21. Immunotherapy for metastatic non-small cell lung cancer : real-world data from an academic Central and Eastern European centerMarija Ivanović, Lea Knez, Ana Herzog, Mile Kovačević, Tanja Čufer, 2021, original scientific article Abstract: Background. Immunotherapy with immune checkpoint inhibitors (ICIs) recently became the standard treatment for patients with advanced non-small cell lung cancer (NSCLC). Here, we present the first results of a real-world observational study on the effectiveness of ICI monotherapy in patients with advanced NSCLC treated at a single academic center in a Central and Eastern European (CEE) country. Materials and methods. Overall, 66 consecutive patients with advanced NSCLC treated with ICIs in everyday clinical practice, either with first-line pembrolizumab (26 patients) or second-line atezolizumab, nivolumab, or pembrolizumab (40 patients), from August 2015 to November 2018, were included. All data were retrieved from a hospital lung cancer registry, in which the data is collected prospectively. Results. Included patients had a median age of 64 years, most were male (55%), 6% were in performance status >/=2, and 18% had controlled central nervous system metastases at baseline. In first-line, the median progression-free survival (mPFS) was 9.3 months, while the median overall survival (mOS) was not reached. The 1-year overall survival (OS) was 62%. In second-line, the mPFS and mOS were 3.5 months and 9.9 months, respectively, with a 1-year OS of 35%. In the overall population, adverse events of any grade were recorded in 79% of patients and of severe grade (3-4) in 12% of patients. Conclusion. The first real-world outcomes of NSCLC immunotherapy from a CEE country suggest comparable effectiveness to those observed in clinical trials and other real-world series, mainly coming from North America and Western European countries. Further data to inform on the real-world effectiveness of immunotherapy worldwide are needed.
Keywords: non-small cell lung carcinoma, immunotherapy, advanced non-small cell lung cancer, real-world data, Central Europe, Europe, Eastern Europe
Published in DiRROS: 12.10.2021; Views: 957; Downloads: 292
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22. Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN) : a retrospective analysis of patients treated through an access programOliver Illini, Maximilian J Hochmair, Hannah Fabikan, Christoph Weinlinger, Amanda Tufman, Aurélie Swalduz, Kristina Lamberg, Sayed M. S. Hashemi, Florian Huemer, Anders Vikström, Katja Mohorčič, 2021, original scientific article Abstract: Introduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown. Methods: A retrospective efficacy and safety analysis was performed on data from RET fusio-%positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021. Results: Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38-89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naïve, while 37 were pretreated with a median of three lines of therapy (range, 1-8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53-81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8-22.4) after a median follow-up of 9 months. In patients with measurable brain metastases (n=8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade >/=3 TRAEs were increased liver enzyme levels (in 10% of patients), prolonged QTc time (4%), abdominal pain (4%), hypertension (4%), and fatigue/asthenia (4%). None of patients discontinued selpercatinib treatment for safety reasons. No new safety concerns were observed, nor where there any treatment-related death. Conclusions: In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated.
Keywords: non-small cell lung carcinoma -- drug therapy -- genetics, molecular targeted therapy, real-world data, selpercatinib, targeted therapy, tyrosine kinase inhibitor
Published in DiRROS: 16.06.2021; Views: 1324; Downloads: 729
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24. New features in the dendroTools R package : bootstrapped and partial correlation coefficients for monthly and daily climate dataJernej Jevšenak, 2020, original scientific article Abstract: Climate-growth relationships are usually analysed using monthly climate data. The dendroTools R package also provides methodological approaches that enable climate-growth analysis for daily climate data. Such analysis reveals more complete climate signal patterns. In this article, new functions of the dendroTools R package are presented. Partial correlation coefficients are now implemented and can be used to calculate the strength of a linear relationship between two variables, while controlling for a third variable. Bootstrapped correlations can then be used to provide insights into the confidence intervals of statistical estimates. The calculation of partial and bootstrapped correlations is available for daily and monthly data. Finally, data transformation, S3 generic plotting and summary functions are also presented here.
