Application of a time-varying covariate model to the analysis of CA 19–9 as a biomarker for time-to-progression (TTP) and overall survival (OS) in patients with advanced pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15545-e15545
Author(s):  
S. Boeck ◽  
R. P. Laubender ◽  
M. Haas ◽  
C. Klose ◽  
F. Kullmann ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Predictive Biomarker ◽  
Cox Proportional Hazards ◽  
Time Varying ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Pre Treatment

e15545 Background: It remains unclear whether baseline CA 19–9 or CA 19–9 kinetics during chemotherapy may serve as predictive biomarker in patients (pts) with pancreatic cancer (PC). Methods: Main inclusion criteria for this retrospective multicenter analysis: histologically confirmed diagnosis of PC, treatment with first-line therapy, pre-treatment CA 19–9 level of > 5.2 U/ml. Analysis of CA 19–9 was exclusively performed using the Elecsys® assay (Roche Diagnostics). The effect of the pre- treatment CA 19–9 level on TTP and OS was modelled by Cox proportional hazards regression. The effect of CA 19–9 kinetics was also modelled by Cox proportional hazards regression where CA 19–9 was treated as time-varying covariate. When modelling CA 19–9 we developed univariate and multivariate Cox models where we selected additional predictors (e.g. performance status) using backward elimination performing likelihood ratio tests on a significance level of 0.05. Results: One-hundred and fifteen pts from 5 German centers were included. Median age was 63 years, 12% had locally advanced and 88% metastatic disease; 73 % of the pts were treated within prospective clinical trials. Median baseline CA 19–9 was 1059 U/ml (range 9.5–100000), median pre- treatment bilirubin 0.6 mg/dl. The median TTP in the study population was 4.4 months, median OS 9.4 months. Univariate analysis showed that the pre-treatment CA 19–9 level (as continuous variable, log [CA 19–9]) was significantly associated with TTP (HR 1.24, 95% CI 1.12–1.37, p<0.001) and OS (HR 1.16, 95% CI 1.06–1.28, p=0.002). These associations remained significant also within a multivariate analysis. For CA 19–9 kinetics during chemotherapy, data from 69 pts (TTP) and 84 pts (OS) were available, respectively; log [CA 19–9] kinetics were found to be a significant predictor for TTP in univariate (HR 1.44, 95% CI 1.25–1.67, p<0.001) and multivariate (HR 1.39, 95% CI 1.19–1.62, p<0.001) analyses, and also for OS (univariate: HR 1.34, 95% CI 1.20–1.49, p<0.001; multivariate: HR 1.39, 95% CI 1.23–1.57, p<0.001). Conclusions: According to this new statistical model, CA 19–9 may serve as a useful predictive biomarker in advanced PC. [Table: see text]

Evaluation of circulating biomarkers of bone metastasis in early-stage breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10613-10613
Author(s):  
Windy Marie Dean-Colomb ◽  
Kenneth R. Hess ◽  
Elliana J. Young ◽  
Terrie Gornet ◽  
Beverly Carol Handy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Stage I ◽  
Clinical Factors ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

10613 Background: Bone is the preferred site for metastasis of breast cancer, affecting approximately 70% of women with advanced disease. N-terminal of procollagen type 1 (P1NP), c-terminal peptide crosslinks (CTX), Osteocalcin (OC) and interleukin-6 (IL-6) are markers of bone turnover that may have clinical utility as predictors of breast cancer recurrence in the bone. Methods: Serum was collected from 168 patients with stage I/II/III breast cancer prior to treatment from 09/2001 to 12/2008 and stored at -80 C. Serum levels of P1NP, CTX, OC and IL-6 were determined using the Roche’s Elecsys 2010 automated immunoassay system. Correlations of biomarker levels with time to bone metastasis (BM) development were assessed with Cox proportional hazards regression analysis and the Kaplan-Meier method. Results: Among the 168 patients analyzed, 60 patients subsequently developed BM. The biomarkers all had skewed distributions with long right tails and thus were all analyzed on the log scale. Residual analysis suggested non-linear relationships between each biomarker and risk of developing BM during follow-up. Thus, we fit Cox proportional hazards regression models for each biomarker with quadratic polynomials (on the log scale). On univariate analysis, these analyses generated p = 0.33 for IL-6, 0.26 for osteocalcin, 0.40 for CTX, and 0.032 for P1NP. Adjusting for clinical factors (stage, age, race, post menopausal, ER/PR status, HER2 status, nuclear grade) yielded p = 0.0035 for the quadratic polynomial for log P1NP. A cut-point of 75 ng/mL identified patients with a short time to development of BM. The 1, 3, and 5-year freedom-from-BM probabilities were 96%, 77% and 66% for the 150 patients with P1NP values ≤ 75 ng/mL and 88%, 45%, and 36% for the 16 patients with P1NP values > 75 ng/mL. The hazard ratio comparing patients with P1NP values ≤ 75 ng/mL to patients with P1NP values > 75 ng/mL was 3.0 (95% CI, 1.5 - 6.2) and p = 0.0075 ng/mL. After adjustment for clinical factors, the hazard ratio was 3.4 (1.5, 7.6) with p = 0.0026. Conclusions: Serum P1NP levels >75 ng/mL correlate with a shorter time to development of BM in patients with stage I-III breast cancer.

