scholarly journals Survival of Bladder or Renal Cancer in Patients With CHEK2 Mutations

2020 ◽  
Author(s):  
Elżbieta Złowocka-Perłowska ◽  
Tadeusz Dębniak ◽  
Marcin Słojewski ◽  
Artur Lemiński ◽  
Michał Soczawa ◽  
...  
Keyword(s):  
Family History ◽  
Kidney Cancer ◽  
Cancer Survival ◽  
Proportional Hazards Model ◽  
Smoking Status ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cancer Family ◽  
Cancer Family History ◽  
Truncating Mutation

Abstract Purpose: The purpose of this study was to compare the survival of CHEK2 mutations positive and CHEK2 mutations negative patients with bladder or kidney cancer. Materials and methods: 1419 patients with bladder and 835 cases with kidney cancer and 8302 controls were genotyped for four CHEK2 variants: 1100delC, del5395, IVS2+1G>A and I157T. Predictors of survival were determined among CHEK2 carriers using the Cox proportional hazards model. The median follow-up was 17 years. Covariates included age (≤65; >66), smoking status (non-smoking; smoking), cancer family history (negative; positive) and gender (females; males). Results: Of the 1419 bladder patients enrolled in the study, 118 (8.32%) carried a CHEK2 mutation (all variants combined) (OR=1.4; 95% CI 1.17–1.78; p=0.0006), including 25 (1.76%) cases with a truncating mutation (OR=1.84; 95% CI, 1.17-2.89; p=0.01) and 93 (6.55%) patients with a missense mutation (OR=1.35; 95% CI, 1.07-1.7; p=0.01). We found no impact of CHEK2 mutations on bladder or kidney cancer survival. The 10-year survival for all CHEK2 mutation for bladder cancer carriers was 19% and for non-carriers was 13% (p=0.7). The 10-year survival for kidney cancer carriers was 6% and for non-carriers was 4% (p=0.9). Conclusion: We found no impact of CHEK2 mutations on bladder or kidney cancer survival regardless of their age, sex, cancer family history and smoking status.

Polymorphisms in Inflammation Genes and Bladder Cancer: From Initiation to Recurrence, Progression, and Survival

2005 ◽  
Vol 23 (24) ◽  
pp. 5746-5756 ◽  
Author(s):  
Dan Leibovici ◽  
H. Barton Grossman ◽  
Colin P. Dinney ◽  
Randal E. Millikan ◽  
Seth Lerner ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Clinical Outcome ◽  
Proportional Hazards Model ◽  
Smoking Status ◽  
Recurrence Risk ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Peroxisome Proliferator ◽  
Necrosis Factor Alpha ◽  
Muscle Invasive

Purpose Since chronic inflammation contributes to tumorigenesis, we hypothesized that the risk and clinical outcome of bladder cancer (BC) might be modulated by genetic variations in inflammation genes. Methods Using the TaqMan method, we genotyped single nucleotide polymorphisms in interleukin (IL) -6 (−174 G→C), IL-8 (−251 T→A), tumor necrosis factor-alpha (TNF-α; −308 G→A), and peroxisome proliferator-activated receptor γ (PPARG; Pro12Ala), and determined their associations with BC initiation and clinical outcome. Results We found that the IL-6 variant genotype (C/C) was associated with an increased BC risk (OR, 1.77; 95% CI, 1.25 to 2.51). There were joint effects between the variant IL-6 genotypes and smoking status, and between the variant genotypes of IL-6 and other genes. To assess effect on recurrence, we grouped non-muscle-invasive BC patients according to intravesical Bacillus Calmette-Guerin (BCG) treatment status: no BCG, induction BCG (iBCG), and maintenance BCG (mBCG). In the Cox proportional hazards model, the variant IL-6 genotype was associated with an increased recurrence risk (hazard ratio [HR], 4.60; 95% CI, 1.24 to 17.09) in patients receiving mBCG. The variant PPARG genotype was associated with a reduced recurrence risk (HR, 0.41; 95% CI, 0.20 to 0.86) among untreated patients. In patients with non-muscle-invasive BC, the variant IL-6 genotype was associated with an increased progression risk (HR, 1.88; 95% CI, 0.80 to 4.11). In patients with invasive BC, variant IL-6 was associated with improved 5-year overall and disease-specific survival (HR, 0.43; 95% CI, 0.19 to 0.94 and HR, 0.39; 95% CI, 0.15 to 1.00, respectively). Conclusion Inflammation gene polymorphisms are associated with modified BC risk, treatment response, and survival.

