Dataset Information

Treatment and overall survival in renal cell carcinoma: a Swedish population-based study (2000-2008).

ABSTRACT: This retrospective register study assessed overall survival (OS) and influential factors on OS in Swedish renal cell carcinoma (RCC) patients.Using three merged national health registers, Cox proportional-hazards analysis was conducted and, in three models, it was used to assess the impact of cytokine (interferon-? and tyrosine kinase inhibitor (TKI; sunitinib or sorafenib) treatment on OS in metastatic (m)RCC.From 2000 to 2008, 8009 patients were diagnosed with RCC and 2753 with mRCC (2002-2008). Median OS in RCC patients diagnosed from 2006 to 2008 compared with 2000-2005 was not reached vs 47.9 months (P<0.001), and in mRCC patients diagnosed from 2006 to 2008 compared with 2002-2005, was 12.4 vs 9.6 months, respectively (P=0.004). Factors associated with significantly improved OS in RCC were female gender, lower age, and previous nephrectomy, and, in mRCC female gender, previous nephrectomy, and any TKI prescription (Model 1: median-adjusted OS, 19.4 months (TKI patients) vs 9.7 months (non-TKI patients); hazard ratio, 0.621; P<0.001).OS was improved in Swedish patients diagnosed with RCC and mRCC in the period 2006-2008 compared with 2000-2005 (RCC) and 2002-2005 (mRCC). Although multifactorial in origin, results suggest that increased nephrectomy rates and the use of TKIs contributed to the improvement seen in mRCC patients.

SUBMITTER: Wahlgren T

PROVIDER: S-EPMC3629428 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Treatment and overall survival in renal cell carcinoma: a Swedish population-based study (2000-2008).

Wahlgren T T Harmenberg U U Sandström P P Lundstam S S Kowalski J J Jakobsson M M Sandin R R Ljungberg B B

British journal of cancer 20130326 7

<h4>Background</h4>This retrospective register study assessed overall survival (OS) and influential factors on OS in Swedish renal cell carcinoma (RCC) patients.<h4>Methods</h4>Using three merged national health registers, Cox proportional-hazards analysis was conducted and, in three models, it was used to assess the impact of cytokine (interferon-α and tyrosine kinase inhibitor (TKI; sunitinib or sorafenib) treatment on OS in metastatic (m)RCC.<h4>Results</h4>From 2000 to 2008, 8009 patients we ...[more]

PMID: 23531701

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Project description:ImportanceAnaplastic thyroid carcinoma (ATC) historically has a 4-month median overall survival (OS) from time of diagnosis, with disease-specific mortality approaching 100%. The association between recent major advancements in treatment and OS has yet to be evaluated.ObjectiveTo evaluate rates of OS in patients with ATC over the last 2 decades.Design, setting, and participantsRetrospective cohort study in a single tertiary care institution. Patients with histopathological confirmation of ATC from January 2000 to October 2019 were included and divided into 3 groups according to date of presentation: 2000-2013, 2014-2016, and 2017-2019.Main outcomes and measuresOverall survival compared among different treatment eras and differing therapies, including targeted therapy, immunotherapy, and surgery.ResultsOf 479 patients (246 men [51%]; median age, 65.0 [range, 21.1-92.6] years) with ATC evaluated, 52 (11%) were stage IVA, 172 (36%) stage IVB, and 255 (53%) stage IVC at presentation. The median OS of the entire cohort was 0.79 years (9.5 months), ranging from 0.01 to 16.63. The OS at 1 and 2 years was 35% (95% CI, 29%-42%) and 18% (95% CI, 13%-23%) in the 2000-2013 group (n = 227), 47% (95% CI, 36%-56%) and 25% (95% CI, 17%-34%) in the 2014-2016 group (n = 100), and 59% (95% CI, 49%-67%) and 42% (95% CI, 30%-53%) in the 2017-2019 group (n = 152), respectively (P < .001). The hazard ratio was 0.50 (95% CI, 0.38-0.67) for the 2017-2019 group compared with the 2000-2013 patients (P < .001). Factors associated with improved OS included targeted therapy (hazard ratio, 0.49; 95% CI, 0.39-0.63; P < .001), the addition of immunotherapy to targeted therapy (hazard ratio, 0.58; 95% CI, 0.36-0.94; P = .03), and surgery following neoadjuvant BRAF-directed therapy (hazard ratio, 0.29; 95% CI, 0.10-0.78; P = .02). Patients undergoing surgery following neoadjuvant BRAF-directed therapy (n = 20) had a 94% 1-year survival with a median follow-up of 1.21 years.Conclusion and relevanceIn this large single-institution cohort study spanning nearly 20 years, changes in patient management appear to be associated with significant increase in survival. The era of untreatable ATC is progressively being replaced by molecular-based personalized therapies, with integration of multidisciplinary therapies including surgery and radiation therapy.

