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.

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]

scholarly journals Effect on Survival of Longer Intervals Between Confirmed Diagnosis and Treatment Initiation Among Low-Income Women With Breast Cancer

2012 ◽  
Vol 30 (36) ◽  
pp. 4493-4500 ◽  
Author(s):  
John M. McLaughlin ◽  
Roger T. Anderson ◽  
Amy K. Ferketich ◽  
Eric E. Seiber ◽  
Rajesh Balkrishnan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
North Carolina ◽  
Low Income ◽  
Late Stage ◽  
Proportional Hazards ◽  
Treatment Initiation ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
The Impact

Purpose To determine the impact of longer periods between biopsy-confirmed breast cancer diagnosis and the initiation of treatment (Dx2Tx) on survival. Patients and Methods This study was a noninterventional, retrospective analysis of adult female North Carolina Medicaid enrollees diagnosed with breast cancer from January 1, 2000, through December, 31, 2002, in the linked North Carolina Central Cancer Registry–Medicaid Claims database. Follow-up data were available through July 31, 2006. Cox proportional hazards regression models were constructed to evaluate the impact on survival of delaying treatment ≥ 60 days after a confirmed diagnosis of breast cancer. Results The study cohort consisted of 1,786 low-income, adult women with a mean age of 61.6 years. A large proportion of the patients (44.3%) were racial minorities. Median time from biopsy-confirmed diagnosis to treatment initiation was 22 days. Adjusted Cox proportional hazards regression showed that although Dx2Tx length did not affect survival among those diagnosed at early stage, among late-stage patients, intervals between diagnosis and first treatment ≥ 60 days were associated with significantly worse overall survival (hazard ratio [HR], 1.66; 95% CI, 1.00 to 2.77; P = .05) and breast cancer–specific survival (HR, 1.85; 95% CI, 1.04 to 3.27; P = .04). Conclusion One in 10 women waited ≥ 60 days to initiate treatment after a diagnosis of breast cancer. Waiting ≥ 60 days to initiate treatment was associated with a significant 66% and 85% increased risk of overall and breast cancer–related death, respectively, among late-stage patients. Interventions designed to increase the timeliness of receiving breast cancer treatments should target late-stage patients, and clinicians should strive to promptly triage and initiate treatment for patients diagnosed at late stage.

scholarly journals Why is renal impairment associated with poorer cancer specific survival in breast cancer patients?: a comparison with patients with other comorbidities

2020 ◽  
Vol 25 (10) ◽  
pp. 1786-1792
Author(s):  
Andy Evans ◽  
Russell Petty ◽  
Jane Macaskill
Keyword(s):  
Breast Cancer ◽  
Renal Function ◽  
Impaired Renal Function ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Study Group ◽  
Cancer Specific Survival ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
The Poor

Abstract Background Our aim is to assess whether the poor breast cancer specific survival (BCSS) seen in women with breast cancer and impaired renal function can be explained by associations with other prognostic factors. Methods The study group was a consecutive series of patients undergoing breast ultrasound (US) who had invasive breast cancer (n = 1171). All women had their US diameter and mean stiffness (kPa) at shear wave elastography (SWE) recorded. The core biopsy grade and receptor status were noted. Core biopsy of abnormal axillary nodes and the patient referral source was also noted. Survival including cause of death was ascertained. Comorbidities at diagnosis were recorded. Patients were divided into those with a GFR<60 (“renal group”), those with other comorbidities and those with none. BCSS was assessed using Kaplan–Meier survival curves and Cox proportional hazards regression. Results One thousand, one hundred and forty-one patients constituted the study group. 107 (9%) patients had impaired renal function, 182 (16%) had other comorbidities while 852 (75%) had no comorbidities. Mean follow-up was 5.8 years. 109 breast cancer and 122 non-breast cancer deaths occurred. BCSS in the renal group was significantly worse than the other groups. Women with renal comorbidity were older, more likely to present symptomatically, have a pre-operative diagnosis of axillary metastases, and have larger and stiffer cancers. Cox proportional hazards regression showed that renal impairment maintained independent significance. Conclusion The poor BCSS in women with impaired renal function is partially explained by advanced tumour stage at presentation. However, impaired renal function maintains an independent prognostic effect.

scholarly journals Rethinking the 8th AJCC System: Is It Suitable for Patients Aged <55 Years With Stage T4N1M0 Follicular Variant of Papillary Thyroid Carcinoma to Be Placed in Stage I?

