Impact of Lesion Morphology on Durability After Angioplasty of Failed Arteriovenous Fistulas in Hemodialysis Patients

2017 ◽  
Vol 25 (5) ◽  
pp. 649-654 ◽  
Author(s):  
Kotaro Suemitsu ◽  
Tatsuya Shiraki ◽  
Osamu Iida ◽  
Hiroki Kobayashi ◽  
Yuki Matsuoka ◽  
...  
Keyword(s):  
Proportional Hazards Model ◽  
Negative Impact ◽  
Positive Impact ◽  
Balloon Dilation ◽  
Primary Patency ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Flow Volume ◽  
Venous Valve

Purpose: To investigate if morphological patterns of arteriovenous fistula (AVF) venous lesions affect primary patency after percutaneous transluminal angioplasty (PTA). Methods: From July 2014 to June 2015, 262 patients underwent PTA for failed AVFs. A total of 104 patients were excluded owing to (1) calcification or AVF occlusion precluding ultrasound examination, (2) central venous or arterial lesions, and (3) no follow-up, leaving 158 patients (mean age 71±12; 96 men) for analysis. More than half of the patients had one or more previous PTAs for the failed AVF. Prior to PTA the stenotic lesions were assessed using ultrasonography to determine stenotic patterns at the minimum lumen area site and to evaluate the flow volume in the brachial artery. Three stenotic patterns were identified: intimal hyperplasia (IH) stenosis (n=110), shrinking lumen stenosis (n=32), and venous valve–related stenosis (n=16). The main outcome measure was primary patency after PTA estimated using Kaplan-Meier analysis. Predictors for loss of primary patency were determined using a multivariate Cox proportional hazards model; the results are presented as the adjusted hazard ratio (HR) and 95% confidence interval (CI). Results: Median follow-up after PTA was 6.3 months (interquartile range 3.3, 10.5). The 6-month primary patency estimates were 56%±5% in the IH group, 40±9% in the shrinking lumen group, and 100% in the valve stenosis group (IH vs shrinking, p=0.013; IH vs valve, p=0.003). In multivariate analysis, shrinking lumen morphology had a negative impact on primary patency (HR 2.05, 95% CI 1.25 to 3.36, p=0.005), while venous valve–related stenosis had a positive impact (HR 0.19, 95% CI 0.04 to 0.79, p=0.023). Flow volume (10-mL/min increments; HR 0.97, 95% CI 0.96 to 0.99, p=0.004) and history of PTA (HR 1.66, 95% CI 1.06 to 2.60, p=0.029) were also independently associated with primary patency after PTA. Conclusion: The patterns of AVF stenosis as determined by ultrasound can affect the outcome of treatment with balloon dilation.

Sequential treatment of advanced or metastatic renal cell carcinoma (mRCC): What is effective? Data from the German RCC registry.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 499-499
Author(s):  
Lothar Mueller ◽  
Peter J. Goebell ◽  
A. Lueck ◽  
Friedrich Overkamp ◽  
Michele Vogt ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Negative Impact ◽  
Positive Impact ◽  
Current Treatment ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Sequential Treatment ◽  
Line Therapy ◽  
Systemic Treatments

499 Background: In addition to Bevacizumab+Interferon, current treatment options of mRCC imply two major intracellular modes of action and thus classes of therapies: the four approved tyrosine kinase inhibitors (TKI) Sunitinib, Sorafenib, Pazopanib, Axitinib and the two inhibitors of the mammalian target of rapamycin (mTOR) Temsirolimus, Everolimus (EVE). With their availability efficacy of sequential treatment has become a central question of clinical research. While clinical trials recruit highly selected patients (pts) and usually focus on a single line of therapy, collected data of clinical registries may represent all patients and all sequential therapies. Methods: Starting in 12/2007 the registry aims to enrol a total of 1500 patients from more than 120 oncology and urology outpatient centres collecting data on all systemic treatments, outcome, patient and tumour characteristics. Here, the effectiveness of two 1st – 2nd-line sequential treatments, TKI–TKI vs TKI–EVE, was investigated with a multivariate cox proportional hazards model considering potential confounding variables (age, comorbidity, body mass index (BMI), duration of 1st-line therapy, Motzer’s score and type of sequential treatment). Results: At the time of analysis, 481 pts had received sequential 1st- and 2nd-line treatment between 2007 and 2012. In total, 70% of pts received 1st-line TKI-treatment. 46% of these pts received the sequential treatment TKI–TKI, 25% received TKI–EVE. In the multivariate analysis, high BMI (HR 0.946, 95% CI 0.9018-0.9923, p<.05) and a long duration of 1st-line-therapy (HR 0.9967, 95% CI 0.9956-0.9979, p<.001) had a significant positive impact on OS, whereas high risk Motzer`s score (HR 8.9992, 95% CI 2.4231-33.4228, p<.01) had a significant negative impact on OS. However, the type of sequential treatment had no impact on OS (HR 1.0658, 95% CI0.6463-1.7576, p=0.802). Conclusions: The RCC Registry provides an overview of the current treatment reality in routine medical practice. TKI are the most frequently applied 1st-line treatments, followed by TKI or mTOR inhibitors. Our data show no difference concerning the effectiveness of the sequential treatment TKI–TKI vs TKI–EVE.

