Real‐world outcomes using PD‐1 antibodies and BRAF + MEK inhibitors for adjuvant melanoma treatment from 39 skin cancer centers in Germany, Austria and Switzerland

Abstract Background Programmed death‐1 (PD‐1) antibodies and BRAF + MEK inhibitors are widely used for adjuvant therapy of fully resected high‐risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real‐world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland. Methods Multicenter, retrospective study investigating stage III–IV melanoma patients receiving adjuvant nivolumab (NIV), pembrolizumab (PEM) or dabrafenib + trametinib (D + T) between 1/2017 and 10/2021. The primary endpoint was 12‐month recurrence‐free survival (RFS). Further analyses included descriptive and correlative statistics, and a multivariate linear‐regression machine learning model to assess the risk of early melanoma recurrence. Results In total, 1198 patients from 39 skin cancer centers from Germany, Austria and Switzerland were analysed. The vast majority received anti PD‐1 therapies (n = 1003). Twelve‐month RFS for anti PD‐1 and BRAF + MEK inhibitor‐treated patients were 78.1% and 86.5%, respectively (hazard ratio [HR] 1.998 [95% CI 1.335–2.991]; p = 0.001). There was no statistically significant difference in overall survival (OS) in anti PD‐1 (95.8%) and BRAF + MEK inhibitor (96.9%) treated patients (p > 0.05) during the median follow‐up of 17 months. Data indicates that anti PD‐1 treated patients who develop immune‐related adverse events (irAEs) have lower recurrence rates compared to patients with no irAEs (HR 0.578 [95% CI 0.443–0.754], p = 0.001). BRAF mutation status did not affect overall efficacy of anti PD‐1 treatment (p > 0.05). In both, anti PD‐1 and BRAF + MEK inhibitor treated cohorts, data did not show any difference in 12‐month RFS and 12‐month OS comparing patients receiving total lymph node dissection (TLND) versus sentinel lymph node biopsy only (p > 0.05). The recurrence prediction model reached high specificity but only low sensitivity with an AUC = 0.65. No new safety signals were detected. Overall, recorded numbers and severity of adverse events were lower than reported in pivotal phase III trials. Conclusions Despite recent advances in adjuvant melanoma treatment, early recurrence remains a significant clinical challenge. This study shows that TLND does not reduce the risk of early melanoma recurrence and should only be considered in selected patients. Data further highlight that variables collected during clinical routine are unlikely to allow for a clinically relevant prediction of individual recurrence risk

Network externalities and the dynamics of markets

Summary in GermanSIGLEAvailable from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, D-21400 Kiel W 66 (1997.09) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

FTPL and the Maturity Structure of Government Debt in the New Keynesian Model

In this paper, we revisit the fiscal theory of the price level (FTPL) within the New Keynesian (NK) model. We show in which cases the average maturity of government debt matters for the transmission of policy shocks. The central task of this paper is to shed light on the theoretical predictions of the maturity structure on macro dynamics with an emphasis on model-implied expectations. In particular, we address the transmission channels of monetary and fiscal policy shocks on the interest rate and inflation dynamics. Our results illustrate the role of the maturity of existing debt in the wake of skyrocketing debt-to-GDP ratios and increasing government expenditures. We highlight our results by quantifying the effects of the large-scale US fiscal packages (CARES) and predict a surge in inflation if the deficits are not sufficiently backed by future surpluses

Network Externalities and the Dynamics of Markets

The evolution of markets on which network externalities prevail can be expected to di#er from "classical markets" where no such externalities exist. We suggest a flexible formal model that describes the dynamics of both types of markets. This leads to a stochastic version of the well known replicator dynamics. Based on this approach we analyze the limit behaviour of di#erent market types where consumers use stochastic decision rules. We show that the market shares converge to the set of equilibria with probability one, where, even under network externalities, several technologies can coexist. On the other hand, even if no network externalities prevail it is possible that only one technology stays in the market. This paper contributes to the work on generalized urn schemes and path dependent processes going on at IIASA. JEL-Classification: D43, D62, D83 Keywords: Network Externalities, Increasing Returns, Lock-In, Replicator Dynamics. -- iii -- Acknowledgements The paper was written..

Wasser- und Stofftransport aus landwirtschaftlich genutzten Flächen in Südwest-Finnland am Ende des 21. Jahrhunderts

vokMAAMY

Climate and air pollution impacts on habitat suitability of Austrian forest ecosystems

Climate change and excess deposition of airborne nitrogen (N) are among the main stressors to floristic biodiversity. One particular concern is the deterioration of valuable habitats such as those protected under the European Habitat Directive. In future, climate-driven shifts (and losses) in the species potential distribution, but also N driven nutrient enrichment may threaten these habitats. We applied a dynamic geochemical soil model (VSD+) together with a novel niche-based plant response model (PROPS) to 5 forest habitat types (18 forest sites) protected under the EU Directive in Austria. We assessed how future climate change and N deposition might affect habitat suitability, defined as the capacity of a site to host its typical plant species. Our evaluation indicates that climate change will be the main driver of a decrease in habitat suitability in the future in Austria. The expected climate change will increase the occurrence of thermophilic plant species while decreasing cold-tolerant species. In addition to these direct impacts, climate change scenarios caused an increase of the occurrence probability of oligotrophic species due to a higher N immobilisation in woody biomass leading to soil N depletion. As a consequence, climate change did offset eutrophication from N deposition, even when no further reduction in N emissions was assumed. Our results show that climate change may have positive side-effects in forest habitats when multiple drivers of change are considered.</p

Regional assessment of the current extent of acidification of surface waters in Europe and North America

Project manager Kari AustnesThe current status of surface water acidification related to air pollution in Europe and North America has been assessed using country reports, monitoring data, critical loads and exceedance data, acid sensitivity and deposition maps, and data reported under the European Commission’s Water Framework Directive (WFD). Acidification is still observed in many countries, but the extent and severity vary. Maps of acid sensitivity and deposition suggest that surface water acidification is present in regions and countries for which no data or reports were delivered for the current assessment. Existing national monitoring varies in the ability to assess the spatial extent of acidification and the recovery responses of acidified sites. The monitoring requirements under the European Union’s National Emission Ceilings Directive are expected to reverse the recent decline in the number of monitoring sites observed in some countries. The information reported under the WFD is currently of limited value in assessing the extent of acidification of surface waters in Europe. Chemical recovery in response to reductions in acid deposition can be slow, and biological recovery can lag severely behind. Despite large and effective efforts across Europe and North America to reduce surface water acidification, air pollution still constitutes a threat to freshwater ecosystems.Norwegian Environment Agency (Miljødirektoratet) United Nations Economic Commission for Europe (UNECE)publishedVersio