Outcomes of patients with high-risk non-muscle invasive bladder cancer (NMIBC) who undergo radical cystectomy after BCG and subsequent salvage intravesical therapy.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 483-483
Author(s):  
Vignesh T. Packiam ◽  
Craig V. Labbate ◽  
Stephen A. Boorjian ◽  
Robert F. Tarrell ◽  
Brittany Adamic ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Oncologic Outcomes ◽  
Intravesical Therapy ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Kaplan Meier

483 Background: We evaluate the impact of salvage intravesical therapy on survival in patients with NMIBC previously treated with BCG who ultimately underwent radical cystectomy (RC). Methods: We retrospectively identified patients with NMIBC who received at least 1 complete induction course of BCG and subsequently underwent RC for bladder cancer between 2000-2018. Patients were stratified by receipt of salvage intravesical therapy following BCG prior to RC. Oncologic outcomes were compared using Cox proportional hazards regression analysis and the Kaplan-Meier method. Results: We identified 371 patients who underwent RC after receiving BCG, of whom 55 (15%) received salvage intravesical therapy, most commonly Mitomycin C (n = 26), Valrubicin (n = 8), Gemcitabine (n = 7), and CG0070 (n = 6). Median follow-up among survivors was 1.1 (IQR 0-4.3) years. Patients who received salvage intravesical therapy were more likely to initially present with CIS (27% vs 17%) and less likely to present with T1 disease (33% vs 50%, both p < 0.05). Receipt of salvage intravesical therapy was not associated with increased risk of adverse pathology (≥pT2 or pN+) at RC (33% vs 41%, p = 0.27). Furthermore, on Kaplan-Meier analysis, receipt of salvage intravesical therapy was not associated with cancer-specific or overall survival. On multivariable Cox proportional hazards regression, clinical stage prior to RC, but not receipt of salvage intravesical therapy, was associated with inferior cancer-specific survival and overall survival. Conclusions: Our results suggest that RC following carefully managed salvage intravesical therapy after BCG is not associated with inferior oncologic outcomes, which can improve patient counseling. [Table: see text]

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.

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.

Association of low RKIP expression with poor prognosis in non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3068-3068
Author(s):  
Lingbin Meng ◽  
Rui Ji ◽  
Damian A. Laber ◽  
Xuebo Yan ◽  
Xiaochun Xu
Keyword(s):  
Overall Survival ◽  
Tumor Size ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Tnm Stage ◽  
Erk Signaling ◽  
Small Cell Lung ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Nsclc Patients

3068 Background: Raf1 kinase inhibitor protein (RKIP) is able to bind Raf1 to inhibit Ras-Raf-MEK-ERK signaling, a major oncogenic pathway. It has been reported that reduced RKIP expression associates with poor prognosis in many cancers, including gastric adenocarcinoma, gliomas and bladder cancer. However, there are only several studies on its role in non-small cell lung cancer (NSCLC) and the conclusion is still controversial. Hence, we performed this study to assess the prognostic significance of RKIP in our NSCLC population. Methods: Between June 2017 and June 2020, 156 NSCLC patients treated at our hospital were included for the present study. None of the patients had received chemotherapy, radiotherapy or surgery before. Their tumor tissues and surrounding normal lung tissues were collected for immunostain and western blot analysis of RKIP expression and ERK signaling. We collected information about gender, age, histological differentiation, tumor size, TNM stage, and lymph node status. Survival curves were analyzed using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic value of various variables in a univariate and multivariate setting. Results: Immunostain and western blot results showed a lower RKIP expression and a higher p-ERK level in cancer tissues compared with the surrounding normal tissues. A reduced RKIP expression with high level of p-ERK was also observed in TNM stages III and IV as compared with I and II. Pearson's chi-squared test confirmed low RKIP expression associated with poorer TNM stage ( p< 0.001) and N-stage ( p< 0.05). No significant correlation was observed between RKIP expression level and gender, age, histological type or tumor size. Kaplan-Meier survival analysis revealed that patients with low RKIP expression had significantly worse overall survival than patients with high RKIP expression ( p= 0.019, log-rank). This conclusion was consistent in the stage I&II patients ( p= 0.011, log-rank) but not in the stage III&IV patients ( p= 0.711, log-rank). Univariate Cox proportional hazards regression analysis indicated Tumor size, TNM stage and RKIP expression significantly affected overall survival of the NSCLC patients. Multivariate Cox proportional hazards regression analysis confirmed RKIP expression remained a significant predictor of survival after correcting for the effects of Tumor size and TNM stage (hazard ratio = 1.730, 95% confidence interval = 1.017 – 2.942, p = 0.043). Conclusions: In this study, low RKIP expression was a poor prognostic indicator in NSCLC as it significantly correlated with poorer TNM stage, N-status, and overall survival. Our findings suggest that by inhibiting Ras-Raf-MEK-ERK pathway RKIP may play an anti-tumor role in NSCLC.