Survival in Subcortical Vascular Dementia: Predictors and Comparison to Probable Alzheimer's Disease in a Tertiary Memory Clinic Population

2015 ◽  
Vol 40 (3-4) ◽  
pp. 210-221 ◽  
Author(s):  
Jong Hun Kim ◽  
Seok Min Go ◽  
Sang Won Seo ◽  
Suk Hui Kim ◽  
Juhee Chin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Family History ◽  
Vascular Dementia ◽  
Proportional Hazards Model ◽  
Late Onset ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Subcortical Vascular Dementia ◽  
History Of

Background: Subcortical vascular dementia (SVaD) is one of the most common dementias, after Alzheimer's disease (AD) dementia. Few survival analyses in SVaD patients have been reported. Methods: The dates and causes of death of 146 SVaD and 725 AD patients were included. We used the Cox proportional hazards model to compare survival between SVaD and AD patients and to explore possible factors related to survival of SVaD patients. Results: The median survival time after the onset of SVaD (109 months) was shorter than that recorded for AD (152 months). The most common cause of death in SVaD was stroke (47.1%). Factors associated with shorter survival in SVaD were late onset, male sex, worse baseline cognition, absence of hypertension and a family history of stroke. Conclusions: Stroke prevention may be important in SVaD treatment because 47.1% of SVaD patients died of stroke. A family history of stroke and absence of hypertension were associated with a shorter survival in SVaD, suggesting the existence of genetic or unknown risk factors.

Gender disparities in hepatocellular cancer survival

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15517-e15517
Author(s):  
A. E. Hendifar ◽  
D. Yang ◽  
S. Iqbal ◽  
H. Lenz ◽  
A. El-Khoueiry
Keyword(s):  
Overall Survival ◽  
Cancer Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Premenopausal Women ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Response To Treatment ◽  
Cancer Specific Survival ◽  
Asian Ethnicity

e15517 Background: Recent reports suggest that estrogen mediated inhibition of IL-6 protects against the development of HCC and may explain the decreased risk of liver cancer in women. We investigated the relation-hip between gender, age, and survival for patients with localized HCC. Methods: We identified 11,097 patients with localized, histologically defined HCC, from 1988- 2003, using the Surveillance, Epidemiology, and End Results (SEER) registry. Age at diagnosis, sex, ethnicity, and overall survival were evaluated using Cox proportional hazards model. The models were adjusted for treatment modality, tumor differentiation, tumor size, lymph node involvement, and number of lesions; they were stratified by year of diagnosis and SEER registry site. Results: 8,111 (73%) patients were men and 2,986 (27%) were women. In univariate and multivariate analyses, female gender, young age (< 55 yo), and Asian ethnicity were all associated with improved overall survival (p<0.001). In patients less than 55 yo, women had a superior OS and cancer specific survival (CSS) when compared to men (OS: 18 months vs. 9, CSS: 31 months vs. 14, p<0.001). Conversely, in patients older than 55, there were no gender differences (OS: 8 months vs. 8, CSS 13 months vs. 11, p = 0.08). Local therapies, including, ablation (HR = 0.47 [0.43–0.53]), hepatectomy (HR = 0.40 [0.36–0.44]), radiation (HR = 0.67 [0.57–0.78]) and transplantation (HR = 0.17 [0.15–0.20]) were also associated with improved survival. There were no interactions identified between gender and treatment use. Conclusions: To our knowledge, this is the first report to highlight the superior outcome of premenopausal women with HCC compared to men. We postulate a potential role for estrogen in influencing the biology of HCC and the response to treatment. These observations are consistent with ones made in other gastrointestinal cancers and with reported preclinical data suggesting a protective role for estrogen. Further studies that confirm these observations and elucidate the biology of estrogen's influence on HCC are needed. [Table: see text] No significant financial relationships to disclose.