Project description:Background:To establish and validate nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with papillary renal cell carcinoma (pRCC). Methods:Patients diagnosed with pRCC between 2010 and 2014 in the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively included in this study and divided into training and validation groups randomly. Uni- and multivariate Cox regression analyses were used to identify significant variables related to OS and CSS in the training group. Based on results of multivariate Cox regression analysis, nomograms for 3- and 5-year CSS and OS were established, respectively. Additionally, Kaplan-Meier (KM) survival curves were produced to learn the actual effects of different variables. Finally, the nomograms were evaluated both in the training group and the validation group using the area under the receiver operating characteristic (ROC) curve, the concordance index (C-index) and calibration curves. Results:A total of 4,859 eligible patients were enrolled, with 3,403 categorized into the training group and 1,456 into the validation group. Seven factors [age, T stage, N stage, M stage, use of surgery/lymph node removal (LNR) and insurance status] were significantly related to OS and seven factors (age, T stage, N stage, M stage and use of surgery/chemotherapy/LNR) were significantly associated with CSS. These factors were eventually included in the predictive nomograms. The C-indexes for OS in the training and validation groups were 0.764 and 0.723 respectively, and 0.859 and 0.824 for CSS. The 3- and 5-year AUCs for OS were 0.779 and 0.752 in the training cohort, and 0.749 and 0.722 in the validation cohort. Similarly, 3- and 5-year AUCs for OS were 0.871 and 0.844 in the training cohort, and 0.853 and 0.822 in the validation group. Finally, the calibration curves suggested that the predictive nomograms had a good consistency between the observed and the predicted survival. Conclusions:It was the first time to develop nomograms to predict the survival outcomes of pRCC patients. The prognostic nomograms were reliable with high accuracy, which might have guiding significance for clinical practice.

Project description:Renal-cell carcinoma (RCC) affects over 330,000 new patients every year, of whom 1/3 present with metastatic RCC (mRCC) at diagnosis. Most mRCC patients treated with a first-line agent relapse within 1 year and need second-line therapy. The present study aims to compare overall survival (OS) between nivolumab and cabozantinib from two recent pivotal studies comparing, respectively, each one of the two emerging treatments against everolimus in patients who relapse following first-line treatment. Comparison is traditionally carried out using the Bucher method, which assumes proportional hazard. Since OS curves intersected in one of the pivotal studies, models not assuming proportional hazards were also considered to refine the comparison. Four Bayesian parametric survival network meta-analysis models were implemented on overall survival (OS) data digitized from the Kaplan-Meier curves reported in the studies. Three models allowing hazard ratios (HR) to vary over time were assessed against a fixed-HR model. The Bucher method favored cabozantinib, with a fixed HR for OS vs. nivolumab of 1.09 (95% confidence interval: [0.77, 1.54]). However, all models with time-varying HR showed better fits than the fixed-HR model. The log-logistic model fitted the data best, exhibiting a HR for OS initially favoring cabozantinib, the trend inverting to favor nivolumab after month 5 (95% credible interval <1 from 10 months). The initial probability of cabozantinib conferring superior OS was 54%, falling to 41.5% by month 24. Numerical differences in study-adjusted OS estimates between the two treatments remained small. This study evidences that HR for OS of nivolumab vs. cabozantinib varies over time, favoring cabozantinib in the first months of treatment but nivolumab afterwards, a possible indication that patients with poor prognosis benefit more from cabozantinib in terms of survival, nivolumab benefiting patients with better prognosis. More evidence, including real-world observational data, is needed to compare effectiveness between cabozantinib and nivolumab.