Effectiveness of Adjuvant Chemotherapy After Radical Nephroureterectomy for Locally Advanced and/or Positive Regional Lymph Node Upper Tract Urothelial Carcinoma

2017 ◽  
Vol 35 (8) ◽  
pp. 852-860 ◽  
Author(s):  
Thomas Seisen ◽  
Ross E. Krasnow ◽  
Joaquim Bellmunt ◽  
Morgan Rouprêt ◽  
Jeffrey J. Leow ◽  
...  
Keyword(s):  
Lymph Node ◽  
Adjuvant Chemotherapy ◽  
Proportional Hazards ◽  
Regional Lymph Node ◽  
Locally Advanced ◽  
Cox Proportional Hazards ◽  
Radical Nephroureterectomy ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Kaplan Meier

Purpose There is limited evidence to support the use of adjuvant chemotherapy (AC) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Against this backdrop, we hypothesized that such treatment is associated with overall survival (OS) benefit in patients with locally advanced and/or positive regional lymph node disease. Patients and Methods Within the National Cancer Database (2004 to 2012), we identified 3,253 individuals who received AC or observation after RNU for pT3/T4 and/or pN+ UTUC. Inverse probability of treatment weighting (IPTW) –adjusted Kaplan-Meier curves and Cox proportional hazards regression analyses were used to compare OS of patients in the two treatment groups. In addition, we performed exploratory analyses of treatment effect according to age, gender, Charlson comorbidity index, pathologic stage (pT3/T4N0, pT3/T4Nx and pTanyN+), and surgical margin status. Results Overall, 762 (23.42%) and 2,491 (76.58%) patients with pT3/T4 and/or pN+ UTUC received AC and observation, respectively, after RNU. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for AC versus observation (47.41 [interquartile range,19.88 to 112.39] v 35.78 [interquartile range, 14.09 to 99.22] months; P < .001). The 5-year IPTW-adjusted rates of OS for AC versus observation were 43.90% and 35.85%, respectively. In IPTW-adjusted Cox proportional hazards regression analysis, AC was associated with a significant OS benefit (hazard ratio, 0.77 [95% CI, 0.68 to 0.88]; P < .001). This benefit was consistent across all subgroups examined (all P < .05), and no significant heterogeneity of treatment effect was observed (all Pinteraction > .05). Conclusion We report an OS benefit in patients who received AC versus observation after RNU for pT3/T4 and/or pN+ UTUC. Although our results are limited by the usual biases related to the observational study design, we believe that the present findings should be considered when advising post-RNU management of advanced UTUC, pending level I evidence.

scholarly journals Metformin Use and Survival of Patients With Pancreatic Cancer: A Cautionary Lesson

2016 ◽  
Vol 34 (16) ◽  
pp. 1898-1904 ◽  
Author(s):  
Roongruedee Chaiteerakij ◽  
Gloria M. Petersen ◽  
William R. Bamlet ◽  
Kari G. Chaffee ◽  
David B. Zhen ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Median Survival ◽  
Patient Selection ◽  
Analytical Methods ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Time Varying ◽  
Covariate Analysis ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

