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 ◽  
...  

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.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4500-4500 ◽  
Author(s):  
Brian I. Rini ◽  
Elizabeth R. Plimack ◽  
Viktor Stus ◽  
Rustem Gafanov ◽  
Robert Hawkins ◽  
...  

4500 Background: In KEYNOTE-426, pembro + axi significantly improved OS (HR 0.53, P < .0001), PFS (HR 0.69, P = .0001), and ORR (59.3% vs 35.7%, P < .0001) vs sunitinib and had manageable toxicity as first-line therapy for mRCC (NCT02853331). The pembro + axi benefit was observed across all IMDC risk groups and regardless of PD-L1 expression. We present data for the combined intermediate/poor risk group and for patients (pts) with sarcomatoid features. Methods: 861 eligible pts with clear-cell mRCC, no prior systemic therapy for mRCC, and KPS ≥70 were randomized 1:1 to pembro 200 mg IV Q3W for a maximum of 35 cycles plus axi 5 mg orally BID (N = 432) or sunitinib 50 mg orally QD (4-wk on/2-wk off) (N = 429). Primary endpoints were OS and PFS (RECIST v1.1 by blinded, independent central review [BICR]). ORR (RECIST v1.1 by BICR) was the key secondary endpoint. The intermediate/poor risk group was prespecified; the sarcomatoid group was exploratory. HRs and their 95% CIs were calculated with a Cox proportional hazards model. None of the analyses were multiplicity-controlled. Results: 592 (68.8%) of all randomized pts were of IMDC intermediate/poor risk — 294 in the pembro + axi arm, 298 in the sunitinib arm. Pembro + axi improved OS (HR 0.52, 95% CI 0.37-0.74; 12-mo rate 87.3% vs 71.3%), PFS (HR 0.67, 95% CI 0.53-0.85; median 12.6 vs 8.2 mo), and ORR (55.8% [95% CI 49.9-61.5] vs 29.5% [24.4-35.1]) in pts with intermediate/poor risk; CR rates were 4.8% (95% CI 2.6-7.9) vs 0.7% (0.1-2.4). Of the 578 pts with known status, 105 (18.2%) had sarcomatoid features — 51 in the pembro + axi arm, 54 in the sunitinib arm. Pembro + axi improved OS (HR 0.58, 95% CI 0.21-1.59; 12-mo rate 83.4% vs 79.5%), PFS (HR 0.54, 95% CI 0.29-1.00; median not reached vs 8.4 mo), and ORR (58.8% [95% CI 44.2-72.4] vs 31.5% [19.5-45.6]) in pts with sarcomatoid features; CR rates were 11.8% (95% CI 4.4-23.9) vs 0% (0.0-6.6). Conclusions: Pembro + axi provides benefit in the combined population of pts with IMDC intermediate or poor risk and in pts whose tumors had sarcomatoid features. The observed benefits were consistent with those seen in the total population. Clinical trial information: NCT02853331.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 420-420
Author(s):  
Gustavo Figueiredo Marcondes Westin ◽  
Samer Alsidawi ◽  
Chandrikha Chandrasekharan ◽  
Andrew M. Briggler ◽  
Brendon Huffman ◽  
...  

420 Background: Advanced biliary cancers respond poorly to chemotherapy and have a dismal survival. Currently gemcitabine-cisplatin (GC) is the standard of care for patients with advanced disease. The efficacy of second line treatment options is not well-defined. We retrospectively evaluated outcomes of patients undergoing second line treatment for advanced biliary cancers at Mayo Clinic. Methods: After obtaining approval from the institutional board review (IRB), we identified 42 patients with advanced and metastatic biliary cancers that progressed after first line (GC) and received second line treatment from 2007-2014. All patients had adequate follow up data. JMP software was used for statistical analysis. Kaplan-Meier method and log-rank tests were used for survival analysis, and multivariate cox proportional hazards model was used to evaluate the prognostic effect of pertinent clinical variables. All tests were two sided and a P value of < 0.05 was considered significant. Results: The median age at diagnosis was 61.5 (range 26-87). The most common regimens used for second line settings were 5-FU-based (69%) followed by gemcitabine-based regimens (19%). The overall response rate (ORR) was 9.1%, while the disease control rate (DCR; stable disease and partial response) was 33%. The median overall survival (mOS) for the entire cohort from first line was 16.8 months (95% CI 12.7-21.7) and the progression-free survival (PFS) was 9.16 months (95% CI 7.3-14.7). From second line start the mOS was 10.4 months (95%; CI 7.3-23.7), and PFS was 2.8 months (95% CI 2.3-4.0). 73% of patients who received second line therapy were alive at 6 months and 50% at 12 months. 25 patients received third line treatment after progression. An univariate and multivariate analysis were performed including age, sex, stage at diagnosis, regimen used, CA19-9 and total body weight loss > 5%, but no significant prognostic factors were identified. Conclusions: Patients with biliary cancers who progress after first line treatment have poor prognosis, but may benefit from second line regimens. 5-FU based regimens were the most commonly used in the second line setting, and 73% of patients who received second line therapy were alive at 6 months.


