of this research belonged to a prospective cohort study of all the patients with Covid-19 in Fereydunshahr City. By conducting PCR tests on 2269 individuals suspected of Covid-19, 880 definite patients of Covid-19 were identified by census method. The death of the patients due to Covid-19 was the failure event. The response variable was the time from the onset of symptoms to the time of death (or censoring) at the end of the study. The data were analyzed through SPSS (version 16) and R software (version 4.3.2) at an error level of 0.05 and fitted with survival parametric models (considering the gamma distribution for the frailty variable) using Akaike's criterion. Results: Based on multiple regression analysis, the risk of death in patients with a history of heart disease was 4.9 times more than of patients without heart disease (95% CI for HR=2.21-10.98, HR=4.9) and in hospitalization patients was 4.2 times more than of outpatient cases (HR=4.2, 95% CI for HR=1.74-10.24). Moreover, increasing the age showed a significant relationship with the mortality rate (95% CI for HR=1.02-1.08, HR=1.05). With the inclusion of fragility variable in the model, the variable of “cardiovascular disease” was recognized as an important risk factor in survival time of patients; while without the fragility variable, this variable was ignored. In this study, according to the Akaike's criterion, the log-normal model showed a goodness of fit with the Covid-19 data. Conclusion: Using the fragility variable in survival regression models of patients with Covid-19, it is possible to identify the factors affecting patient mortality that it’s impossible to identify these risk factors in conventional models.

Is there an increased revision rate due to early tibial component loosening with a modern total knee arthroplasty design? A retrospective analysis from a large volume arthroplasty centre

BackgroundThe Attune TKR was introduced in 2011 as a successor to its predicate design The PFC Sigma. However, following reports of early failures, there are ongoing concerns related to increased loosening rates. Given the concerns, this study aimed to compare revision rates of the Attune implant to an established predicate, and other implant designs used in a high-volume arthroplasty center.MethodsWe identified 10,202 patients who underwent primary cemented TKR at our institution with a minimum of 1 year follow-up, involving 2406 Attune TKR (557 S +), 4642 PFC TKR, 3154 other designs. Primary outcomes were revision for all-causes, aseptic loosening of any component, and aseptic tibial loosening. Kaplan–Meier survival and Cox regression models were used to compare groups. Matched cohorts were selected for radiographic analysis.Results308 knees were revised. The Attune cohort had the lowest risk of revision, with a rate of 2.98 per 1000 implant-years while the PFC and All Other Implant groups had a rate of 3.15 and 4.4 respectively. Aseptic loosing was the most common cause for revision, with 76% (65/88) involving the tibia. Survival analysis showed no significant differences between the Attune and other cohorts. Radiolucent lines were detected in 7.1% of the Attune S + group, 6.8% of the standard Attune group, and 6.3% of the PFC group, with no significant differences found between them.ConclusionThis study represents the largest non-registry review of the Attune TKR in comparison to a predicate and other designs. There was no significant increased revision rate for all-cause revision or aseptic loosening, or peri-implant radiolucencies. It appears that increased loosening may not be as concerning as originally thought.Level of EvidenceLevel III.

Outcomes of Cardiac Resynchronization Therapy by New York Heart Association Class: A Patient-Level Meta-Analysis.

Data on the benefits of cardiac resynchronization therapy (CRT) in patients with severe heart failure symptoms are limited. We investigated the relative effects of CRT in patients with ambulatory New York Heart Association (NYHA) IV versus III functional class at the time of device implantation. In this meta-analysis, we pooled patient-level data from the MIRACLE (Multicenter InSync Randomized Clinical Evaluation), MIRACLE-ICD (Multicenter InSync Implantable Cardioversion Defibrillation Randomized Clinical Evaluation), and COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trials. Outcomes evaluated were time to the composite end point of the first heart failure hospitalization or all-cause mortality, and time to all-cause mortality alone. The association between CRT and outcomes was evaluated using a Bayesian hierarchical Weibull survival regression model. We assessed if this association differed between NYHA III and IV groups by adding an interaction term between CRT and NYHA class as a random effect. A sensitivity analysis was performed by including data from RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure). Our pooled analysis included 2309 patients. Overall, CRT was associated with a longer time to heart failure hospitalization or all-cause mortality (adjusted hazard ratio [aHR], 0.79 [95% credible interval [CI], 0.64-0.99]; posterior probability or P=0.044), with a similar association with time to all-cause mortality (aHR, 0.78 [95% CI, 0.59-1.03]; P=0.083). Associations of CRT with outcomes were not significantly different for those in NYHA III and IV classes (ratio of aHR, 0.72 [95% CI, 0.30-1.27]; P=0.23 for heart failure hospitalization/mortality; ratio of aHR, 0.70 [95% CI, 0.35-1.34]; P=0.27 for all-cause mortality alone). The sensitivity analysis, including RAFT data, did not show a significant relative CRT benefit between NYHA III and IV classes. Overall, there was no significant difference in the association of CRT with either outcome for patients in NYHA functional class III compared with functional class IV.