Comparison of outcomes with pembrolizumab monotherapy (P) versus combination with chemotherapy (P+C) in advanced non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21579-e21579
Author(s):  
Kartik Sehgal ◽  
Ritu R. Gill ◽  
Poorva Bindal ◽  
Anita Geevarghese Koshy ◽  
Danielle C McDonald ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Advanced Nsclc ◽  
Proportional Hazards Model ◽  
Smoking Status ◽  
Performance Status ◽  
Objective Response ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Ecog Performance Status

e21579 Background: P and P+C are standard-of-care (SOC) treatment options for advanced NSCLC. However, they have not yet been directly compared in clinical trials. Methods: We conducted a retrospective cohort study of patients with advanced NSCLC who initiated treatment with SOC P±C at our center from 2/11/16 to 10/15/19 (data cutoff 1/15/20). Patient demographic, clinicopathologic, therapeutic and outcomes data were extracted. All radiographic scans were independently evaluated by a thoracic radiologist using iRECIST. Survival time was defined from the start of P±C. Kaplan-Meier and Cox proportional hazards model were utilized. Results: Of 103 patients with median follow up of 17.7 months, 74 (71.8%) had received P, while 29 (28.2%) had received P+C. In PD-L1 tumor proportion score (TPS) unselected population, there were no significant differences in age, sex, smoking status, driver mutation, tumor mutational burden (TMB), line of therapy, ECOG performance status (PS) or immune-related adverse events (irAE) between P and P+C groups. 71.6% in P vs 13.8% in P+C had PD-L1 TPS ≥50% (p < 0.001). There were no significant differences between the two groups in objective response rate (ORR), disease control rate (DCR), unadjusted progression-free survival (PFS) or unadjusted overall survival (OS) (Table). Multivariable adjustment for confounding factors between P+C vs P revealed no differences in OS [hazard ratio (HR) for death, 1.53, 95% CI 0.55 – 4.25] or PFS [HR for progression/death, 1.75, 95% CI 0.63 – 4.91]. Further stratification into PD-L1 TPS ≥50% and < 50% showed no significant differences between P+C vs. P in adjusted OS [HR for death, TPS < 50%- 1.54 (95% CI 0.59 – 4.03); TPS ≥50%- 0.71 (95% CI 0.11 – 4.52)] or PFS [HR for progression/death, TPS < 50%- 1.58 (95% CI 0.72 – 3.48); TPS ≥50%- 0.64 (95% CI 0.06 – 6.93)]. ECOG PS and development of irAE influenced OS in all groups, while TMB was relevant in PD-L1 ≥50% only. Conclusions: Our study shows no significant differences in outcomes with P vs P+C in advanced NSCLC in a real-world setting, albeit with limitations of single-center design, limited sample size, different line settings and lack of disease burden stratification. Ongoing phase III trials comparing front line P vs P+C will definitively address the long-term clinical benefits -if any- of combining cytotoxic chemotherapy with anti-PD-1 drugs. [Table: see text]

scholarly journals The prognostic significance of smoking cessation after acute coronary syndromes: an observational, multicentre study from the Melbourne interventional group registry

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e016874 ◽  
Author(s):  
Matias B Yudi ◽  
Omar Farouque ◽  
Nick Andrianopoulos ◽  
Andrew E Ajani ◽  
Katie Kalten ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Secondary Prevention ◽  
Proportional Hazards Model ◽  
Smoking Status ◽  
Prognostic Significance ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Coronary Syndrome ◽  
Interventional Group ◽  
Persistent Smoking