γ-H2AX as a novel prognostic marker in patients with non-small lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17553-e17553
Author(s):  
Dimitrios Matthaios ◽  
Panagiotis Hountis ◽  
Grigorios Trypsianis ◽  
Athanasios Zissimopoulos ◽  
Demosthenes Bouros ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Regression Analysis ◽  
Proportional Hazards ◽  
Prognostic Indicator ◽  
Cox Proportional Hazards ◽  
Independent Effect ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

e17553 Background: Phosphorylation of the H2AX histone is an early indicator of DNA double-strand breaks and of the resulting DNA damage response. In the present study we assessed the expression of γ-Η2ΑΧ in a cohort of 96 patients with non-small cell lung carcinoma and evaluated its role as a prognostic indicator in resectable NCSLC patients. Methods: 96 parafin-embedded specimens of non-small lung cancer patients were examined. All patients underwent radical thoracic surgery of primary tumor (lobectomy or pneumonectomy) and regional lymph nodes dissection. γ-Η2ΑΧ expression was assessed by standard immunohistochemistry.Multivariate Cox proportional hazards regression analysis, using a backward selection approach, were performed to explore the independent effect of variables on survival. All tests were two tailed and statistical significance was considered for p values <0.05. Results: Follow-up was available for all patients; mean duration of follow-up was 27.50 ± 14.07 months (range 0.2-57 months, median 24 months). Sixty-three patients (65.2%) died during the follow-up period. The mean survival time was 32.2 ± 1.9 months (95% CI = 28.5 to 35.8 months; median 30.0 months); one, two and three-year survival rates were 86.5 ± 3.5%, 57.3 ± 5.1% and 37.1 ± 5.4% respectively. Low γ-H2AX expression was associated with a significant better survival as compared with those having high γ-H2AX expression (23.2 months for high γ-Η2ΑΧ expressin vs 35.3 months for low γ-H2AX expression, p=0.009; HR=1.95, 95% CI=1.15-3.30). Further investigation with multivariate Cox proportional hazards regression analysis revealed that high expression of γ-H2AX remained independent prognostic factors of worse overall survival (HR=2.15, 95% CI=1.22-3.79, p=0.026). Conclusions: Our study is the first study to demonstrate that overexpression of γ-Η2ΑΧ is an independent prognostic indicator of worse overall survival in patients with non-small lung cancer. Further studies are needed to confirm our results.

The Timing of Subsequent Treatment for Teeth Restored with Large Amalgams and Crowns: Factors Related to the Need for Subsequent Treatment

2004 ◽  
Vol 83 (11) ◽  
pp. 854-858 ◽  
Author(s):  
J.L. Kolker ◽  
P.C. Damiano ◽  
M.P. Jones ◽  
D.V. Dawson ◽  
D.J. Caplan ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Subsequent Treatment ◽  
Cox Proportional Hazards ◽  
Regression Modeling ◽  
Survival Curves ◽  
Rank Tests ◽  
Factors Associated ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Kaplan Meier