Surgical resection of glioblastoma in the very elderly: An analysis of survival outcomes using the surveillance, epidemiology, and end results database

ObjectivePatients with glioblastoma (GBM) often undergo surgery to prolong survival. However, the use of surgery, and more specifically achieving gross total resection (GTR), in patients >80 years old has yet to be fully assessed. Using the Surveillance, Epidemiology, and End Results (SEER) database, we aim to assess the efficacy of surgical resection, radiotherapy (RT) and chemotherapy (CT) on overall survival (OS) in very elderly GBM patients compared to elderly counterparts (age 65–79 years). MethodsThe SEER database was queried for all patients >65 years old with GBM (2000–2020). Patients not undergoing surgery or biopsy were excluded. Patients were stratified by age, and demographic relationships were assessed with chi-squared testing for categorical variables. Bivariable models were created using Kaplan-Meier survival estimates. All significant variables from bivariable analysis were included on multivariable Cox survival regression models to determine independent associations between clinical variables and OS. ResultsA total of 27,090 operative GBM patients were identified; 1868 patients (15.92 %) were very elderly and 10,092 patients (84.38 %) were elderly. Very elderly patients were less likely to undergo GTR (28 % vs 35 %, p<0.001), RT (59 % vs 78 %, p<0.001) and CT (40 % vs 66 %, p<0.001). In multivariable Cox regression analysis, very elderly patients who achieved GTR (HR=.696, p<0.001), received RT (HR=0.583, p<0.001) and underwent CT (HR=0.4197, p<0.001) had significantly improved OS compared to very elderly patients that did not undergo these treatment options. ConclusionCurrently, very elderly GBM patients undergo lower rates of aggressive surgery, RT and CT. However, very elderly patients that undergo surgery, RT and CT may have a survival advantage. These treatments should be considered as potential options for this patient population.

Determinants of Human Asymmetry: Does Asymmetrical Retinal Vasculature Predict Asymmetry Elsewhere in the Body?

The aim of this study was to explore retinal vasculature asymmetry (ReVA) patterns in subjects from the islands of Vis and Korcula and the city of Split, Croatia. Asymmetry estimates were based on topographic image analysis of non-mydriatic retinal fundus photographs and compared with nine ophthalmic measurements, three Doppler-based pressure indices and eight frequencies of audiometry. ReVA was also correlated to the genomic runs of homozygosity (ROHs) and used in a Cox regression survival model, where we adjusted for the effects of sex, age and comorbidity. In 1873 subjects, ReVA estimates were significantly correlated with most ophthalmic asymmetry measures, less strongly with the ankle-brachial pressure index and only modestly with higher-amplitude audiometry asymmetries (lowest p = 0.020). ReVA was significantly correlated with the number of ROHs (r = 0.229, p < 0.001) but less strongly with the ROH length (r = 0.101, p < 0.001). The overlap of asymmetries was low, with only 107 subjects (5.7% of the total sample) who had two or more instances in which they were among the top 10%. Multiple asymmetries did not affect survival (HR = 0.74, 95% confidence intervals 0.45-1.22). Retinal vasculature asymmetry is a poor predictor of asymmetry elsewhere in the body. Despite its existence and apparent association with comorbidities, the observed extent of retinal vasculature asymmetry did not affect the lifespan in this population.

A Fast Survival Support Vector Regression Approach to Large Scale Credit Scoring via Safe Screening.

Survival models have found wider and wider applications in credit scoring recently due to their ability to estimate the dynamics of risk over time. In this research, we propose a Buckley-James safe sample screening support vector regression (BJS4VR) algorithm to model large-scale survival data by combing the Buckley-James transformation and support vector regression. Different from previous support vector regression survival models, censored samples here are imputed using a censoring unbiased Buckley-James estimator. Safe sample screening is then applied to discard samples that guaranteed to be non-active at the final optimal solution from the original data to improve efficiency. Experimental results on the large-scale real lending club loan data have shown that the proposed BJS4VR model outperforms existing popular survival models such as RSFM, CoxRidge and CoxBoost in terms of both prediction accuracy and time efficiency. Important variables highly correlated with credit risk are also identified with the proposed method.