2021 ◽  
pp. 93-122
Author(s):  
E. S. Andronova ◽  
A. I. Rey ◽  
G. R. Akzhigitova

This paper explores firm survival in Russian retail industry in cases of digital multi-sided platforms penetration such as aggregator Yandex.Market, marketplace Wildberries, electronic store Ozon and classified-ad service Avito. The panel data set of 130 thousand firms was analyzed using two methods: non-parametric Kaplan—Meier estimator and semi-parametric Cox proportional hazards model with time dependent covariates. Kaplan—Meier estimator calculates the survival function for censored data. Cox proportional hazards model examines the effect of platform penetration on hazard rates of differently sized firms in various industry spheres. Platforms-aggregators Yandex.Market and Wildberries have a strong positive impact on firm survival while platformsdisruptors Ozon and Avito increase likelihood of firm failure. The main results of platform influence in various industry spheres are as follows: the aggregator of price offers has a more positive impact on segments with high information asymmetry; and firms specialized on Wildberries key product categories enjoy lower hazard ratios of bankruptcy or liquidation. These hypotheses are not supported for Ozon and Avito platforms.


2017 ◽  
Vol 25 (5) ◽  
pp. 649-654 ◽  
Author(s):  
Kotaro Suemitsu ◽  
Tatsuya Shiraki ◽  
Osamu Iida ◽  
Hiroki Kobayashi ◽  
Yuki Matsuoka ◽  
...  

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.


Crisis ◽  
2018 ◽  
Vol 39 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Kuan-Ying Lee ◽  
Chung-Yi Li ◽  
Kun-Chia Chang ◽  
Tsung-Hsueh Lu ◽  
Ying-Yeh Chen

Abstract. Background: We investigated the age at exposure to parental suicide and the risk of subsequent suicide completion in young people. The impact of parental and offspring sex was also examined. Method: Using a cohort study design, we linked Taiwan's Birth Registry (1978–1997) with Taiwan's Death Registry (1985–2009) and identified 40,249 children who had experienced maternal suicide (n = 14,431), paternal suicide (n = 26,887), or the suicide of both parents (n = 281). Each exposed child was matched to 10 children of the same sex and birth year whose parents were still alive. This yielded a total of 398,081 children for our non-exposed cohort. A Cox proportional hazards model was used to compare the suicide risk of the exposed and non-exposed groups. Results: Compared with the non-exposed group, offspring who were exposed to parental suicide were 3.91 times (95% confidence interval [CI] = 3.10–4.92 more likely to die by suicide after adjusting for baseline characteristics. The risk of suicide seemed to be lower in older male offspring (HR = 3.94, 95% CI = 2.57–6.06), but higher in older female offspring (HR = 5.30, 95% CI = 3.05–9.22). Stratified analyses based on parental sex revealed similar patterns as the combined analysis. Limitations: As only register-­based data were used, we were not able to explore the impact of variables not contained in the data set, such as the role of mental illness. Conclusion: Our findings suggest a prominent elevation in the risk of suicide among offspring who lost their parents to suicide. The risk elevation differed according to the sex of the afflicted offspring as well as to their age at exposure.


2020 ◽  
Vol 132 (4) ◽  
pp. 998-1005 ◽  
Author(s):  
Haihui Jiang ◽  
Yong Cui ◽  
Xiang Liu ◽  
Xiaohui Ren ◽  
Mingxiao Li ◽  
...  

OBJECTIVEThe aim of this study was to investigate the relationship between extent of resection (EOR) and survival in terms of clinical, molecular, and radiological factors in high-grade astrocytoma (HGA).METHODSClinical and radiological data from 585 cases of molecularly defined HGA were reviewed. In each case, the EOR was evaluated twice: once according to contrast-enhanced T1-weighted images (CE-T1WI) and once according to fluid attenuated inversion recovery (FLAIR) images. The ratio of the volume of the region of abnormality in CE-T1WI to that in FLAIR images (VFLAIR/VCE-T1WI) was calculated and a receiver operating characteristic curve was used to determine the optimal cutoff value for that ratio. Univariate and multivariate analyses were performed to identify the prognostic value of each factor.RESULTSBoth the EOR evaluated from CE-T1WI and the EOR evaluated from FLAIR could divide the whole cohort into 4 subgroups with different survival outcomes (p < 0.001). Cases were stratified into 2 subtypes based on VFLAIR/VCE-T1WIwith a cutoff of 10: a proliferation-dominant subtype and a diffusion-dominant subtype. Kaplan-Meier analysis showed a significant survival advantage for the proliferation-dominant subtype (p < 0.0001). The prognostic implication has been further confirmed in the Cox proportional hazards model (HR 1.105, 95% CI 1.078–1.134, p < 0.0001). The survival of patients with proliferation-dominant HGA was significantly prolonged in association with extensive resection of the FLAIR abnormality region beyond contrast-enhancing tumor (p = 0.03), while no survival benefit was observed in association with the extensive resection in the diffusion-dominant subtype (p=0.86).CONCLUSIONSVFLAIR/VCE-T1WIis an important classifier that could divide the HGA into 2 subtypes with distinct invasive features. Patients with proliferation-dominant HGA can benefit from extensive resection of the FLAIR abnormality region, which provides the theoretical basis for a personalized resection strategy.