Purpose The inclusion of metformin in the treatment arms of cancer clinical trials is based on improved survival that has been demonstrated in retrospective epidemiologic studies; however, unintended biases may exist when analysis is performed by using a conventional Cox proportional hazards regression model with dichotomous ever/never categorization. We examined the impact of metformin exposure definitions, analytical methods, and patient selection on the estimated effect size of metformin exposure on survival in a large cohort of patients with pancreatic ductal adenocarcinoma (PDAC). Patients and Methods Of newly diagnosed patients with PDAC with diabetes, 980 were retrospectively included, and exposure to metformin documented. Median survival was assessed by using Kaplan-Meier and log-rank methods. Hazard ratios (HR) and 95% CIs were computed to compare time-varying covariate analysis with conventional Cox proportional hazards regression analysis. Results Median survival of metformin users versus nonusers was 9.9 versus 8.9 months, respectively. By the time-varying covariate analysis, metformin use was not statistically significantly associated with improved survival (HR, 0.93; 95% CI, 0.81 to1.07; P = .28). There was no evidence of benefit in the subset of patients who were naïve to metformin at the time of PDAC diagnosis (most representative of patients enrolled in clinical trials; HR, 1.01; 95% CI, 0.80 to 1.30; P = .89); however, when the analysis was performed by using the conventional Cox model, an artificial survival benefit of metformin was detected (HR, 0.88; 95% CI, 0.77 to 1.01; P = .08), which suggested biased results from the conventional Cox analysis. Conclusion Our findings did not suggest the benefit of metformin use after patients are diagnosed with PDAC. We highlight the importance of patient selection and appropriate statistical analytical methods when studying medication exposure and cancer survival.

scholarly journals Hepatoid Adenocarcinoma of the Lung: A Systematic Review of the Literature From 1981 to 2020

2021 ◽  
Vol 11 ◽  
Author(s):  
Zan Hou ◽  
Jiaqing Xie ◽  
Li Zhang ◽  
Gangyi Dai ◽  
Yuanhang Chen ◽  
...  
Keyword(s):  
Regression Model ◽  
Proportional Hazards ◽  
Locally Advanced ◽  
Pik3ca Mutation ◽  
Cox Proportional Hazards ◽  
Hepatoid Adenocarcinoma ◽  
Adenocarcinoma Of The Lung ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
First Case

ObjectivesWe report the first case of hepatoid adenocarcinoma of the lung (HAL) with PIK3CA mutation. In addition, we analyzed data from HAL cases over the past 40 years to study its main treatment methods, prognosis, and the relationship between prognosis and the serum alpha-fetoprotein (AFP) level before treatment.MethodsWe report a 66-year-old male case who was diagnosed with locally advanced HAL with PIK3CA mutation and carried out a systematic literature search for HAL cases documented between 1981 and 2020. General patient information including case characteristics was extracted and summarized. The median OS (mOS) of HAL patients was determined using the KM survival curve. The Cox proportional hazards regression model was used to evaluate the effect of tumor size, location, and serum AFP value before treatment and radical surgery (RS) on the prognosis of patients.ResultsA total of 46 studies including 51 HAL patients was included in our review. Our study revealed that 52.9% of tumors were located in the upper lobe of the right lung. The proportion of serum AFP-positive patients before treatment, early-stage patients (TNM stage I and II), and patients who had received surgery were 69.2%, 34.1%, and 40%, respectively. The mOS of HAL patients was 16.0 months. The 2-year and 5-year survival rates of the patients were 35.3% and 8.0%, respectively. In the subgroup analysis, the 2-year survival rate for patients who received RS was 62.5%, while for patients who were unable to undergo RS, it was only 12.5% (p = 0.009). The Cox proportional hazards regression model indicated that RS can significantly improve the prognosis of HAL patients (p = 0.011), although the location and size of tumor as well as the serum AFP value before treatment had no significant effect on their prognosis (p = 0.82, p = 0.96, p = 0.25).ConclusionsHAL patients have a poor prognosis, and the survival benefits for patients receiving chemoradiotherapy or chemotherapy alone appear to be limited. We demonstrate statistically for the first time that pretreatment serum AFP values are not related to the prognosis of HAL patients and RS can significantly improve patient prognosis.

scholarly journals Replacement of potatoes with other vegetables and risk of myocardial infarction in the Danish Diet, Cancer and Health cohort