Crowns and large amalgams protect structurally compromised teeth to various degrees in different situations. The aim of this investigation was to evaluate the survival of teeth with these two types of restorations and the factors associated with better outcomes. Retrospective administrative and chart data were used. Survival was defined and modeled as: (1) receipt of no treatment and (2) receipt of no catastrophic treatment over five- and 10-year periods. Analyses included: Kaplan-Meier survival curves, Log-Rank tests, and Cox proportional hazards regression modeling. Crowns survived longer with no treatment and with no catastrophic treatment; however, mandibular large amalgams were least likely to have survived with no treatment, and maxillary large amalgams were least likely to have survived with no catastrophic treatment. Having no adjacent teeth also decreased survival. Crowns survived longer than large amalgams, but factors such as arch type and the presence of adjacent teeth contributed to the survival of large amalgams.

scholarly journals T83. SUBSTANCE-INDUCED PSYCHOSIS LINKED TO BOTH INFECTIONS AND SCHIZOPHRENIA

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S263-S263
Author(s):  
Carsten Hjorthøj ◽  
Marie Starzer ◽  
Michael Benros ◽  
Merete Nordentoft
Keyword(s):  
Bipolar Disorder ◽  
Proportional Hazards ◽  
Strong Support ◽  
Cox Proportional Hazards ◽  
Schizophrenia Spectrum Disorders ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Long Term Prognosis ◽  
Time Varying Covariates

Abstract Background Substance-induced psychosis is an under-researched phenomenon, and little is known about its etiology (other than exposure to substances) and long-term prognosis. In this presentation, we aim to present results from two recent studies, one of which was recently published and the other is currently in the process of being analyzed. The first study investigates rates and predictors of conversion from substance-induced psychosis; the second study investigates the association between severe infections and substance-induced psychosis, including the contribution of infections on conversion to schizophrenia. Methods Both studies utilized the nationwide Danish registers. In study 1, we included all people diagnosed with substance-induced psychosis from 1994 to 2014 (n=6,788). These were followed using the Kaplan-Meier method and Cox proportional hazards regression to estimate rates and predictors of conversion to schizophrenia or bipolar disorder. In study 2, we included the entire Danish population born since 1981 (n=2,256,779). These were followed in Cox proportional hazards regression models, linking hospital-requiring infections as time-varying covariates to development of substance-induced psychosis. In further analyses, we followed those who had developed substance-induced psychosis to determine whether infections would influence the risk of converting to schizophrenia. Results Study 1: Overall, 32.2% (95% CI 29.7–34.9) of patients with a substance-induced psychosis converted to either bipolar or schizophrenia-spectrum disorders. The highest conversion rate was found for cannabis-induced psychosis, with 47.4% (95% CI 42.7–52.3) converting to either schizophrenia or bipolar disorder. Young age was associated with a higher risk of converting to schizophrenia. Self-harm was significantly linked to a higher risk of converting to both schizophrenia and bipolar disorder. Study 2: Infections increased the risk of substance-induced psychosis (HR=1.30, 95% CI 1.22–1.39) in the fully adjusted model. Hepatitis was the infection most strongly associated with substance-induced psychosis, at HR=3.42 (95% CI 2.47–4.74). Different sites of infections showed associations with different types of substance-induced psychosis. Finally, hepatitis increased the risk of conversion to schizophrenia with HR=1.87 (95% CI 1.07–3.26). Discussion Substance-induced psychosis is strongly associated with the development of severe mental illness, and a long follow-up period is needed to identify the majority of cases. Infections appear to play a role in the etiology of substance-induced psychosis which is very similar to the role infections play in the etiology of schizophrenia. This lends strong support to the existence of an immune-related component to psychosis in general, and not just to schizophrenia.