Transitioning from the University to the Workplace: A Duration Model with Grouped Data

Labor market surveys usually measure unemployment duration in time intervals. In these cases, traditional duration models such as Cox regression and parametric survival models are not suitable for studying the duration of unemployment spells. In order to deal with this above issue, we use Han and Hausman’s ordered logit model for grouped durations, which has more flexibility than standard specifications. In particular, its flexibility arises from the fact that we do not need to specify any functional form for the baseline hazard function—it also circumvents problems associated with heterogeneity. The focus of interest is on the first unemployment duration of higher education graduates. The analysis is accomplished by using a large dataset from a graduate survey of Spanish university graduates. The results show that the university-to-work transition of higher education graduates is significantly associated with the graduate’s age, participation in internship programs, field of study, type of university, and gender. Specifically, graduates who participated in internship programs, engineering graduates, and graduates from private universities experience a smooth transition.

Time trends of the association of body mass index with mortality in 3.5 million young Swedish adults

PurposeWe investigated time trends of the obesity-mortality association, accounting for age, sex, and cause-specific deaths. MethodsWe analysed pooled nationwide data in Sweden for 3,472,310 individuals aged 17–39 years at baseline in 1963–2016. Cox regression and flexible parametric survival models investigated BMI-mortality associations in sub-groups of sex and baseline calendar years (men: <1975, 1975–1985, ≥1985 and women: <1985, 1985–1994, ≥1995). ResultsComparing men with obesity vs. normal weight, all-cause and “other-cause” mortality associations decreased over periods; HR (95% CI) 1.92 (1.83–2.01) and 1.70 (1.58–1.82) for all-cause and 1.72 (1.58–1.87) and 1.40 (1.28–1.53) for “other-cause” mortality in <1975 and ≥1985, but increased for CVD mortality; HR 2.71 (2.51–2.94) and 3.91 (3.37–4.53). Higher age at death before 1975 coincided with more obesity-related deaths at higher ages. Furthermore, the all-cause mortality association for different ages in men showed no clear differences between periods (p-interaction=0.09), suggesting no calendar effect after accounting for attained age. Similar, but less pronounced, results were observed in women. Associations with cancer mortality showed no clear trends in men or in women. ConclusionsAccounting for differences in age and death causes between calendar periods when investigating BMI-mortality time trends may avoid misinterpreting the risks associated with obesity over time.

Using the Bayesian method to estimate and comparison the regression of the exponential and gamma survival (Simulation)

Parametric regression models It is one of the oldest and most common regression models and can be defined as one of the statistical methods that is used to describe and estimate the relationship between a dependent random variable and explanatory random variables. These models have types, including quantitative models, of their linear and non-linear types, and qualitative models that The dependent variable is a binary response variable. These models are characterized by the fact that all cases that are studied are assumed to be normally distributed and measurable, and that the regression function determines the parameters that cannot be changed except by changing the number of variables included in the study, relying on probability distributions, which are the exponential distribution and the Gamma, we will obtain parametric regression models, which are the exponential regression model, and the gamma regression model, relying on the Cox regression model to be used in forming these models, which are models that require the presence of information and hypotheses about the distribution of the population used in the test that is appropriate for the units or data, as well as the variables that enter. The test or experiment on which the survival function is based, in this thesis, it was proposed to estimate the parameters of these models using the Bayesian method. The simulation method was used to generate data that follows parametric survival regression models according to various factors. The simulation results showed that the third model of the exponential probability distribution of the survival function shows the lowest value according to the MSE criterion. This indicates that Increasing the sample size typically reduces the standard mean error (MSE), which is used as an indicator of the differences between expected and actual values in statistical estimates. Simply put, the larger the sample size, the more accurate the statistical predictions are and the lower the standard deviation from the actual values, indicating that larger samples often contribute to improving the accuracy of statistical estimates.