2021 ◽  
pp. 1-21
Author(s):  
Anne Mette L. Würtz ◽  
Mette D. Hansen ◽  
Anne Tjønneland ◽  
Eric B. Rimm ◽  
Erik B. Schmidt ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Similar Pattern ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Heterogeneous Group ◽  
Dietary Guidelines ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Root Vegetables

ABSTRACT Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29,142 women and 26,029 men aged 50-64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazards ratios (HR) with 95% CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13.6 years of follow-up, 656 female and 1,694 male cases were identified. Among women, the adjusted HR for MI was 1.02 (95% CI: 0.93, 1.13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0.93 (95% CI: 0.77, 1.13) for replacement of potatoes with fruiting vegetables and 0.91 (95% CI: 0.77, 1.07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups.

Development and Validation of a Prognostic Nomogram Model for Recurrence of Non-Muscle Invasive Bladder Cancer

2021 ◽  
Author(s):  
Sanhe Liu ◽  
Yongzhi Li ◽  
Diansheng Cui ◽  
Yuexia Jiao ◽  
Liqun Duan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Risk Stratification ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Muscle Invasive Bladder Cancer ◽  
Clinicopathologic Characteristics ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Muscle Invasive

Abstract BackgroundDifferent recurrence probability of non-muscle invasive bladder cancer (NMIBC) requests different adjuvant treatments and follow-up strategies. However, there is no simple, intuitive, and generally accepted clinical recurrence predictive model available for NMIBC. This study aims to construct a predictive model for the recurrence of NMIBC based on demographics and clinicopathologic characteristics from two independent centers. MethodsDemographics and clinicopathologic characteristics of 511 patients with NMIBC were retrospectively collected. Recurrence free survival (RFS) was estimated using the Kaplan-Meier method and log-rank tests. Univariate Cox proportional hazards regression analysis was used to screen variables associated with RFS, and a multivariate Cox proportional hazards regression model with a stepwise procedure was used to identify those factors of significance. A final nomogram model was built using the multivariable Cox method. The performance of the nomogram model was evaluated with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed with bootstrap resampling. X-tile software was used for risk stratification calculated by the nomogram model. ResultsIndependent prognostic factors including tumor stage, recurrence status, and European Association of Urology (EAU) risk stratification group were introduced to the nomogram model. The model showed acceptable calibration and discrimination (area under the receiver operating characteristic [ROC] curve was 0.85; the consistency index [C-index] was 0.79 [95% CI: 0.76 to 0.82]), which was superior to the EAU risk stratification group alone. The decision curve also proved well clinical usefulness. Moreover, all populations could be stratified into three distinct risk groups by the nomogram model. ConclusionsWe established and validated a novel nomogram model that can provide individual prediction of RFS for patients with NMIBC. This intuitively prognostic nomogram model may help clinicians in postoperative treatment and follow-up decision-making.

Antibiotic and acid-suppression medications during early childhood are associated with obesity

Gut ◽  
2018 ◽  
Vol 68 (1) ◽  
pp. 62-69 ◽  
Author(s):  
Christopher M Stark ◽  
Apryl Susi ◽  
Jill Emerick ◽  
Cade M Nylund
Keyword(s):  
Early Childhood ◽  
Department Of Defense ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Event Analysis ◽  
Early Exposure ◽  
Single Event ◽  
Inclusion Criteria ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

ObjectiveGut microbiota alterations are associated with obesity. Early exposure to medications, including acid suppressants and antibiotics, can alter gut biota and may increase the likelihood of developing obesity. We investigated the association of antibiotic, histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) prescriptions during early childhood with a diagnosis of obesity.DesignWe performed a cohort study of US Department of Defense TRICARE beneficiaries born from October 2006 to September 2013. Exposures were defined as having any dispensed prescription for antibiotic, H2RA or PPI medications in the first 2 years of life. A single event analysis of obesity was performed using Cox proportional hazards regression.Results333 353 children met inclusion criteria, with 241 502 (72.4%) children prescribed an antibiotic, 39 488 (11.8%) an H2RA and 11 089 (3.3%) a PPI. Antibiotic prescriptions were associated with obesity (HR 1.26; 95% CI 1.23 to 1.28). This association persisted regardless of antibiotic class and strengthened with each additional class of antibiotic prescribed. H2RA and PPI prescriptions were also associated with obesity, with a stronger association for each 30-day supply prescribed. The HR increased commensurately with exposure to each additional medication group prescribed.ConclusionsAntibiotics, acid suppressants and the combination of multiple medications in the first 2 years of life are associated with a diagnosis of childhood obesity. Microbiota-altering medications administered in early childhood may influence weight gain.