ObjectiveWe aim to ascertain the prognostic significance of persistent smoking and smoking cessation after an acute coronary syndrome (ACS) in the era of percutaneous coronary intervention (PCI) and optimal secondary prevention pharmacotherapy.MethodsConsecutive patients from the Melbourne Interventional Group registry (2005–2013) who were alive at 30 days post-ACS presentation were included in our observational cohort study. Patients were divided into four categories based on their smoking status: non-smoker; ex-smoker (quit >1 month before ACS); recent quitter (smoker at presentation but quit by 30 days) and persistent smoker (smoker at presentation and at 30 days). The primary endpoint was survival ascertained through the Australian National Death Index linkage. A Cox-proportional hazards model was used to estimate the adjusted HR and 95% CI for survival.ResultsOf the 9375 patients included, 2728 (29.1%) never smoked, 3712 (39.6%) were ex-smokers, 1612 (17.2%) were recent quitters and 1323 (14.1%) were persistent smokers. Cox-proportional hazard modelling revealed, compared with those who had never smoked, that persistent smoking (HR 1.78, 95% CI 1.36 to 2.32, p<0.001) was an independent predictor of increased hazard (mean follow-up 3.9±2.2 years) while being a recent quitter (HR 1.27, 95% CI 0.96 to 1.68, p=0.10) or an ex-smoker (HR 1.03, 95% CI 0.87 to 1.22, p=0.72) were not.ConclusionsIn a contemporary cohort of patients with ACS, those who continued to smoke had an 80% risk of lower survival while those who quit had comparable survival to lifelong non-smokers. This underscores the importance of smoking cessation in secondary prevention despite the improvement in management of ACS with PCI and pharmacotherapy.

scholarly journals Smoking cessation and incident dementia in elderly Japanese: the Ohsaki Cohort 2006 Study

2020 ◽  
Vol 35 (9) ◽  
pp. 851-860
Author(s):  
Yukai Lu ◽  
Yumi Sugawara ◽  
Shu Zhang ◽  
Yasutake Tomata ◽  
Ichiro Tsuji
Keyword(s):  
Smoking Cessation ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Smoking Status ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Term Care ◽  
Incident Dementia ◽  
Increased Risk ◽  
Elderly Japanese

Abstract To investigate the association of smoking status and years since smoking cessation with the risk of incident dementia among elderly Japanese. We conducted a longitudinal analysis of smoking status and smoking cessation with dementia in prospective cohort study of 12,489 Japanese individuals aged ≥ 65 years who were followed up for 5.7 years. Information on smoking status and other lifestyle factors was collected via a questionnaire in 2006. Data on incident dementia were retrieved from the public Long-term Care Insurance Database. The Cox proportional hazards model was used to estimate the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident dementia. During 61,613 person-years of follow-up, 1110 cases (8.9%) of incident dementia were documented. Compared with individuals who had never smoked, current smokers showed a higher risk of dementia (HR 1.46, 95% CI 1.17, 1.80). Among ex-smokers, the risk for those who had stopped smoking for ≤ 2 years was still high (HR 1.39, 95% CI 0.96, 2.01), however, quitting smoking for 3 years or longer mitigated the increased risk incurred by smokers; the multivariable HRs (95% CIs) were 1.03 (0.70, 1.53) for those who had stopped smoking for 3–5 years, 1.04 (0.74, 1.45) for 6–10 years, 1.19 (0.84, 1.69) for 11–15 years, and 0.92 (0.73, 1.15) for > 15 years. Our study suggests that the risk of incident dementia among ex-smokers becomes the same level as that of never smokers if they maintain abstinence from smoking for at least 3 years.

scholarly journals Questioning the sex-specific differences in the association of smoking on the survival rate of hospitalized COVID-19 patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255692
Author(s):  
Athar Khalil ◽  
Radhika Dhingra ◽  
Jida Al-Mulki ◽  
Mahmoud Hassoun ◽  
Neil Alexis
Keyword(s):  
Survival Rate ◽  
Smoking Prevalence ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Smoking Status ◽  
Survival Rates ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Current Cigarette Smoking ◽  
High Smoking Prevalence