scholarly journals Risk factors associated with major adverse cardiac and cerebrovascular events following percutaneous coronary intervention: a 10-year follow-up comparing random survival forest and Cox proportional-hazards model

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Farhadian ◽  
Sahar Dehdar Karsidani ◽  
Azadeh Mozayanimonfared ◽  
Hossein Mahjub
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Coronary Intervention ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Cerebrovascular Events ◽  
Long Term Follow Up ◽  
Stent Length

Abstract Background Due to the limited number of studies with long term follow-up of patients undergoing Percutaneous Coronary Intervention (PCI), we investigated the occurrence of Major Adverse Cardiac and Cerebrovascular Events (MACCE) during 10 years of follow-up after coronary angioplasty using Random Survival Forest (RSF) and Cox proportional hazards models. Methods The current retrospective cohort study was performed on 220 patients (69 women and 151 men) undergoing coronary angioplasty from March 2009 to March 2012 in Farchshian Medical Center in Hamadan city, Iran. Survival time (month) as the response variable was considered from the date of angioplasty to the main endpoint or the end of the follow-up period (September 2019). To identify the factors influencing the occurrence of MACCE, the performance of Cox and RSF models were investigated in terms of C index, Integrated Brier Score (IBS) and prediction error criteria. Results Ninety-six patients (43.7%) experienced MACCE by the end of the follow-up period, and the median survival time was estimated to be 98 months. Survival decreased from 99% during the first year to 39% at 10 years' follow-up. By applying the Cox model, the predictors were identified as follows: age (HR = 1.03, 95% CI 1.01–1.05), diabetes (HR = 2.17, 95% CI 1.29–3.66), smoking (HR = 2.41, 95% CI 1.46–3.98), and stent length (HR = 1.74, 95% CI 1.11–2.75). The predictive performance was slightly better by the RSF model (IBS of 0.124 vs. 0.135, C index of 0.648 vs. 0.626 and out-of-bag error rate of 0.352 vs. 0.374 for RSF). In addition to age, diabetes, smoking, and stent length, RSF also included coronary artery disease (acute or chronic) and hyperlipidemia as the most important variables. Conclusion Machine-learning prediction models such as RSF showed better performance than the Cox proportional hazards model for the prediction of MACCE during long-term follow-up after PCI.

scholarly journals Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

2020 ◽  
Author(s):  
Yuko Yamaguchi ◽  
Marta Zampino ◽  
Toshiko Tanaka ◽  
Stefania Bandinelli ◽  
Yusuke Osawa ◽  
...  
Keyword(s):  
Older Adults ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Differentiation Factor ◽  
Hazards Model ◽  
Increased Risk ◽  
The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P&lt;.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

scholarly journals Clinical impact of regression from sustained to paroxysmal atrial fibrillation: the Fushimi AF registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Fujino ◽  
H Ogawa ◽  
S Ikeda ◽  
K Doi ◽  
Y Hamatani ◽  
...  
Keyword(s):  
Cardiac Death ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Clinical Impact ◽  
Cox Proportional Hazards Model ◽  
Cardiac Events ◽  
Hazards Model ◽  
Adverse Cardiac Events