Homologous recombination deficiency score served as an independent prognosis factor in esophageal squamous cell carcinoma.

e16080 Background: Homologous recombination deficiency (HRD) is a functional impairment of the homologous recombination repair (HRR) pathway, pivotal for mending DNA double-strand breaks, contributing significantly to cancer-associated genomic instability. While BRCA mutations traditionally underlie HRR defects, recent studies highlight varied responses to poly (ADP-ribose) polymerase (PARP) inhibitors based on specific HRR-related gene alterations. Despite HRD's relevance in various cancers, its role in esophageal squamous cell carcinoma (ESCC) remains underexplored. Methods: We conducted a retrospective analysis of HRD scores in 96 ESCC patients, assessing correlations with clinical characteristics and survival outcomes. Genomic sequencing was performed using a customized superHRD NGS panel. HRD scores were calculated based on 54,000 single-nucleotide polymorphisms, employing Kruskal-Wallis ranksum tests and two cut-off points for quantitative analysis. Kaplan-Meier survival and Cox regression model were employed to evaluate disease-free survival (DFS) and overall survival (OS). Results: Higher HRD scores correlated with advanced tumor stages, recurrence, and specific gene mutations ( TP53 and ABCB1). APC mutations were associated with lower HRD scores. Patients with high HRD scores demonstrated significantly shorter disease-free survival (DFS) and a trend towards shorter overall survival (OS), especially those who did not receive adjuvant therapy, emphasizing HRD's prognostic value. Conversely, HRD-high patients undergoing adjuvant therapy showed a tendency towards extended OS. Multivariate analysis identified HRD as an independent prognostic factor (HR = 2.814 for recurrence, HR = 1.772 for death). Validation with The Cancer Genome Atlas (TCGA) ESCC dataset supported our findings. Conclusions: This study unveils associations between HRD scores, clinical characteristics, and genomic mutations in ESCC, emphasizing HRD's potential as a prognostic biomarker. HRD assessment may aid in patient stratification and personalized treatment strategies. Future investigations should explore underlying molecular mechanisms and therapeutic implications of HRD-associated pathways in ESCC management.

Prospective “common arm” comparison of US SWOG S0424 and Japanese JME studies in early-stage non-small cell lung cancer (NSCLC): Survival differences in the context of race, gender and smoking.

8036 Background: In NSCLC, overall frequencies and subtype distribution of EGFR and KRAS mutations differ significantly between Japanese and US patients. In many NSCLC clinical trials, Japanese patient outcomes appear superior to those in western populations. Since 2009, SWOG and Japanese investigators have used the “Common Arm” analytic method to interpret globally-conducted lung cancer clinical trials, providing a mechanism for direct patient-level comparisons in matching trials performed in the US and Japan. S0424 and the Japanese Molecular Epidemiology Study (JME) are large prospective molecular epidemiology studies conducted by SWOG and Japanese investigators and prospectively planned for “Common Arm” analysis. We investigated the effects of mutation distribution on overall survival in early stage NSCLC using data from JME and S0424. Methods: Both studies were designed to accrue representative proportions of ever-smokers (ES) versus never-smokers (NS) in male and female cohorts. Accrual to S0424 was completed in 2011 with 981 pts enrolled (Cheng et al JNCI 2018); JME was completed in 2012 with 957 pts (Kawaguchi et al JCO 2016). A comprehensive questionnaire was used to capture lifestyle, carcinogenic exposures, demographic and clinical data. Five years of follow-up was completed for each study. The association between baseline characteristics and mutation types were analyzed using multivariate logistic regression. The product-limit method was used to estimate overall survival and Cox regression models were fit to estimate hazard ratios. p-values were two-sided and p-values &lt; 0.05 were considered significant. Results: Evaluable pts: 876 for JME; 957 for S0424. Demographic distribution: S0424: 87% Caucasian, 5% Asian, 4% Black; JME: 100% Japanese. As expected, multivariate logistic models adjusting for age, smoking status, gender and BMI showed JME were more likely to have EGFR mutations (p &lt; 0.0001) and less likely to have KRAS mutations (p = 0.02). EGFR mutations were associated with never-smoking (p &lt; 0.0001) and female sex (p &lt; 0.0001); KRAS was associated with smoking (p &lt; 0.0001). Adjusting for age, smoking status and gender, overall survival was greater in JME patients (p &lt; 0.0001,HR = 0.49 (95% CI: 0.40-0.60)). In the subset of pts without an EGFR mutation, survival still favored the JME cohort (p &lt; 0.001, HR = 0.68 (0.53-0.86). Conclusions: Patient level comparison of US (SWOG) and Japanese (JME) patients with early stage NSCLC demonstrated longer survival in Japanese patients even after adjusting for EGFR mutation frequency. Identification of factors that contribute to this finding are under investigation. Female sex remained a risk factor for EGFR mutation-driven disease in both populations. This analysis forms the basis for applying this population-related model in other clinical settings.