scholarly journals Identification of Arp2/3 Complex Subunits as Prognostic Biomarkers for Hepatocellular Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Shenglan Huang ◽  
Dan Li ◽  
LingLing Zhuang ◽  
Liying Sun ◽  
Jianbing Wu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Expression ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Gene Set Enrichment Analysis ◽  
Prognostic Biomarkers ◽  
Migration And Invasion ◽  
Regression Analyses ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

The actin-related protein 2/3 complex (Arp2/3) is a major actin nucleator that has been widely reported and plays an important role in promoting the migration and invasion of various cancers. However, the expression patterns and prognostic values of Arp2/3 subunits in hepatocellular carcinoma (HCC) remain unclear. In this study, The Cancer Genome Atlas (TCGA) and UCSC Xena databases were used to obtain mRNA expression and the corresponding clinical information, respectively. The differential expression and Arp2/3 subunits in HCC were analyzed using the “limma” package of R 4.0.4 software. The prognostic value of each subunit was evaluated using Kaplan–Meier survival analysis and Cox proportional hazards regression analyses. The results revealed that mRNA expression of Arp2/3 members (ACTR2, ACTR3, ARPC1A, APRC1B, ARPC2, ARPC3, ARPC4, ARPC5, and ARPC5L) was upregulated in HCC. Higher expression of Arp2/3 members was significantly correlated with worse overall survival (OS) and shorter progression-free survival (PFS) in HCC patients. Cox proportional hazards regression analyses demonstrated that ACTR3, ARPC2, and ARPC5 were independent prognostic biomarkers of survival in patients with HCC. The relation between tumor immunocyte infiltration and the prognostic subunits was determined using the TIMER 2.0 platform and the GEPIA database. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms of prognostic subunits in the carcinogenesis of HCC. The results revealed that ACTR3, ARPC2, and ARPC5 were significantly positively correlated with the infiltration of immune cells in HCC. The GSEA results indicated that ACTR3, ARPC2, and ARPC5 are involved in multiple cancer-related pathways that promote the development of HCC. In brief, various analyses indicated that Arp2/3 complex subunits were significantly upregulated and predicted worse survival in HCC, and they found that ACTR3, ARPC2, and ARPC5 could be used as independent predictors of survival and might be applied as promising molecular targets for diagnosis and therapy of HCC in the future.

Serum FGF21 Is Associated with Future Cardiovascular Events in Patients with Coronary Artery Disease

Cardiology ◽  
2018 ◽  
Vol 139 (4) ◽  
pp. 212-218 ◽  
Author(s):  
Yun Shen ◽  
Xueli Zhang ◽  
Yiting Xu ◽  
Qin Xiong ◽  
Zhigang Lu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Regression Analysis ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Artery Disease

Objectives: To investigate whether serum fibroblast growth factor 21 (FGF21) levels can be used to predict the future development of major adverse cardiovascular events (MACEs). Methods: This study included 253 patients who received subsequent follow-up, and complete data were collected for 234 patients. Independent predictors of MACEs were identified by using the Cox proportional-hazards regression analysis. The prognostic value of FGF21 levels for MACEs was evaluated by Kaplan-Meier survival analysis. Results: Of 229 patients finally enrolled in the analysis, 27/60 without coronary artery disease (CAD) at baseline experienced a MACE, and 132/169 patients with CAD at baseline experienced a MACE. Among patients with CAD at baseline, serum FGF21 levels were significantly higher in patients with MACEs (p < 0.05) than in patients without MACEs. Kaplan-Meier survival analysis showed patients with a higher serum FGF21 had a significantly lower event-free survival (p = 0.001) than those with a lower level. Further Cox proportional-hazards regression analysis, including the traditional risk factors for cardiovascular disease, showed that serum FGF21 was an independent predictor of MACE occurrence. Conclusions: In patients with CAD at baseline, an elevated serum FGF21 level was associated with the development of a MACE in the future.

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