Abstract Background Atrial fibrillation (AF) commonly progresses from paroxysmal type to sustained type in the natural course of the disease, and we previously demonstrated that the progression of AF was associated with increased risk of clinical adverse events. There are some patients, though less frequently, who regress from sustained to paroxysmal AF, but the clinical impact of the regression of AF remains unknown. Purpose We sought to investigate whether regression from sustained to paroxysmal AF is associated with better clinical outcomes. Methods Using the dataset of the Fushimi AF Registry, patients who were diagnosed as sustained (persistent or permanent) AF at baseline were studied. Conversion of sustained AF to paroxysmal AF during follow-up was defined as regression of AF. Major adverse cardiac events (MACE) were defined as the composite of cardiac death, stroke, and hospitalization for heart failure (HF). Event rates were compared between the patients with and without regression of AF. In patients with sustained AF at baseline, predictors of MACE were identified using Cox proportional hazards model. Results Among 2,253 patients who were diagnosed as sustained AF at baseline, regression of AF was observed in 9.0% (202/2,253, 2.0 per 100 patient-years) during a median follow-up of 4.0 years. Of these, 24.3% (49/202, 4.6 per 100 patient-years) of the patients finally recurred to sustained AF during follow-up. The proportion of asymptomatic patients was lower in patients with regression of AF than those without (with vs without regression; 49.0% vs 69.5%, p&lt;0.01). The percentage of beta-blocker use at baseline was similar between the two groups (37.2% vs 33.8%, p=0.34). The prevalence of patients who underwent catheter ablation or electrical cardioversion during follow-up was higher in patients with regression of AF (catheter ablation: 15.8% vs 5.5%; p&lt;0.01, cardioversion: 4.0% vs 1.4%; p&lt;0.01, respectively). The rate of MACE was significantly lower in patients with regression of AF as compared with patients who maintained sustained AF (3.7 vs 6.2 per 100 patient-years, log-rank p&lt;0.01). Figure shows the Kaplan-Meier curves for MACE, cardiac death, hospitalization for heart failure, and stroke. In patients with sustained AF at baseline, multivariable Cox proportional hazards model demonstrated that regression of AF was an independent predictor of lower MACE (adjusted hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.28 to 0.88, p=0.02), stroke (HR: 0.51, 95% CI: 0.30 to 0.88, p=0.02), and hospitalization for HF (HR: 0.50, 95% CI: 0.29 to 0.85, p=0.01). Conclusion Regression from sustained to paroxysmal AF was associated with a lower incidence of adverse cardiac events. Funding Acknowledgement Type of funding source: None

CTIM-10. REPRODUCIBILITY OF CLINICAL TRIALS USING CMV-TARGETED DENDRITIC CELL VACCINES IN PATIENTS WITH GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi51-vi51
Author(s):  
Kristen Batich ◽  
Duane Mitchell ◽  
Patrick Healy ◽  
James Herndon ◽  
Gloria Broadwater ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Recurrent Glioblastoma ◽  
Cox Proportional Hazards Model ◽  
Total N ◽  
Dc Vaccine ◽  
Dc Vaccines

Abstract INTRODUCTION Vaccination with dendritic cells (DCs) fares poorly in primary and recurrent glioblastoma (GBM). Moreover, GBM vaccine trials are often underpowered due to limited sample size. METHODS To address these limitations, we conducted three sequential clinical trials utilizing Cytomegalovirus (CMV)-specific DC vaccines in patients with primary GBM. Autologous DCs were generated and electroporated with mRNA encoding for the CMV protein pp65. Serial vaccination was given throughout adjuvant temozolomide cycles, and 111Indium radiolabeling was implemented to assess migration efficiency of DC vaccines. Patients were followed for median overall survival (mOS) and OS. RESULTS Our initial study was the phase II ATTAC study (NCT00639639; total n=12) with 6 patients randomized to vaccine site preconditioning with tetanus-diphtheria (Td) toxoid. This led to an expanded cohort trial (ATTAC-GM; NCT00639639) of 11 patients receiving CMV DC vaccines containing granulocyte-macrophage colony-stimulating factor (GM-CSF). Follow-up data from ATTAC and ATTAC-GM revealed 5-year OS rates of 33.3% (mOS 38.3 months; CI95 17.5-undefined) and 36.4% (mOS 37.7 months; CI95 18.2-109.1), respectively. ATTAC additionally revealed a significant increase in DC migration to draining lymph nodes following Td preconditioning (P=0.049). Increased DC migration was associated with OS (Cox proportional hazards model, HR=0.820, P=0.023). Td-mediated increased migration has been recapitulated in our larger confirmatory trial ELEVATE (NCT02366728) of 43 patients randomized to preconditioning (Wilcoxon rank sum, Td n=24, unpulsed DC n=19; 24h, P=0.031 and 48h, P=0.0195). In ELEVATE, median follow-up of 42.2 months revealed significantly longer OS in patients randomized to Td (P=0.026). The 3-year OS for Td-treated patients in ELEVATE was 34% (CI95 19-63%) compared to 6% given unpulsed DCs (CI95 1-42%). CONCLUSION We report reproducibility of our findings across three sequential clinical trials using CMV pp65 DCs. Despite their small numbers, these successive trials demonstrate consistent survival outcomes, thus supporting the efficacy of CMV DC vaccine therapy in GBM.