Introduction In the absence of a universally accepted association between smoking and COVID-19 health outcomes, we investigated this relationship in a representative cohort from one of the world’s highest tobacco consuming regions. This is the first report from the Middle East and North Africa that tackles specifically the association of smoking and COVID-19 mortality while demonstrating a novel sex-discrepancy in the survival rates among patients. Methods Clinical data for 743 hospitalized COVID-19 patients was retrospectively collected from the leading centre for COVID-19 testing and treatment in Lebanon. Logistic regression, Kaplan-Meier survival curves and Cox proportional hazards model adjusted for age and stratified by sex were used to assess the association between the current cigarette smoking status of patients and COVID-19 outcomes. Results In addition to the high smoking prevalence among our hospitalized COVID-19 patients (42.3%), enrolled smokers tended to have higher reported ICU admissions (28.3% vs 16.6%, p<0.001), longer length of stay in the hospital (12.0 ± 7.8 vs 10.8 days, p<0.001) and higher death incidences as compared to non-smokers (60.5% vs 39.5%, p<0.001). Smokers had an elevated odds ratio for death (OR = 2.3, p<0.001) and for ICU admission (OR = 2.0, p<0.001) which remained significant in a multivariate regression model. Once adjusted for age and stratified by sex, our data revealed that current smoking status reduces survival rate in male patients ([HR] = 1.9 [95% (CI), 1.029–3.616]; p = 0.041) but it does not affect survival outcomes among hospitalized female patients([HR] = 0.79 [95% CI = 0.374–1.689]; p = 0.551). Conclusion A high smoking prevalence was detected in our hospitalized COVID-19 cohort combined with worse prognosis and higher mortality rate in smoking patients. Our study was the first to highlight potential sex-specific consequences for smoking on COVID-19 outcomes that might further explain the higher vulnerability to death from this disease among men.

scholarly journals Haemoglobin A1c and hearing impairment: longitudinal analysis using a large occupational health check-up data of Japan

BMJ Open ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. e023220 ◽  
Author(s):  
Satsue Nagahama ◽  
Ikuko Kashino ◽  
Huanhuan Hu ◽  
Akiko Nanri ◽  
Kayo Kurotani ◽  
...  
Keyword(s):  
Hearing Impairment ◽  
High Frequency ◽  
Proportional Hazards Model ◽  
Smoking Status ◽  
Hearing Threshold ◽  
Low Frequency ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Health Check ◽  
Haemoglobin A1c

ObjectivesThe aim of this study was to determine whether haemoglobin A1c (HbA1c) level is associated with the incidence of hearing impairment accounting for smoking status and diabetic condition at baseline.MethodsParticipants were 131 689 men and 71 286 women aged 30–65 years and free of hearing impairment at baseline (2008) who attended Japanese occupational annual health check-ups from 2008 to 2015. We defined low-frequency hearing impairment at a hearing threshold >30 dB at 1 kHz and high frequency at >40 dB at 4 kHz in the better ear in pure-tone audiometric tests. HbA1c was categorised into seven categories. The association between HbA1c and hearing impairment was assessed using the Cox proportional hazards model.ResultsOn 5 years mean follow-up, high HbA1c was associated with high-frequency hearing impairment. In non-smokers, HbA1c≥8.0% was associated with high-frequency hearing impairment, with a multivariable HR (95% CI) compared with HbA1c 5.0%–5.4% of 1.46 (1.10 to 1.94) in men and 2.15 (1.13 to 4.10) in women. There was no significant association between HbA1c and hearing impairment in smokers. A J-shaped association between HbA1c and high-frequency hearing impairment was observed for participants with diabetes at baseline. HbA1c was not associated with low-frequency hearing impairment among any participants.ConclusionsHbA1c ≥8.0% of non-smokers and ≥7.3% of participants with diabetes was associated with high-frequency hearing impairment. These findings indicate that appropriate glycaemic control may prevent diabetic-related hearing impairment.

scholarly journals An Application of the Cox-Aalen Model for Breast Cancer Survival

2016 ◽  
Vol 35 (1) ◽  
Author(s):  
Ileana Baldi ◽  
Giovannino Ciccone ◽  
Antonio Ponti ◽  
Stefano Rosso ◽  
Roberto Zanetti ◽  
...  
Keyword(s):  
Cancer Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Model ◽  
Tumour Size ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Aalen Model ◽  
Cancer Registry Data ◽  
Hazards Model

Semiparametric hazard function regression models are among the well studied risk models in survival analysis. The Cox proportional hazards model has been a popular choice in modelling data from epidemiological settings. The Cox-Aalen model is one of the tools for handling the problem of non-proportional effects in the Cox model. We show an application on Piedmont cancer registry data. We initially fit standard Cox model and with the help of the score process we detect the violation of the proportionality assumption. Covariates and risk factors that, on the basis of clinical reasoning, best model baseline hazard are then moved into the additive part of the Cox-Aalen model. Multiplicative effects results are consistent with those of the Cox model whereas only the Cox-Aalen model fully represents the timevarying effect of tumour size.

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