scholarly journals Prognostic Nomograms for Predicting Overall Survival and Cancer-Specific Survival in Patients with Angiosarcoma, a SEER population-based study

2021 ◽  
Author(s):  
Ting Jiang ◽  
Zixiang Ye ◽  
TianYu Shao ◽  
YiYang Luo ◽  
BinBin Wang
Keyword(s):  
Overall Survival ◽  
Regression Analysis ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Predictive Ability ◽  
Training Group ◽  
Cox Proportional Hazards ◽  
Cancer Specific Survival ◽  
Cox Regression Analysis ◽  
Cancer Management

Abstract Backgrounds: Angiosarcoma (AS) is a kind of highly aggressive cancer with high occurrence and mortality rates. This study aimed to establish a comprehensive and validated prognostic nomogram with various clinical indicators in patients with AS.Methods: Data of patients with AS diagnosed after surgery between 2010 and 2015 was retrieved from the Surveillance Epidemiology and End Results (SEER) database. Univariate and multivariate Cox proportional hazards regression analysis were performed to identify the independent prognostic factors associated with survival to construct the predictive nomogram of 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates. Concordance-index(C-index), calibration plots and receiver operating characteristic (ROC) curves were applied to evaluate the predictive ability of the nomograms. The further decision curve analysis (DCA) was drawn to confirm the clinical usefulness of the nomograms.Results: 323 patients in total with AS were divided into the training group (N =226) and the validation group (N = 97). After the multivariate Cox regression analysis, gender, age, AJCC stage group 7th ed, T, N and M stage 7th ed, histologic grade and primary site were statistically identified as independent factors with OS and CSS (P<0.05). The C-index of the nomograms for OS and CCS in the training cohort was 0.760 (95%CI: 0.674–0.847) and 0.793 (95%CI: 0.687–0.898), meanwhile, the C-index of those in the validation cohort was 0.790 (95%CI: 0.725–0.855) and 0.888 (95%CI: 0.799–0.976) respectively. The results of calibration plots and ROC curve showed the nomograms qualified to measure the risk and prognosis. DCA exhibited good clinical utility of nomograms.Conclusion: Our study has developed novel and practical nomograms for predicting prognosis in patients with AS contributing to cancer management.

Bypass Grafting vs Endovascular Therapy in Patients With Non-Dialysis-Dependent Chronic Kidney Disease and Chronic Limb-Threatening Ischemia (CRITISCH Registry)

2020 ◽  
Vol 27 (4) ◽  
pp. 599-607
Author(s):  
Konstantinos Stavroulakis ◽  
Asimakis Gkremoutis ◽  
Matthias Borowski ◽  
Giovanni Torsello ◽  
Dittmar Böckler ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Chronic Kidney Disease ◽  
Overall Survival ◽  
Kidney Disease ◽  
Endovascular Therapy ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Cox Proportional Hazards ◽  
Bypass Grafting ◽  
Cox Regression Analysis

Purpose: To report the outcomes of bypass grafting (BG) vs endovascular therapy (EVT) in patients with non-dialysis-dependent chronic kidney disease (CKD) and chronic limb-threatening ischemia (CLTI). Materials and Methods: The CRITISCH Registry is a prospective, national, interdisciplinary, multicenter registry evaluating the current practice of all available treatment options in 1200 consecutive CLTI patients. For the purposes of this analysis, only the 337 patients with non-dialysis-dependent CKD treated by either BG (n=86; median 78 years, 48 men) or EVT (n=251; median age 80 years, 135 men) were analyzed. The primary composite outcome was amputation-free survival (AFS); secondary outcomes were overall survival (OS) and amputation-free time (AFT). All outcomes were evaluated in Cox proportional hazards models; the results are reported as the hazard ratio (HR) and 95% confidence interval (CI). Results: The Cox regression analysis revealed a significantly greater hazard of amputation or death after BG (HR 1.78, 95% CI 1.05 to 3.03, p=0.028). The models for AFT and overall survival also suggested a higher hazard for BG, but the differences were not significant (AFT: HR 1.66, 95% CI 0.78 to 3.53, p=0.188; OS: HR 1.41, 95% CI 0.80 to 2.47, p=0.348). The absence of runoff vessels (HR 1.73, 95% CI 1.15 to 2.60, p=0.008) was associated with a decreased AFS. The likelihood of amputation was higher in male patients (HR 2.21, 95% CI 1.10 to 4.45, p=0.027) and was associated with a lack of runoff vessels (HR 1.95, 95% CI 0.96 to 3.95, p=0.065) and myocardial infarction (HR 3.74, 95% CI 1.23 to 11.35, p=0.020). Death was more likely in patients without runoff vessels (HR 1.76, 95% CI 1.11 to 2.80, p=0.016) and those with a higher risk score (HR 1.73, 95% CI 1.03 to 2.91, p=0.038). Conclusion: This analysis suggested that BG was associated with poorer AFS than EVT in patients with non-dialysis-dependent CKD and CLTI. Male sex, previous myocardial infarction, and the absence of runoff vessels were additionally identified as predictors of poorer outcomes.