Abstract 15567: Residual Cholesterol and Cardiovascular Events in Patients With Coronary Artery Disease Under Different Glucose Metabolism Status

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jian-jun Li ◽  
Yexuan Cao ◽  
Hui-Wen Zhang ◽  
Jing-Lu Jin ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Glucose Metabolism ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Significant Difference ◽  
Artery Disease

Introduction: The atherogenicity of residual cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). Hypothesis: This study aimed to examine the prognostic value of plasma RC, clinically presented as triglyceride-rich lipoprotein-cholesterol (TRL-C) or remnant-like lipoprotein particles-cholesterol (RLP-C), in CAD patients with different glucose metabolism status. Methods: Fasting plasma TRL-C and RLP-C levels were directly calculated or measured in 4331 patients with CAD. Patients were followed for incident MACEs for up to 8.6 years and categorized according to both glucose metabolism status [DM, pre-DM, normal glycaemia regulation (NGR)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. Results: During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NGR groups (p>0.05). When stratified by status of glucose metabolism and RC levels, highest levels of RLP-C, calculated and measured TRL-C were significant and independent predictors of developing MACEs in pre-DM (HR: 2.10, 1.98, 1.92, respectively; all p<0.05) and DM (HR: 2.25, 2.00, 2.16, respectively; all p<0.05). Conclusions: In this large cohort study with long-term follow-up, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting RC might be a target for patients with impaired glucose metabolism.

scholarly journals Incidence and Predictors of Hospitalization in Patients with Atrial Fibrillation: Results from the Chinese Atrial Fibrillation Registry Study

2020 ◽  
Author(s):  
Zhaojie Dong ◽  
Xin Du ◽  
Shangxin Lu ◽  
Chao Jiang ◽  
Shijun Xia ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cardiovascular Diseases ◽  
Proportional Hazards Model ◽  
Cox Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Chronic Obstructive ◽  
Unique Identifier ◽  
Clinical Trial Registration

Abstract Background: Patients with atrial fibrillation (AF) underwent a high risk of hospitalization, which, however, has not been paid much attention in clinic. Therefore, we aimed to assess the incidence, causes and predictors of hospitalization in AF patients.Methods: From August 2011 to December 2017, 20,172 AF patients from the Chinese Atrial Fibrillation Registry (China-AF) Study were enrolled in this study. We described the incidence, causes of hospitalization according to age and gender categories. The Cox proportional hazards model was employed to identify predictors of first all-cause and first cause-specific hospitalization. Results: After a mean follow-up of 37.3 ± 20.4 months, 7,512 (37.2%) AF patients experienced one or more hospitalizations. The overall incidence of all-cause hospitalization was 24.0 per 100 patient-years. Patients aged < 65 years were predominantly hospitalized for AF (42.1% of the total frequency of hospitalizations); while patients aged 65-74 and ≥ 75 years were mainly hospitalized for non-cardiovascular diseases (43.6% and 49.3%, respectively). Multivariate Cox model analysis verified the higher risk of hospitalization in patients complicated with heart failure (HF)[hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.08-1.24], established coronary artery disease (CAD) (HR 1.26, 95%CI 1.19-1.34), ischemic stroke/transient ischemic attack (TIA) (HR 1.26, 95%CI 1.18-1.33), diabetes (HR 1.16, 95%CI 1.10-1.22), chronic obstructive pulmonary disease (COPD) (HR 1.41, 95%CI 1.13-1.76), gastrointestinal disorder (HR 1.39, 95%CI 1.23-1.58), and renal dysfunction (HR 1.31, 95%CI 1.16-1.48). Conclusions: More than one-third of AF patients included in this study were hospitalized at least once during almost 3 years of follow-up. The main cause for hospitalization among elderly patients (≥65 years) is non-cardiovascular diseases rather than AF. Multidisciplinary management of comorbidities should be advocated as strategies to reduce hospitalization in AF patients.Clinical Trial Registration: URL: http://www.chictr.org.cn/showproj.aspx?proj=5831. Unique identifier: ChiCTR-OCH-13003729.