Project description:ContextCurrent guidelines suggest several targeted therapies (TTs) and immunotherapies (ITs) in the treatment of advanced or metastatic renal cell carcinoma (mRCC). Ideal sequencing of these treatments is unclear.ObjectiveThe primary objective was to evaluate the overall survival (OS) data of the treatments approved for mRCC. Secondary objectives included evaluating other signs of efficacy and adverse events.Evidence acquisitionWe reviewed the current Food and Drug Administration-approved treatments for mRCC. Trials associated with approval were reviewed. We also included pre- and postapproval publications when appropriate.Evidence synthesisThere is minimal evidence supporting OS benefit for the nine approved TTs. They result in adverse events and are a considerable economic burden. For these reasons, their future role in mRCC treatment should be re-evaluated, given the emergence of IT that have demonstrated OS benefits. Accumulating long-term survival data with high-dose interleukin-2 treatment suggests that this older treatment could still be considered for eligible patients. Checkpoint inhibitors have shown promising OS and durable responses; as such, the high cost of treatment might be justified. However, the available evidence does not suggest that adding TT to IT would increase efficacy over IT alone, but would add toxicity.ConclusionsTrial data supporting OS benefit are much stronger for ITs than for TTs. Combining checkpoint inhibitors with TTs has not been shown to produce better OS than checkpoint inhibitors alone, while more adverse events are present. Granting drug approvals based on efficacy without demonstrated OS benefit should be revisited.Patient summaryApproved treatments for metastatic kidney cancer include targeted and immune-based therapies. The former commonly produces temporary tumour shrinkage, but survival benefits are unclear. All approved immunotherapies have increased survival, and a proportion of patients appear cured.

Project description:Study questionIs first birth Caesarean delivery associated with a lower likelihood of subsequent childbearing when compared with first birth vaginal delivery?Summary answerIn this study of US women whose first delivery was in 2000, those who had a Caesarean delivery were less likely to have a subsequent live birth than those who delivered vaginally.What is already knownSome studies have reported lower birth rates subsequent to Caesarean delivery in comparison with vaginal delivery, while other studies have reported no difference.Study design, size, durationWe conducted a retrospective cohort study of 52 498 women who had a first singleton live birth in the State of Pennsylvania, USA in 2000 and were followed to the end of 2008 via Pennsylvania birth certificate records to identify subsequent live births during the 8- to 9-year follow-up period.Participants/materials, setting, methodsBirth certificate records of first singleton births were linked to the hospital discharge data for each mother and newborn, and linked to all birth certificate records for each mother's subsequent deliveries which occurred in 2000 to the end of 2008. Poisson regression models were used to evaluate the association between first birth factors and whether or not there was a subsequent live birth during the follow-up period.Main results and the role of chanceOver an average of 8.5 years of follow-up, 40.2% of women with a Caesarean first birth did not have a subsequent live birth, compared with 33.1% of women with a vaginal first birth (risk ratio (RR): 1.21, 95% confidence interval (CI): 1.18-1.25). Adjustment for the demographic confounders of maternal age, race, education, marital status and health insurance coverage attenuated the RR to 1.16 (95% CI: 1.13-1.19). Specific pregnancy and childbirth-related complications associated with not having a subsequent live birth included diabetes-related disorders, abnormalities of organs and soft tissues of the pelvis, fetal abnormalities, premature or prolonged rupture of membranes, hypertensive disorders, amnionitis, fetal distress and other maternal health problems. However, adjustment for the pregnancy and childbirth complications had little effect on the RR of not having a subsequent live birth (RR = 1.15, 95% CI: 1.11-1.19).Limitations, reasons for cautionWe were unable to distinguish between women who did not have a subsequent live birth and those who moved out of the state, which may have introduced a selection bias if those who had Caesarean births were more likely to emigrate than those who delivered vaginally. In addition we were unable to measure pre-pregnancy body mass index, weight gain during pregnancy and prior infertility, which would have been helpful in our efforts to reduce selection bias.Wider implications of the findingsThe results of this study provide further corroboration of previous studies that have reported reduced fertility subsequent to Caesarean section in comparison with vaginal delivery.Study funding/potential competing interestsThis study was funded by the US National Institute of Child Health and Human Development (NICHD, R01-HD052990). No competing interests are declared.

Dataset Information

Treatment and overall survival in renal cell carcinoma: a Swedish population-based study (2000-2008).

Publications

Treatment and overall survival in renal cell carcinoma: a Swedish population-based study (2000-2008).

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