scholarly journals Prognostic Factors and a Nomogram Predicting Overall Survival in Patients with Limb Chondrosarcomas: A Population-Based Study

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Xinjie Wu ◽  
Yanlei Wang ◽  
Wei Sun ◽  
Mingsheng Tan
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Clinical Decision Making ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Training Group ◽  
Clinical Decision ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Predictive Values

Introduction. We aimed to develop and validate a nomogram for predicting the overall survival of patients with limb chondrosarcomas. Methods. The Surveillance, Epidemiology, and End Results (SEER) program database was used to identify patients diagnosed with chondrosarcomas, from which data was extracted from 18 registries in the United States between 1973 and 2016. A total of 813 patients were selected from the database. Univariate and multivariate analyses were performed using Cox proportional hazards regression models on the training group to identify independent prognostic factors and construct a nomogram to predict the 3- and 5-year survival probability of patients with limb chondrosarcomas. The predictive values were compared using concordance indexes ( C -indexes) and calibration plots. Results. All 813 patients were randomly divided into a training group ( n = 572 ) and a validation group ( n = 241 ). After univariate and multivariate Cox regression, a nomogram was constructed based on a new model containing the predictive variables of age, site, grade, tumor size, histology, stage, and use of surgery, radiotherapy, or chemotherapy. The prediction model provided excellent C -indexes (0.86 and 0.77 in the training and validation groups, respectively). The good discrimination and calibration of the nomograms were demonstrated for both the training and validation groups. Conclusions. The nomograms precisely and individually predict the overall survival of patients with limb chondrosarcomas and could assist personalized prognostic evaluation and individualized clinical decision-making.

scholarly journals Integrated Analysis of lncRNA-Associated ceRNA Network Identifies Two lncRNA Signatures as a Prognostic Biomarker in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Shuyan Zhang ◽  
Shanshan Li ◽  
Jian-Lin Guo ◽  
Ningyi Li ◽  
Cai-Ning Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Cox Proportional Hazards ◽  
Integrated Analysis ◽  
Survival Prediction ◽  
Survival Prognosis ◽  
Cox Regression Analysis ◽  
Cerna Network

Background. Gastric cancer (GC) is a malignant tumour that originates in the gastric mucosal epithelium and is associated with high mortality rates worldwide. Long noncoding RNAs (lncRNAs) have been identified to play an important role in the development of various tumours, including GC. Yet, lncRNA biomarkers in a competing endogenous RNA network (ceRNA network) that are used to predict survival prognosis remain lacking. The aim of this study was to construct a ceRNA network and identify the lncRNA signature as prognostic factors for survival prediction. Methods. The lncRNAs with overall survival significance were used to construct the ceRNA network. Function enrichment, protein-protein interaction, and cluster analysis were performed for dysregulated mRNAs. Multivariate Cox proportional hazards regression was performed to screen the potential prognostic lncRNAs. RT-qPCR was used to measure the relative expression levels of lncRNAs in cell lines. CCK8 assay was used to assess the proliferation of GC cells transfected with sh-lncRNAs. Results. Differentially expressed genes were identified including 585 lncRNAs, 144 miRNAs, and 2794 mRNAs. The ceRNA network was constructed using 35 DElncRNAs associated with overall survival of GC patients. Functional analysis revealed that these dysregulated mRNAs were enriched in cancer-related pathways, including TGF-beta, Rap 1, calcium, and the cGMP-PKG signalling pathway. A multivariate Cox regression analysis and cumulative risk score suggested that two of those lncRNAs (LINC01644 and LINC01697) had significant prognostic value. Furthermore, the results indicate that LINC01644 and LINC01697 were upregulated in GC cells. Knockdown of LINC01644 or LINC01697 suppressed the proliferation of GC cells. Conclusions. The authors identified 2-lncRNA signature in ceRNA regulatory network as prognostic biomarkers for the prediction of GC patient survival and revealed that silencing LINC01644 or LINC01697 inhibited the proliferation of GC cells.