Risks ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 103
Author(s):  
Morne Joubert ◽  
Tanja Verster ◽  
Helgard Raubenheimer ◽  
Willem D. Schutte

Survival analysis is one of the techniques that could be used to predict loss given default (LGD) for regulatory capital (Basel) purposes. When using survival analysis to model LGD, a proposed methodology is the default weighted survival analysis (DWSA) method. This paper is aimed at adapting the DWSA method (used to model Basel LGD) to estimate the LGD for International Financial Reporting Standard (IFRS) 9 impairment requirements. The DWSA methodology allows for over recoveries, default weighting and negative cashflows. For IFRS 9, this methodology should be adapted, as the estimated LGD is a function of in the expected credit losses (ECL). Our proposed IFRS 9 LGD methodology makes use of survival analysis to estimate the LGD. The Cox proportional hazards model allows for a baseline survival curve to be adjusted to produce survival curves for different segments of the portfolio. The forward-looking LGD values are adjusted for different macro-economic scenarios and the ECL is calculated for each scenario. These ECL values are probability weighted to produce a final ECL estimate. We illustrate our proposed IFRS 9 LGD methodology and ECL estimation on a dataset from a retail portfolio of a South African bank.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Farhadian ◽  
Sahar Dehdar Karsidani ◽  
Azadeh Mozayanimonfared ◽  
Hossein Mahjub

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.


Author(s):  
Yuko Yamaguchi ◽  
Marta Zampino ◽  
Toshiko Tanaka ◽  
Stefania Bandinelli ◽  
Yusuke Osawa ◽  
...  

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.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Funada ◽  
Y Goto ◽  
T Maeda ◽  
H Okada ◽  
M Takamura

Abstract Background/Introduction Shockable rhythm after cardiac arrest is highly expected after early initiation of bystander cardiopulmonary resuscitation (CPR) owing to increased coronary perfusion. However, the relationship between bystander CPR and initial shockable rhythm in patients with out-of-hospital cardiac arrest (OHCA) remains unclear. We hypothesized that chest-compression-only CPR (CC-CPR) before emergency medical service (EMS) arrival has an equivalent effect on the likelihood of initial shockable rhythm to the standard CPR (chest compression plus rescue breathing [S-CPR]). Purpose We aimed to examine the rate of initial shockable rhythm and 1-month outcomes in patients who received bystander CPR after OHCA. Methods The study included 59,688 patients (age, ≥18 years) who received bystander CPR after an OHCA with a presumed cardiac origin witnessed by a layperson in a prospectively recorded Japanese nationwide Utstein-style database from 2013 to 2017. Patients who received public-access defibrillation before arrival of the EMS personnel were excluded. The patients were divided into CC-CPR (n=51,520) and S-CPR (n=8168) groups according to the type of bystander CPR received. The primary end point was initial shockable rhythm recorded by the EMS personnel just after arrival at the site. The secondary end point was the 1-month outcomes (survival and neurologically intact survival) after OHCA. In the statistical analyses, a Cox proportional hazards model was applied to reflect the different bystander CPR durations before/after propensity score (PS) matching. Results The crude rate of the initial shockable rhythm in the CC-CPR group (21.3%, 10,946/51,520) was significantly higher than that in the S-CPR group (17.6%, 1441/8168, p&lt;0.0001) before PS matching. However, no significant difference in the rate of initial shockable rhythm was found between the 2 groups after PS matching (18.3% [1493/8168] vs 17.6% [1441/8168], p=0.30). In the Cox proportional hazards model, CC-CPR was more negatively associated with the initial shockable rhythm before PS matching (unadjusted hazards ratio [HR], 0.97; 95% confidence interval [CI], 0.94–0.99; p=0.012; adjusted HR, 0.92; 95% CI, 0.89–0.94; p&lt;0.0001) than S-CPR. After PS matching, however, no significant difference was found between the 2 groups (adjusted HR of CC-CPR compared with S-CPR, 0.97; 95% CI, 0.94–1.00; p=0.09). No significant differences were found between C-CPR and S-CPR in the 1-month outcomes after PS matching as follows, respectively: survival, 8.5% and 10.1%; adjusted odds ratio, 0.89; 95% CI, 0.79–1.00; p=0.07; cerebral performance category 1 or 2, 5.5% and 6.9%; adjusted odds, 0.86; 95% CI, 0.74–1.00; p=0.052. Conclusions Compared with S-CPR, the CC-CPR before EMS arrival had an equivalent multivariable-adjusted association with the likelihood of initial shockable rhythm in the patients with OHCA due to presumed cardiac causes that was witnessed by a layperson. Funding Acknowledgement Type of funding source: None


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