The Freestyle Valve in Severe Necrotizing Aortic Root Endocarditis: Comorbidity Upon Outcome

2021 ◽  
Author(s):  
Lorenz Hansen ◽  
Ann-Kathrin Ozga ◽  
Michael Klusmeier ◽  
Mathias Hillebrand ◽  
Aysun Tulun ◽  
...  
Keyword(s):  
General Population ◽  
Aortic Root ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Patch Repair ◽  
Patient Specific ◽  
Standardized Mortality Ratio ◽  
Term Outcome

Abstract Background Treatment of severe necrotizing aortic root endocarditis (SNARE) carries a substantial perioperative risk. As an alternative to homografts, we assessed short-term outcome and future prognosis in patients undergoing root replacement using the Freestyle valve. Methods Between 2000 and 2018, a total of 45 patients (mean age 70.9 ± 8.3 years, 66% men) underwent aortic root replacement for SNARE using the Freestyle valve. Mean Society of Thoracic Surgeons mortality score and EuroScore II were 22.6% ± 17.1 and 29.3% ± 20.9, respectively. Prosthetic endocarditis was present in 70.1%, and aortic annulus patch repair was performed in 64% of the patients. Median follow-up was 3.6 years (range: 0.1–14.5) and was 100% complete. Results The 30-day mortality was 15.5%. During follow-up, there were no reoperations, while reinfection was suspected in one patient. Survival was significantly inferior to the general population with a standardized mortality ratio of 10.7 (95% confidence interval [CI]: 9.1–12.6) (p < 0.0001). In 30-day survivors and after correction for significant comorbidities in a Cox proportional hazards model, estimated survival probabilities at 1, 5, and 10 years were 98.7 (95% CI: 92.5–99.8%), 94.1 (77.9–98.5%), and 63.8 (28.4–85.2%). Estimated mean difference in survival probability was better for the general population after postoperative year 6, but within the 95% CI for no difference. Conclusion Use of the Freestyle valve is reliable solution for the most complex cases with a low rate of reinfection. Early mortality is substantial and caused by the patient's condition and severity of the infection. Excess late mortality can be attributed to patient-specific comorbidities.

Post hoc analysis of the CLEAR study in advanced renal cell carcinoma (RCC): Effect of subsequent therapy on survival outcomes in the lenvatinib (LEN) + everolimus (EVE) versus sunitinib (SUN) treatment arms.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4562-4562
Author(s):  
Thomas E. Hutson ◽  
Toni K. Choueiri ◽  
Robert J. Motzer ◽  
Sun Young Rha ◽  
Anna Alyasova ◽  
...  
Keyword(s):  
Median Duration ◽  
Proportional Hazards Model ◽  
Objective Response ◽  
Anticancer Therapy ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
The Sun ◽  
Post Hoc ◽  
The Impact