Impact of cytoreductive surgery on outcomes of metastatic appendiceal carcinoma: a real-world, population-based study

2020 ◽  
Vol 9 (6) ◽  
pp. 431-439
Author(s):  
Omar Abdel-Rahman
Keyword(s):  
Overall Survival ◽  
Regression Analysis ◽  
Metastatic Disease ◽  
Cytoreductive Surgery ◽  
Mucinous Adenocarcinoma ◽  
Cox Regression ◽  
Cancer Specific Survival ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Appendiceal Carcinoma

Aim: To evaluate the impact of cytoreductive surgery on the outcomes of patients with metastatic appendiceal carcinoma. Methods: Surveillance, Epidemiology and End Results (SEER) database was accessed and patients with metastatic appendiceal carcinoma diagnosed (2010–2015) were reviewed. Kaplan–Meier survival estimates/log-rank testing were then used to assess overall survival outcomes according to cytoreductive surgery. Multivariable Cox regression analysis was then used to evaluate factors affecting cancer-specific survival. Factors included in this model were age, race, sex, stage and histology and cytoreductive surgery. Results: A total of 1339 patients with metastatic appendiceal carcinoma were included in the current study. Using Kaplan–Meier survival estimates to evaluate overall survival, patients with surgery for metastatic disease have better overall survival compared with patients without surgery for metastatic disease (p < 0.001). Stratifying survival analysis according to histology, the overall survival benefit from surgery for the metastases seems to be limited to patients with mucinous adenocarcinoma (p = 0.002) rather than patients with nonmucinous adenocarcinoma (p = 0.401). Multivariable Cox regression analysis was then conducted to evaluate factors predicting cancer-specific survival. The following factors were associated with worse cancer-specific survival: African-American race (hazard ratio [HR]: 1.356; 95% CI: 1.036–1.774; p = 0.026), more advanced stage (HR: 3.910; 95% CI: 2.735–5.588; p < 0.001), nonmucinous adenocarcinoma (HR for signet ring carcinoma vs mucinous adenocarcinoma: 2.119; 95% CI: 1.674–2.683; p < 0.001) and no surgical resection of metastatic disease (HR: 1.273; 95% CI: 1.067–1.519; p < 0.001). Conclusion: The current study suggests that among patients with metastatic appendiceal carcinoma, surgical cytoreduction of metastatic disease is associated with improved outcomes for patients with mucinous adenocarcinoma but not in patients with nonmucinous adenocarcinoma.

scholarly journals An immune-relevant signature of nine genes as a prognostic biomarker in patients with gastric carcinoma

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 850-859
Author(s):  
Bing Wang ◽  
Yang Zhang
Keyword(s):  
Regression Analysis ◽  
High Risk ◽  
Gastric Carcinoma ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Risk Group ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Cox Regression Analysis

AbstractBackgroundAs one of the most common malignant tumors worldwide, the morbidity and mortality of gastric carcinoma (GC) are gradually increasing. The aim of this study was to construct a signature according to immune-relevant genes to predict the survival outcome of GC patients using The Cancer Genome Altas (TCGA).MethodsUnivariate Cox regression analysis was used to assess the relationship between immune-relevant genes regarding the prognosis of patients with GC. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to select prognostic immune-relevant genes and to establish the signature for the prognostic evaluation of patients with GC. Multivariate Cox regression analysis and Kaplan–Meier survival analysis were used to assess the independent prognostic ability of the immune-relevant gene signature.ResultsA total of 113 prognostic immune-relevant genes were identified using univariate Cox proportional hazards regression analysis. A signature of nine immune-relevant genes was constructed using the LASSO Cox regression. The GC samples were assigned to two groups (low- and high risk) according to the optimal cutoff value of the signature score. Compared with the patients in the high-risk group, patients in the low-risk group had a significantly better prognosis in the TCGA and GSE84437 cohorts (log-rank test P < 0.001). Multivariate Cox regression analysis demonstrated that the signature of nine immune-relevant genes might serve as an independent predictor of GC.ConclusionsOur results showed that the signature of nine immune-relevant genes may potentially serve as a prognostic prediction for patients with GC, which may contribute to the decision-making of personalized treatment for the patients.

