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Objective To evaluate serum tumor markers (STM) as predictive biomarkers in advanced non-small cell lung cancer (NSCLC) treated with chemo-immunotherapy. Methods Patients having received platinum-based chemo-(CHT) and PD-1/PD-L1-directed immune checkpoint inhibitor (ICI) combination therapy were retrospectively followed. Carcinoembryonic antigen (CEA), carbohydrate antigen 19–9 (CA19-9), cytokeratin-19 fragments (CYFRA 21–1) and neuron specific enolase (NSE) were routinely measured at NSCLC diagnosis. The marker with the highest relative elevation was defined “leading STM”, its change was assessed between CHT-ICI as well as mono-ICI maintenance initiation and the respective subsequent restaging. Corresponding computed tomography evaluations were analyzed using response evaluation criteria in solid tumors (RECIST). For CHT-ICI combination and subsequent mono-ICI-maintenance therapy, leading STM and RECIST response were evaluated regarding progression-free (PFS) and overall survival (OS) in Kaplan–Meier analyses. Results Among 80 CHT-ICI patients (41% women, mean age 63 years), median PFS was 5 months (M;4,9), median OS was 15M (10,/). PFS was significantly (p=0.042) longer, when the leading STM had decreased at first restaging under CHT-ICI combination therapy (9M (5,12; n=41) vs 5M (3,6; n=16)). In the 54 (67.5%) patients who received subsequent mono-ICI maintenance therapy, STM decrease was similarly associated with significantly (p<0.001) longer PFS (16M (7,/; n=16) vs 3.5M (2,6; n=22)). Patients with radiologically stable or progressive disease and concomitant leading STM decrease had similar PFS in the CHT-ICI combination phase (4M (3,7; n=16) vs 4.5M (2,6; n=14)), but longer PFS in the mono-ICI maintenance setting (13M (7,16; n=10) vs 3M (2,4; n=17)). Median OS was not reached in most subgroups. Conclusion Leading STM dynamics provide predictive biomarker information additional to radiological response evaluation patients receiving CHT-ICI combination therapy, especially in the mono-ICI maintenance setting.

In order to enhance steam mass flow through a turbine it becomes necessary to reduce the flow resistance of the turbine inlet valves. Consequently, a replacement of the high pressure turbine inlet valves is required. The valve combination described in this paper consists of a control valve and an emergency stop valve, opposite to the control valve. Both valves share a common valve seat. The control valve is a single-seat valve with integral pilot disc. A pre-stoke is introduced to allow for moderate opening forces. The emergency stop valve closes in countercurrent with the steam mass flow. The flow through the valve is analyzed by steady state and transient computational flow simulations. In addition to the steam mass flow, the forces acting upon the valve are determined. Transient behavior will be investigated by means of analyzing pressure fluctuations. Therefore frequencies caused by the steam flow are determined in the range up to 2000Hz. It will be shown that neither steady state nor transient simulations with a simple eddy viscosity turbulence model are capable to correctly predict the complex flow inside the valve. More sophisticated turbulence modeling like Large-Eddy simulation is thus inevitable. Furthermore, the physical phenomena causing the transient behavior are discussed. All findings are verified by comparison of the CFD with the measurements.