4562 Background: The multicenter, open-label, randomized, phase 3 CLEAR study showed that LEN + EVE had a significant PFS benefit (HR 0.65, 95% CI 0.53-0.80, P<0.001) and improved objective response rate (relative risk 1.48, 95% CI 1.26-1.74) vs SUN in the first-line treatment of patients (pts) with advanced RCC. The difference in overall survival (OS) for LEN + EVE vs SUN was not statistically significant (HR 1.15, 95% CI 0.88-1.50) (Motzer R et al. NEJM. 2021). Post hoc subgroup analyses were performed to assess the impact of subsequent therapy on OS. Methods: Pts in the CLEAR study were randomly assigned (1:1:1) to 1 of 3 treatment arms, including LEN 18 mg + EVE 5 mg once daily (QD) and SUN 50 mg QD (4 weeks on then 2 weeks off). These post hoc analyses examined OS by subsequent systemic anticancer medication in the LEN + EVE and SUN arms. Hazard ratios (HR; LEN + EVE vs SUN) were based on stratified (geographic region and MSKCC prognostic risk groups) Cox proportional hazards model. Results: Among 1069 pts with advanced RCC randomized in the CLEAR study, 714 pts were randomly assigned to the LEN + EVE and SUN arms (N=357/each). The median duration of survival follow-up was 27 months in the LEN + EVE arm and 26 months in the SUN arm. Given the shorter median duration of study treatment with SUN (7.8 months) vs LEN + EVE (11.0 months), more pts in the SUN arm received subsequent anticancer therapy during survival follow-up (LEN + EVE, n=167; SUN, n=206). Among pts who received subsequent therapy, pts in the LEN + EVE arm had a longer median time from randomization to initiation of subsequent therapy vs those in the SUN arm (8.0 vs 6.6 months, respectively). OS for the overall population, for pts with no subsequent anticancer therapy, and for pts with no subsequent immunotherapy is shown in the table. In the US population subgroup (LEN + EVE, n=62; SUN, n=61) of the CLEAR study, in which a similar number of pts received subsequent systemic anticancer therapies in the LEN + EVE vs SUN arms (62.9% vs 65.6%, respectively), OS was comparable among the 2 arms (HR 0.95, 95% CI 0.51-1.76). Overall, the safety profile was consistent with the known safety profiles of LEN + EVE and SUN. In both arms, most treatment-emergent deaths were due to progressive disease; there were few treatment-related deaths (<1%, per arm) and no clustering of events. Conclusions: In the CLEAR study, LEN + EVE met the primary endpoint of a significant benefit in PFS vs SUN. The results of these exploratory analyses suggest that subsequent systemic anticancer therapy affected the OS outcome results for LEN + EVE vs SUN in the CLEAR study. Clinical trial information: NCT02811861. [Table: see text]

Abstract WP79: Choice Of Treatment And Effect On Hemorrhage Rates Of Unruptured Intracranial Aneurysms

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
James Torner ◽  
Jie Zhang ◽  
David Piepgras ◽  
John Huston ◽  
Irene Meissner ◽  
...  
Keyword(s):  
Intracranial Aneurysms ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Interventional Procedure ◽  
Careful Consideration ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Unruptured Intracranial Aneurysms ◽  
Increased Risk

INTRODUCTION: The decision regarding whether to perform an interventional procedure as a strategy to prevent hemorrhage of an unruptured intracranial aneurysm (UIA) requires careful consideration of procedural risk and the UIA natural history. No randomized trial data are available. The International Study of Unruptured Intracranial Aneurysms (ISUIA) included a prospective cohort, examining hemorrhage risk and treatment risk. Hypothesis: The purpose of this analysis was to compare the factors related to treatment selection and determination of the number of hemorrhages prevented. Methods: Patients were allocated into the initial treatment and untreated cohorts based upon observation or treatment practices in 61 centers from 1991-1998. 1691 patients were in the observational cohort, 471 were in the endovascular cohort and 1917 patients were in the surgical cohort. The cohorts were followed for a median follow-up of 9.2 years. Outcomes were determined prospectively and with central review. The data were grouped together and analyzed to determine treatment decisions. A Cox proportional hazards model predicting hemorrhage developed in the observation cohort and was applied to the surgery and endovascular cohorts across the follow-up period. Results: Significant baseline variable differences between treated and observed patients were aneurysm size, symptoms, age, prior SAH group, geographical region, treatment percentage, aneurysm daughter sacs or multiple lobes, and history of hypertension, smoking and myocardial infarction. Aneurysm site and family history were not significant. Site, size, and aspirin use were significant predictors of hemorrhage. Long-term the predicted hemorrhage rates were 6.7% at 5 years and 8.0% at 10 years in the surgery group and 8.1% and 9.6% for the endovascular group, respectively. For comparison the rates in the observed cohort were 4.1% and 4.8%, respectively. Conclusions: Decisions for treatment are influenced by patient characteristics such as age and medical history, aneurysm characteristics such as size and morphology and center and regional practices. Patients in the treated cohorts were at moderately increased risk for hemorrhage compared to those in the observed cohort.

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