scholarly journals A seven-gene prognostic signature predicts overall survival of patients with lung adenocarcinoma (LUAD)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aisha Al-Dherasi ◽  
Qi-Tian Huang ◽  
Yuwei Liao ◽  
Sultan Al-Mosaib ◽  
Rulin Hua ◽  
...  
Keyword(s):  
Overall Survival ◽  
Regression Analysis ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Training Group ◽  
The Cancer Genome Atlas ◽  
Individual Treatment ◽  
Significant Implication ◽  
Prognostic Signature ◽  
Cox Regression Analysis

Abstract Background Lung adenocarcinoma (LUAD) is one of the most common types in the world with a high mortality rate. Despite advances in treatment strategies, the overall survival (OS) remains short. Our study aims to establish a reliable prognostic signature closely related to the survival of LUAD patients that can better predict prognosis and possibly help with individual monitoring of LUAD patients. Methods Raw RNA-sequencing data were obtained from Fudan University and used as a training group. Differentially expressed genes (DEGs) for the training group were screened. The univariate, least absolute shrinkage and selection operator (LASSO), and multivariate cox regression analysis were conducted to identify the candidate prognostic genes and construct the risk score model. Kaplan–Meier analysis, time-dependent receiver operating characteristic (ROC) curve were used to evaluate the prognostic power and performance of the signature. Moreover, The Cancer Genome Atlas (TCGA-LUAD) dataset was further used to validate the predictive ability of prognostic signature. Results A prognostic signature consisting of seven prognostic-related genes was constructed using the training group. The 7-gene prognostic signature significantly grouped patients in high and low-risk groups in terms of overall survival in the training cohort [hazard ratio, HR = 8.94, 95% confidence interval (95% CI)] [2.041–39.2]; P = 0.0004), and in the validation cohort (HR = 2.41, 95% CI [1.779–3.276]; P < 0.0001). Cox regression analysis (univariate and multivariate) demonstrated that the seven-gene signature is an independent prognostic biomarker for predicting the survival of LUAD patients. ROC curves revealed that the 7-gene prognostic signature achieved a good performance in training and validation groups (AUC = 0.91, AUC = 0.7 respectively) in predicting OS for LUAD patients. Furthermore, the stratified analysis of the signature showed another classification to predict the prognosis. Conclusion Our study suggested a new and reliable prognostic signature that has a significant implication in predicting overall survival for LUAD patients and may help with early diagnosis and making effective clinical decisions regarding potential individual treatment.

scholarly journals Sleeping Late Increases the Risk of Myocardial Infarction in the Middle-Aged and Older Populations

2021 ◽  
Vol 8 ◽  
Author(s):  
Yajuan Fan ◽  
Yanhua Wu ◽  
Yuan Peng ◽  
Binbin Zhao ◽  
Jian Yang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Regression Analysis ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Cox Proportional Hazards ◽  
Health Study ◽  
Sleep Habits ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Delayed Sleep