Utilization and sequencing of targeted therapy and cytoreductive nephrectomy in non–clear cell metastatic kidney cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 615-615
Author(s):  
Liam Connor Macleod ◽  
Scott S. Tykodi ◽  
Sarah Holt ◽  
John L. Gore
Keyword(s):  
Overall Survival ◽  
Targeted Therapy ◽  
Kidney Cancer ◽  
Proportional Hazards ◽  
Clear Cell ◽  
Cox Proportional Hazards ◽  
Average Treatment Effect ◽  
Targeted Agents ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

615 Background: Many patients with metastatic kidney cancer (mRCC) are ineligible for trials due to non-clear cell histology. Efficacy of targeted therapy agents in non-clear cell mRCC is still being investigated. We hypothesized that sequencing CN upfront is associated with improved overall survival. We analyze a population-based cohort of non-clear cell mRCC patients in the targeted therapy era. Methods: Patients from the SEER-Medicare files (2005-2011) with non-clear cell mRCC were categorized as having received upfront targeted therapy or upfront CN. Additional exclusions were age < 66 to avoid confounding by uncaptured non-Medicare coverage, and competing stage IV cancer. Targeted therapy was identified through Medicare Part D files. Cox proportional hazards regression determined association between treatment groups, clinical and cancer-related characteristics, and the main outcome, median overall survival (OS). Propensity matching controlled for measurable confounding in treatment selection. Results: Of 1,326 mRCC cases, 528 met inclusion criteria of whom 433 (82%) received targeted agents and 172 (33%) underwent CN. Of those not having CN, 74% were diagnosed by biopsy, 10% by cytology, and 16% radiographically (confirmed at autopsy). Thirteen percent received CN then targeted therapy (OS 14 mos, IQR 9-25), 2.5% received targeted therapy then CN (OS 14 mos, IQR 9-26), 18% received CN only (OS 14 mos, IQR5-40), 67% received targeted therapy only (OS 9 mos, IQR 4-19). On multivariable Cox proportional hazards regression upfront CN (regardless of post-CN therapy) was associated with improved OS (HR 0.54,95% CI 0.41,0.72). Using propensity scores, upfront CN patients (N = 161) were matched to upfront targeted therapy patient (N = 111) and the average treatment effect of CN was 8.3 months survival improvement (95% CI 4.0, 13.2). Conclusions: Although utilization of targeted agents in non-clear cell mRCC exceeds 80%, those with greatest OS received CN either upfront or after targeted therapy, though the latter was rare (2.5%). The variety of sequencing strategies observed is evidence of uncertainty regarding the best care for non-clear cell mRCC patients given limited options.

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 Persistent SARS-CoV-2 RNA Shedding Without Evidence of Infectiousness: A Cohort Study of Individuals With COVID-19

2021 ◽  
Author(s):  
Daniel Owusu ◽  
Mary A Pomeroy ◽  
Nathaniel M Lewis ◽  
Ashutosh Wadhwa ◽  
Anna R Yousaf ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Viral Rna ◽  
Cox Proportional Hazards Regression ◽  
Viral Culture ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Participant Characteristics ◽  
Pcr Test

Abstract Background To better understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding and infectivity, we estimated SARS-CoV-2 RNA shedding duration, described participant characteristics associated with the first negative rRT-PCR test (resolution), and determined if replication-competent viruses was recoverable ≥10 days after symptom onset. Methods We collected serial nasopharyngeal specimens from 109 individuals with rRT-PCR–confirmed COVID-19 in Utah and Wisconsin. We calculated viral RNA shedding resolution probability using the Kaplan-Meier estimator and evaluated characteristics associated with shedding resolution using Cox proportional hazards regression. We attempted viral culture for 35 rRT-PCR–positive nasopharyngeal specimens collected ≥10 days after symptom onset. Results The likelihood of viral RNA shedding resolution at 10 days after symptom onset was approximately 3%. Time to shedding resolution was shorter among participants aged &lt;18 years (adjusted hazards ratio [aHR], 3.01; 95% confidence interval [CI], 1.6–5.6) and longer among those aged ≥50 years (aHR, 0.50; 95% CI, .3–.9) compared to participants aged 18–49 years. No replication-competent viruses were recovered. Conclusions Although most patients were positive for SARS-CoV-2 for ≥10 days after symptom onset, our findings suggest that individuals with mild to moderate COVID-19 are unlikely to be infectious ≥10 days after symptom onset.

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