Keywords: dendroTools, daily climate data, partial correlations, bootstrap, dendroclimatology
Published in DiRROS: 24.09.2020; Views: 1268; Downloads: 573
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25. Completeness of tuberculosis (TB) notification : inventory studies and capture-recapture analyses, six European Union countries, 2014 to 2016Masja Straetemans, Mirjam I Bakker, Sandra Alba, Christina Mergenthaler, Ente Rood, Peter H Andersen, Henrieke Schimmel, Aleksandar Šimunović, Petra Svetina, Carlos Carvalho, 2020, original scientific article Abstract: Background. Progress towards the World Health Organization's End TB Strategy is monitored by assessing tuberculosis (TB) incidence, often derived from TB notification, assuming complete case detection and reporting. This assumption is unlikely to hold in many settings, including European Union (EU) countries. Aim. We aimed to assess observed and estimated completeness of TB notification through inventory studies and capture-recapture (CRC) methodology in six EU countries: Croatia, Denmark, Finland, the Netherlands, Portugal, Slovenia. Methods. We performed record linkage, case ascertainment and CRC analyses of data collected retrospectively from at least three national TB-related registers in each country between 2014 and 2016. Results. Observed completeness of TB notification by inventory studies was 73.9% in Croatia, 98.7% in Denmark, 83.6% in Finland, 81.6% in the Netherlands, 85.8% in Portugal and 100% in Slovenia. Subsequent CRC analysis estimated completeness of TB notification to be 98.4% in Denmark, 76.5% in Finland and 77.0% in Portugal. In Croatia, CRC analyses produced implausible results while in the Netherlands and Slovenia, it was methodologically considered not meaningful. Conclusion. Inventory studies and CRC methodology suggest a TB notification completeness between 73.9% and 100% in the six EU countries. Mandatory reporting by clinicians and laboratories, and cross-checking of registers, strongly contributes to accurate notification rates, but hospital episode registers likely contain a considerable proportion of false-positive TB records and are thus less useful. Further strengthening routine surveillance to count TB cases, i.e. incidence, accurately by employing record-linkage of high-quality TB registers should make CRC studies obsolete in EU countries.
Keywords: Mycobacterium tuberculosis, tuberculosis, incidence, public health surveillance, registries, reporting, notification, data collection, data analysis
Published in DiRROS: 27.07.2020; Views: 1515; Downloads: 1074
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26. Daily climate data reveal stronger climate-growth relationships for an extended European tree-ring networkJernej Jevšenak, 2019, original scientific article Abstract: An extended European tree-ring network was compiled from various sources of tree-ring data from Europe, northern Africa and western Asia. A total of 1860 tree-ring chronologies were used to compare correlation coefficients calculated with aggregated day-wise and month-wise mean temperature, sums of precipitation and standardised precipitation-evapotranspiration index (SPEI). For the daily approach, climate data were aggregated over periods ranging from 21 to 365 days. Absolute correlations calculated with day-wise aggregated climate data were on average higher by 0.060 (temperature data), 0.076 (precipitation data) and 0.075 (SPEI data). Bootstrapped correlations are computationally expensive and were therefore calculated on a 69.4% subset of the data. Bootstrapped correlations indicated statistically significant differences between the daily and monthly approach in approximately 1% of examples. A comparison of time windows used for calculations of correlations revealed slightly later onset and earlier ending day of the year for the daily approach, while the largest differences between the two approaches arise from window lengths: Correlations calculated with day-wise aggregated climate data were calculated using fewer days than the monthly approach. Differences in the onset and ending dates of periods for the daily and monthly approaches were greater for precipitation and SPEI data than for temperature data.
Keywords: tree rings, dendroclimatology, tree-ring network, daily climate data, climate-growth relationships, dendroTools
Published in DiRROS: 21.08.2019; Views: 2287; Downloads: 1058
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27. Estimation of carbon fluxes from Eddy covariance data and satellite-derived vegetation indices in a Karst grassland (Podgorski Kras, Slovenia)Koffi Dodji Noumonvi, Mitja Ferlan, Klemen Eler, Giorgio Alberti, Alessandro Peressotti, Sofia Cerasoli, 2019, original scientific article Keywords: eddy covariance, carbon flux, GPP, NEE, vegetation indices, remote sensing, satellite data, GPP map
Published in DiRROS: 10.04.2019; Views: 2551; Downloads: 1538
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28. DendroTools : R package for studying linear and nonlinear responses between tree-rings and daily environmental dataJernej Jevšenak, Tom Levanič, original scientific article Abstract: We introduce in this paper the dendroTools R package for studying the statistical relationships between tree-ring parameters and daily environmental data. The core function of the package is daily_response(), which works by sliding a moving window through daily environmental data and calculating statistical metrics with one or more tree ring proxies. Possible metrics are correlation coefficient, coefficient of determination and adjusted coeffi- cient of determination. In addition to linear regression, it is possible to use a nonlinear artificial neural network with the Bayesian regularization training algorithm (brnn). dendroTools provides the opportunity to use daily climate data and robust nonlinear functions for the analysis of climate-growth relationships. Models should thus be better adapted to the real (continuous) growth of trees and should gain in predictive capabilities. The dendroTools R package is freely available in the CRAN repository. The functionality of the package is demonstrated on two examples, one using a mean vessel area (MVA) chronology and one a traditional tree-ring width (TRW).
Keywords: dendroclimatology, daily climate data, running window, nonlinear modelling, tree-ring proxies, climate reconstruction
Published in DiRROS: 16.04.2018; Views: 3027; Downloads: 1895
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