Objective: Sleep has a significant influence on the incidence of myocardial infarction (MI). The purpose of this study was to investigate the association between sleep timing including bedtime, wake-up time and sleep midpoint, and the incidence of MI.Methods: A total of 4,576 patients (2,065 men, 2,511 women; age 63.4 ± 11.0 years) were selected from the Sleep Heart Health Study. Sleep timings on weekdays and weekends were recorded or calculated based on the sleep habits questionnaire completed by the participants at baseline. Bedtime was divided into 10:00 PM and before, 10:01 PM−11:00 PM, 11:01 PM−12:00 AM, and later than 12:00 AM. Cox proportional hazards regression analysis was used to examine the relationship between sleep timings and MI.Results: Participants with a weekday bedtime later than 12:00 AM, between 11:01 PM−12:00 AM, and 10:00 PM or before had a higher incidence of MI than those with a bedtime between 10:01 PM and 11:00 PM (9.2% vs. 7.0% vs. 6.9% vs. 5.1%, respectively; P = 0.008). Multivariable Cox regression analysis showed that sleeping on weekdays later than 12:00 AM was associated with an increased risk of incident MI after adjusting for potential covariates (hazard ratio, 1.628; 95% confidence interval, 1.092–2.427; P = 0.017). However, there was no significant association between late bedtime on weekends and MI. In addition, no significant association of late wake-up time and delayed sleep midpoint on both weekdays and weekends with the incidence of MI was observed.Conclusion: Sleeping late on weekday (&gt;12:00 AM) independently increased the risk of MI. This finding emphasizes the importance of a proper bedtime for the maintenance of the health of the cardiovascular system.

scholarly journals Systemic Inflammatory Cytokines Associate With SARS-COV-2 Viral Shedding Time in Covid-19 Inpatients

2020 ◽  
Author(s):  
Jing Shi ◽  
Chongsheng Cheng ◽  
Muqing Yu ◽  
Xiaochen Li ◽  
Ke Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Regression Analysis ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Interleukin 2 ◽  
Cox Proportional Hazards ◽  
Cox Regression Analysis ◽  
Global Challenge ◽  
Viral Shedding ◽  
Virus Clearance

Abstract Background: Since December 2019, coronavirus disease 2019 (COVID-19), as an infectious disease with cytokine storm, has become an emerging global challenge. To assess the duration of SARS-COV-2 viral shedding and associated risk factors in COVID-19 patients.Methods: COVID-19 patients with interleukin (IL)-1b, soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α cytokines data consecutively admitted to Tongji Hospital from January 27, 2020 through February 5, 2020 were enrolled and been followed up until March 24, 2020. We utilized Kaplan-Meier method and Cox proportional hazards regression analysis to assess the duration of viral shedding and risk factors affecting virus clearance.Results: 246 inpatients with laboratory confirmed COVID-19 were enrolled. The median duration of viral shedding was 24 days, ranging from 6 to 63 days. Age, severity of COVID-19, albumin, lactate dehydrogenase (LDH), D-dimer, ferritin and sIL-2R were associated with duration of viral shedding. Administration of lopinavir-ritonavir, arbidol, oseltamivir and intravenous immunoglobulin did not shorten viral shedding time. Multivariate cox regression analysis revealed that sIL-2R, LDH and severity of COVID-19 were independent factors associated with duration of viral shedding. At stratified analysis, the viral shedding time was positively correlated with age, sIL-2R and LDH in non-corticosteroid subgroup, while negatively correlated with lymphocyte count in corticosteroid group. Conclusions: The present study demonstrated that elevated sIL-2R, increased LDH and severe status were related to prolongation of viral shedding in COVID-19 inpatients. Further research is urgent to investigate the mechanism of immune reaction involved in the virus clearance process and aim to the optimal antiviral therapy.

scholarly journals 1319. Assessment of Spectrum Score-Based Antibiotic De-Escalation in Patients with Nosocomial Pneumonia

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S748-S748
Author(s):  
Daniel T Ilges ◽  
Elizabeth Neuner ◽  
Tamara Krekel ◽  
David J Ritchie ◽  
Nicholas B Hampton ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Treatment Failure ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Multivariate Regression Analysis ◽  
Cox Proportional Hazards ◽  
Empiric Antibiotic Therapy ◽  
Cox Regression Analysis ◽  
Patient Admissions ◽  
The Impact