2020 ◽  
Vol 10 ◽  
Author(s):  
Wei Long ◽  
Di Hu ◽  
Ling Zhou ◽  
Yueye Huang ◽  
Wen Zeng ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Mortality Rates ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Stage Ii ◽  
Cancer Specific Survival ◽  
Factors Associated ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
New System

PurposeThe newest (8th) edition of the TNM staging system published in 2017. In this edition, some significant changes happened from the previous edition. As a result, down-staging appeared in nearly one third of DTC patients. However, we don’t know whether the new system predicts the survival of FVPTC patients accurately. Therefore, it is necessary to thoroughly evaluate the correlation between the new system and survival prediction in terms of FVPTC.MethodsWe enrolled 17,662 FVPTC patients from the Surveillance, Epidemiology, and End Results database. Factors associated with survival were identified by Cox regression analyses. The mortality rates per 1,000 person-years were calculated and compared. Cox proportional hazards regression quantified the risk of survival, and survival curves were produced by Kaplan-Meier analyses using log-rank tests.ResultsAge at diagnosis, race, T-stage at diagnosis, distant metastasis, radiation therapy, and surgery were independent factors associated with cancer-specific survival. Patients aged &lt;55 years with stage T4N1M0 FVPTC had higher mortality rates per 1,000 person-years than patients in the same stage according to the 8th AJCC System. Cox proportional hazards regression reflected that patients aged &lt;55 years with stage T1-3, any N, M0 or T4N0M0 disease (p=0.001) and patients aged ≥55 years with T1-2N0M0 disease (p=0.004) had significantly lower risks of cancer-specific survival (CSS) than those aged &lt;55 years with stage T4N1M0 disease. The CSS curve of patients aged &lt;55 years with stage T4N1M0 disease showed a decline on comparison with others belonging to stage I (p&lt;0.001); and the curve was even not different from patients in stage II and stage III (p&gt;0.05).ConclusionPatients aged &lt;55 years with stage T4N1M0 FVPTC had worse survival than patients in stage I; no difference was seen on comparison with stage II patients. We recommend this group of patients be upstaged in the 8th AJCC system.

Effect of Severity of Rod Contour on Posterior Rod Failure in the Setting of Lumbar Pedicle Subtraction Osteotomy (PSO)

Neurosurgery ◽  
2012 ◽  
Vol 72 (2) ◽  
pp. 276-283 ◽  
Author(s):  
Jessica A. Tang ◽  
Jeremi M. Leasure ◽  
Justin S. Smith ◽  
Jenni M. Buckley ◽  
Dimitriy Kondrashov ◽  
...  
Keyword(s):  
Fatigue Life ◽  
Proportional Hazards ◽  
Mechanical Test ◽  
Pedicle Subtraction Osteotomy ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Rod System ◽  
Flat Back

Abstract BACKGROUND: Rod failure has been reported clinically in pedicle subtraction osteotomy (PSO) to correct flat back deformity. OBJECTIVE: To characterize the fatigue life of posterior screw-rod constructs in the setting of PSO as a function of the severity of rod contour angle. METHODS: A modified ASTM F1717 to 04 was used. Rods were contoured to the appropriate angle for the equivalent 20-, 40-, or 60-degree PSO angles. Testing was performed on a mechanical test frame at 400/40 N and 250/25 N, and specimens were cycled at 4 Hz to failure or run-out at 2 000 000 cycles. The effect of the screw-rod system on fatigue strength of curved rods was compared using Cox proportional hazards regression. RESULTS: At 400 N/40 N, Cox proportional hazards regression indicated that contouring rods from a 20-degree PSO angle to either 40 or 60 degrees significantly decreased fatigue life (hazard ratio = 7863.6, P = .0144). However, contouring rods from a 40-degree PSO angle to 60 degrees had no significant effect on the fatigue life (P &gt; .05). At 250 N/25 N, Cox proportional hazards regression indicated that contouring rods from a 20-degree PSO angle to either 40 or 60 degrees significantly decreased fatigue life (hazard ratio = 7863.6, P = .0144). Furthermore, contouring rods from a 40-degree PSO angle to 60 degrees had a significant effect on the fatigue life (hazard ratio = 7863.6, P = .0144). CONCLUSION: Results suggest that in the setting of PSO, the fatigue life of posterior spinal fixation rods depends largely on the severity of the rod angle used to maintain the vertebral angle created by the PSO and is significantly lowered by rod contouring.

scholarly journals Kawasaki Disease Increases the Incidence of Myopia

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yung-Jen Kung ◽  
Chang-Ching Wei ◽  
Liuh An Chen ◽  
Jiin Yi Chen ◽  
Ching-Yao Chang ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Regression Model ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Health Concern ◽  
Rank Test ◽  
Research Database ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

The prevalence of myopia has rapidly increased in recent decades and has led to a considerable global public health concern. In this study, we elucidate the relationship between Kawasaki disease (KD) and the incidence of myopia. We used Taiwan’s National Health Insurance Research Database to conduct a population-based cohort study. We identified patients diagnosed with KD and individuals without KD who were selected by frequency matched based on sex, age, and the index year. The Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence intervals for the comparison of the 2 cohorts. The log-rank test was used to test the incidence of myopia in the 2 cohorts. A total of 532 patients were included in the KD cohort and 2128 in the non-KD cohort. The risk of myopia (hazard ratio, 1.31; 95% confidence interval, 1.08–1.58; P<0.01) was higher among patients with KD than among those in the non-KD cohort. The Cox proportional hazards regression model showed that irrespective of age, gender, and urbanization, Kawasaki disease was an independent risk factor for myopia. Patients with Kawasaki disease exhibited a substantially higher risk for developing myopia.

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.

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