Abstract Background Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) cause significant morbidity and mortality. Guidelines recommend broad-spectrum empiric antibiotic therapy, including treatment for Pseudomonas aeruginosa (PSAR) and methicillin-resistant Staphylococcus aureus (MRSA), followed by de-escalation (DE). This study sought to assess the impact of DE on treatment failure. Methods This single-center retrospective cohort study screened all adult patients with a discharge diagnosis code for pneumonia from 2016–2019. Patients were enrolled if they met pre-defined criteria for HAP/VAP ≥48 hours after admission. Date of pneumonia diagnosis was defined as day 0. Spectrum scores were calculated, and DE was defined as a score reduction on day 3 versus day 1. Patients with DE were compared to patients with no de-escalation (NDE). Data were compared using chi-square, Mann-Whitney U, or T-tests. The primary outcome was composite treatment failure, defined as all-cause mortality or re-admission for pneumonia within 30 days of diagnosis, analyzed using a Cox proportional hazards analysis to control for confounding variables. Figure 1. Study Schematic Table 1. Spectrum Score Assignment Results Of 11860 admissions screened, 1812 unique patient-admissions were included (1102 HAP, 710 VAP). Fewer patients received DE (876 DE vs. 1026 NDE). Groups were well-matched at baseline, although more patients receiving DE had respiratory cultures ordered (56.6% vs. 50.6%, P=0.011). Patients receiving DE experienced a 65% and 44% reduction in anti-MRSA and anti-PSAR therapies by day 3, respectively. There was no difference in composite treatment failure (35.0% DE vs. 33.8% NDE, P=0.604). DE was not associated with treatment failure on Cox multivariate regression analysis (HR 1.13, 95% CI 0.97-1.33, P=0.149). Patients receiving DE had fewer antimicrobial days (median 9 vs. 11, P&lt; 0.0001), episodes of Clostridioides difficile (2.2% vs. 3.8%, P=0.046), and days of hospitalization (median 20 vs. 22 days, P=0.006). Figure 2: Median Spectrum Scores (SS) Days 0 to 28 Table 2: Cox Regression Analysis Conclusion DE and NDE resulted in similar rates of composite treatment failure at 30 days; however, DE was associated with fewer antimicrobial days, episodes of C. difficile, and days of hospitalization. Spectrum scores can objectively identify DE, but further studies are needed to fully understand their utility in this context. Disclosures Tamara Krekel, PharmD, BCPS, BCIDP, Merck (Speaker’s Bureau) David J. Ritchie, PharmD, BCPS (AQ-ID), AbbVie (Speaker’s Bureau)Merck (Speaker’s Bureau)

Impact of metformin on prostate cancer (PC) outcomes in the E3805 CHAARTED trial.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 181-181 ◽  
Author(s):  
David Frazier Jarrard ◽  
Yu-Hui Chen ◽  
Glenn Liu ◽  
Michael Anthony Carducci ◽  
Mario A. Eisenberger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Local Therapy ◽  
Cox Proportional Hazards ◽  
Clinicopathologic Characteristics ◽  
Cox Regression Analysis ◽  
Anticancer Properties ◽  
Cox Proportional Hazards Models

181 Background: To evaluate whether metformin (Met) a widely-used, nontoxic oral antidiabetic drug with putative anticancer properties leads to improvements in prostate cancer (PC) outcomes in the CHAARTED trial. Methods: In the CHAARTED database where metformin use at baseline was recorded prospectively, we identified patients with metastatic PC who underwent either ADT alone or ADT and docetaxel (D) chemotherapy. Cox proportional hazards models were used to determine the effect of Metformin on outcomes. Results: A total of 788 patients (median age, 63 y) had complete data after randomization. Comparison of ADT+D+Met (n = 39) to ADT+D (n = 357) and ADT+Met (n = 29) to ADT alone (n = 363) revealed similar clinicopathologic characteristics. Cause of death was PC in 13(81%) of ADT+D+Met, 72(85%) ADT+D, 9(82%) ADT+Met and 105(84%) ADT alone groups. See table for PC outcomes and overall survival by metformin use. Cox regression analysis for overall survival stratified by stratification factors at randomization demonstrates Met use was associated with a trend for worse overall survival (HR 1.47 95%CI: [0.95,2.26], p = 0.08) with adjustment for treatment arm and prior local therapy. In contrast, ADT+D use (HR 0.62; 95%CI: [0.47,0.81]) and prior local therapy with surgery or radiation (HR 0.56; 95% CI: [0.38, 0.82]) were associated with improved survival. Conclusions: In this study, baseline metformin did not improve PC outcomes. Partial support and drug supply by Sanofi. Clinical trial information: NCT00309985. [Table: see text]

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